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Sample records for ii hfir target

  1. Microstructural comparison of HT-9 irradiated in HFIR and EBR-II

    International Nuclear Information System (INIS)

    Gelles, D.S.

    1985-05-01

    A series of specimens of HT-9 heat 91354 have been examined following irradiation in HFIR to 39 dpa at 300, 400, 500 and 600 0 C and following irradiation in EBR-II to 29 dpa at 390 and 500 0 C. HFIR irradiation was found to have promoted helium bubble formation at all temperatures and voids at 400 0 C. Cavitation had not been observed at lower fluence, nor was it found in EBR-II irradiated specimens. The onset of void swelling in HFIR is attributed to helium generation. The observations provide an explanation for saturation of ductile-brittle transition temperature shifts with increasing fluence

  2. HTCAP-1: a program for calcuating operating temperatures in HFIR target irradiation experiments

    International Nuclear Information System (INIS)

    Kania, M.J.; Howard, A.M.

    1980-06-01

    The thermal modeling code, HTCAP-1, calculates in-reactor operating temperatures of fueled specimens contained in the High Flux Isotope Reactor (HFIR) target irradiation experiments (HT-series). Temperature calculations are made for loose particle and bonded fuel rod specimens. Maximum particle surface temperatures are calculated for the loose particles and centerline and surface temperatures for the fuel rods. Three computational models are employed to determine fission heat generation rates, capsule heat transfer analysis, and specimen temperatures. This report is also intended to be a users' manual, and the application of HTCAP-1 to the HT-34 irradiation capsule is presented

  3. HTCAP: a FORTRAN IV program for calculating coated-particle operating temperatures in HFIR target irradiation experiments

    International Nuclear Information System (INIS)

    Kania, M.J.

    1976-05-01

    A description is presented of HTCAP, a computer code that calculates in-reactor operating temperatures of loose coated ThO 2 particles in the HFIR target series of irradiation tests. Three computational models are employed to determine the following: (1) fission heat generation rates, (2) capsule heat transfer analysis, and (3) maximum particle surface temperature within the design of an HT capsule. Maximum particle operating temperatures are calculated at daily intervals during each irradiation cycle. The application of HTCAP to sleeve CP-62 of HT-15 is discussed, and the results are compared with those obtained in an earlier thermal analysis on the same capsule. Agreement is generally within +-5 percent, while decreasing the computational time by more than an order of magnitude. A complete FORTRAN listing and summary of required input data are presented in appendices. Included is a listing of the input data and a tabular output from the thermal analysis of sleeve CP-62 of HT-15

  4. Recovery and purification of nickel-63 from HFIR-irradiated targets

    International Nuclear Information System (INIS)

    Williams, D.F.; O'Kelley, G.D.; Knauer, J.B.; Porter, C.E.; Wiggins, J.T.

    1993-06-01

    The production of large quantities of high-specific-activity 63 Ni (>10 Ci/g) requires both a highly enriched 62 Ni target and a long irradiation period at high neutron flux. Trace impurities in the nickel and associated target materials are also activated and account for a significant fraction of the discharged activity and essentially all of the gamma activity. While most of these undesirable activation products can be removed as chloride complexes during anion exchange, chromium, present at 51 Cr, and scandium, present as 46 Sc, are exceptions and require additional processing to achieve the desired purity. Optimized flowsheets are discussed based upon the current development and production experience

  5. High Flux Isotope Reactor (HFIR)

    Data.gov (United States)

    Federal Laboratory Consortium — The HFIR at Oak Ridge National Laboratory is a light-water cooled and moderated reactor that is the United States’ highest flux reactor-based neutron source. HFIR...

  6. HFIR spent fuel management alternatives

    International Nuclear Information System (INIS)

    Begovich, J.M.; Green, V.M.; Shappert, L.B.; Lotts, A.L.

    1992-01-01

    The High Flux Isotope Reactor (HFIR) at Martin Marietta Energy Systems' Oak Ridge National Laboratory (ORNL) has been unable to ship its spent fuel to Savannah River Site (SRS) for reprocessing since 1985. The HFIR storage pools are expected to fill up in the February 1994 to February 1995 time frame. If a management altemative to existing HFIR pool storage is not identified and implemented before the HFIR pools are full, the HFIR will be forced to shut down. This study investigated several alternatives for managing the HFIR spent fuel, attempting to identify options that could be implemented before the HFIR pools are full. The options investigated were: installing a dedicated dry cask storage facility at ORNL, increasing HFIR pool storage capacity by clearing the HFIR pools of debris and either close-packing or stacking the spent fuel elements, storing the spent fuel at another ORNL pool, storing the spent fuel in one or more hot cells at ORNL, and shipping the spent fuel offsite for reprocessing or storage elsewhere

  7. HFIR Fuel Casting Support

    Energy Technology Data Exchange (ETDEWEB)

    Imhoff, Seth D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gibbs, Paul Jacob [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Solis, Eunice Martinez [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-09-28

    Process exploration for fuel production for the High Flux Isotope Reactor (HFIR) using cast LEU-10wt.%Mo as an initial processing step has just begun. This project represents the first trials concerned with casting design and quality. The studies carried out over the course of this year and information contained in this report address the initial mold development to be used as a starting point for future operations. In broad terms, the final billet design is that of a solid rolling blank with an irregular octagonal cross section. The work covered here is a comprehensive view of the initial attempts to produce a sound casting. This report covers the efforts to simulate, predict, cast, inspect, and revise the initial mold design.

  8. Upgraded HFIR Fuel Element Welding System

    International Nuclear Information System (INIS)

    Sease, John D.

    2010-01-01

    The welding of aluminum-clad fuel plates into aluminum alloy 6061 side plate tubing is a unique design feature of the High Flux Isotope Reactor (HFIR) fuel assemblies as 101 full-penetration circumferential gas metal arc welds (GMAW) are required in the fabrication of each assembly. In a HFIR fuel assembly, 540 aluminum-clad fuel plates are assembled into two nested annular fuel elements 610 mm (24-inches) long. The welding process for the HFIR fuel elements was developed in the early 1960 s and about 450 HFIR fuel assemblies have been successfully welded using the GMAW process qualified in the 1960 s. In recent years because of the degradation of the electronic and mechanical components in the old HFIR welding system, reportable defects in plate attachment or adapter welds have been present in almost all completed fuel assemblies. In October 2008, a contract was awarded to AMET, Inc., of Rexburg, Idaho, to replace the old welding equipment with standard commercially available welding components to the maximum extent possible while maintaining the qualified HFIR welding process. The upgraded HFIR welding system represents a major improvement in the welding system used in welding HFIR fuel elements for the previous 40 years. In this upgrade, the new inner GMAW torch is a significant advancement over the original inner GMAW torch previously used. The innovative breakthrough in the new inner welding torch design is the way the direction of the cast in the 0.762 mm (0.030-inch) diameter aluminum weld wire is changed so that the weld wire emerging from the contact tip is straight in the plane perpendicular to the welding direction without creating any significant drag resistance in the feeding of the weld wire.

  9. Precipitation response of annealed type 316 stainless steel in HFIR irradiations at 550 to 6800C

    International Nuclear Information System (INIS)

    Maziasz, P.J.

    1978-01-01

    Precipitation in annealed type 316 stainless steel after HFIR irradiation at 550--680 0 C to fluences producing 2000--3300 at. ppM He and 30--47 dpa is changed relative to fast reactor or thermal aging exposure to similar temperatures and times. The phases observed after HFIR irradiation are the same as those observed after aging to temperatures 70--200 0 C higher or for much longer times. There is a similar temperature shift in addition to different phases observed for HFIR irradiation compared with EBR-II. The changes observed are coincident with including simultaneous helium production to high levels in the irradiation damage products of the material

  10. Bearings for the HFIR control plates

    International Nuclear Information System (INIS)

    Abbatiello, A.A.

    1975-08-01

    Recent accelerated wear of HFIR bearings seems to be a more advanced stage of the situation encountered in 1967. The latest observations are in agreement with the hypothesis that high-frequency impact loads at a 30 0 angle on these bearings are the apparent basic cause of their short life. In view of the limited possibilities for change at this stage of HFIR operation, the region of best payoff seems to be an increase in the load-carrying area at some acceptable sacrifice of low rolling friction. On this basis three types of bearings are proposed for test--two of these are journal types and one is a slider type. The next planned shutdown for major parts replacement provides an opportunity to test these modified bearing types in the HFIR under full mechanical operating conditions but without nuclear operation. The program is recommended for consideration and adoption. (U.S.)

  11. Plant monitoring and signal validation at HFIR

    International Nuclear Information System (INIS)

    Mullens, J.A.

    1991-01-01

    This paper describes a monitoring system for the Oak Ridge National Laboratory's (ORNL'S) High Flux Isotope Reactor (HFIR). HFIR is an 85 MW pressurized water reactor designed to produce isotopes and intense neutron beams. The monitoring system is described with respect to plant signals and computer system; monitoring overview; data acquisition, logging and network distribution; signal validation; status displays; reactor condition monitoring; reactor operator aids. Future work will include the addition of more plant signals, more signal validation and diagnostic capabilities, improved status display, integration of the system with the RELAP plant simulation and graphical interface, improved operator aids, and an alarm filtering system. 8 refs., 7 figs. (MB)

  12. Irradiation performance of HTGR fertile fuel in HFIR target capsules HT-12 through HT-15. Part I. Experiment description and fission product behavior

    International Nuclear Information System (INIS)

    Kania, M.J.; Lindemer, T.B.; Morgan, M.T.; Robbins, J.M.

    1977-02-01

    Sixteen types of Biso-coated designs, on ThO 2 kernels, were irradiated in High Flux Isotope Reactor target capsules HT-12 through HT-15. The report addresses the description of the experiment and extensive postirradiation analyses and experiments to determine fertile-particle burnup, fuel coating failures, and fission product behavior. Several low-temperature isotropic (LTI) pyrocarbon coatings, which ''survived'' according to visual inspection, were shown to have developed permeability during irradiation. These particles were irradiated at temperatures approximately equal to 1250 0 C and to burnups equal to or greater than 8 percent fission per initial heavy-metal atom (FIMA). No evidence of permeability was found in similar particles irradiated at temperatures approximately equal to 1550 0 C and burnups approximately equal to 16 percent FIMA. Failures due to permeability were not detectable by visual inspection but required a more extensive investigation by the 1000 0 C gaseous chlorine leaching technique. Maximum particle surface operating temperatures were found to be approximately 300 0 C in excess of design limits of 900 0 C (low-temperature magazines) and 1250 0 C (high-temperature magazines). The extremes of high temperatures and fast neutron fluences up to 1.6 x 10 22 neutrons/cm 2 produced severe degradation and swelling of the Poco graphite magazines and sample holders

  13. Postirradiation evaluations of capsules HANS-1 and HANS-2 irradiated in the HFIR target region in support of fuel development for the advanced neutron source

    International Nuclear Information System (INIS)

    Hofman, G.L.; Snelgrove, J.L.; Copeland, G.L.

    1995-08-01

    This report describes the design, fabrication, irradiation, and evaluation of two capsule tests containing U 3 Si 2 fuel particles in contact with aluminum. The tests were in support of fuel qualification for the Advanced Neutron Source (ANS) reactor, a high-powered research reactor that was planned for the Oak Ridge National Laboratory. At the time of these tests, the fuel consisted of U 3 Si 2 , containing highly enriched uranium dispersed in aluminum at a volume fraction of ∼0.15. The extremely high thermal flux in the target region of the High Flux Isotope Reactor provided up to 90% burnup in one 23-d cycle. Temperatures up to 450 degrees C were maintained by gamma heating. Passive SiC temperature monitors were employed. The very small specimen size allowed only microstructural examination of the fuel particles but also allowed many specimens to be tested at a range of temperatures. The determination of fission gas bubble morphology by microstructural examination has been beneficial in developing a fuel performance model that allows prediction of fuel performance under these extreme conditions. The results indicate that performance of the reference fuel would be satisfactory under the ANS conditions. In addition to U 3 Si 2 , particles of U 3 Si, UAl 2 , UAl x , and U 3 O 8 were tested

  14. Reevaluation of HFIR source term: Supplement 2

    International Nuclear Information System (INIS)

    Thomas, W.E.

    1986-11-01

    The HFIR source term has been reevaluated to assess the impact of the increase in core lifetime from 15 to 24 days. Calculations were made to determine the nuclide activities of the iodines, noble gases, and other fission products. The results show that there is no significant change in off-site dose due to the increased fuel cycle for the release scenario postulated in ORNL-3573

  15. Neutron-antineutron transition search at HFIR reactor

    International Nuclear Information System (INIS)

    Kamyshkov, Yuri A.

    1997-01-01

    A new experiment to search for neutron-antineutron transitions was recently proposed for High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL). In this paper the physics motivation of a new search, the scheme and the discovery potential of the proposed HFIR-based experiment are discussed

  16. Neutron-antineutron transition search at HFIR Reactor

    International Nuclear Information System (INIS)

    Kamyshkov, Y.A.

    1997-01-01

    A new experiment to search for neutron-antineutron transitions was recently proposed for High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL). In this paper the physics motivation of a new search, the scheme and the discovery potential of the proposed HFIR-based experiment are discussed

  17. RTNS-II [Rotating Target Neutron Source II] operational summary

    International Nuclear Information System (INIS)

    Heikkinen, D.W.

    1988-09-01

    The Rotating Target Neutron Source II facility (RTNS-II) operated for over nine years. Its purpose was to provide high intensities of 14 MeV neutrons for materials studies in the fusion energy program. For the period from 1982-1987, the facility was supported by both the US (Department of Energy) and Japan (Ministry of Education, Culture, and Science). RTNS-II contains two accelerator-based neutron sources which use the T(d,n) 4 He reaction. In this paper, we will summarize the operational history of RTNS-II. Typical operating parameters are given. In addition, a brief description of the experimental program is presented. The current status and future options for the facility are discussed. 7 refs., 5 tabs

  18. Electroforming copper targets for RTNS-II

    International Nuclear Information System (INIS)

    Kelley, W.K.; Dini, J.W.; Logan, C.M.

    1981-01-01

    Copper targets used in RTNS II, which is the world's most intense 14-MeV neutron source, contain water cooling channels for temperature control. There are two methods for fabricating these targets: (1) diffusion bonding a copper panel containing photoetched channels to another copper panel, and (2) an electroforming technique which involves filling the photoetched channels with wax, plating thick copper to seal over the channels and then removing the wax. Development of this latter process and results obtained with it are described

  19. Fabrication procedures for HFIR control plates

    Energy Technology Data Exchange (ETDEWEB)

    Bowden, G.A.; Hicks, G.R.; Knight, R.W.

    1984-10-01

    The HFIR control system uses Alclad cylindrically shaped components, which have regions containing 31 vol % Eu/sub 2/O/sub 3/ and 38 vol % Ta, respectively. Exacting control of the water passage between these components and adjacent reactor parts is mandatory, and precise dimensional control of the finished products is required. This report describes the procedures developed for manufacturing outer control plates and inner control cylinders. Results are cited which demonstrate that circular-shaped outer control plates can be produced with less than 0.025-in. variation from the specified 9.300-in. radius in any region of the plate. Other results show that, by the exercise of careful control, inner control, inner control plates can be welded into cylindrical geometry with diametrical variations held to less than +- 0.010 in. of the intended 17.846-in. average diam. The cylinders can then be explosively sized, while under compression, with diametric variations of less than 0.005 in. while controlling roundness variations to less than 0.030 in. from the specified 17.842-in. finished diam.

  20. Fabrication procedures for HFIR control plates

    International Nuclear Information System (INIS)

    Bowden, G.A.; Hicks, G.R.; Knight, R.W.

    1984-10-01

    The HFIR control system uses Alclad cylindrically shaped components, which have regions containing 31 vol % Eu 2 O 3 and 38 vol % Ta, respectively. Exacting control of the water passage between these components and adjacent reactor parts is mandatory, and precise dimensional control of the finished products is required. This report describes the procedures developed for manufacturing outer control plates and inner control cylinders. Results are cited which demonstrate that circular-shaped outer control plates can be produced with less than 0.025-in. variation from the specified 9.300-in. radius in any region of the plate. Other results show that, by the exercise of careful control, inner control, inner control plates can be welded into cylindrical geometry with diametrical variations held to less than +- 0.010 in. of the intended 17.846-in. average diam. The cylinders can then be explosively sized, while under compression, with diametric variations of less than 0.005 in. while controlling roundness variations to less than 0.030 in. from the specified 17.842-in. finished diam

  1. Production of transplutonium elements in the high flux isotope reactor (HFIR)

    International Nuclear Information System (INIS)

    Bigelow, J.E.; Corbett, B.L.; King, L.J.; McGuire, S.C.; Sims, T.M.

    1980-01-01

    The techniques described have been demonstrated to be adequate to predict the contents of transplutonium element production targets which have been irradiated in the HFIR. The deviations, at least for isotopes of mass 253 or less, are generally within the usual analytical uncertainties, or else are for isiotopes which are of little overall import to the program. Work is especially needed to get a better picture of the production of 250 Cm, 254 Es, 255 Es, and ultimately 257 Fm, since researchers are frequently stating their interest in obtaining larger quantities of these rare and difficult-to-produce nuclides

  2. Development of High Flux Isotope Reactor (HFIR) subcriticality monitoring methods

    International Nuclear Information System (INIS)

    Rothrock, R.B.

    1991-01-01

    Use of subcritical source multiplication measurements during refueling has been investigated as a possible replacement for out-of-reactor subcriticality measurements formerly made on fresh HFIR fuel elements at the ORNL Critical Experiment Facility. These measurements have been used in the past for preparation of estimated critical rod positions, and as a partial verification, prior to reactor startup, that the requirements for operational shutdown margin would be met. Results of subcritical count rate data collection during recent HFIR refuelings and supporting calculations are described illustrating the intended measurement method and its expected uncertainty. These results are compared to historical uses of the out-of-reactor core measurements and their accuracy requirements, and a planned in-reactor test is described which will establish the sensitivity of the method and calibrate it for future routine use during HFIR refueling. 2 refs., 1 fig., 2 tabs

  3. Production of medical radioisotopes in the ORNL High Flux Isotope Reactor (HFIR) for cancer treatment and arterial restenosis therapy after PTCA

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.; Beets, A.L.; Mirzadeh, S.; Alexander, C.W.; Hobbs, R.L.

    1998-01-01

    The High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory (ORNL) represents an important resource for the production of a wide variety of medical radioisotopes. In addition to serving as a key production site for californium-252 and other transuranic elements, important examples of therapeutic radioisotopes which are currently routinely produced in the HFIR for distribution include dysprosium-166 (parent of holmium-166), rhenium-186, tin-117m and tungsten-188 (parent of rhenium-188). The nine hydraulic tube (HT) positions in the central high flux region permit the insertion and removal of targets at any time during the operating cycle and have traditionally represented a major site for production of medical radioisotopes. To increase the irradiation capabilities of the HFIR, special target holders have recently been designed and fabricated which will be installed in the six Peripheral Target Positions (PTP), which are also located in the high flux region. These positions are only accessible during reactor refueling and will be used for long-term irradiations, such as required for the production of tin-117m and tungsten-188. Each of the PTP tubes will be capable of housing a maximum of eight HT targets, thus increasing the total maximum number of HT targets from the current nine, to a total of 57. In this paper the therapeutic use of reactor-produced radioisotopes for bone pain palliation and vascular brachytherapy and the therapeutic medical radioisotope production capabilities of the ORNL HFIR are briefly discussed

  4. Calculation of RABBIT and Simulator Worth in the HFIR Hydraulic Tube and Comparison with Measured Values

    Energy Technology Data Exchange (ETDEWEB)

    Slater, CO

    2005-09-08

    To aid in the determinations of reactivity worths for target materials in a proposed High Flux Isotope Reactor (HFIR) target configuration containing two additional hydraulic tubes, the worths of cadmium rabbits within the current hydraulic tube were calculated using a reference model of the HFIR and the MCNP5 computer code. The worths were compared to measured worths for both static and ejection experiments. After accounting for uncertainties in the calculations and the measurements, excellent agreement between the two was obtained. Computational and measurement limitations indicate that accurate estimation of worth is only possible when the worth exceeds 10 cents. Results indicate that MCNP5 and the reactor model can be used to predict reactivity worths of various samples when the expected perturbations are greater than 10 cents. The level of agreement between calculation and experiment indicates that the accuracy of such predictions would be dependent solely on the quality of the nuclear data for the materials to be irradiated. Transients that are approximated by ''piecewise static'' computational models should likewise have an accuracy that is dependent solely on the quality of the nuclear data.

  5. Final report of the HFIR [High Flux Isotope Reactor] irradiation facilities improvement project

    International Nuclear Information System (INIS)

    Montgomery, B.H.; Thoms, K.R.; West, C.D.

    1987-09-01

    The High-Flux Isotope Reactor (HFIR) has outstanding neutronics characteristics for materials irradiation, but some relatively minor aspects of its mechanical design severely limited its usefulness for that purpose. In particular, though the flux trap region in the center of the annular fuel elements has a very high neutron flux, it had no provision for instrumentation access to irradiation capsules. The irradiation positions in the beryllium reflector outside the fuel elements also have a high flux; however, although instrumented, they were too small and too few to replace the facilities of a materials testing reactor. To address these drawbacks, the HFIR Irradiation Facilities Improvement Project consisted of modifications to the reactor vessel cover, internal structures, and reflector. Two instrumented facilities were provided in the flux trap region, and the number of materials irradiation positions in the removable beryllium (RB) was increased from four to eight, each with almost twice the available experimental space of the previous ones. The instrumented target facilities were completed in August 1986, and the RB facilities were completed in June 1987

  6. Calibration of NRSF2 Instrument at HFIR

    International Nuclear Information System (INIS)

    Tang, Fei; Hubbard, Camden R.

    2006-01-01

    the sample table, 2θ 0 offset, and response of the position sensitive detector; (2) Counting statistics - if the peak profile count is too low, then the peak position derived from fitting a profile and background will have larger error. Therefore, adequate counting statistics and well-defined peaks are always good for precise peak position determination; and (3) Sample - Large grain size materials make it difficult to get enough diffracting grains, contributing to the different profile. With a low number the peak becomes 'spot' and results in inaccuracy in peak position. Texture in the sample can change the effective elastic constants and also affect the peak intensity. Phase and composition inhomogeneity can make it difficult to determine an accurate stress-free d 0 for strain calculation. A partially buried gauge volume due to proximity to the sample surface or buried interface can also shift the peak position. The calibration method presented in this report will address the first two categories of difficulties listed above. The FWHM can be minimized for each sample d-spacing by adjusting the horizontal bending of the monochromator crystal. For the monochromator, the optimum FWHM lies between 70 and 110 degree. This range is selected in order to maintain an approximately equiaxed gauge volume and avoid significant increases in peak breadth for the detectors above and below the horizontal plane. To adequately calibrate the position sensitive detectors, 2θ 0 , and wavelength, a set of high purity reference powders were selected. Since the selected reference powders have define grain size is, the measurement errors from sample grain size and texture can be excluded, although there may still be micro-strain in the powders, which can broaden the reference peak. In this report, the calibration procedure for the NRSF2 instrument will be presented and calibration results for five monochromator settings from HFIR cycle 403 will be presented. The monochromator settings

  7. A summary of the artificial intelligence applications at the HFIR

    International Nuclear Information System (INIS)

    Wehe, D.K.; Clapp, N.E.; Clark, F.H.; Mullens, J.A.; Otaduy, P.J.

    1986-01-01

    The AI group within the Instrumental and Controls Division at the Oak Ridge National Laboratory is developing expertise in AI techniques, and applying it to various projects. One such project involves the High Flux Isotope Reactor (HFIR). This paper summarizes the progress which has been made in the first year of this three-year project. While the HFIR is as a research reactor, it shares many of the characteristics of a full-scale, commercial PWR. It has a pressurized primary system (including a component similar to a pressurizer), with multiple primary and secondary coolant legs. In essence, it possesses many of the complexities found in commercial plants. The principle differences are its small, loosely coupled, annular core which produces 100 MWt, the concentric, cylindrical control elements which are located external to the core, and the beryllium reflectors which are external to the control elements. Much like a commercial plant, operational emphasis is placed on maximizing fuel utilization and plant, availability, while minimizing safety risks, radiation exposure, and production of low-level wastes. Thus, the HFIR is a realistic platform for developing and testing real-time expert systems for the nuclear industry

  8. Performance of HTGR fertile particles irradiated in HFIR capsule HT-32

    International Nuclear Information System (INIS)

    Long, E.L. Jr.; Robbins, J.M.; Tiegs, T.N.; Kania, M.J.

    1980-04-01

    The HT-32 experiment was an uninstrumented capsule irradiated for four cycles in the target position of the High-Flux Isotope Reactor (HFIR). The experiment was designed to: provide supplemental simulated fuel rods for thermal transport and expansion measurements; test fertile kernels with Al 2 O 3 and SiO 2 additives for improved fission product retention; study the stability and permeability of low-temperature isotropic (LTI) pyrocarbon coatings; test Biso- and Triso-coatings derived in a large (0.24-m-dia) coating furnace with a frit distributor; investigate the performance of particles with an outer layer of SiC both as loose particles and as resin-bonded fuel rods; and evaluate high-density alumina as a potential high-temperature thermometry sheathing material

  9. The High Flux Isotope Reactor (HFIR) cold source project at ORNL

    International Nuclear Information System (INIS)

    Selby, D.

    1998-01-01

    The scope of this project includes the development, design, procurement/fabrication, testing, and installation of all of the components necessary to produce a working cold source within an existing HFIR beam tube hole in the pressure vessel. All aspects of the cold source design will be based on demonstrated technology adapted to the HFIR design and operating conditions

  10. Tritium-target performance at RTNS-II

    International Nuclear Information System (INIS)

    Heikkinen, D.W.; Logan, C.M.

    1982-01-01

    The Rotating Target Neutron Source (RTNS-II) uses a 360-keV deuteron beam and the 3 He(d,n) 4 He reaction to generate 14-MeV neutrons. The neutrons are used for fusion materials damage studies. The tritium target consists of a band of titanium tritide on copper alloy substrates of 23- or 50-cm diameter. During operation, the substrates are internally cooled and rotated at approx. 4000 rpm to withstand beam intensities in excess of 100 mA. Neutron production data have been accumulated for fifty-eight 23-cm and five 50-cm targets. From these data, using a non-linear least-squares fitting procedure, target performance parameters have been obtained which permit a quantitative comparison of individual targets. Average parameters are obtained for the 23- and 50-cm targets

  11. Meeting notes of the High Flux Isotope Reactor (HFIR) futures group

    Energy Technology Data Exchange (ETDEWEB)

    Houser, M.M. [comp.

    1995-08-01

    This report is a compilation of the notes from the ten meetings. The group charter is: (1) to identify and characterize the range of possibilities and necessities for keeping the HFIR operating for at least the next 15 years; (2) to identify and characterize the range of possibilities for enhancing the scientific and technical utility of the HFIR; (3) to evaluate the benefits or impacts of these possibilities on the various scientific fields that use the HFIR or its products; (4) to evaluate the benefits or impacts on the operation and maintenance of the HFIR facility and the regulatory requirements; (5) to estimate the costs, including operating costs, and the schedules, including downtime, for these various possibilities; and one possible impact of proposed changes may be to stimulate increased pressure for a reduced enrichment fuel for HFIR.

  12. Meeting notes of the High Flux Isotope Reactor (HFIR) futures group

    International Nuclear Information System (INIS)

    Houser, M.M.

    1995-08-01

    This report is a compilation of the notes from the ten meetings. The group charter is: (1) to identify and characterize the range of possibilities and necessities for keeping the HFIR operating for at least the next 15 years; (2) to identify and characterize the range of possibilities for enhancing the scientific and technical utility of the HFIR; (3) to evaluate the benefits or impacts of these possibilities on the various scientific fields that use the HFIR or its products; (4) to evaluate the benefits or impacts on the operation and maintenance of the HFIR facility and the regulatory requirements; (5) to estimate the costs, including operating costs, and the schedules, including downtime, for these various possibilities; and one possible impact of proposed changes may be to stimulate increased pressure for a reduced enrichment fuel for HFIR

  13. Fracture analysis of HFIR beam tube caused by radiation embrittlement

    International Nuclear Information System (INIS)

    Chang, S.J.

    1994-01-01

    With an attempt to estimate the neutron beam tube embrittlement condition for the Oak Ridge High Flux Isotope Reactor (HFIR), fracture mechanics calculations are carried out in this paper. The analysis provides some numerical result on how the tube has been structurally weakened. In this calculation, a lateral impact force is assumed. Numerical result is obtained on how much the critical crack size should be reduced if the beam tube has been subjected to an extended period of irradiation. It is also calculated that buckling strength of the tube is increased, not decreased, with irradiation

  14. Cadmium verification measurements of HFIR shroud assembly 22

    International Nuclear Information System (INIS)

    Chapman, J.A.; Schultz, F.J.

    1994-04-01

    This report discusses radiation-based nondestructive examination methods which have been used to successfully verify the presence of cadmium in High Flux Isotope Reactor (HFIR) spent-fuel shroud assembly number 22 (SA22). These measurements show, in part, that SA22 is certified to meet the criticality safety specifications for a proposed reconfiguration of the HFIR spent-fuel storage array. Measurement of the unique 558.6-keV gamma-ray from neutron radiative capture on cadmium provided conclusive evidence for the presence of cadmium in the outer shroud of the assembly. Cadmium verification in the center post and outer shroud was performed by measuring the degree of neutron transmission in SA22 relative to two calibration shroud assemblies. Each measurement was performed at a single location on the center post and outer shroud. These measurements do not provide information on the spatial distribution or uniformity of cadmium within an assembly. Separate measurements using analog and digital radiography were performed to (a) globally map the continuity of cadmium internal mass, and (b) locally determine the thickness of cadmium. Radiography results will be reported elsewhere. The measurements reported here should not be used to infer the thickness of cadmium in either the center post or outer shroud of an assembly

  15. Extraction of 152Gd from HFIR control plates

    International Nuclear Information System (INIS)

    Kohring, M.W.

    1986-01-01

    The primary method of 153 Gd production at the Oak Ridge National Lab. (ORNL) research reactors since 1980 has been the irradiation of a natural europium oxide powder (Eu 2 O 3 ) followed by the chemical extraction of the gadolinium fraction. The specific activity of the resulting source is 45 to 50 Ci/g with a radiochemical purity of > 99.99%. A potential alternative method involves the extraction of gadolinium from the europium-bearing region of highly radioactive, spent control plates used in the High Flux Isotope Reactor (HFIR), followed by neutron irradiation. This alternative to the traditional process is attractive in that chemical separation of the europium and gadolinium occurs before the 153 Gd production irradiation, thus reducing process and decay losses and, most significantly, the gadolinium is highly enriched in the parent isotope, 152 Gd. Investigation into the usefulness of the gadolinium isotopes contained in spent HFIR control plates began in the late 1960s. However, separation of the gadolinium from the europium to the purity levels required for a marketable specific activity could not be attained. Due to the recent increase in 153 Gd demand and separation process improvements, research into this valuable source of parent material was resurrected

  16. Status of High Flux Isotope Reactor (HFIR) post-restart safety analysis and documentation upgrades

    International Nuclear Information System (INIS)

    Cook, D.H.; Radcliff, T.D.; Rothrock, R.B.; Schreiber, R.E.

    1990-01-01

    The High Flux Isotope Reactor (HFIR), an experimental reactor located at the Oak Ridge National Laboratory (ORNL) and operated for the US Department of Energy by Martin Marietta Energy Systems, was shut down in November, 1986 after the discovery of unexpected neutron embrittlement of the reactor vessel. The reactor was restarted in April, 1989, following an extensive review by DOE and ORNL of the HFIR design, safety, operation, maintenance and management, and the implementation of several upgrades to HFIR safety-related hardware, analyses, documents and procedures. This included establishing new operating conditions to provide added margin against pressure vessel failure, as well as the addition, or upgrading, of specific safety-related hardware. This paper summarizes the status of some of the follow-on (post-restart) activities which are currently in progress, and which will result in a comprehensive set of safety analyses and documentation for the HFIR, comparable with current practice in commercial nuclear power plants. 8 refs

  17. Calculations for HFIR [High Flux Isotope Reactor] fuel plate non- bonding and fuel segregation uncertainty factors

    International Nuclear Information System (INIS)

    Kirkpatrick, J.R.

    1990-10-01

    The effects of non-bonds and of fuel segregation on the package factors of the heat flux in the High Flux Isotope Reactor (HFIR) are examined. The effects of the two defects are examined both separately and together. It is concluded that the peaking factors that are used in the present HFIR thermal analysis code are conservative and thus no changes in the peaking factors are necessary to continue to ensure that HFIR is safe. A study was made of the effect of the non-bond spot diameter on the peaking factor. The conclusion is that the spot can have diameter more than three times the maximum value allowed by the specifications before the peaking factor is greater than the maximum value specified in the present HFIR thermal analysis code. 6 refs., 7 figs., 8 tabs

  18. Justification for an Increase in Authorized Operating Power at HFIR

    International Nuclear Information System (INIS)

    Primm, Trent; Ilas, Germina

    2011-01-01

    Using verified and validated reactor physics methods coupled to a currently accepted thermal hydraulic analysis methodology, onset of incipient boiling power agrees well with the currently-accepted safety basis value. The MCNP-based methodology is acceptable for scoping studies of LEU fuel conversion. A balance-of-plant assessment would have to be conducted to determine if the power up-rate to 100 MW could be supported for LEU fuel. While analyses performed 45 years ago have been shown to be in agreement with today s methods, there is an advantage to the current methodology in that people working at HFIR today can explain/justify/defend the safety analyses rather than relying solely on documentation.

  19. Baseball II-T, a new target plasma startup experiment

    International Nuclear Information System (INIS)

    Chargin, A.; Denhoy, B.; Frank, A.; Thomas, S.

    1975-01-01

    A brief description is given of modifications and additions to the existing Baseball II experiment. These changes will make it possible to study target plasma buildup in a steady-state magnetic field. This experiment, now called Baseball II-T + will use a pellet generator to deliver ammonia pellets into the center of the magnetic mirror field where they will be heated with a 300-J, 50-ns, CO 2 laser. The plasma created by this method will have a density of approximately 10 13 cm -3 and a temperature of about 1 keV. This target plasma will be used for neutral beam injection startup studies with a 50-A, 20-keV neutral beam. Later, the beam power will be increased to study buildup. With ion injection energies of up to 50 keV, it may be possible to achieve etatau as high as 10 12 cm -3 s. The new components necessary to achieve these goals are described

  20. High Flux Isotopes Reactor (HFIR) Cooling Towers Demolition Waste Management

    Energy Technology Data Exchange (ETDEWEB)

    Pudelek, R. E.; Gilbert, W. C.

    2002-02-26

    This paper describes the results of a joint initiative between Oak Ridge National Laboratory, operated by UT-Battelle, and Bechtel Jacobs Company, LLC (BJC) to characterize, package, transport, treat, and dispose of demolition waste from the High Flux Isotope Reactor (HFIR), Cooling Tower. The demolition and removal of waste from the site was the first critical step in the planned HFIR beryllium reflector replacement outage scheduled. The outage was scheduled to last a maximum of six months. Demolition and removal of the waste was critical because a new tower was to be constructed over the old concrete water basin. A detailed sampling and analysis plan was developed to characterize the hazardous and radiological constituents of the components of the Cooling Tower. Analyses were performed for Resource Conservation and Recovery Act (RCRA) heavy metals and semi-volatile constituents as defined by 40 CFR 261 and radiological parameters including gross alpha, gross beta, gross gamma, alpha-emitting isotopes and beta-emitting isotopes. Analysis of metals and semi-volatile constituents indicated no exceedances of regulatory limits. Analysis of radionuclides identified uranium and thorium and associated daughters. In addition 60Co, 99Tc, 226Rm, and 228Rm were identified. Most of the tower materials were determined to be low level radioactive waste. A small quantity was determined not to be radioactive, or could be decontaminated. The tower was dismantled October 2000 to January 2001 using a detailed step-by-step process to aid waste segregation and container loading. The volume of waste as packaged for treatment was approximately 1982 cubic meters (70,000 cubic feet). This volume was comprised of plastic ({approx}47%), wood ({approx}38%) and asbestos transite ({approx}14%). The remaining {approx}1% consisted of the fire protection piping (contaminated with lead-based paint) and incidental metal from conduit, nails and braces/supports, and sludge from the basin. The waste

  1. Irradiation performance of HTGR fuel in HFIR experiment HRB-13

    International Nuclear Information System (INIS)

    Tiegs, T.N.

    1982-03-01

    Irradiation capsule HRB-13 tested High-Temperature Gas-Cooled Reactor (HTGR) fuel under accelerated conditions in the High Flux Isotope Reactor (HFIR) at ORNL. The ORNL part of the capsule was designed to provide definitive results on how variously misshapen kernels affect the irradiation performance of weak-acid-resin (WAR)-derived fissile fuel particles. Two batches of WAR fissile fuel particles were Triso-coated and shape-separated into four different fractions according to their deviation from spericity, which ranged from 9.6 to 29.7%. The fissile particles were irradiated for 7721 h. Heavy-metal burnups ranged from 80 to 82.5% FIMA (fraction of initial heavy-metal atoms). Fast neutron fluences (>0.18 MeV) ranged from 4.9 x 10 25 neutrons/m 2 to 8.5 x 10 25 neutrons/m 2 . Postirradiation examination showed that the two batches of fissile particles contained chlorine, presumably introduced during deposition of the SiC coating

  2. Operating and maintenance manual for the HFIR production model homogeneity scanner

    International Nuclear Information System (INIS)

    Reynolds, J.W.; Shipp, R.L.; Sliski, T.F.; Longaker, W.H.; Klindt, K.K.

    1984-12-01

    The fuel material in a HFIR fuel is U 3 O 8 dispersed in aluminum, resembling an airfoil in cross section. To ensure uniform generation of heat within the plate, all plates must be tested (nondestructively) to determine that the U 3 O 8 content is within specified limits. The HFIR homogeneity scanner developed for this purpose is a density/thickness gauge that bombards a plate with a highly collimated, 0.062-in.-diam beam of x rays and detects those transmitted through the plate. Variations in the transmitted x rays due to absorption in the fuel plate are a measure of fuel denisty. In addition to the fuel plates for HFIR, fuel plates for several other reactors, such as the Oak Ridge Research Reactor (ORR) are also checked by the homogeneity scanner by using other sets of standards. All of the other reactors have a uniform cross section. This manual describes procedures for its electronic components

  3. Safety analysis report for packaging: the ORNL HFIR spent-fuel-element shipping cask

    International Nuclear Information System (INIS)

    Evans, J.H.; Chipley, K.K.; Eversole, R.E.; Just, R.A.; Llewellyn, G.H.

    1977-11-01

    The Oak Ridge National Laboratory High Flux Isotope Reactor (HFIR) spent-fuel-element shipping cask is used to transport HFIR, Oak Ridge Research Reactor (ORR), and other reactor fuel elements. The cask was analytically evaluated to determine its compliance with the applicable regulations governing containers in which radioactive materials are transported. Computational procedures and tests were used to determine behavior of the cask relative to the general standards for the hypothetical accident conditions. The results of the evaluation show that the cask is in compliance with the applicable regulations

  4. Safety analysis report for packaging: the ORNL HFIR unirradiated fuel element shipping container

    International Nuclear Information System (INIS)

    Evans, J.H.; Boulet, J.A.M.; Eversole, R.E.

    1977-11-01

    The ORNL HFIR unirradiated fuel element shipping container was designed and fabricated at the Oak Ridge National Laboratory for the transport of HFIR unirradiated fuel elements. The container was evaluated analytically and experimentally to determine its compliance with the applicable regulations governing containers in which radioactive and fissile materials are transported, and the evaluation is the subject of this report. Computational and test procedures were used to determine the structural integrity and thermal behavior of the cask relative to the general standards for normal conditions of transport and the standards for the hypothetical accident conditions. The results of the evaluation demonstrate that the container is in compliance with the applicable regulations

  5. An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II

    NARCIS (Netherlands)

    Hasper, Hester E.; Kramer, Naomi E.; Smith, James L.; Hillman, J. D.; Zachariah, Cherian; Kuipers, Oscar P.; de Kruijff, Ben; Breukink, Eefjan

    2006-01-01

    Lantibiotics are polycyclic peptides containing unusual amino acids, which have binding specificity for bacterial cells, targeting the bacterial cell wall component lipid II to form pores and thereby lyse the cells. Yet several members of these lipid II - targeted lantibiotics are too short to be

  6. In-situ measurement of the electrical conductivity of aluminum oxide in HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J.; White, D.P.; Snead, L.L. [Oak Ridge National Lab., TN (United States)] [and others

    1996-10-01

    A collaborative DOE/Monbusho irradiation experiment has been completed which measured the in-situ electrical resistivity of 12 different grades of aluminum oxide during HFIR neutron irradiation at 450{degrees}C. No evidence for bulk RIED was observed following irradiation to a maximum dose of 3 dpa with an applied dc electric field of 200 V/mm.

  7. MODELING OF TARGETED DRUG DELIVERY PART II. MULTIPLE DRUG ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    A. V. Zaborovskiy

    2017-01-01

    Full Text Available In oncology practice, despite significant advances in early cancer detection, surgery, radiotherapy, laser therapy, targeted therapy, etc., chemotherapy is unlikely to lose its relevance in the near future. In this context, the development of new antitumor agents is one of the most important problems of cancer research. In spite of the importance of searching for new compounds with antitumor activity, the possibilities of the “old” agents have not been fully exhausted. Targeted delivery of antitumor agents can give them a “second life”. When developing new targeted drugs and their further introduction into clinical practice, the change in their pharmacodynamics and pharmacokinetics plays a special role. The paper describes a pharmacokinetic model of the targeted drug delivery. The conditions under which it is meaningful to search for a delivery vehicle for the active substance were described. Primary screening of antitumor agents was undertaken to modify them for the targeted delivery based on underlying assumptions of the model.

  8. Preliminary Multiphysics Analyses of HFIR LEU Fuel Conversion using COMSOL

    Energy Technology Data Exchange (ETDEWEB)

    Freels, James D [ORNL; Bodey, Isaac T [ORNL; Arimilli, Rao V [ORNL; Curtis, Franklin G [ORNL; Ekici, Kivanc [ORNL; Jain, Prashant K [ORNL

    2011-06-01

    4 of this report. The HFIR LEU conversion project has also obtained the services of Dr. Prashant K. Jain of the Reactor & Nuclear Systems Division (RNSD) of ORNL. Prashant has quickly adapted to the COMSOL tools and has been focusing on thermal-structure interaction (TSI) issues and development of alternative 3D model approaches that could yield faster-running solutions. Prashant is the primary contributor to Section 5 of the report. And finally, while incorporating findings from all members of the COMSOL team (i.e., the team) and contributing as the senior COMSOL leader and advocate, Dr. James D. Freels has focused on the 3D model development, cluster deployment, and has contributed primarily to Section 3 and overall integration of this report. The team has migrated to the current release of COMSOL at version 4.1 for all the work described in this report, except where stated otherwise. Just as in the performance of the research, each of the respective sections has been originally authored by the respective authors. Therefore, the reader will observe a contrast in writing style throughout this document.

  9. Safety and environmental requirements and design targets for TIBER-II

    International Nuclear Information System (INIS)

    Piet, S.J.

    1987-09-01

    A consistent set of safety and environmental requirements and design targets was proposed and adopted for the TIBER-II (Tokamak Ignition/Burn Experimental Reactor) design effort. TIBER-II is the most recent US version of a fusion experimental test reactor (ETR). These safety and environmental design targets were one contribution of the Fusion Safety Program in the TIBER-II design effort. The other contribution, safety analyses, is documented in the TIBER-II design report. The TIBER-II approach, described here, concentrated on logical development of, first, a complete and consistent set of safety and environmental requirements that are likely appropriate for an ETR, and, second, an initial set of design targets to guide TIBER-II. Because of limited time in the TIBER-II design effort, the iterative process only included one iteration - one set of targets and one design. Future ETR design efforts should therefore build on these design targets and the associated safety analyses. 29 refs., 5 figs., 3 tabs

  10. Microstructural development of PCAs irradiated in HFIR at 300 to 4000C

    International Nuclear Information System (INIS)

    Tanaka, M.P.; Maziasz, P.J.; Hishinuma, A.; Hamada, S.

    1986-01-01

    Microstructural developments were determined on solution-annealed (SA) and cold-worked (CW) JPCA and US PCAs irradiated in the High Flux Isotope Reactor (HFIR) at 300 and 400 0 C. Irradiation produced damage levels of about 10 and 34 dpa and helium concentrations of around 580 and 2500 at. ppM, respectively. High concentrations of fine bubbles and MC precipitates, as well as Frank faulted loops, were observed in both SA and CW PCAs. Mutual stability of the MC particles and associated fine bubbles contributed to the extension of the transient regime of swelling to higher fluence. The irradiation responses of JPCA and US-PCA were similar in the HFIR, despite minor compositional differences (P,B) between the two materials. Useful fusion applications of SA-PCA as well as CW-PCA in the 300 0 C temperature range are suggested from these data

  11. Evaluation of HFIR vessel surveillance data and hydro-test conditions

    International Nuclear Information System (INIS)

    Cheverton, R.D.; Nanstad, R.K.

    1994-01-01

    Surveillance specimens for the High Flux Isotope Reactor (HFIR) pressure vessel were removed and tested during 1993, after the vessel had accumulated 701,469 MWd of operation. The data agree well with HFIR surveillance data obtained in previous years. In conjunction with this effort, the vessel hydro-test conditions were reevaluated and found to be more than adequate. In view of this result, and because there are economic incentives for reducing the frequency of hydro testing, an analysis was performed to determine the minimum permissible frequency. The value obtained is substantially less than that presently specified. It was also determined that a somewhat lower cooling-tower-basin temperature is acceptable (improves operational flexibility). In 1986, after ∼20 years of reactor operation, it was discovered that the vessel embrittlement rate was substantially greater than expected. Possible reasons for the accelerated rate are reviewed in this report

  12. External event Probabilistic Risk Assessment for the High Flux Isotope Reactor (HFIR)

    International Nuclear Information System (INIS)

    Flanagan, G.F.; Johnson, D.H.; Buttemer, D.; Perla, H.F.; Chien, S.H.

    1989-01-01

    The High Flux Isotope Reactor (HFIR) is a high performance isotope production and research reactor which has been in operation at Oak Ridge National Laboratory (ORNL) since 1965. In late 1986 the reactor was shut down as a result of discovery of unexpected neutron embrittlement of the reactor vessel. In January of 1988 a level 1 Probabilistic Risk Assessment (PRA) (excluding external events) was published as part of the response to the many reviews that followed the shutdown and for use by ORNL to prioritize action items intended to upgrade the safety of the reactor. A conservative estimate of the core damage frequency initiated by internal events for HFIR was 3.11 x 10 -4 . In June 1989 a draft external events initiated PRA was published. The dominant contributions from external events came from seismic, wind, and fires. The overall external event contribution to core damage frequency is about 50% of the internal event initiated contribution and is dominated by seismic events

  13. Design of a creep experiment for SiC/SiC composites in HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Hecht, S.L.; Hamilton, M.L.; Jones, R.H. [and others

    1997-08-01

    A new specimen was designed for performing in-reactor creep tests on composite materials, specifically on SiC/SiC composites. The design was tailored for irradiation at 800{degrees}C in a HFIR RB position. The specimen comprises a composite cylinder loaded by a pressurized internal bladder that is made of Nb1Zr. The experiment was designed for approximately a one year irradiation.

  14. Design of a creep experiment for SiC/SiC composites in HFIR

    International Nuclear Information System (INIS)

    Hecht, S.L.; Hamilton, M.L.; Jones, R.H.

    1997-01-01

    A new specimen was designed for performing in-reactor creep tests on composite materials, specifically on SiC/SiC composites. The design was tailored for irradiation at 800 degrees C in a HFIR RB position. The specimen comprises a composite cylinder loaded by a pressurized internal bladder that is made of Nb1Zr. The experiment was designed for approximately a one year irradiation

  15. Evaluation of fatigue properties of HFIR-irradiated nimonic PE-16 at 4300C

    International Nuclear Information System (INIS)

    Grossbeck, M.L.; Liu, K.C.

    1984-01-01

    Nimonic PE-16 was irradiated in the HFIR to 6 to 9 dpa and 560 to 1000 at. ppM He at 430 0 C. Postirradiation fatigue tests revealed a reduction in fatigue life by about a factor of 10 at 430 0 C. In contrast with AISI type 316 stainless steel, no endurance limit was observed. All irradiated specimens exhibited some intergranular fracture with an increasing tendency toward cleavage like intragranular fracture for low strain ranges

  16. Fatigue performance of HFIR-irradiated Nimonic PE-16 at 4300C

    International Nuclear Information System (INIS)

    Grossbeck, M.L.; Liu, K.C.

    1983-01-01

    Nimonic PE-16 was irradiated in the HFIR to 6 to 9 dpa and 560 to 1000 at. ppM He at 430 0 C. Postirradiation fatigue tests revealed a reduction in fatigue life by about a factor of 10 at 430 0 C. In contrast to AISI type 316 stainless steel, no endurance limit was observed. All irradiated specimens exhibited some intergranular fracture with an increasing tendency toward cleavage-like intragranular fracture for low strain ranges

  17. Management of safety and risk at the HFIR [High-Flux Isotope Reactor

    International Nuclear Information System (INIS)

    Glovier, H.A.

    1990-01-01

    This paper discusses the management of safety and risk at the High-Flux Isotope Reactor (HFIR), a category A research reactor at Oak Ridge National Laboratory (ORNL). The HFIR went critical in 1966 and operated at its designed 100 MW for 20 yr until it was shut down on November 14, 1986. It operated at a >90% availability and without significant event during this period. The result was a complacent management program lacking rigor. This complacency came to an end with the Chernobyl accident, which led to the appointment of an internal committee to assess the safety of ORNL reactor operations. This committee found that HFIR pressure vessel material specimens removed several years earlier had not been analyzed. This issue led to a general review of management practices that were found lacking in quality assurance, safety documentation, training process, and emergency planning, among others. Management accountability was lacking, as shown by design basis and safety analyses that were not up to data and by the fact that reactor operators whose requalification examinations had not been graded were allowed to continue operating the reactor over a long period of time. Between shutdown in 1986 and restart in April 1989, significant management changes and initiatives were made in the area of risk and safety management of ORNL reactors. These are presented briefly in this paper

  18. A liquid hydrogen target for the calibration of the MEG and MEG II liquid xenon calorimeter

    Energy Technology Data Exchange (ETDEWEB)

    Signorelli, G., E-mail: giovanni.signorelli@pi.infn.it [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Baldini, A.M. [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Bemporad, C.; Cei, F.; Nicolò, D. [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Università di Pisa, Dipartimento di Fisica, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Galli, L.; Gallucci, G.; Grassi, M. [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Papa, A. [Paul Scherrer Institut, 5232 Villigen (Switzerland); Sergiampietri, F. [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Venturini, M. [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126 Pisa (Italy)

    2016-07-11

    We designed, built and operated a liquid hydrogen target for the calibration of the liquid xenon calorimeter of the MEG experiment. The target was used throughout the entire data taking period, from 2008 to 2013 and it is being refurbished and partly re-designed to be integrated and used in the MEG-II experiment.

  19. Features of target cell lysis by class I and class II MHC restricted cytolytic T lymphocytes

    International Nuclear Information System (INIS)

    Maimone, M.M.; Morrison, L.A.; Braciale, V.L.; Braciale, T.J.

    1986-01-01

    The lytic activity of influenza virus-specific muvine cytolytic T lymphocyte (CTL) clones that are restricted by either H-2K/D (class I) or H-2I (class II) major histocompatibility (MHC) locus products was compared on an influenza virus-infected target cell expressing both K/D and I locus products. With the use of two in vitro measurements of cytotoxicity, conventional 51 Cr release, and detergent-releasable radiolabeled DNA (as a measure of nuclear disintegration in the early post-lethal hit period), the authors found no difference between class I and class II MHC-restricted CTL in the kinetics of target cell destruction. In addition, class II MHC-restricted antiviral CTL failed to show any lysis of radiolabeled bystander cells. Killing of labeled specific targets by these class II MHC-restricted CTL was also efficiently inhibited by unlabeled specific competitor cells in a cold target inhibition assay. In sum, these data suggest that class I and class II MHC-restricted CTL mediate target cell destruction by an essentially similar direct mechanism

  20. Heat transfer calculations for the High Flux Isotope Reactor (HFIR). Technical specifications: bases for safety limits and limiting safety system settings

    International Nuclear Information System (INIS)

    Sims, T.M.; Swanks, J.H.

    1977-09-01

    Heat transfer analyses, in support of the preparation of the HFIR technical specifications, were made to establish the bases for the safety limits and limiting safety system settings applicable to the HFIR. The results of these analyses, along with the detailed bases, are presented

  1. Preliminary Assessment of the Impact on Reactor Vessel dpa Rates Due to Installation of a Proposed Low Enriched Uranium (LEU) Core in the High Flux Isotope Reactor (HFIR)

    Energy Technology Data Exchange (ETDEWEB)

    Daily, Charles R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-10-01

    An assessment of the impact on the High Flux Isotope Reactor (HFIR) reactor vessel (RV) displacements-per-atom (dpa) rates due to operations with the proposed low enriched uranium (LEU) core described by Ilas and Primm has been performed and is presented herein. The analyses documented herein support the conclusion that conversion of HFIR to low-enriched uranium (LEU) core operations using the LEU core design of Ilas and Primm will have no negative impact on HFIR RV dpa rates. Since its inception, HFIR has been operated with highly enriched uranium (HEU) cores. As part of an effort sponsored by the National Nuclear Security Administration (NNSA), conversion to LEU cores is being considered for future HFIR operations. The HFIR LEU configurations analyzed are consistent with the LEU core models used by Ilas and Primm and the HEU balance-of-plant models used by Risner and Blakeman in the latest analyses performed to support the HFIR materials surveillance program. The Risner and Blakeman analyses, as well as the studies documented herein, are the first to apply the hybrid transport methods available in the Automated Variance reduction Generator (ADVANTG) code to HFIR RV dpa rate calculations. These calculations have been performed on the Oak Ridge National Laboratory (ORNL) Institutional Cluster (OIC) with version 1.60 of the Monte Carlo N-Particle 5 (MCNP5) computer code.

  2. The Monbusho/US shielded HFIR irradiation experiment: HFIR-MFE-RB-11J and 12J (P3-3)

    Energy Technology Data Exchange (ETDEWEB)

    Grossbeck, M.L.; Lenox, K.E.; Janney, M.A. [Oak Ridge National Lab., TN (United States)] [and others

    1997-08-01

    This experiment is a joint project between the Japanese Monbushu, the Japan Atomic Energy Research Institute, and the U.S. Fusion Energy Sciences Program. It is the first of a series of experiments using europium oxide as a thermal neutron shield to minimize transmutations in vanadium alloys and ferritic/martensitic steels. The europium oxide shields were developed using ceramic processing techniques culminating in cold pressing and sintering. This experiment, which is a prototype for future fast neutron experiments in the HFIR, contains approximately 3200 specimens of 18 different types. The experiment began operating at 300 and 500{degrees}C in February 1997 and is projected to attain its goal fluence of {approximately} 5 dpa in February 1998.

  3. 3D COMSOL Simulations for Thermal Deflection of HFIR Fuel Plate in the "Cheverton-Kelley" Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Prashant K [ORNL; Freels, James D [ORNL; Cook, David Howard [ORNL

    2012-08-01

    Three dimensional simulation capabilities are currently being developed at Oak Ridge National Laboratory using COMSOL Multiphysics, a finite element modeling software, to investigate thermal expansion of High Flux Isotope Reactor (HFIR) s low enriched uranium fuel plates. To validate simulations, 3D models have also been developed for the experimental setup used by Cheverton and Kelley in 1968 to investigate the buckling and thermal deflections of HFIR s highly enriched uranium fuel plates. Results for several simulations are presented in this report, and comparisons with the experimental data are provided when data are available. A close agreement between the simulation results and experimental findings demonstrates that the COMSOL simulations are able to capture the thermal expansion physics accurately and that COMSOL could be deployed as a predictive tool for more advanced computations at realistic HFIR conditions to study temperature-induced fuel plate deflection behavior.

  4. Assessment of helium effects on swelling by reirradiation in FFTF of Path A alloys previously irradiated in HFIR

    International Nuclear Information System (INIS)

    Maziasz, P.J.; Garner, F.A.; Brager, H.R.

    1985-01-01

    Specimens of the Path A Prime Candidate Alloys and of N-lot SS 316 were irradiated in HFIR at 400 to 600 0 C to fluences producing approximately 10 to 44 dpa and 500 to 3600 at. ppm He, in both the solution annealed and 20 to 25% cold-worked conditions. The cavity swelling and total microstructural evolution of most samples were observed via transmission electron microscopy on identical disks irradiated side by side in HFIR, and immersion densities were also measured prior to insertion into FFTF/MOTA (Materials Open Test Assembly of the Fast Flux Test Facility). These disks are being irradiated in the FFTF/MOTA (cycles 5 and 6), side by side with disks of the same materials which were not previously irradiated in HFIR. These specimens have been divided into two subsets for discharges after 30 and 60 dpa. 4 references, 1 table

  5. Fuel loading and homogeneity analysis of HFIR design fuel plates loaded with uranium silicide fuel

    International Nuclear Information System (INIS)

    Blumenfeld, P.E.

    1995-08-01

    Twelve nuclear reactor fuel plates were analyzed for fuel loading and fuel loading homogeneity by measuring the attenuation of a collimated X-ray beam as it passed through the plates. The plates were identical to those used by the High Flux Isotope Reactor (HFIR) but were loaded with uranium silicide rather than with HFIR's uranium oxide fuel. Systematic deviations from nominal fuel loading were observed as higher loading near the center of the plates and underloading near the radial edges. These deviations were within those allowed by HFIR specifications. The report begins with a brief background on the thermal-hydraulic uncertainty analysis for the Advanced Neutron Source (ANS) Reactor that motivated a statistical description of fuel loading and homogeneity. The body of the report addresses the homogeneity measurement techniques employed, the numerical correction required to account for a difference in fuel types, and the statistical analysis of the resulting data. This statistical analysis pertains to local variation in fuel loading, as well as to ''hot segment'' analysis of narrow axial regions along the plate and ''hot streak'' analysis, the cumulative effect of hot segment loading variation. The data for all twelve plates were compiled and divided into 20 regions for analysis, with each region represented by a mean and a standard deviation to report percent deviation from nominal fuel loading. The central regions of the plates showed mean values of about +3% deviation, while the edge regions showed mean values of about -7% deviation. The data within these regions roughly approximated random samplings from normal distributions, although the chi-square (χ 2 ) test for goodness of fit to normal distributions was not satisfied

  6. Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

    Directory of Open Access Journals (Sweden)

    Mostafa Wanees Ahmed El husseny

    2017-01-01

    Full Text Available Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM, insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.

  7. Achieving increased spent fuel storage capacity at the High Flux Isotope Reactor (HFIR)

    International Nuclear Information System (INIS)

    Cook, D.H.; Chang, S.J.; Dabs, R.D.; Freels, J.D.; Morgan, K.A.; Rothrock, R.B.; Griess, J.C.

    1994-01-01

    The HFIR facility was originally designed to store approximately 25 spent cores, sufficient to allow for operational contingencies and for cooling prior to off-site shipment for reprocessing. The original capacity has now been increased to 60 positions, of which 53 are currently filled (September 1994). Additional spent cores are produced at a rate of about 10 or 11 per year. Continued HFIR operation, therefore, depends on a significant near-term expansion of the pool storage capacity, as well as on a future capability of reprocessing or other storage alternatives once the practical capacity of the pool is reached. To store the much larger inventory of spent fuel that may remain on-site under various future scenarios, the pool capacity is being increased in a phased manner through installation of a new multi-tier spent fuel rack design for higher density storage. A total of 143 positions was used for this paper as the maximum practical pool capacity without impacting operations; however, greater ultimate capacities were addressed in the supporting analyses and approval documents. This paper addresses issues related to the pool storage expansion including (1) seismic effects on the three-tier storage arrays, (2) thermal performance of the new arrays, (3) spent fuel cladding corrosion concerns related to the longer period of pool storage, and (4) impacts of increased spent fuel inventory on the pool water quality, water treatment systems, and LLLW volume

  8. Microstructure of HFIR-irradiated 12-Cr 1 MoVW ferritic steel

    International Nuclear Information System (INIS)

    Vitek, J.M.; Klueh, R.L.

    1983-01-01

    As part of the fusion materials development program in the United States, a 12 Cr-1 MoVW ferritic steel was irradiated in the High Flux Isotope Reactor (HFIR) to a damage level of 36 dpa at 300, 400, 500, and 600 0 C. During irradiation in HFIR, a transmutation reaction of nickel results in the production of helium, to a level of 99 at. ppM in the present experiment. The microstructures were evaluated after irradiation and the results are presented. Cavities were found at all temperatures. Small cavities (3 to 9 nm) were observed after irradiation at 300, 500 and 600 0 C. At 500 and 600 0 C, the cavities were found preferentially at dislocations, lath boundaries, and prior austenite grain boundaries. After irradiation at 400 0 C, larger cavities (4 to 30 nm) were observed homogeneously distributed throughout the tempered martensite structure. The maximum swelling was 0.07% after irradiation at 400 0 C. Comparision of the results with other studies in which helium was not present at such high levels indicated helium enhances the swelling of 12 Cr-1 MoVW

  9. Reirradiation in FFTF of swelling-resistant Path A alloys previously irradiated in HFIR

    International Nuclear Information System (INIS)

    Maziasz, P.J.

    1985-01-01

    Disks of Path A Prime Candidate Alloys (in several pretreatment conditions) and several heats of cold-worked (CW) type 316 and D9 type austenitic stainless steels have been irradiated in HFIR at 300, 500, and 600 0 C to fluences producing about 10 to 44 dpa and 450 to 3600 at. ppm He. These samples are being reirradiated in the Materials Open Test Assembly (MOTA) in FFTF at 500 and 600 0 C, together (side by side) with previously unirradiated disks of exactly the same materials, to greater than 100 dpa. These samples many of which have either very fine helium cluster or helium bubble distributions after HFIR irradiation, are intended to test the possibility and magnitude of a helium-induced extension of the initial low-swelling transient regime relative to the void swelling behavior normally found during FFTF irradiation. Further, these samples will reveal the microstructural stability or evolution differences that correlate with such helium effects. 17 references, 4 tables

  10. Evaluation of HFIR [High Flux Isotope Reactor] pressure-vessel integrity considering radiation embrittlement

    International Nuclear Information System (INIS)

    Cheverton, R.D.; Merkle, J.G.; Nanstad, R.K.

    1988-04-01

    The High Flux Isotope Reactor (HFIR) pressure vessel has been in service for 20 years, and during this time, radiation damage was monitored with a vessel-material surveillance program. In mid-November 1986, data from this program indicated that the radiation-induced reduction in fracture toughness was greater than expected. As a result, a reevaluation of vessel integrity was undertaken. Updated methods of fracture-mechanics analysis were applied, and an accelerated irradiations program was conducted using the Oak Ridge Research Reactor. Results of these efforts indicate that (1) the vessel life can be extended 10 years if the reactor power level is reduced 15% and if the vessel is subjected to a hydrostatic proof test each year; (2) during the 10-year life extension, significant radiation damage will be limited to a rather small area around the beam tubes; and (3) the greater-than-expected damage rate is the result of the very low neutron flux in the HFIR vessel relative to that in samples of material irradiated in materials-testing reactors (a factor of ∼10 4 less), that is, a rate effect

  11. TALE-PvuII Fusion Proteins – Novel Tools for Gene Targeting

    Science.gov (United States)

    Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

    2013-01-01

    Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity. PMID:24349308

  12. TALE-PvuII fusion proteins--novel tools for gene targeting.

    Science.gov (United States)

    Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

    2013-01-01

    Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity.

  13. New Ablation-Resistant Material Candidate for Hypersonic Applications: Synthesis, Composition, and Oxidation Resistance of HfIr3-Based Solid Solution.

    Science.gov (United States)

    Lozanov, Victor V; Baklanova, Natalya I; Bulina, Natalia V; Titov, Anatoly T

    2018-04-18

    The peculiarities of the solid-state interaction in the HfC-Ir system have been studied within the 1000-1600 °C temperature range using a set of modern analytical techniques. It was stated that the interaction of HfC with iridium becomes noticeable at temperatures as low as 1000-1100 °C and results in the formation of HfIr 3 -based substitutional solid solution. The homogeneity range of the HfIr 3± x phase was evaluated and refined as HfIr 2.43 -HfIr 3.36 . The durability of the HfIr 3 -based system under extreme environmental conditions was studied. It was shown that the HfIr 3 -based material displays excellent ablation resistance under extreme environmental conditions. The benefits of the new designed material result from its relative oxygen impermeability and special microstructure similar to superalloys. The results obtained in this work allow us to consider HfIr 3 as a very promising candidate for extreme applications.

  14. Preliminary Evaluation of Alternate Designs for HFIR Low-Enriched Uranium Fuel

    Energy Technology Data Exchange (ETDEWEB)

    Renfro, David [ORNL; Chandler, David [ORNL; Cook, David [ORNL; Ilas, Germina [ORNL; Jain, Prashant [ORNL; Valentine, Jennifer [ORNL

    2014-10-30

    Engineering design studies of the feasibility of conversion of the High Flux Isotope Reactor (HFIR) from high-enriched uranium (HEU) to low-enriched uranium (LEU) fuel are ongoing at Oak Ridge National Laboratory (ORNL) as part of an effort sponsored by the U.S. Department of Energy’s Global Threat Reduction Initiative (GTRI)/Reduced Enrichment for Research and Test Reactors (RERTR) program. The fuel type selected by the program for the conversion of the five high-power research reactors in the U.S. that still use HEU fuel is a new U-Mo monolithic fuel. Studies by ORNL have previously indicated that HFIR can be successfully converted using the new fuel provided (1) the reactor power can be increased from 85 MW to 100 MW and (2) the fuel can be fabricated to a specific reference design. Fabrication techniques for the new fuel are under development by the program but are still immature, especially for the “complex” aspects of the HFIR fuel design. In FY 2012, the program underwent a major shift in focus to emphasize developing and qualifying processes for the fabrication of reliable and affordable LEU fuel. In support of this new focus and in an effort to ensure that the HFIR fuel design is as suitable for reliable fabrication as possible, ORNL undertook the present study to propose and evaluate several alternative design features. These features include (1) eliminating the fuel zone axial contouring in the previous reference design by substituting a permanent neutron absorber in the lower unfueled region of all of the fuel plates, (2) relocating the burnable neutron absorber from the fuel plates of the inner fuel element to the side plates of the inner fuel element (the fuel plates of the outer fuel element do not contain a burnable absorber), (3) relocating the fuel zone inside the fuel plate to be centered on the centerline of the depth of the plate, and (4) reshaping the radial contour of the relocated fuel zone to be symmetric about this centerline. The

  15. Preliminary Evaluation of Alternate Designs for HFIR Low-Enriched Uranium Fuel

    Energy Technology Data Exchange (ETDEWEB)

    Renfro, David G [ORNL; Chandler, David [ORNL; Cook, David Howard [ORNL; Ilas, Germina [ORNL; Jain, Prashant K [ORNL; Valentine, Jennifer R [ORNL

    2014-11-01

    Engineering design studies of the feasibility of conversion of the High Flux Isotope Reactor (HFIR) from high-enriched uranium (HEU) to low-enriched uranium (LEU) fuel are ongoing at Oak Ridge National Laboratory (ORNL) as part of an effort sponsored by the U.S. Department of Energy s Global Threat Reduction Initiative (GTRI)/Reduced Enrichment for Research and Test Reactors (RERTR) program. The fuel type selected by the program for the conversion of the five high-power research reactors in the U.S. that still use HEU fuel is a new U-Mo monolithic fuel. Studies by ORNL have previously indicated that HFIR can be successfully converted using the new fuel provided (1) the reactor power can be increased from 85 MW to 100 MW and (2) the fuel can be fabricated to a specific reference design. Fabrication techniques for the new fuel are under development by the program but are still immature, especially for the complex aspects of the HFIR fuel design. In FY 2012, the program underwent a major shift in focus to emphasize developing and qualifying processes for the fabrication of reliable and affordable LEU fuel. In support of this new focus and in an effort to ensure that the HFIR fuel design is as suitable for reliable fabrication as possible, ORNL undertook the present study to propose and evaluate several alternative design features. These features include (1) eliminating the fuel zone axial contouring in the previous reference design by substituting a permanent neutron absorber in the lower unfueled region of all of the fuel plates, (2) relocating the burnable neutron absorber from the fuel plates of the inner fuel element to the side plates of the inner fuel element (the fuel plates of the outer fuel element do not contain a burnable absorber), (3) relocating the fuel zone inside the fuel plate to be centered on the centerline of the depth of the plate, and (4) reshaping the radial contour of the relocated fuel zone to be symmetric about this centerline. The present

  16. Comparison of Calculated and Measured Neutron Fluence in Fuel/Cladding Irradiation Experiments in HFIR

    International Nuclear Information System (INIS)

    Ellis, Ronald James

    2011-01-01

    A recently-designed thermal neutron irradiation facility has been used for a first series of irradiations of PWR fuel pellets in the high flux isotope reactor (HFIR) at Oak Ridge National Laboratory. Since June 2010, irradiations of PWR fuel pellets made of UN or UO 2 , clad in SiC, have been ongoing in the outer small VXF sites in the beryllium reflector region of the HFIR, as seen in Fig. 1. HFIR is a versatile, 85 MW isotope production and test reactor with the capability and facilities for performing a wide variety of irradiation experiments. HFIR is a beryllium-reflected, light-water-cooled and -moderated, flux-trap type reactor that uses highly enriched (in 235 U) uranium (HEU) as the fuel. The reactor core consists of a series of concentric annular regions, each about 2 ft (0.61 m) high. A 5-in. (12.70-cm)-diam hole, referred to as the flux trap, forms the center of the core. The fuel region is composed of two concentric fuel elements made up of many involute-shaped fuel plates: an inner element that contains 171 fuel plates, and an outer element that contains 369 fuel plates. The fuel plates are curved in the shape of an involute, which provides constant coolant channel width between plates. The fuel (U 3 O 8 -Al cermet) is nonuniformly distributed along the arc of the involute to minimize the radial peak-to-average power density ratio. A burnable poison (B 4 C) is included in the inner fuel element primarily to reduce the negative reactivity requirements of the reactor control plates. A typical HEU core loading in HFIR is 9.4 kg of 235 U and 2.8 g of 10 B. The thermal neutron flux in the flux trap region can exceed 2.5 x 10 15 n/cm 2 · s while the fast flux in this region exceeds 1 x 10 15 n/cm 2 · s. The inner and outer fuel elements are in turn surrounded by a concentric ring of beryllium reflector approximately 1 ft (0.30 m) thick. The beryllium reflector consists of three regions: the removable reflector, the semi-permanent reflector, and the

  17. Enhanced radiation response in radioresistant MCF-7 cells by targeting peroxiredoxin II

    Directory of Open Access Journals (Sweden)

    Diaz AJG

    2013-10-01

    Full Text Available Anthony Joseph Gomez Diaz,1 Daniel Tamae,2 Yun Yen,3 JianJian Li,4 Tieli Wang1 1Department of Chemistry and Biochemistry, California State University at Dominguez Hills, Carson, CA, 2Center of Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, 3Department of Clinical and Molecular Pharmacology, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA, 4Department of Radiation Oncology, University of California Davis, Sacramento, CA, USA Abstract: In our previous study, we identified that a protein target, peroxiredoxin II (PrxII, is overexpressed in radioresistant MCF+FIR3 breast-cancer cells and found that its expression and function is associated with breast-cancer radiation sensitivity or resistance. Small interference RNA (siRNA targeting PrxII gene expression was able to sensitize MCF+FIR3 radioresistant breast-cancer cells to ionizing radiation. The major focus of this work was to investigate how the radiation response of MCF+FIR3 radioresistant cells was affected by the siRNA that inhibits PrxII gene expression. Our results, presented here, show that silencing PrxII gene expression increased cellular toxicity by altering cellular thiol status, inhibiting Ca2+ efflux from the cells, and perturbing the intracellular Ca2+ homeostasis. By combining radiotherapy and siRNA technology, we hope to develop new therapeutic strategies that may have potential to enhance the efficacy of chemotherapeutic agents due to this technology's property of targeting to specific cancer-related genes. Keywords: siRNA, PrxII, radiation resistance, Ca2+, MCF+FIR3

  18. Modernization of the High Flux Isotope Reactor (HFIR) to Provide a Cold Neutron Source and Experimentation Facility

    International Nuclear Information System (INIS)

    Rothrock, Benjamin G.; Farrar, Mike B.

    2009-01-01

    In June 1961, construction was started on the High Flux Isotope Reactor (HFIR) facility inside the Oak Ridge National Laboratory (ORNL), at the recommendation of the U.S. Atomic Energy Commission (AEC) Division of Research. Construction was completed in early 1965 with criticality achieved on August 25, 19651. From the first full power operating cycle beginning in September 1966, the HFIR has achieved an outstanding record of service to the scientific community. In early 1995, the ORNL deputy director formed a group to examine the need for upgrades to the HFIR following the cancellation of the Advanced Neutron Source Project by DOE. This group indicated that there was an immediate need for the installation of a cold neutron source facility in the HFIR to produce cold neutrons for neutron scattering research uses. Cold neutrons have long wavelengths in the range of 4-12 angstroms. Cold neutrons are ideal for research applications with long length-scale molecular structures such as polymers, nanophase materials, and biological samples. These materials require large scale examination (and therefore require a longer wavelength neutron). These materials represent particular areas of science are at the forefront of current research initiatives that have a potentially significant impact on the materials we use in our everyday lives and our knowledge of biology and medicine. This paper discusses the installation of a cold neutron source at HFIR with respect to the project as a modernization of the facility. The paper focuses on why the project was required, the scope of the cold source project with specific emphasis on the design, and project management information.

  19. U-target irradiation at FRM II aiming the production of Mo-99 - A feasibility study

    International Nuclear Information System (INIS)

    Gerstenberg, H.; Mueller, C.; Neuhaus, I.; Roehrmoser, A.

    2010-01-01

    Following the shortage in radioisotope availability the Technische Unversitaet Muenchen and the Belgian Institut National des Radioelements conducted a common study on the suitability of the FRM II reactor for the generation of Mo-99 as a fission product. A suitable irradiation channel was determined and neutronic calculations resulted in sufficiently high neutron flux densities to make FRM II a promising candidate for Mo-99 production. In addition the feasibility study provides thermohydraulic calculations as input for the design and integration of the additional cooling circuit into the existing heat removal systems of FRM II. The required in-house processes for a regular uranium target irradiation programme have been defined and necessary upgrades identified. Finally the required investment cost was estimated and a possible time schedule was given. (author)

  20. Tensile properties of vanadium alloys irradiated at 200{degrees}C in the HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Chung, H.M.; Nowicki, L.; Smith, D.L. [Argonne National Lab., IL (United States)

    1997-08-01

    Vanadium alloys were irradiated in a helium environment to {approx}10 dpa at {approx}200{degrees}C in the High Flux Isotope Reactor (HFIR). This report presents results of postirradiation tests of tensile properties of laboratory heats of V-(1-18)Ti, V-4Cr-4Ti, V-8Cr-6Ti, V-9Cr-5Ti, V-3Ti-1Si, and V-3Ti-0.1C alloys. Because of significant loss of work-hardening capability, all alloys except V-18Ti exhibited a very low uniform plastic strain <1%. For V-Ti. The mechanism of the loss of work-hardening capability in the other alloys is not understood.

  1. Ductility and microstructure of precipitation-strengthened alloys irradiated in HFIR

    International Nuclear Information System (INIS)

    Yang, W.J.S.; Hamilton, M.L.

    1983-08-01

    Six γ' and γ'/γ'' strengthened Ni-base alloys have shown near-zero ductility after irradiation at 300 to 600 0 C in HFIR to a peak exposure of 9 dpa. Microstructural examination of the irradiated specimens showed that the loss of ductility in these alloys arises from the simultaneous existence of a strong matrix and weak grain boundaries. The strong matrix is attributed to the irradiation-induced γ' and γ'/γ'' precipitates, the faulted loops and a high density of fine helium bubbles. The weak grain boundaries are attributed to the formation of an unfavorable precipitate, such as eta-plates, recrystallized grains, a thin layer of γ' and helium bubbles

  2. 2D Thermal Hydraulic Analysis and Benchmark in Support of HFIR LEU Conversion using COMSOL

    Energy Technology Data Exchange (ETDEWEB)

    Freels, James D [ORNL; Bodey, Isaac T [ORNL; Lowe, Kirk T [ORNL; Arimilli, Rao V [ORNL

    2010-09-01

    The research documented herein was funded by a research contract between the Research Reactors Division (RRD) of Oak Ridge National Laboratory (ORNL) and the University of Tennessee, Knoxville (UTK) Mechanical, Aerospace and Biomedical Engineering Department (MABE). The research was governed by a statement of work (SOW) which clearly defines nine specific tasks. This report is outlined to follow and document the results of each of these nine specific tasks. The primary goal of this phase of the research is to demonstrate, through verification and validation methods, that COMSOL is a viable simulation tool for thermal-hydraulic modeling of the High Flux Isotope Reactor (HFIR) core. A secondary goal of this two-dimensional phase of the research is to establish methodology and data base libraries that are also needed in the full three-dimensional COMSOL simulation to follow. COMSOL version 3.5a was used for all of the models presented throughout this report.

  3. Microstructural design of PCA austenitic stainless steel for improved resistance to helium embrittlement under HFIR irradiation

    International Nuclear Information System (INIS)

    Maziasz, P.J.; Braski, D.N.

    1983-01-01

    Several variants of Prime Candidate Alloy (PCA) with different preirradiation thermal-mechanical treatments were irradiated in HFIR and were evaluated for embrittlement resistance via disk-bend tensile testing. Comparison tests were made on two heats of 20%-cold-worked type 316 stainless steel. None of the alloys were brittle after irradiation at 300 to 400 0 C to approx. 44 dpa and helium levels of 3000 to approx.3600 at. ppm. However, all were quite brittle after similar exposure at 600 0 C. Embrittlement varied with alloy and pretreatment for irradiation to 44 dpa at 500 0 C and to 22 dpa at 600 0 C. Better relative embrittlement resistance among PCA variants was found in alloys which contained prior grain boundary MC carbide particles that remained stable under irradiation

  4. Neutron scattering for studies of soft matter at SNS and HFIR

    International Nuclear Information System (INIS)

    Smith, Gregory S.

    2013-01-01

    In this talk, we will present an overview of the scientific program of the Structure and Dynamics of Soft Matter Group, in the Biology and Soft Matter Division of the Neutron Sciences Directorate. From the broader area of soft materials research, the group members have chosen four main areas of scientific focus including: Confinement and Low-Dimensional Systems, Structure and Dynamics of Colloids, Nanoparticle-Polymer Composites, Transport in Membranes, and New Neutron Techniques for soft matter science. We will present several examples of neutron scattering experimental studies in each of these areas highlighting the experimental and theoretical (or modeling) capabilities of the group at both HFIR and SNS. Example topics to be discussed include SANS, reflectometry, and/or quasielastic studies of membranes on patterned interfaces, dynamics and structure of soft colloidal materials (including both polymeric dendrimers and biomimetic materials), gas confinement in mesoporous structures, transport in polyelectrolyte thin films, and development of spin-echo SANS concepts. (author)

  5. Improved swelling resistance for PCA austenitic stainless steel under HFIR irradiation through microstructural control

    International Nuclear Information System (INIS)

    Maziasz, P.J.; Braski, D.N.

    1983-01-01

    Six microstructural variants of Prime Candidate Alloy (PCA) were evaluated for swelling resistance during HFIR irradiation, together with several heats of type 316 stainless steel (316). Swelling was negligible in all the steels at 300 0 C after approx. 44 dpa. At 500 to 600 0 C 25%-cold-worked PCA showed better void swelling resistance than type 316 at approx. 44 dpa. There was less swelling variability among alloys at 400 0 C, but again 25%-cold-worked PCA was the best. Microstructurally, swelling resistance correlated with development of fine, stable bubbles whereas high swelling was due to coarser distributions of bubbles becoming unstable and converting to voids (bias-driven cavities)

  6. Saturation behavior of irradiation hardening in F82H irradiated in the HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, T. [Blanket Engineering Group, Japan Atomic Energy Agency, Naka, Ibaraki (Japan); Shiba, K.; Tanigawa, H.; Ando, M. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan); Klueh, R.L. [Oak Ridge National Laboratory, TN (United States); Stoller, R. [ORNL - Oak Ridge National Laboratory, Materials Science and Technology Div., Oak Ridge, AK TN (United States)

    2007-07-01

    Full text of publication follows: Post irradiation tensile tests on reduced activation ferritic/martensitic steel, F82H have been conducted over the past two decades using Japan Materials Testing Reactor (JMTR) of JAEA, and Fast Flux Testing Facility (FFTF) of PNNL and High Flux Isotope Reactor (HFIR) of ORNL, USA, under Japan/US collaboration programs. According to these results, F82H does not demonstrate irradiation hardening above 673 K up to 60 dpa. The current study has been concentrated on hardening behavior at temperature around 573 K. A series of low temperature irradiation experiment has been conducted at the HFIR under the international collaborative research between JAEA/US-DOE. In this collaboration, the irradiation condition is precisely controlled by the well matured capsule designing and instrumentation. This paper summarizes recent results of the irradiation experiments focused on F82H and its modified steels compared with the irradiation properties database on F82H. Post irradiation tensile tests have been conducted on the F82H and its modified steels irradiated at 573 K and the dose level was up to 25 dpa. According to these results, irradiation hardening of F82H is saturated by 9 dpa and the as-irradiated 0.2 % proof stress is less than 1 GPa at ambient temperature. The deterioration of total elongation was also saturated by 9 dpa irradiation. The ductility of some modified steels which showed larger total elongation than that of F82H before irradiation become the same level as that of standard F82H steel after irradiation, even though its magnitude of irradiation hardening is smaller than that of F82H. This suggests that the more ductile steel demonstrates the more ductility loss at this temperature, regardless to the hardening level. The difference in ductility loss behavior between various tensile specimens will be discussed as the ductility could depend on the specimen dimension. (authors)

  7. PLANS FOR WARM DENSE MATTER EXPERIMENTS AND IFE TARGET EXPERIMENTS ON NDCX-II

    International Nuclear Information System (INIS)

    Waldron, W.L.; Barnard, J.J.; Bieniosek, F.M.; Friedman, A.; Henestroza, E.; Leitner, M.; Logan, B.G.; Ni, P.A.; Roy, P.K.; Seidl, P.A.; Sharp, W.M.

    2008-01-01

    The Heavy Ion Fusion Science Virtual National Laboratory (HIFS-VNL) is currently developing design concepts for NDCX-II, the second phase of the Neutralized Drift Compression Experiment, which will use ion beams to explore Warm Dense Matter (WDM) and Inertial Fusion Energy (IFE) target hydrodynamics. The ion induction accelerator will consist of a new short pulse injector and induction cells from the decommissioned Advanced Test Accelerator (ATA) at Lawrence Livermore National Laboratory (LLNL). To fit within an existing building and to meet the energy and temporal requirements of various target experiments, an aggressive beam compression and acceleration schedule is planned. WDM physics and ion-driven direct drive hydrodynamics will initially be explored with 30 nC of lithium ions in experiments involving ion deposition, ablation, acceleration and stability of planar targets. Other ion sources which may deliver higher charge per bunch will be explored. A test stand has been built at Lawrence Berkeley National Laboratory (LBNL) to test refurbished ATA induction cells and pulsed power hardware for voltage holding and ability to produce various compression and acceleration waveforms. Another test stand is being used to develop and characterize lithium-doped aluminosilicate ion sources. The first experiments will include heating metallic targets to 10,000 K and hydrodynamics studies with cryogenic hydrogen targets

  8. Source Terms for HFIR Beam Tube Shielding Analyses, and a Complete Shielding Analysis of the HB-3 Tube

    International Nuclear Information System (INIS)

    Bucholz, J.A.

    2000-01-01

    The High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory is in the midst of a massive upgrade program to enhance experimental facilities. The reactor presently has four horizontal experimental beam tubes, all of which will be replaced or redesigned. The HB-2 beam tube will be enlarged to support more guide tubes, while the HB-4 beam tube will soon include a cold neutron source

  9. Source Terms for HFIR Beam Tube Shielding Analyses, and a Complete Shielding Analysis of the HB-3 Tube

    Energy Technology Data Exchange (ETDEWEB)

    Bucholz, J.A.

    2000-07-01

    The High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory is in the midst of a massive upgrade program to enhance experimental facilities. The reactor presently has four horizontal experimental beam tubes, all of which will be replaced or redesigned. The HB-2 beam tube will be enlarged to support more guide tubes, while the HB-4 beam tube will soon include a cold neutron source.

  10. SVMRFE based approach for prediction of most discriminatory gene target for type II diabetes

    Directory of Open Access Journals (Sweden)

    Atul Kumar

    2017-06-01

    Full Text Available Type II diabetes is a chronic condition that affects the way our body metabolizes sugar. The body's important source of fuel is now becoming a chronic disease all over the world. It is now very necessary to identify the new potential targets for the drugs which not only control the disease but also can treat it. Support vector machines are the classifier which has a potential to make a classification of the discriminatory genes and non-discriminatory genes. SVMRFE a modification of SVM ranks the genes based on their discriminatory power and eliminate the genes which are not involved in causing the disease. A gene regulatory network has been formed with the top ranked coding genes to identify their role in causing diabetes. To further validate the results pathway study was performed to identify the involvement of the coding genes in type II diabetes. The genes obtained from this study showed a significant involvement in causing the disease, which may be used as a potential drug target.

  11. Group II intron inhibits conjugative relaxase expression in bacteria by mRNA targeting

    Science.gov (United States)

    Piazza, Carol Lyn; Smith, Dorie

    2018-01-01

    Group II introns are mobile ribozymes that are rare in bacterial genomes, often cohabiting with various mobile elements, and seldom interrupting housekeeping genes. What accounts for this distribution has not been well understood. Here, we demonstrate that Ll.LtrB, the group II intron residing in a relaxase gene on a conjugative plasmid from Lactococcus lactis, inhibits its host gene expression and restrains the naturally cohabiting mobile element from conjugative horizontal transfer. We show that reduction in gene expression is mainly at the mRNA level, and results from the interaction between exon-binding sequences (EBSs) in the intron and intron-binding sequences (IBSs) in the mRNA. The spliced intron targets the relaxase mRNA and reopens ligated exons, causing major mRNA loss. Taken together, this study provides an explanation for the distribution and paucity of group II introns in bacteria, and suggests a potential force for those introns to evolve into spliceosomal introns. PMID:29905149

  12. Fracture fragility of HFIR vessel caused by random crack size or random toughness

    International Nuclear Information System (INIS)

    Chang, Shih-Jung; Proctor, L.D.

    1993-01-01

    This report discuses the probability of fracture (fracture fragility) versus a range of applied hoop stresses along the HFIR vessel which is obtained as an estimate of its fracture capacity. Both the crack size and the fracture toughness are assumed to be random variables that follow given distribution functions. Possible hoop stress is based on the numerical solution of the vessel response by applying a point pressure-pulse it the center of the fluid volume within the vessel. Both the fluid-structure interaction and radiation embrittlement are taken into consideration. Elastic fracture mechanics is used throughout the analysis. The probability of vessel fracture for a single crack caused by either a variable crack depth or a variable toughness is first derived. Then the probability of fracture with multiple number of cracks is obtained. The probability of fracture is further extended to include different levels of confidence and variability. It, therefore, enables one to estimate the high confidence and low probability capacity accident load

  13. Stress analysis of the HFIR HB-2 and HB-3 beam tube nozzles

    International Nuclear Information System (INIS)

    Williams, P.T.

    1998-08-01

    The results of three-dimensional linear elastic stress analyses of the HFIR HB-2 and HB-3 nozzles are presented in this report. Finite element models were developed using the PATRAN pre-processing code and translated into ABAQUS input file format. A scoping analysis using simple geometries with internal pressure loading was carried out to assess the capabilities of the ABAQUS/Standard code to calculate maximum principal stress distributions within cylinders with and without holes. These scoping calculations were also used to provide estimates for the variation in tangential stress around the rim of a nozzle using the superposition of published closed-form solutions for the stress around a hole in an infinite flat plate under uniaxial tension. From the results of the detailed finite element models, peak stress concentration factors (based on the maximum principal stresses in tension) were calculated to be 3.0 for the HB-2 nozzle and 2.8 for the HB-3 nozzle. Submodels for each nozzle were built to calculate the maximum principal stress distribution in the weldment region around the nozzle, where displacement boundary conditions for the submodels were automatically calculated by ABAQUS using the results of the global nozzle models. Maximum principal stresses are plotted and tabulated for eight positions around each nozzle and nozzle weldment

  14. Neutron and Gamma Fluxes and dpa Rates for HFIR Vessel Beltline Region (Present and Upgrade Designs)

    Energy Technology Data Exchange (ETDEWEB)

    Blakeman, E.D.

    2001-01-11

    The Oak Ridge National Laboratory (ORNL) High Flux Isotope Reactor (HFIR) is currently undergoing an upgrading program, a part of which is to increase the diameters of two of the four radiation beam tubes (HB-2 and HB-4). This change will cause increased neutron and gamma radiation dose rates at and near locations where the tubes penetrate the vessel wall. Consequently, the rate of radiation damage to the reactor vessel wall at those locations will also increase. This report summarizes calculations of the neutron and gamma flux (particles/cm{sup 2}/s) and the dpa rate (displacements/atom/s) in iron at critical locations in the vessel wall. The calculated dpa rate values have been recently incorporated into statistical damage evaluation codes used in the assessment of radiation induced embrittlement. Calculations were performed using models based on the discrete ordinates methodology and utilizing ORNL two-dimensional and three-dimensional discrete ordinates codes. Models for present and proposed beam tube designs are shown and their results are compared. Results show that for HB-2, the dpa rate in the vessel wall where the tube penetrates the vessel will be increased by {approximately}10 by the proposed enlargement. For HB-4, a smaller increase of {approximately}2.6 is calculated.

  15. Fabrication and operation of HFIR-MFE RB* spectrally tailored irradiation capsules

    International Nuclear Information System (INIS)

    Longest, A.W.; Pawel, J.E.; Heatherly, D.W.; Sitterson, R.G.; Wallace, R.L.

    1993-01-01

    Fabrication and operation of four HFIR-MFE RB * capsules (60, 200, 330, and 400 degrees C) to accommodate MFE specimens previously irradiated in spectrally tailored experiments in the ORR are proceeding satisfactorily. With the exception of the 60 degrees C capsule, where the test specimens were in direct contact with the reactor cooling water, specimen temperatures (monitored by 21 thermocouples) are controlled by varying the thermal conductance of a thin gap region between the specimen holder outer sleeve and containment tube. Irradiation of the 60 and 330 degrees C capsules, which started on July 17, 1990, was completed on November 14, 1992, after 24 cycles of irradiation to an incremental damage level of approximately 10.9 displacements per atom (dpa). Assembly of the follow-up 200 and 400 degrees C capsules was completed in November 1992, and their planned 20-cycle irradiation to approximately 9.1 incremental dpa was started on November 21, 1992. As of February 11, 1993, the 200 and 400 degrees C capsules had successfully completed three cycles of irradiation to approximately 1.4 incremental dpa

  16. A design concept of target-moderator-reflector assemblies for KENS-II

    International Nuclear Information System (INIS)

    Watanabe, N.

    1991-01-01

    A design concept of KENS-II target-moderator-reflector assemblies is described. One of the assemblies is dedicated to the cold neutron source, and the other, to the thermal and epithermal neutron source. A flux-trap type moderator-configuration was adopted with a vertical proton-beam injection scheme. All moderators for the cold neutron source are coupled liquid hydrogen moderators with premoderators. A new scheme of proton beam delivery is proposed. The new system can provide several times higher total performance than a reference system based on a traditional single assembly with all decoupled moderators in a wing geometry and with a horizontal proton-beam injection scheme. (author)

  17. GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates.

    Science.gov (United States)

    Liu, Ran; Fu, Zheng; Zhao, Meng; Gao, Xiangqian; Li, Hong; Mi, Qian; Liu, Pengxing; Yang, Jinna; Yao, Zhi; Gao, Qingzhi

    2017-06-13

    Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glucose, mannose and galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-flouromalonato-platinum(II) complexes for a comprehensive evaluation on their selective tumor targeting. Besides highly improved water solubility, these sugar-conjugates presented improved cytotoxicity than oxaliplatin in glucose tranporters (GLUTs) overexpressing cancer cell lines and exhibited no cross-resistance to cisplatin. For the highly water soluble glucose-conjugated complex (5a), two novel in vivo assessments were conducted and the results revealed that 5a was more efficacious at a lower equitoxic dose (70% MTD) than oxaliplatin (100% MTD) in HT29 xenograft model, and it was significantly more potent than oxaliplatin in leukemia-bearing DBA/2 mice as well even at equimolar dose levels (18% vs 90% MTD). GLUT inhibitor mediated cell viability analysis, GLUT1 knockdown cell line-based cytotoxicity evaluation, and platinum accumulation study demonstrated that the cellular uptake of the sugar-conjugates was regulated by GLUT1. The higher intrinsic DNA reactivity of the sugar-conjugates was confirmed by kinetic study of platinum(II)-guanosine adduct formation. The mechanistic origin of the antitumor effect of the fluorine complexes was found to be forming the bifunctional Pt-guanine-guanine (Pt-GG) intrastrand cross-links with DNA. The results provide a rationale for Warburg effect targeted anticancer drug design.

  18. Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/ Rho kinase pathways targeted to lipid rafts.

    Science.gov (United States)

    Burger, Dylan; Montezano, Augusto C; Nishigaki, Nobuhiro; He, Ying; Carter, Anthony; Touyz, Rhian M

    2011-08-01

    Circulating microparticles are increased in cardiovascular disease and may themselves promote oxidative stress and inflammation. Molecular mechanisms underlying their formation and signaling are unclear. We investigated the role of reactive oxygen species (ROS), Rho kinase, and lipid rafts in microparticle formation and examined their functional significance in endothelial cells (ECs). Microparticle formation from angiotensin II (Ang II)-stimulated ECs and apolipoprotein E(-/-) mice was assessed by annexin V or by CD144 staining and electron microscopy. Ang II promoted microparticle formation and increased EC O(2)(-) generation and Rho kinase activity. Ang II-stimulated effects were inhibited by irbesartan (Ang II receptor type I blocker) and fasudil (Rho kinase inhibitor). Methyl-β-cyclodextrin and nystatin, which disrupt lipid rafts/caveolae, blocked microparticle release. Functional responses, assessed in microparticle-stimulated ECs, revealed increased O(2)(-) production, enhanced vascular cell adhesion molecule/platelet-EC adhesion molecule expression, and augmented macrophage adhesion. Inhibition of epidermal growth factor receptor blocked the prooxidative and proinflammatory effects of microparticles. In vitro observations were confirmed in apolipoprotein E(-/-) mice, which displayed vascular inflammation and high levels of circulating endothelial microparticles, effects that were reduced by apocynin. We demonstrated direct actions of Ang II on endothelial microparticle release, mediated through NADPH oxidase, ROS, and Rho kinase targeted to lipid rafts. Microparticles themselves stimulated endothelial ROS formation and inflammatory responses. Our findings suggest a feedforward system whereby Ang II promotes EC injury through its own endothelial-derived microparticles.

  19. The SNS/HFIR Web Portal System How Can it Help Me?

    International Nuclear Information System (INIS)

    Miller, Stephen D.; Geist, Al; Herwig, Kenneth W.; Peterson, Peter F.; Reuter, Michael A.; Ren, Shelly; Bilheux, Jean-Christophe; Campbell, Stuart I.; Kohl, James Arthur; Vazhkudai, Sudharshan S.; Cobb, John W.; Lynch, Vickie E.; Chen, Meili; Trater, James R.

    2010-01-01

    In a busy world, continuing with the status-quo, to do things the way we are already familiar, often seems to be the most efficient way to conduct our work. We look for the value-add to decide if investing in a new method is worth the effort. How shall we evaluate if we have reached this tipping point for change? For contemporary researchers, understanding the properties of the data is a good starting point. The new generation of neutron scattering instruments being built are higher resolution and produce one or more orders of magnitude larger data than the previous generation of instruments. For instance, we have grown out of being able to perform some important tasks with our laptops the data are too big and the computations would simply take too long. These large datasets can be problematic as facility users now begin to grapple with many of the same issues faced by more established computing communities. These issues include data access, management, and movement, data format standards, distributed computing, and collaboration among others. The Neutron Science Portal has been architected, designed, and implemented to provide users with an easy-to-use interface for managing and processing data, while also keeping an eye on meeting modern cybersecurity requirements imposed on institutions. The cost of entry for users has been lowered by utilizing a web interface providing access to backend portal resources. Users can browse or search for data which they are allowed to see, data reduction applications can be run without having to load the software, sample activation calculations can be performed for SNS and HFIR beamlines, McStas simulations can be run on TeraGrid and ORNL computers, and advanced analysis applications such as those being produced by the DANSE project can be run. Behind the scenes is a live cataloging system which automatically catalogs and archives experiment data via the data management system, and provides proposal team members access to their

  20. Charpy impact test results of ferritic alloys from the HFIR[High Flux Isotope Reactor]-MFE-RB2 test

    International Nuclear Information System (INIS)

    Hu, W.L.; Gelles, D.S.

    1987-03-01

    Miniature Charpy specimens of HT-9 in base metal, weld metal and heat affected zone (HAZ) metal conditions, and 9Cr-1Mo in base metal and weld metal conditions have been tested following irradiation in HFIR-MFE-RB2 at 55 0 C to ≅10 dpa. All specimen conditions have degraded properties (both DBTT and USE) in comparison with specimens irradiated to lower dose. 9Cr-Mo degraded more than HT-9 and weld metal performed worse than base metal which performed worse than HAZ material. Property degradation was approximately linear as a function of dose, indicating that degradation response had not saturated by 10 dpa

  1. Summary of the U.S. specimen matrix for the HFIR 13J varying temperature irradiation capsule

    International Nuclear Information System (INIS)

    Zinkle, S.J.

    1998-01-01

    The US specimen matrix for the collaborative DOE/Monbusho HFIR 13J varying temperature irradiation capsule contains two ceramics and 29 different metals, including vanadium alloys, ferritic/martensitic steels, pure iron, austenitic stainless steels, nickel alloys, and copper alloys. This experiment is designed to provide fundamental information on the effects of brief low-temperature excursions on the tensile properties and microstructural evolution of a wide range of materials irradiated at nominal temperatures of 350 and 500 C to a dose of ∼5 dpa. A total of 340 miniature sheet tensile specimens and 274 TEM disks are included in the US-supplied matrix for the irradiation capsule

  2. Analysis of in-situ electrical conductivity data from the HFIR TRIST-ER1 experiment

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J.; Snead, L.L. [Oak Ridge National Lab., TN (United States); Shikama, T. [Tohoku Univ. (Japan)] [and others

    1997-08-01

    The current vs. applied voltage data generated from the HFIR TRIST-ER1 experiment have been analyzed to determine the electrical conductivity of the 15 aluminum oxide specimens and the MgO-insulated electrical cables as a function of irradiation dose. With the exception of the 0.05%Cr-doped sapphire (ruby) specimen, the electrical conductivity of the alumina specimens remained at the expected radiation induced conductivity (RIC) level of <10{sup -6} S/m during full-power reactor irradiation (10-16 kGy/s) at 450-500{degrees}C up to a maximum dose of {approximately}3 dpa. The ruby specimen showed a rapid initial increase in conductivity to {approximately}2 x 10{sup -4} S/m after {approximately}0.1 dpa, followed by a gradual decrease to <1 x 10{sup -6} S/m after 2 dpa. Nonohmic electrical behavior was observed in all of the specimens, and was attributed to preferential attraction of ionized electrons in the capsule gas to the unshielded low-side bare electrical leads emanating from the subcapsules. The electrical conductivity was determined from the slope of the specimen current vs. voltage curve at negative voltages, where the gas ionization effect was minimized. Dielectric breakdown tests performed on unirradiated mineral-insulated coaxial cables identical to those used in the high voltage coaxial cables during the 3-month irradiation is attributable to thermal dielectric breakdown in the glass seals at the end of the cables, as opposed to a radiation-induced electrical degradation (RIED) effect.

  3. Analysis of in-situ electrical conductivity data from the HFIR TRIST-ER1 experiment

    International Nuclear Information System (INIS)

    Zinkle, S.J.; Snead, L.L.; Shikama, T.

    1997-01-01

    The current vs. applied voltage data generated from the HFIR TRIST-ER1 experiment have been analyzed to determine the electrical conductivity of the 15 aluminum oxide specimens and the MgO-insulated electrical cables as a function of irradiation dose. With the exception of the 0.05%Cr-doped sapphire (ruby) specimen, the electrical conductivity of the alumina specimens remained at the expected radiation induced conductivity (RIC) level of -6 S/m during full-power reactor irradiation (10-16 kGy/s) at 450-500 degrees C up to a maximum dose of ∼3 dpa. The ruby specimen showed a rapid initial increase in conductivity to ∼2 x 10 -4 S/m after ∼0.1 dpa, followed by a gradual decrease to -6 S/m after 2 dpa. Nonohmic electrical behavior was observed in all of the specimens, and was attributed to preferential attraction of ionized electrons in the capsule gas to the unshielded low-side bare electrical leads emanating from the subcapsules. The electrical conductivity was determined from the slope of the specimen current vs. voltage curve at negative voltages, where the gas ionization effect was minimized. Dielectric breakdown tests performed on unirradiated mineral-insulated coaxial cables identical to those used in the high voltage coaxial cables during the 3-month irradiation is attributable to thermal dielectric breakdown in the glass seals at the end of the cables, as opposed to a radiation-induced electrical degradation (RIED) effect

  4. The High Flux Isotope Reactor (HFIR) cold source project at ORNL

    International Nuclear Information System (INIS)

    Selby, D.L.; Lucas, A.T.; Chang, S.J.; Freels, J.D. . E-mail-yb2@ornl.gov

    1998-01-01

    Following the decision to cancel the Advanced Neutron Source (ANS) Project at Oak Ridge National Laboratory (ORNL), it was determined that a hydrogen cold source should be retrofitted into an existing beam tube of the High Flux Isotope Reactor (HFIR) at ORNL. The preliminary design of this system has been completed and an 'approval in principle' of the design has been obtained from the internal ORNL safety review committees and the U.S. Department of Energy (DOE) safety review committee. The cold source concept is basically a closed loop forced flow supercritical hydrogen system. The supercritical approach was chosen because of its enhanced stability in the proposed high heat flux regions. Neutron and gamma physics of the moderator have been analyzed using the 3D Monte Carlo code MCNP 1 A D structural analysis model of the moderator vessel, vacuum tube, and beam tube was completed to evaluate stress loadings and to examine the impact of hydrogen detonations in the beam tube. A detailed ATHENA 2 system model of the hydrogen system has been developed to simulate loop performance under normal and off-normal transient conditions. Semi-prototypic hydrogen loop tests of the system have been performed at the Arnold Engineering Design Center (AEDC) located in Tullahoma, Tennessee to verify the design and benchmark the analytical system model. A 3.5 kW refrigerator system has been ordered and is expected to be delivered to ORNL by the end of this calendar year. Our present schedule shows the assembling of the cold source loop on site during the fall of 1999 for final testing before insertion of the moderator plug assembly into the reactor beam tube during the end of the year 2000. (author)

  5. Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia

    Science.gov (United States)

    Yoshida, Tadashi; Tabony, A. Michael; Galvez, Sarah; Mitch, William E.; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

    2013-01-01

    Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Many factors are involved in the development of cachexia, and there is increasing evidence that angiotensin II (Ang II), the main effector molecule of the renin-angiotensin system (RAS), plays an important role in this process. Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme (ACE) inhibitor treatment improves weight loss. In rodent models, an increase in systemic Ang II leads to weight loss through increased protein breakdown, reduced protein synthesis in skeletal muscle and decreased appetite. Ang II activates the ubiquitin-proteasome system via generation of reactive oxygen species and via inhibition of the insulin-like growth factor-1 signaling pathway. Furthermore, Ang II inhibits 5′ AMP-activated protein kinase (AMPK) activity and disrupts normal energy balance. Ang II also increases cytokines and circulating hormones such as tumor necrosis factor-α, interleukin-6, serum amyloid-A, glucocorticoids and myostatin, which regulate muscle protein synthesis and degradation. Ang II acts on hypothalamic neurons to regulate orexigenic/anorexigenic neuropeptides, such as neuropeptide-Y, orexin and corticotropin-releasing hormone, leading to reduced appetite. Also, Ang II may regulate skeletal muscle regenerative processes. Several clinical studies have indicated that blockade of Ang II signaling via ACE inhibitors or Ang II type 1 receptor blockers prevents weight loss and improves muscle strength. Thus the RAS is a promising target for the treatment of muscle atrophy in patients with CHF and CKD. PMID:23769949

  6. Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

    Czech Academy of Sciences Publication Activity Database

    Yan, B.; Stantic, M.; Zobalová, Renata; Bezawork-Geleta, A.; Stapelberg, M.; Stursa, J.; Prokopová, Kateřina; Dong, L.; Neužil, Jiří

    2015-01-01

    Roč. 15, č. 401 (2015) ISSN 1471-2407 R&D Projects: GA MZd NT14078; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * Mitochondrially targeted vitamin E succinate * Complex II Subject RIV: FD - Oncology ; Hematology Impact factor: 3.265, year: 2015

  7. Project Plan Remote Target Fabrication Refurbishment Project

    International Nuclear Information System (INIS)

    Bell, Gary L.; Taylor, Robin D.

    2009-01-01

    In early FY2009, the DOE Office of Science - Nuclear Physics Program reinstated a program for continued production of 252 Cf and other transcurium isotopes at the Radiochemical Engineering Development Center (REDC) at Oak Ridge National Laboratory (ORNL). The FY2009 major elements of the workscope are as follows: (1) Recovery and processing of seven transuranium element targets undergoing irradiation at the High Flux Isotope Reactor (HFIR) at ORNL; (2) Development of a plan to manufacture new targets for irradiation beginning in early- to mid-FY10 to supply irradiated targets for processing Campaign 75 (TRU75); and (3) Refurbishment of the target manufacturing equipment to allow new target manufacture in early FY10 The 252 Cf product from processing Campaign 74 (recently processed and currently shipping to customers) is expected to supply the domestic demands for a period of approximately two years. Therefore it is essential that new targets be introduced for irradiation by the second quarter of FY10 (HFIR cycle 427) to maintain supply of 252 Cf; the average irradiation period is ∼10 HFIR cycles, requiring about 1.5 calendar years. The strategy for continued production of 252 Cf depends upon repairing and refurbishing the existing pellet and target fabrication equipment for one additional target production campaign. This equipment dates from the mid-1960s to the late 1980s, and during the last target fabrication campaign in 2005- 2006, a number of component failures and operations difficulties were encountered. It is expected that following the target fabrication and acceptance testing of the targets that will supply material for processing Campaign 75 a comprehensive upgrade and replacement of the remote hot-cell equipment will be required prior to subsequent campaigns. Such a major refit could start in early FY 2011 and would take about 2 years to complete. Scope and cost estimates for the repairs described herein were developed, and authorization for the work

  8. Possible Therapeutic Application of Targeting Type II Natural Killer T Cell-Mediated Suppression of Tumor Immunity

    Science.gov (United States)

    Kato, Shingo; Berzofsky, Jay A.; Terabe, Masaki

    2018-01-01

    Natural killer T (NKT) cells are a unique T cell subset that exhibits characteristics from both the innate immune cells and T cells. There are at least two subsets of NKT cells, type I and type II. These two subsets of NKT cells have opposite functions in antitumor immunity. Type I NKT cells usually enhance and type II NKT cells suppress antitumor immunity. In addition, these two subsets of NKT cells cross-regulate each other. In this review, we mainly focus on immunosuppressive NKT cells, type II NKT cells. After summarizing their definition, experimental tools to study them, and subsets of them, we will discuss possible therapeutic applications of type II NKT cell pathway targeted therapies. PMID:29520281

  9. Simulations on Nickel target preparation and separation of Ni(II)-Cu(II) matrix for production of radioisotope "6"4Cu

    International Nuclear Information System (INIS)

    Sunarhadijoso Soenarjo; Wira Y Rahman; Sriyono; Triyanto

    2011-01-01

    The simulations on Nickel target preparation and separation of Ni(II)-Cu(II) matrix has been carried out as a preliminary study for production of medical radioisotope Cu-64 based on nuclear reaction of "6"4Ni (p,n) "6"4Cu. The nickel target preparation was performed by means of electroplating method using acidic solution of nickel chloride - boric acid mixture and basic solution of nickel sulphate - nickel chloride mixture on a silver - surfaced-target holder. The simulated solution of Ni(II) - Cu(II) matrix was considered as the solution of post-proton-irradiated nickel target containing both irradiated nickel and radioactive copper, but in the presented work the proton irradiation of nickel target was omitted, while the radioactive copper was originally obtained from neutron irradiation of CuO target. The separation of radioactive copper from the nickel target matrix was based on anion exchange column chromatography in which the radiocopper was conditioned to form anion complex CuCl_4"2"- and retained on the column while the nickel was kept in the form of Ni"2"+ cation and eluted off from the column. The retained radioactive copper was then eluted out the column in the condition of dilute HCl changing back the copper anion complex into Cu"2"+ cation. It was found that the electroplating result from the acidic solution was more satisfied than that from the basic solution. By conditioning the matrix solution at HCl 6 M, the radioactive copper was found in the forms of Cu"2"+ and CuCl_4"2"- while the nickel was totally in the form of Ni"2"+. In the condition of HCl 9 M, the radioactive copper was mostly in the form of CuCl_4"2"- while the nickel was found as both Ni"2"+ and NiCl_4"2"-. The best condition of separation was in HCl 8 M in which the radioactive copper was mostly in the form of CuCl_4"2"- while the nickel was mostly in the form of Ni"2"+. The retained CuCl_4"2"- was then changed back into Cu_2_+ cation form and eluted out the column by using HCl 0.05 M

  10. Analysis of dpa Rates in the HFIR Reactor Vessel using a Hybrid Monte Carlo/Deterministic Method*

    Directory of Open Access Journals (Sweden)

    Risner J.M.

    2016-01-01

    Full Text Available The Oak Ridge High Flux Isotope Reactor (HFIR, which began full-power operation in 1966, provides one of the highest steady-state neutron flux levels of any research reactor in the world. An ongoing vessel integrity analysis program to assess radiation-induced embrittlement of the HFIR reactor vessel requires the calculation of neutron and gamma displacements per atom (dpa, particularly at locations near the beam tube nozzles, where radiation streaming effects are most pronounced. In this study we apply the Forward-Weighted Consistent Adjoint Driven Importance Sampling (FW-CADIS technique in the ADVANTG code to develop variance reduction parameters for use in the MCNP radiation transport code. We initially evaluated dpa rates for dosimetry capsule locations, regions in the vicinity of the HB-2 beamline, and the vessel beltline region. We then extended the study to provide dpa rate maps using three-dimensional cylindrical mesh tallies that extend from approximately 12 in. below to approximately 12 in. above the height of the core. The mesh tally structures contain over 15,000 mesh cells, providing a detailed spatial map of neutron and photon dpa rates at all locations of interest. Relative errors in the mesh tally cells are typically less than 1%.

  11. Simulated Irradiation of Samples in HFIR for use as Possible Test Materials in the MPEX (Material Plasma Exposure Experiment) Facility

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, Ronald James [ORNL; Rapp, Juergen [ORNL

    2014-01-01

    The importance of Plasma Material Interaction (PMI) is a major concern in fusion reactor design and analysis. The Material-Plasma Exposure eXperiment (MPEX) facility will explore PMI under fusion reactor plasma conditions. Samples with accumulated displacements per atom (DPA) damage produced by irradiations in the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL) will be studied in the MPEX facility. The project presented in this paper involved performing assessments of the induced radioactivity and resulting radiation fields of a variety of potential fusion reactor materials. The scientific code packages MCNP and SCALE were used to simulate irradiation of the samples in HFIR; generation and depletion of nuclides in the material and the subsequent composition, activity levels, gamma radiation fields, and resultant dose rates as a function of cooling time. These state-of-the-art simulation methods were used in addressing the challenge of the MPEX project to minimize the radioactive inventory in the preparation of the samples for inclusion in the MPEX facility.

  12. Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation.

    Science.gov (United States)

    Liu, Chang; Rajapakse, Angana G; Riedo, Erwin; Fellay, Benoit; Bernhard, Marie-Claire; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

    2016-02-05

    Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Here we demonstrate that Arg-II(-/-) mice reveal decreased hepatic steatosis, macrophage infiltration, TNF-α and IL-6 as compared to the wild type (WT) littermates fed high fat diet (HFD). A higher AMPK activation (no difference in mTOR signaling), lower levels of lipogenic transcription factor SREBP-1c and activity/expression of lipogenic enzymes were observed in the Arg-II(-/-) mice liver. Moreover, release of TNF-α and IL-6 from bone marrow-derived macrophages (BMM) of Arg-II(-/-) mice is decreased as compared to WT-BMM. Conditioned medium from Arg-II(-/-)-BMM exhibits weaker activity to facilitate triglyceride synthesis paralleled with lower expression of SREBP-1c and SCD-1 and higher AMPK activation in hepatocytes as compared to that from WT-BMM. These effects of BMM conditioned medium can be neutralized by neutralizing antibodies against TNF-α and IL-6. Thus, Arg-II-expressing macrophages facilitate diet-induced NAFLD through TNF-α and IL-6 in obesity.

  13. Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity.

    Science.gov (United States)

    Huang, Ji; Rajapakse, Angana; Xiong, Yuyan; Montani, Jean-Pierre; Verrey, François; Ming, Xiu-Fen; Yang, Zhihong

    2016-01-01

    Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II -/- ) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II -/- mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II -/- mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II -/- mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

  14. Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Ji Huang

    2016-11-01

    Full Text Available Obesity is associated with development and progression of chronic kidney disease (CKD. Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I and arginase-II (Arg-II in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS, leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT C57BL/6 mice and mice deficient in Arg-II gene (Arg-II-/- were fed with either a normal chow (NC or a high-fat-diet (HFD for 14 weeks (starting at the age of 7 weeks to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal ROS levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II-/- mice. Moreover, mesangial expansion as analysed by Periodic Acid Schiff (PAS staining and renal expression of vascular adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II-/- mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II-/- mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

  15. Simulated Target Preparation and Separation of Cd (II) - In (III) Matrices Using 8-Hydroxyquinoline Reagent for Producing Indium - III Radioisotope

    International Nuclear Information System (INIS)

    Sunarhadijoso Soenarjo; Swasono R Tamat; Lukiyawati; Lintang Maharani

    2002-01-01

    The potency of production and application of 111 In in Indonesia is not supported yet by capability in required processing technology. The presented paper is a preliminary study on processing technology of 111 In production from 112 Cd target covering simulated target preparation and separation of Cd(II)-In(III) matrices. The target preparation was performed by means of electroplating of CdSO 4 solution prepared from reaction of CdO and sulphuric acid. The separation of Cd(II)-In(III) matrices was proceeded by means of solvent extraction in the presence of 8-hydroxyquinoline as In(III)-complexing agent. The Cd-electroplating deposit was satisfactorily found by using 40-60 mA currents with an electroplating time of 5-7 hours. Simulated matrix solution containing mixture of Cd(II) and In(III) was extracted into chloroform with the presence of 8-hydroxyquinoline. The chloroform phase being assumed to contain In(III)-8-hydroxyquinoline complex was then re-extracted with 1 M HCl or saline solution. Each extraction fraction was spectrophotometrically identified in the region of 200-400 nm. From the resulting absorption spectra, it can be shown that the In(III) species is selectively separated from the Cd(II)-matrix. The use of saline in the re-extraction process is better then 1 M HCl solution due to solubility of 8-hydroxyquinoline in HCl. (author)

  16. OBJECT KINETIC MONTE CARLO SIMULATIONS OF RADIATION DAMAGE IN TUNGSTEN SUBJECTED TO NEUTRON FLUX WITH PKA SPECTRUM CORRESPONDING TO THE HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.; Roche, Kenneth J.; Kurtz, Richard J.; Wirth, Brian D.

    2015-12-31

    The objective of this work is to study the damage accumulation in pure tungsten (W) subjected to neutron bombardment with a primary knock-on atom (PKA) spectrum corresponding to the High Flux Isotope Reactor (HFIR), using the object kinetic Monte Carlo (OKMC) method.

  17. The SNS/HFIR Web Portal System - How Can it Help Me?

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Stephen D; Geist, Al; Herwig, Kenneth W; Peterson, Peter F; Reuter, Michael A; Ren, Shelly; Bilheux, Jean-Christophe; Campbell, Stuart I; Kohl, James A; Vazhkudai, Sudharshan S; Cobb, John W; Lynch, Vickie E; Chen Meili; Trater, James R; Smith, Bradford C; Swain, Tom; Huang Jian [University of Tennessee, Knoxville, TN (United States); Mikkelson, Ruth; Mikkelson, Dennis, E-mail: millersd@ornl.gov

    2010-11-01

    In a busy world, continuing with the status-quo, to do things the way we are already familiar, often seems to be the most efficient way to conduct our work. We look for the value-add to decide if investing in a new method is worth the effort. How shall we evaluate if we have reached this tipping point for change? For contemporary researchers, understanding the properties of the data is a good starting point. The new generation of neutron scattering instruments being built are higher resolution and produce one or more orders of magnitude larger data than the previous generation of instruments. For instance, we have grown out of being able to perform some important tasks with our laptops - the data are too big and the computations would simply take too long. These large datasets can be problematic as facility users now begin to grapple with many of the same issues faced by more established computing communities. These issues include data access, management, and movement, data format standards, distributed computing, and collaboration among others. The Neutron Science Portal has been architected, designed, and implemented to provide users with an easy-to-use interface for managing and processing data, while also keeping an eye on meeting modern cybersecurity requirements imposed on institutions. The cost of entry for users has been lowered by utilizing a web interface providing access to backend portal resources. Users can browse or search for data which they are allowed to see, data reduction applications can be run without having to load the software, sample activation calculations can be performed for SNS and HFIR beamlines, McStas simulations can be run on TeraGrid and ORNL computers, and advanced analysis applications such as those being produced by the DANSE project can be run. Behind the scenes is a 'live cataloging' system which automatically catalogs and archives experiment data via the data management system, and provides proposal team members

  18. The SNS/HFIR Web Portal System - How Can it Help Me?

    International Nuclear Information System (INIS)

    Miller, Stephen D; Geist, Al; Herwig, Kenneth W; Peterson, Peter F; Reuter, Michael A; Ren, Shelly; Bilheux, Jean-Christophe; Campbell, Stuart I; Kohl, James A; Vazhkudai, Sudharshan S; Cobb, John W; Lynch, Vickie E; Chen Meili; Trater, James R; Smith, Bradford C; Swain, Tom; Huang Jian; Mikkelson, Ruth; Mikkelson, Dennis

    2010-01-01

    In a busy world, continuing with the status-quo, to do things the way we are already familiar, often seems to be the most efficient way to conduct our work. We look for the value-add to decide if investing in a new method is worth the effort. How shall we evaluate if we have reached this tipping point for change? For contemporary researchers, understanding the properties of the data is a good starting point. The new generation of neutron scattering instruments being built are higher resolution and produce one or more orders of magnitude larger data than the previous generation of instruments. For instance, we have grown out of being able to perform some important tasks with our laptops - the data are too big and the computations would simply take too long. These large datasets can be problematic as facility users now begin to grapple with many of the same issues faced by more established computing communities. These issues include data access, management, and movement, data format standards, distributed computing, and collaboration among others. The Neutron Science Portal has been architected, designed, and implemented to provide users with an easy-to-use interface for managing and processing data, while also keeping an eye on meeting modern cybersecurity requirements imposed on institutions. The cost of entry for users has been lowered by utilizing a web interface providing access to backend portal resources. Users can browse or search for data which they are allowed to see, data reduction applications can be run without having to load the software, sample activation calculations can be performed for SNS and HFIR beamlines, McStas simulations can be run on TeraGrid and ORNL computers, and advanced analysis applications such as those being produced by the DANSE project can be run. Behind the scenes is a 'live cataloging' system which automatically catalogs and archives experiment data via the data management system, and provides proposal team members access to

  19. The SNS/HFIR Web Portal System - How Can it Help Me?

    Science.gov (United States)

    Miller, Stephen D.; Geist, Al; Herwig, Kenneth W.; Peterson, Peter F.; Reuter, Michael A.; Ren, Shelly; Bilheux, Jean-Christophe; Campbell, Stuart I.; Kohl, James A.; Vazhkudai, Sudharshan S.; Cobb, John W.; Lynch, Vickie E.; Chen, Meili; Trater, James R.; Smith, Bradford C.; (William Swain, Tom; Huang, Jian; Mikkelson, Ruth; Mikkelson, Dennis; een, Mar K. L. Gr

    2010-11-01

    In a busy world, continuing with the status-quo, to do things the way we are already familiar, often seems to be the most efficient way to conduct our work. We look for the value-add to decide if investing in a new method is worth the effort. How shall we evaluate if we have reached this tipping point for change? For contemporary researchers, understanding the properties of the data is a good starting point. The new generation of neutron scattering instruments being built are higher resolution and produce one or more orders of magnitude larger data than the previous generation of instruments. For instance, we have grown out of being able to perform some important tasks with our laptops - the data are too big and the computations would simply take too long. These large datasets can be problematic as facility users now begin to grapple with many of the same issues faced by more established computing communities. These issues include data access, management, and movement, data format standards, distributed computing, and collaboration among others. The Neutron Science Portal has been architected, designed, and implemented to provide users with an easy-to-use interface for managing and processing data, while also keeping an eye on meeting modern cybersecurity requirements imposed on institutions. The cost of entry for users has been lowered by utilizing a web interface providing access to backend portal resources. Users can browse or search for data which they are allowed to see, data reduction applications can be run without having to load the software, sample activation calculations can be performed for SNS and HFIR beamlines, McStas simulations can be run on TeraGrid and ORNL computers, and advanced analysis applications such as those being produced by the DANSE project can be run. Behind the scenes is a "live cataloging" system which automatically catalogs and archives experiment data via the data management system, and provides proposal team members access to

  20. The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts

    DEFF Research Database (Denmark)

    Eskildsen, Tilde V; Schneider, Mikael; Sandberg, Maria B

    2015-01-01

    INTRODUCTION: MicroRNAs (miRNAs) are emerging as key regulators of cardiovascular development and disease; however, the cardiac miRNA target molecules are not well understood. We and others have described the Angiotensin II (AngII)-induced miR-132/212 family as novel regulators of cardiovascular...... in silico and in vitro experiments to identify miR-132/212 molecular targets in primary rat cardiac fibroblasts. RESULTS: MiR-132/212 overexpression increased fibroblast cell size and mRNA arrays detected several hundred genes that were differentially expressed, including a wide panel of receptors...... pathways that fine-tuned by miR-132/212, suggesting a role for this miRNA family as master signalling switches in cardiac fibroblasts. Our data underscore the potential for miRNA tools to manipulate a large array of molecules and thereby control biological function....

  1. Mobile group II intron based gene targeting in Lactobacillus plantarum WCFS1.

    Science.gov (United States)

    Sasikumar, Ponnusamy; Paul, Eldho; Gomathi, Sivasamy; Abhishek, Albert; Sasikumar, Sundaresan; Selvam, Govindan Sadasivam

    2016-10-01

    The usage of recombinant lactic acid bacteria for delivery of therapeutic proteins to the mucosa has been emerging. In the present study, an attempt was made to engineer a thyA mutant of Lactobacillus plantarum (L. plantarum) using lactococcal group II intron Ll.LtrB for the development of biologically contained recombinant L. plantarum for prevention of calcium oxalate stone disease. The 3 kb Ll.LtrB intron donor cassettes from the source vector pACD4C was PCR amplified, ligated into pSIP series of lactobacillus vector pLp_3050sAmyA, yielding a novel vector pLpACD4C (8.6 kb). The quantitative real-time PCR experiment shows 94-fold increased expression of Ll.LtrB intron and 14-fold increased expression of ltrA gene in recombinant L. plantarum containing pLpACD4C. In order to target the thyA gene, the potential intron RNA binding sites in the thyA gene of L. plantarum was predicted with help of computer algorithm. The insertion location 188|189s of thyA gene (lowest E-0.134) was chosen and the wild type intron Ll.LtrB was PCR modified, yielding a retargeted intron of pLpACDthyA. The retargeted intron was expressed by using induction peptide (sppIP), subsequently the integration of intron in thyA gene was identified by PCR screening and finally ThyA - mutant of L. plantarum (ThyA18) was detected. In vitro growth curve result showed that in the absence of thymidine, colony forming units of mutant ThyA18 was decreased, whereas high thymidine concentration (10 μM) supported the growth of the culture until saturation. In conclusion, ThyA - mutant of L. plantarum (ThyA18) constructed in this study will be used as a biologically contained recombinant probiotic to deliver oxalate decarboxylase into the lumen for treatment of hyperoxaluria and calcium oxalate stone deposition. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Swelling and microstructural development in path A PCA and type 316 stainless steel irradiated in HFIR to about 22 dpa

    International Nuclear Information System (INIS)

    Maziasz, P.J.; Braski, D.N.

    1983-01-01

    Irradiation of several microstructural variants of PCA and 20%-cold-worked N-lot type 316 stainess steel (CW 316) in HFIR to about 10 dpa produced no visible cavities at 300 0 C, bubbles at 400 0 C, and varying distributions of bubbles and voids at 500 and 600 0 C. The PCA-B1 swells the most and CW 316 (N-lot) the least at 600 0 C. Irradiations have been extended to about 22 dpa. The PCA-Al swells 0.06%/dpa at 600 0 C but at a much lower rate at 500 0 C. The PCA-A3 shows the lowest swelling at 600 0 C, about the half the swelling rate of type 316 stainless steel

  3. Tensile properties and bend ductility of (Fe,Ni)3V long-range-ordered alloys after irradiation in HFIR

    International Nuclear Information System (INIS)

    Braski, D.N.

    1984-01-01

    The objective of this work was to determine the effect of neutron irradiation on the tensile properties and bend ductility of (Fe,Ni) 3 V long-range-ordered (LRO) alloys. Several (Fe,Ni) 3 V LRO alloys were irradiated in HFIR-CTR-42 and -43 at 400 to 600 0 C, to approximately 10 dpa and approximately 1000 at. ppm He. Additions of cerium or carbon and the use of cold-worked microstructures did not improve the embrittlement resistance of the LRO alloys. The LRO-37-5RS alloy, with a microstructure produced by rapid solidification, exhibited the highest ductilities, and further study of the RS microstructure is warranted. The correlation between bend ductility and tensile ductility was poor

  4. Effects of HFIR irradiation at 550C on the microstructure and toughness of HT-9 and 9Cr-1Mo

    International Nuclear Information System (INIS)

    Gelles, D.S.; Hu, W.L.; Huang, F.H.; Johnson, G.D.

    1984-01-01

    Results are reported for base metal and weld metal specimens of HT-9 and Modified 9Cr-1Mo following irradiation in HFIR at 55 0 C to 5 dpa. The DBTT shifts in irradiated base metal specimens were 30 0 C for HT-9 and 90 0 C for 9Cr-1Mo with further shifts of 20 0 C for weld metal. Concurrently, strength as measured by hardness increased 15 percent for HT-9 and 25 percent for 9Cr-1Mo. The hardness increases can be attributed in part to defect clusters 1.5 to 3.0 nm in diameter at densities approaching 10 17 cm -3 and also to lower rates of cavity nucleation ahead of the propagating crack

  5. A cryostat to hold frozen-spin polarized HD targets in CLAS: HDice-II

    Energy Technology Data Exchange (ETDEWEB)

    Lowry, M.M., E-mail: mlowry@jlab.org [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Bass, C.D. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); D' Angelo, A. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Universita' di Roma ‘Tor Vergata’, and INFN Sezione di Roma ‘Tor Vergata’, Via della Ricerca Scientifica, 1, I-00133 Roma (Italy); Deur, A.; Dezern, G. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Hanretty, C. [University of Virginia, 1400 University Avenue, Charlottesville, VA 22903 (United States); Ho, D. [Carnegie-Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213 (United States); Kageya, T.; Kashy, D. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Khandaker, M. [Norfolk State University, 700 Park Avenue, Norfolk, VA 23504 (United States); Laine, V. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Université Blaise Pascal, 34 Avenue Carnot, 63000 Clermont-Ferrand (France); O' Connell, T. [University of Connecticut, 115 N Eagleville Road, Storrs-Mansfield, CT 06269 (United States); Pastor, O. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Peng, P. [University of Virginia, 1400 University Avenue, Charlottesville, VA 22903 (United States); Sandorfi, A.M. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Sokhan, D. [Institut de Physique Nucleaire, Bat 100 – M053, Orsay 91406 (France); and others

    2016-04-11

    The design, fabrication, operation, and performance of a {sup 3/4}He dilution refrigerator and superconducting magnet system for holding a frozen-spin polarized hydrogen deuteride target in the Jefferson Laboratory CLAS detector during photon beam running is reported. The device operates both vertically (for target loading) and horizontally (for target bombardment). The device proves capable of maintaining a base temperature of 50 mK and a holding field of 1 T for extended periods. These characteristics enabled multi-month polarization lifetimes for frozen spin HD targets having proton polarization of up to 50% and deuteron up to 27%.

  6. Proton and neutron polarized targets for nucleon-nucleon experiments at SATURNE II

    International Nuclear Information System (INIS)

    Ball, J.; Combet, M.; Sans, J.L.; Benda, B.; Chaumette, P.; Deregel, J.; Durand, G.; Dzyubak, A.P.; Gaudron, C.; Lehar, F.; Janout, Z.; Khachaturov, B.A.

    1996-01-01

    A SATURNE polarized target has been used for nucleon-nucleon elastic scattering and transmission experiments for 15 years. The polarized proton target is a 70 cm 3 cartridge loaded with Pentanol-2. For polarized neutron target, two cartridges loaded with 6 LiD and 6 LiH are set in the refrigerator and can be quickly inserted in the beam. First experiments using 6 Li products in quasielastic pp or pn analyzing power measurements are compared with the same observables measured in a free nucleon-nucleon scattering using polarized proton targets. Angular distribution as a function of a kinematically conjugate angle and coplanarity in nucleon-nucleon scattering is shown for different targets. (author)

  7. Diffuse Reflectance Spectroscopy of Hidden Objects. Part II: Recovery of a Target Spectrum.

    Science.gov (United States)

    Pomerantsev, Alexey L; Rodionova, Oxana Ye; Skvortsov, Alexej N

    2017-08-01

    In this study, we consider the reconstruction of a diffuse reflectance near-infrared spectrum of an object (target spectrum) in case the object is covered by an interfering absorbing and scattering layer. Recovery is performed using a new empirical method, which was developed in our previous study. We focus on a system, which consists of several layers of polyethylene (PE) film and underlayer objects with different spectral features. The spectral contribution of the interfering layer is modeled by a three-component two-parameter multivariate curve resolution (MCR) model, which was built and calibrated using spectrally flat objects. We show that this model is applicable to real objects with non-uniform spectra. Ultimately, the target spectrum can be reconstructed from a single spectrum of the covered target. With calculation methods, we are able to recover quite accurately the spectrum of a target even when the object is covered by 0.7 mm of PE.

  8. Autonomous Collaborative Agents for Onboard Multi-Sensor Re-Targeting, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In our Phase I effort we developed a prototype software-agent based framework to provide for autonomous re-targeting of sensors hosted on satellites in polar orbits,...

  9. Mitochondrial complex II, a novel target for anti-cancer agents

    Czech Academy of Sciences Publication Activity Database

    Klučková, Katarína; Bezawork-Geleta, A.; Rohlena, Jakub; Dong, L.; Neužil, Jiří

    2013-01-01

    Roč. 1827, č. 5 (2013), s. 552-564 ISSN 0005-2728 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP301/12/1851 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitochondrion * Complex II * Anti-cancer agent Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.829, year: 2013

  10. Rotational Characterization of Hayabusa II Target Asteroid (162173) 1999 JU3

    OpenAIRE

    Moskovitz, Nicholas; Abe, Shinsuke; Pan, Kang-Shian; Osip, David; Pefkou, Dimitra; Melita, Mario; Elias, Mauro; Kitazato, Kohei; Bus, Schelte; DeMeo, Francesca; Binzel, Richard; Abell, Paul

    2013-01-01

    The Japanese Space Agency's Hayabusa II mission is scheduled to rendezvous with and return a sample from the near-Earth asteroid (162173) 1999 JU3. Previous visible-wavelength spectra of this object show significant variability across multiple epochs which could be the result of a compositionally heterogeneous surface. We present new visible and near-infrared spectra to demonstrate that thermally altered carbonaceous chondrites are plausible compositional analogs, however this is a tentative ...

  11. Non-surgical breast-conservation treatment (KORTUC-BCT) using a new image-guided, enzyme-targeted, and breast cancer stem cell targeted radiosensitization treatment (KORTUC II) for patients with stage I or II breast cancer

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Kubota, Kei; Tadokoro, Michiko

    2012-01-01

    injected into breast tumor tissue twice a week under ultrasound guidance, just prior to each administration of radiation therapy, and we confirmed an even distribution of micro-bubbles of oxygen throughout the target tumor. The injection was started at the 6th fraction of radiation therapy. This injection protocol effectively preserves oxygen concentration in the tumor tissue for more than 24 h following intra-tumoral injection (Tokuhiro S, et al: Oncol Letters 1:1025-1028, 2010). Concerning radiation therapy, hypofraction radiotherapy was given using tangential fields approach and Field-in-field method; energy level was 4MV and the total radiation therapy dose was 44 Gy administered as 2.75 Gy/fraction. An electron boost of 3 Gy was added 3 times just following the 14th, 15th and 16th administrations of 4 MV X-ray irradiation. From a needle biopsy specimen, hormonal status (estrogen and progesterone receptors), HER-2 antigen, and CD44 receptor were examined by immunohistochemistry. Treatment was well tolerated with a minimum of adverse effects in all 39 patients. A total of 36 patients achieved clinically complete response on dynamic MRI study, and the study has not been performed yet for another 3. All of the patients did not show any complications (with the exception of mild dermatitis of Grade I for 24 and Grade II for 15), and cosmetic results were excellent/good for 35 patients. 15 patients under 75 y with stage II breast cancer underwent induction chemotherapy (EC and/or Taxan) prior to the KORTUC II treatment, and 36 patients with estrogen receptor-positive tumors also undertook hormonal therapy following KORTUC II. The mean follow-up period at the end of September 2011 was 30.1 months, at which time all 39 patients were alive without any distant metastases. Only 1 patient had local recurrence, which was discovered at 34 months follow-up. Non-surgical BCT (KORTUC-BCT) can be performed with KORTUC II. KORTUC II has 3 major characteristics: it is image-guided by

  12. Benchmark calculations on residue production within the EURISOL DS project; Part II: thick targets

    CERN Document Server

    David, J.-C; Boudard, A; Doré, D; Leray, S; Rapp, B; Ridikas, D; Thiollière, N

    Benchmark calculations on residue production using MCNPX 2.5.0. Calculations were compared to mass-distribution data for 5 different elements measured at ISOLDE, and to specific activities of 28 radionuclides in different places along the thick target measured in Dubna.

  13. Target-plasma production by laser irradiation of a pellet in the Baseball II-T experiment

    International Nuclear Information System (INIS)

    Damm, C.C.; Foote, J.H.; Futch, A.H.; Goodman, R.K.; Hornady, R.S.; Osher, J.E.; Porter, G.D.

    1977-01-01

    One way to generate a plasma target that can be used in conjunction with an injected neutral beam to initiate a high-energy plasma in a steady-state, magnetic-mirror field is by the laser irradiation of a solid pellet located within the confinement region. In the Lawrence Livermore Laboratory Baseball II-T experiment, a CO 2 laser was used to provide a two-sided irradiation of an ammonia pellet; the maximum laser intensity on the pellet was approximately 4 x 10 12 W/cm 2 . The 150-μm-dia pellets were guided to the laser focal spot in the Baseball II-T magnetic field using steering voltages controlled by a microcomputer-based system. Diagnostics showed complete ionization of the pellet, average ion energies in the keV range, synchronized triggering of the laser and the neutral beam, and rapid expansion of the plasma to a diameter that was a good match to the diameter of the neutral beam. Predictions obtained from the LASNEX code compared well with measured results. Although the laser-pellet approach was proven usable as a target-plasma startup system, it would be much more complicated and expensive than the method in which streaming plasma is used to trap the neutal beams

  14. WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures

    Directory of Open Access Journals (Sweden)

    Kenyon Colin

    2009-05-01

    Full Text Available Abstract Background Despite continuous efforts of the international community to reduce the impact of malaria on developing countries, no significant progress has been made in the recent years and the discovery of new drugs is more than ever needed. Out of the many proteins involved in the metabolic activities of the Plasmodium parasite, some are promising targets to carry out rational drug discovery. Motivation Recent years have witnessed the emergence of grids, which are highly distributed computing infrastructures particularly well fitted for embarrassingly parallel computations like docking. In 2005, a first attempt at using grids for large-scale virtual screening focused on plasmepsins and ended up in the identification of previously unknown scaffolds, which were confirmed in vitro to be active plasmepsin inhibitors. Following this success, a second deployment took place in the fall of 2006 focussing on one well known target, dihydrofolate reductase (DHFR, and on a new promising one, glutathione-S-transferase. Methods In silico drug design, especially vHTS is a widely and well-accepted technology in lead identification and lead optimization. This approach, therefore builds, upon the progress made in computational chemistry to achieve more accurate in silico docking and in information technology to design and operate large scale grid infrastructures. Results On the computational side, a sustained infrastructure has been developed: docking at large scale, using different strategies in result analysis, storing of the results on the fly into MySQL databases and application of molecular dynamics refinement are MM-PBSA and MM-GBSA rescoring. The modeling results obtained are very promising. Based on the modeling results, In vitro results are underway for all the targets against which screening is performed. Conclusion The current paper describes the rational drug discovery activity at large scale, especially molecular docking using FlexX software

  15. The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part II

    Directory of Open Access Journals (Sweden)

    Aristo Vojdani

    2011-01-01

    Full Text Available Decades of research went into understanding the role that Th1 autoreactive T-cells play in neuroinflammation. Here we describe another effector population, the IL-17-producing T-helper lineage (Th17, which drives the inflammatory process. Through the recruitment of inflammatory infiltration neutrophils and the activation of matrix metalloproteinases, IL-17, a cytokine secreted by Th17 cells, contributes to blood-brain barrier breakdown and the subsequent attraction of macrophages and monocytes into the nervous system. The entry of cells along with the local production of inflammatory cytokines leads to myelin and axonal damage. This activation of the inflammatory response system is induced by different pathogenic factors, such as gut bacterial endotoxins resulting in progressive neurodegeneration by Th17 cells. Through the understanding of the role of bacterial endotoxins and other pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting IL-17 activity. Targeted therapy can restore the integrity of the intestinal and blood-brain barriers using probiotics, N-acetyl-cysteine, α-lipoic acid, resveratrol and others for their patients with autoimmunities, in particular those with neuroinflammation and neurodegeneration.

  16. Hardness distribution and tensile properties in an electron-beam-welded F82H irradiated in HFIR

    International Nuclear Information System (INIS)

    Hashimoto, N.; Oka, H.; Muroga, T.; Kimura, A.; Sokolov, M.A.; Yamamoto, T.

    2014-01-01

    F82H-IEA and its EB-weld joint were irradiated at 573 and 773 K up to 9.6 dpa in the HFIR and the irradiation effect on its mechanical properties and microstructure were investigated. A hardness profile across the weld joint before irradiation showed the hardness in transformed region (TR) was high and especially that in the edge of TR was the highest (high hardness region: HHR) compared to base metal. This hardness distribution corresponds to grain size distribution. After irradiation, hardening in HHR was small compared to other region in the sample. In tensile test, the amount of hardening in yield strength and ultimate tensile strength of F82H EB-weld joint was almost similar to that of F82H-1EA but the fracture position of EB-weld joint was at the boundary of TR and BM. Therefore, the TR/BM boundary is the structural weak point in F82H EB-weld joint after irradiation. As the plastic instability was observed, the dislocation channeling deformation can be expected though the dislocation channel was not observed in this study. (author)

  17. Microstructural evolution of HFIR-irradiated low activation F82H and F82H-10B steels

    International Nuclear Information System (INIS)

    Wakai, E.; Shiba, K.; Sawai, T.; Hashimoto, N.; Robertson, J.P.; Klueh, R.L.

    1998-01-01

    Microstructures of reduced-activation F82H (8Cr-2W-0.2V-0.04Ta) and the F82H steels doped with 10 B, irradiated at 250 and 300 C to 3 and 57 dpa in the High Flux Isotope Reactor (HFIR), were examined by TEM. In the F82H irradiated at 250 C to 3 dpa, dislocation loops, small unidentified defect clusters with a high number density, and a few MC precipitates were observed in the matrix. The defect microstructure after 300 C irradiation to 57 dpa is dominated by the loops, and the number density of loops was lower than that of the F82H- 10 B steel. Cavities were observed in the F82H- 10 B steels, but the swelling value is insignificant. Small particles of M 6 C formed on the M 23 C 6 carbides that were present in both steels before the irradiation at 300 C to 57 dpa. A low number density of MC precipitate particles formed in the matrix during irradiation at 300 C to 57 dpa

  18. Up-regulation of hexokinaseII in myeloma cells: targeting myeloma cells with 3-bromopyruvate.

    Science.gov (United States)

    Nakano, Ayako; Miki, Hirokazu; Nakamura, Shingen; Harada, Takeshi; Oda, Asuka; Amou, Hiroe; Fujii, Shiro; Kagawa, Kumiko; Takeuchi, Kyoko; Ozaki, Shuji; Matsumoto, Toshio; Abe, Masahiro

    2012-02-01

    Hexokinase II (HKII), a key enzyme of glycolysis, is widely over-expressed in cancer cells. However, HKII levels and its roles in ATP production and ATP-dependent cellular process have not been well studied in hematopoietic malignant cells including multiple myeloma (MM) cells.We demonstrate herein that HKII is constitutively over-expressed in MM cells. 3-bromopyruvate (3BrPA), an inhibitor of HKII, promptly and substantially suppresses ATP production and induces cell death in MM cells. Interestingly, cocultures with osteoclasts (OCs) but not bone marrow stromal cells (BMSCs) enhanced the phosphorylation of Akt along with an increase in HKII levels and lactate production in MM cells. The enhancement of HKII levels and lactate production in MM cells by OCs were mostly abrogated by the PI3K inhibitor LY294002, suggesting activation of glycolysis in MM cells by OCs via the PI3K-Akt-HKII pathway. Although BMSCs and OCs stimulate MM cell growth and survival, 3BrPA induces cell death in MM cells even in cocultures with OCs as well as BMSCs. Furthermore, 3BrPA was able to diminish ATP-dependent ABC transporter activity to restore drug retention in MM cells in the presence of OCs. These results may underpin possible clinical application of 3BrPA in patients with MM.

  19. Target mediated drug disposition with drug-drug interaction, Part II: competitive and uncompetitive cases.

    Science.gov (United States)

    Koch, Gilbert; Jusko, William J; Schropp, Johannes

    2017-02-01

    We present competitive and uncompetitive drug-drug interaction (DDI) with target mediated drug disposition (TMDD) equations and investigate their pharmacokinetic DDI properties. For application of TMDD models, quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are necessary to reduce the number of parameters. To realize those approximations of DDI TMDD models, we derive an ordinary differential equation (ODE) representation formulated in free concentration and free receptor variables. This ODE formulation can be straightforward implemented in typical PKPD software without solving any non-linear equation system arising from the QE or QSS approximation of the rapid binding assumptions. This manuscript is the second in a series to introduce and investigate DDI TMDD models and to apply the QE or QSS approximation.

  20. Taurine-modified Ru(ii)-complex targets cancerous brain cells for photodynamic therapy.

    Science.gov (United States)

    Du, Enming; Hu, Xunwu; Roy, Sona; Wang, Peng; Deasy, Kieran; Mochizuki, Toshiaki; Zhang, Ye

    2017-05-30

    The precision and efficacy of photodynamic therapy (PDT) is essential for the treatment of brain tumors because the cancer cells are within or adjacent to the delicate nervous system. Taurine is an abundant amino acid in the brain that serves the central nervous system (CNS). A taurine-modified polypyridyl Ru-complex was shown to have optimized intracellular affinity in cancer cells through accumulation in lysosomes. Symmetrical modification of this Ru-complex by multiple taurine molecules enhanced the efficiency of molecular emission with boosted generation of reactive oxygen species. These characteristic features make the taurine-modified Ru-complex a potentially effective photosensitizer for PDT of target cancer cells, with outstanding efficacy in cancerous brain cells.

  1. Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

    International Nuclear Information System (INIS)

    Yan, Bing; Stantic, Marina; Zobalova, Renata; Bezawork-Geleta, Ayenachew; Stapelberg, Michael; Stursa, Jan; Prokopova, Katerina; Dong, Lanfeng; Neuzil, Jiri

    2015-01-01

    Accumulating evidence suggests that breast cancer involves tumour-initiating cells (TICs), which play a role in initiation, metastasis, therapeutic resistance and relapse of the disease. Emerging drugs that target TICs are becoming a focus of contemporary research. Mitocans, a group of compounds that induce apoptosis of cancer cells by destabilising their mitochondria, are showing their potential in killing TICs. In this project, we investigated mitochondrially targeted vitamin E succinate (MitoVES), a recently developed mitocan, for its in vitro and in vivo efficacy against TICs. The mammosphere model of breast TICs was established by culturing murine NeuTL and human MCF7 cells as spheres. This model was verified by stem cell marker expression, tumour initiation capacity and chemotherapeutic resistance. Cell susceptibility to MitoVES was assessed and the cell death pathway investigated. In vivo efficacy was studied by grafting NeuTL TICs to form syngeneic tumours. Mammospheres derived from NeuTL and MCF7 breast cancer cells were enriched in the level of stemness, and the sphere cells featured altered mitochondrial function. Sphere cultures were resistant to several established anti-cancer agents while they were susceptible to MitoVES. Killing of mammospheres was suppressed when the mitochondrial complex II, the molecular target of MitoVES, was knocked down. Importantly, MitoVES inhibited progression of syngeneic HER2 high tumours derived from breast TICs by inducing apoptosis in tumour cells. These results demonstrate that using mammospheres, a plausible model for studying TICs, drugs that target mitochondria efficiently kill breast tumour-initiating cells. The online version of this article (doi:10.1186/s12885-015-1394-7) contains supplementary material, which is available to authorized users

  2. Therapeutic targeting of angiotensin II receptor type 1 to regulate androgen receptor in prostate cancer.

    Science.gov (United States)

    Takahashi, Satoru; Uemura, Hiroji; Seeni, Azman; Tang, Mingxi; Komiya, Masami; Long, Ne; Ishiguro, Hitoshi; Kubota, Yoshinobu; Shirai, Tomoyuki

    2012-10-01

    With the limited strategies for curative treatment of castration-resistant prostate cancer (CRPC), public interest has focused on the potential prevention of prostate cancer. Recent studies have demonstrated that an angiotensin II receptor blocker (ARB) has the potential to decrease serum prostate-specific antigen (PSA) level and improve performance status in CRPC patients. These facts prompted us to investigate the direct effects of ARBs on prostate cancer growth and progression. Transgenic rat for adenocarcinoma of prostate (TRAP) model established in our laboratory was used. TRAP rats of 3 weeks of age received ARB (telmisartan or candesartan) at the concentration of 2 or 10 mg/kg/day in drinking water for 12 weeks. In vitro analyses for cell growth, ubiquitylation or reporter gene assay were performed using LNCaP cells. We found that both telmisartan and candesartan attenuated prostate carcinogenesis in TRAP rats by augmentation of apoptosis resulting from activation of caspases, inactivation of p38 MAPK and down-regulation of the androgen receptor (AR). Further, microarray analysis demonstrated up-regulation of estrogen receptor β (ERβ) by ARB treatment. In both parental and androgen-independent LNCaP cells, ARB inhibited both cell growth and AR-mediated transcriptional activity. ARB also exerted a mild additional effect on AR-mediated transcriptional activation by the ERβ up-regulation. An intervention study revealed that PSA progression was prolonged in prostate cancer patients given an ARB compared with placebo control. These data provide a new concept that ARBs are promising potential chemopreventive and chemotherapeutic agents for prostate cancer. Copyright © 2012 Wiley Periodicals, Inc.

  3. Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: Clinical Phase I/II trials

    International Nuclear Information System (INIS)

    Chen Zhinan; Mi Li; Xu Jing

    2006-01-01

    Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine ( 131 I) metuximab injection (Licartin), a novel 131 I-labeled HAb18G/CD147-specific monoclonal antibody F(ab') 2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p 131 I) metuximab injection is safe and active for HCC patients

  4. Mitochondria are the primary target in the induction of apoptosis by chiral ruthenium(II) polypyridyl complexes in cancer cells.

    Science.gov (United States)

    Wang, Jin-Quan; Zhang, Ping-Yu; Qian, Chen; Hou, Xiao-Juan; Ji, Liang-Nian; Chao, Hui

    2014-03-01

    A series of novel chiral ruthenium(II) polypyridyl complexes (Δ-Ru1, Λ-Ru1, Δ-Ru2, Λ-Ru2, Δ-Ru3, Λ-Ru3) were synthesized and evaluated to determine their antiproliferative activities. Colocalization, inductively coupled plasma mass spectrometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay studies showed that these ruthenium(II) complexes accumulated preferentially in the mitochondria and exhibited cytotoxicity against various cancer cells in vitro. The complex Δ-Ru1 is of particular interest because it was found to have half-maximal inhibitory concentrations comparable to those of cisplatin and better activity than cisplatin against a cisplatin-resistant cell line, A549-CP/R. Δ-Ru1 induced alterations in the mitochondrial membrane potential and triggered intrinsic mitochondria-mediated apoptosis in HeLa cells, which involved the regulation of Bcl-2 family members and the activation of caspases. Taken together, these data suggest that Δ-Ru1 may be a novel mitochondria-targeting anticancer agent.

  5. THE SPITZER INFRARED SPECTROGRAPH DEBRIS DISK CATALOG. II. SILICATE FEATURE ANALYSIS OF UNRESOLVED TARGETS

    Energy Technology Data Exchange (ETDEWEB)

    Mittal, Tushar [Department of Earth and Planetary Science, University of California Berkeley, Berkeley, CA 94720-4767 (United States); Chen, Christine H. [Space Telescope Science Institute, 3700 San Martin Drive Baltimore, MD 21218 (United States); Jang-Condell, Hannah [Department of Physics and Astronomy, University of Wyoming, Laramie, WY 82071 (United States); Manoj, P. [Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400 005 (India); Sargent, Benjamin A. [Center for Imaging Science and Laboratory for Multiwavelength Astrophysics, Rochester Institute of Technology, 54 Lomb Memorial Drive, Rochester, NY 14623 (United States); Watson, Dan M. [Department of Physics and Astronomy, University of Rochester, Rochester, NY 14627 (United States); Lisse, Carey M., E-mail: cchen@stsci.edu [Johns Hopkins University Applied Physics Laboratory, 11100 Johns Hopkins Road, Laurel, MD 20723 (United States)

    2015-01-10

    During the Spitzer Space Telescope cryogenic mission, astronomers obtained Infrared Spectrograph (IRS) observations of hundreds of debris disk candidates that have been compiled in the Spitzer IRS Debris Disk Catalog. We have discovered 10 and/or 20 μm silicate emission features toward 120 targets in the catalog and modeled the IRS spectra of these sources, consistent with MIPS 70 μm observations, assuming that the grains are composed of silicates (olivine, pyroxene, forsterite, and enstatite) and are located either in a continuous disk with power-law size and surface density distributions or thin rings that are well-characterized using two separate dust grain temperatures. For systems better fit by the continuous disk model, we find that (1) the dust size distribution power-law index is consistent with that expected from a collisional cascade, q = 3.5-4.0, with a large number of values outside this range, and (2) the minimum grain size, a {sub min}, increases with stellar luminosity, L {sub *}, but the dependence of a {sub min} on L {sub *} is weaker than expected from radiation pressure alone. In addition, we also find that (3) the crystalline fraction of dust in debris disks evolves as a function of time with a large dispersion in crystalline fractions for stars of any particular stellar age or mass, (4) the disk inner edge is correlated with host star mass, and (5) there exists substantial variation in the properties of coeval disks in Sco-Cen, indicating that the observed variation is probably due to stochasticity and diversity in planet formation.

  6. Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation.

    Science.gov (United States)

    Balamurugan, Appakalai N; Green, Michael L; Breite, Andrew G; Loganathan, Gopalakrishnan; Wilhelm, Joshua J; Tweed, Benjamin; Vargova, Lenka; Lockridge, Amber; Kuriti, Manikya; Hughes, Michael G; Williams, Stuart K; Hering, Bernhard J; Dwulet, Francis E; McCarthy, Robert C

    2016-01-01

    Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation. We used a factorial approach to evaluate the effect of high and low target activities of recombinant class I (rC1) and class II (rC2) collagenase on human islet yield. Consequently, 4 different enzyme formulations with divergent C1:C2 collagenase mass ratios were assessed, each supplemented with the same dose of neutral protease. Both split pancreas and whole pancreas models were used to test enzyme targets (n = 20). Islet yield/g pancreas was compared with historical enzymes (n = 42). Varying the Wunsch (rC2) and collagen degradation activity (CDA, rC1) target dose, and consequently the C1:C2 mass ratio, had no significant effect on tissue digestion. Digestions using higher doses of Wunsch and CDA resulted in comparable islet yields to those obtained with 60% and 50% of those activities, respectively. Factorial analysis revealed no significant main effect of Wunsch activity or CDA for any parameter measured. Aggregate results from 4 different collagenase formulations gave 44% higher islet yield (>5000 islet equivalents/g) in the body/tail of the pancreas (n = 12) when compared with those from the same segment using a standard natural collagenase/protease mixture (n = 6). Additionally, islet yields greater than 5000 islet equivalents/g pancreas were also obtained in whole human pancreas. A broader C1:C2 ratio can be used for human islet isolation than has been used in the past. Recombinant collagenase is an effective replacement for the natural enzyme and we have determined that high islet yield can be obtained even with low doses of rC1:rC2, which is beneficial for the survival of islets.

  7. MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

    Energy Technology Data Exchange (ETDEWEB)

    Hua, Wei [Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Sa, Ke-Di; Zhang, Xiang; Jia, Lin-Tao; Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Yang, An-Gang [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Zhang, Rui, E-mail: ruizhang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Fan, Jing, E-mail: jingfan@fmmu.edu.cn [Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Bian, Ka, E-mail: kakamax85@hotmail.com [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Department of Otolaryngology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

    2015-08-07

    The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells.

  8. MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

    International Nuclear Information System (INIS)

    Hua, Wei; Sa, Ke-Di; Zhang, Xiang; Jia, Lin-Tao; Zhao, Jing; Yang, An-Gang; Zhang, Rui; Fan, Jing; Bian, Ka

    2015-01-01

    The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells

  9. The DOS 1 neutron dosimetry experiment at the HB-4-A key 7 surveillance site on the HFIR pressure vessel

    International Nuclear Information System (INIS)

    Farrell, K.; Kam, F.B.; Baldwin, C.A.

    1994-01-01

    A comprehensive neutron dosimetry experiment was made at one of the prime surveillance sites at the High Flux Isotope Reactor (HFIR) pressure vessel to aid radiation embrittlement studies of the vessel and to benchmark neutron transport calculations. The thermal neutron flux at the key 7, position 5 site was found, from measurements of radioactivation of four cobalt wires and four silver wires, to be 2.4 x 10 12 n·m -2 ·s -1 . The thermal flux derived from two helium accumulation monitors was 2.3 x 10 12 n·m -2 · -1 . The thermal flux estimated by neutron transport calculations was 3.7 x 10 12 n·m -2 s -1 . The fast flux, >1 MeV, determined from two nickel activation wires, was 1.5 x 10 12 n·m -2 ·s -1 , in keeping with values obtained earlier from stainless steel surveillance monitors and with a computed value of 1.2 x 10 13 n·m -2 · -1 . The fast fluxes given by two reaction-product-type monitors, neptunium-237 and beryllium, were 2.6 x 10 13 n·m -2 ·s -1 and 2.2 x 10 13 n·m -2 s -1 , respectively. Follow-up experiments indicate that these latter high values of fast flux are reproducible but are false; they are due to the creation of greater levels of reaction products by photonuclear events induced by an exceptionally high ratio of gamma flux to fast neutron flux at the vessel

  10. A Potential Bone-Targeting Hypotoxic Platinum(II) Complex with an Unusual Cytostatic Mechanism toward Osteosarcoma Cells.

    Science.gov (United States)

    Zhang, Zhenqin; Zhu, Zhenzhu; Luo, Cheng; Zhu, Chengcheng; Zhang, Changli; Guo, Zijian; Wang, Xiaoyong

    2018-03-19

    Osteosarcoma (OS) is the most common primary pediatric bone tumor lethal to children and adolescents. Chemotherapeutic agents such as cisplatin are not effective for OS because of their poor accessibility to this cancer and severe systemic toxicity. In this study, a lipophilic platinum(II) complex bearing a bisphosphonate bone-targeting moiety, cis-[PtL(NH 3 ) 2 Cl]NO 3 {BPP; L = tetraethyl [2-(pyridin-2-yl)ethane-1,1-diyl]bisphosphonate}, was prepared and characterized by NMR, electrospray ionization mass spectrometry, and single-crystal X-ray crystallography. The cytotoxicity of BPP toward OS cell lines U2OS and MG-63 was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. BPP exhibits moderate inhibition against U2OS cells through a mechanism involving both DNA binding and a mevalonate pathway. The acute toxicity of BPP to mice is 7-fold lower than that of cisplatin. The relative low systemic toxicity may result from the steric hindrance of the ligand, which blocks BPP approaching the bases of DNA. The results suggest that incorporating bisphosphonates into a platinum complex not only enhances its bone-targeting property but also minimizes its reactivity toward DNA and thereby lowers the systematic toxicity of the complex. The diminished cytotoxicity of BPP could be compensated for by increasing the therapeutic dose with marginal harm. This strategy provides a new possibility for overcoming the ineffectiveness and systemic toxicity of platinum drugs in the treatment of OS.

  11. Targeting Hypertension with Valsartan: Lessons Learned from the Valsartan/HCTZ Versus Amlodipine in Stage II Hypertensive Patients (VAST Trial

    Directory of Open Access Journals (Sweden)

    Luis M Ruilope

    2006-03-01

    Full Text Available Many patients with hypertension, especially those at increased risk because of additional cardiovascular risk factors, require treatment with more than one antihypertensive agent to achieve target blood pressure (BP goals. Many different classes of antihypertensive agents are available: a renin-angiotensin-aldosterone system (RAAS blocker and a diuretic are widely used in combination.Here we report the results of the recently completed Valsartan/HCTZ versus Amlodipine in STage II hypertensive patients (VAST trial. In this 24-week study, patients with moderate hypertension and at least one other cardiovascular risk factor were treated with a combination of valsartan 160 mg and hydrochlorothiazide (HCTZ 12.5 or 25 mg once daily (o.d., or with amlodipine monotherapy (10 mg o.d.. Overall, valsartan plus HCTZ 25 mg reduced systolic BP significantly more than amlodipine monotherapy, and with fewer adverse events. In addition, combination therapy resulted in a trend towards more favourable outcomes with respect to pro-thrombotic and proinflammatory markers than amlodipine alone.

  12. Targeting Hypertension with Valsartan: Lessons Learned from the Valsartan/HCTZ Versus Amlodipine in Stage II Hypertensive Patients (VAST Trial

    Directory of Open Access Journals (Sweden)

    Luis M Ruilope

    2006-03-01

    Full Text Available Many patients with hypertension, especially those at increased risk because of additional cardiovascular risk factors, require treatment with more than one antihypertensive agent to achieve target blood pressure (BP goals. Many different classes of antihypertensive agents are available: a renin-angiotensin-aldosterone system (RAAS blocker and a diuretic are widely used in combination. Here we report the results of the recently completed Valsartan/HCTZ versus Amlodipine in STage II hypertensive patients (VAST trial. In this 24-week study, patients with moderate hypertension and at least one other cardiovascular risk factor were treated with a combination of valsartan 160 mg and hydrochlorothiazide (HCTZ 12.5 or 25 mg once daily (o.d., or with amlodipine monotherapy (10 mg o.d.. Overall, valsartan plus HCTZ 25 mg reduced systolic BP significantly more than amlodipine monotherapy, and with fewer adverse events. In addition, combination therapy resulted in a trend towards more favourable outcomes with respect to pro-thrombotic and pro-inflammatory markers than amlodipine alone.

  13. Methylation of WNT target genes AXIN2 and DKK1 as robust biomarkers for recurrence prediction in stage II colon cancer

    NARCIS (Netherlands)

    Kandimalla, R.; Linnekamp, J. F.; van Hooff, S.; Castells, A.; Llor, X.; Andreu, M.; Jover, R.; Goel, A.; Medema, J. P.

    2017-01-01

    Stage II colon cancer (CC) still remains a clinical challenge with patient stratification for adjuvant therapy (AT) largely relying on clinical parameters. Prognostic biomarkers are urgently needed for better stratification. Previously, we have shown that WNT target genes AXIN2, DKK1, APCDD1, ASCL2

  14. Small interfering RNA targeted to stem-loop II of the 5' untranslated region effectively inhibits expression of six HCV genotypes

    Directory of Open Access Journals (Sweden)

    Dash Srikanta

    2006-11-01

    Full Text Available Abstract Background The antiviral action of interferon alpha targets the 5' untranslated region (UTR used by hepatitis C virus (HCV to translate protein by an internal ribosome entry site (IRES mechanism. Although this sequence is highly conserved among different clinical strains, approximately half of chronically infected hepatitis C patients do not respond to interferon therapy. Therefore, development of small interfering RNA (siRNA targeted to the 5'UTR to inhibit IRES mediated translation may represent an alternative approach that could circumvent the problem of interferon resistance. Results Four different plasmid constructs were prepared for intracellular delivery of siRNAs targeting the stem loop II-III of HCV 5' UTR. The effect of siRNA production on IRES mediated translation was investigated using chimeric clones between the gene for green fluorescence protein (GFP and IRES sequences of six different HCV genotypes. The siRNA targeted to stem loop II effectively mediated degradation of HCV IRES mRNA and inhibited GFP expression in the case of six different HCV genotypes, where as siRNAs targeted to stem loop III did not. Furthermore, intracytoplasmic expression of siRNA into transfected Huh-7 cells efficiently degraded HCV genomic RNA and inhibited core protein expression from infectious full-length infectious clones HCV 1a and HCV 1b strains. Conclusion These in vitro studies suggest that siRNA targeted to stem-loop II is highly effective inhibiting IRES mediated translation of the major genotypes of HCV. Stem-loop II siRNA may be a good target for developing an intracellular immunization strategy based antiviral therapy to inhibit hepatitis C virus strains that are not inhibited by interferon.

  15. Irradiation performance of HTGR Biso fertile particles in HFIR experiments HT-17, -18, and -19

    International Nuclear Information System (INIS)

    Long, E.L. Jr.; Beatty, R.L.; Robbins, J.M.; Kania, M.J.; Eatherly, W.P.

    1978-11-01

    A series of Biso-coated fertile particles was irradiated in the target facility of the High-Flux Isotope Reactor. The primary objectives of this experiment were to relate the fast-neutron stability of dense propylene-derived pyrocarbons to preferred orientation and to relate irradiation performance to preirradiation characterization values. Coating characterization included x-ray BAF, optical anisotropy, gaseous permeability, small-angle x-ray scattering, and thickness and density determinations. Other objectives were to test Biso-coated large-diameter ThO 2 kernels and coatings derived from propylene diluted with CO 2 rather than argon. Visual examination of the irradiated particles showed that the majority had failed as a result of fast-neutron damage

  16. Destruction of Ion-Exchange Resin In Waste From the HFIR, T1 and T2 Tanks Using Fenton's Reagent

    International Nuclear Information System (INIS)

    Taylor, P.A.

    2002-01-01

    The use of Fenton's reagent (hydrogen peroxide and a ferrous iron catalyst) has been tested as a method for destroying ion-exchange resin in radioactive waste from three underground storage tanks at the Oak Ridge National Laboratory. The resin in these wastes must be destroyed before they can be transferred to the Melton Valley Storage Tanks (MVSTs) prior to solidification and disposal at the Waste Isolation Pilot Plant. The reaction with ion-exchange resin requires a dilute acidic solution (pH = 3 to 5) and moderate temperatures (T = 60 to 100 C). Laboratory-scale tests of the process have been successfully completed using both simulants and actual waste samples. The ion-exchange resin is oxidized to carbon dioxide and inorganic salts. The reaction rate is quite slow for temperatures below 70 C but increases almost linearly as the temperature of the slurry increases from 70 to 90 C. Pilot-scale tests have demonstrated the process using larger samples of actual waste slurries. A sample from the High Flux Isotope Reactor (HFIR) tank, containing 500 mL of settled solids (resin and inorganic sludge) in a total volume of 1800 mL, was successfully treated to meet MVST waste acceptance requirements in 9 h of processing time, using 1650 mL of 50 wt% hydrogen peroxide. A composite sample from the T1 and T2 tanks, which contained 1000 mL of settled solids in a total volume of 2000 mL required 8 h of treatment, using 1540 mL of 50 wt% peroxide, to meet waste acceptance requirements. Hydrogen peroxide reaction rates were 0.71 to 0.74 g H 2 O 2 /L/min, with very low (<2000 mg/L) concentrations of peroxide in the slurry. The reaction produces mostly carbon dioxide gas during the early part of the treatment, when organic carbon concentrations in the slurry are high, and then produces increasing amounts of oxygen as the organic carbon concentration drops. Small amounts (<3 vol%) of carbon monoxide are also generated. The off-gas from the pilot-scale tests, which was 81 vol

  17. Cytotoxicity and cell death mechanisms induced by the polyamine-vectorized anti-cancer drug F14512 targeting topoisomerase II.

    Science.gov (United States)

    Brel, Viviane; Annereau, Jean-Philippe; Vispé, Stéphane; Kruczynski, Anna; Bailly, Christian; Guilbaud, Nicolas

    2011-12-15

    The polyamines transport system (PTS) is usually enhanced in cancer cells and can be exploited to deliver anticancer drugs. The spermine-conjugated epipodophyllotoxin derivative F14512 is a topoisomerase II poison that exploits the PTS to target preferentially tumor cells. F14512 has been characterized as a potent anticancer drug candidate and is currently in phase 1 clinical trials. Here we have analyzed the mechanisms of cell death induced by F14512, compared to the parent drug etoposide lacking the polyamine tail. F14512 proved to be >30-fold more cytotoxic than etoposide against A549 non-small cell lung cancer cells and triggers less but unrecoverable DNA damages. The cytotoxic action of F14512 is extremely rapid (within 3 h) and does not lead to a marked accumulation in the S-phase of the cell cycle, unlike etoposide. Interestingly, A549 cells treated with F14512 were less prone to undergo apoptosis (neither caspases-dependent nor caspases-independent pathways) or autophagy but preferentially entered into senescence. Drug-induced senescence was characterized qualitatively and quantitatively by an increased β-galactosidase activity, both by cytochemical staining and by flow cytometry. A morphological analysis by electron microscopy revealed the presence of numerous multi-lamellar and vesicular bodies and large electron-lucent (methuosis-like) vacuoles in F14512-treated cell samples. The mechanism of drug-induced cell death is thus distinct for F14512 compared to etoposide, and this difference may account for their distinct pharmacological profiles and the markedly superior activity of F14512 in vivo. This study suggests that senescence markers should be considered as potential pharmacodynamic biomarkers of F14512 antitumor activity. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Void formation and helium effects in 9Cr-1MoVNb and 12Cr-1MoVW steels irradiated in HFIR and FFTF at 400/degree/C

    International Nuclear Information System (INIS)

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

    1988-01-01

    Martensitic/ferritic 9Cr-1MoVNb and 12Cr-1MoVW steels doped with up to 2 wt% Ni have up to 450 appm He after HFIR irradiation to /approximately/38 dpa, but only 5 appm He after 47 dpa in FFTF. No fine He bubbles and few or no larger voids were observable in any of these steels after FFTF irradiation at 407/degree/C. By contrast, many voids were found in the undoped steels (30-90 appm He) irradiated in HFIR at 400/degree/C, while voids plus many more fine He bubbles were found in the Ni-doped steels (400-450 appm He). Irradiation in both reactors at /approximately/400/degree/C produced significant changes in the as-tempered lath/subgrain boundary, dislocation, and precipitation structures that were sensitive to alloy composition, including doping with Ni. However, for each specific alloy the irradiation-produced changes were exactly the same comparing samples irradiated in FFTF and HFIR, particularly the Ni-doped steels. Therefore, the increased void formation appears solely due to the increased helium generation found in HFIR. While the levels of void swelling are relatively low after 37-39 dpa in HFIR (0.1-0.4%), details of the microstructural evolution suggest that void nucleation is still progressing, and swelling could increase with dose. The effect of helium on void swelling remains a valid concern for fusion application that requires higher dose experiments. 15 refs., 14 figs., 8 tabs

  19. Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity.

    Science.gov (United States)

    Minus, Matthew B; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M; Long, Xin; Krueger, Michael J; Stevens, Alexandra; Kolosov, Mikhail I; Tweardy, David J; Sison, Edward Allan R; Redell, Michele S; Ball, Zachary T

    2015-10-26

    Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Multi-unit inertial fusion plants based on HYLIFE-II, with shared heavy-ion RIA driver and target factory, producing electricity and hydrogen fuel

    Energy Technology Data Exchange (ETDEWEB)

    Logan, G.; Moir, R. [Lawrence Livermore National Lab., CA (United States); Hoffman, M. [Univ. of California, Davis, CA (United States)

    1994-05-05

    Following is a modification of the IFEFUEL systems code, called IFEFUEL2, to treat specifically the HYLIFE-II target chamber concept. The same improved Recirculating Induction Accelerator (RIA) energy scaling model developed recently by Bieri is used in this survey of the economics of multi-unit IFE plants producing both electricity and hydrogen fuel. Reference cases will assume conventional HI-indirect target gains for a 2 mm spot, and improved HYLIFE-II BoP models as per Hoffman. Credits for improved plant availability and lower operating costs due to HYLIFE-II`s 30-yr target chamber lifetime are included, as well as unit cost reductions suggested by Delene to credit greater {open_quotes}learning curve{close_quotes} benefits for the duplicated portions of a multi-unit plant. To illustrate the potential impact of more advanced assumptions, additional {open_quotes}advanced{close_quotes} cases will consider the possible benefits of an MHD + Steam BoP, where direct MHD conversion of plasma from baseball-size LiH target blanket shells is assumed to be possible in a new (as yet undesigned) liquid Flibe-walled target chamber, together and separately, with advanced, higher-gain heavy-ion targets with Fast Ignitors. These runs may help decide the course of a possible future {open_quotes}HYLIFE-III{close_quotes} IFE study. Beam switchyard and final focusing system costs per target chamber are assumed to be consistent with single-sided illumination, for either {open_quotes}conventional{close_quotes} or {open_quotes}advanced{close_quotes} indirect target gain assumptions. Target costs are scaled according to the model by Woodworth. In all cases, the driver energy and rep rate for each chosen number of target chambers and total plant output will be optimized to minimize the cost of electricity (CoE) and the associated cost of hydrogen (CoH), using a relationship between CoE and CoH to be presented in the next section.

  1. Yeast screens identify the RNA polymerase II CTD and SPT5 as relevant targets of BRCA1 interaction.

    Directory of Open Access Journals (Sweden)

    Craig B Bennett

    2008-01-01

    Full Text Available BRCA1 has been implicated in numerous DNA repair pathways that maintain genome integrity, however the function responsible for its tumor suppressor activity in breast cancer remains obscure. To identify the most highly conserved of the many BRCA1 functions, we screened the evolutionarily distant eukaryote Saccharomyces cerevisiae for mutants that suppressed the G1 checkpoint arrest and lethality induced following heterologous BRCA1 expression. A genome-wide screen in the diploid deletion collection combined with a screen of ionizing radiation sensitive gene deletions identified mutants that permit growth in the presence of BRCA1. These genes delineate a metabolic mRNA pathway that temporally links transcription elongation (SPT4, SPT5, CTK1, DEF1 to nucleopore-mediated mRNA export (ASM4, MLP1, MLP2, NUP2, NUP53, NUP120, NUP133, NUP170, NUP188, POM34 and cytoplasmic mRNA decay at P-bodies (CCR4, DHH1. Strikingly, BRCA1 interacted with the phosphorylated RNA polymerase II (RNAPII carboxy terminal domain (P-CTD, phosphorylated in the pattern specified by the CTDK-I kinase, to induce DEF1-dependent cleavage and accumulation of a RNAPII fragment containing the P-CTD. Significantly, breast cancer associated BRCT domain defects in BRCA1 that suppressed P-CTD cleavage and lethality in yeast also suppressed the physical interaction of BRCA1 with human SPT5 in breast epithelial cells, thus confirming SPT5 as a relevant target of BRCA1 interaction. Furthermore, enhanced P-CTD cleavage was observed in both yeast and human breast cells following UV-irradiation indicating a conserved eukaryotic damage response. Moreover, P-CTD cleavage in breast epithelial cells was BRCA1-dependent since damage-induced P-CTD cleavage was only observed in the mutant BRCA1 cell line HCC1937 following ectopic expression of wild type BRCA1. Finally, BRCA1, SPT5 and hyperphosphorylated RPB1 form a complex that was rapidly degraded following MMS treatment in wild type but not BRCA1

  2. Single photon emission computed tomographic studies (SPECT) of hepatic arterial perfusion scintigraphy (HAPS) in patients with colorectal liver metastases: improved tumour targetting by microspheres with angiotensin II.

    Science.gov (United States)

    Goldberg, J A; Bradnam, M S; Kerr, D J; McKillop, J H; Bessent, R G; McArdle, C S; Willmott, N; George, W D

    1987-12-01

    As intra-arterial chemotherapy for liver metastases of colorectal origin becomes accepted, methods of further improving drug delivery to the tumour have been devised. Degradable microspheres have been shown to reduce regional blood flow by transient arteriolar capillary block, thereby improving uptake of a co-administered drug, when injected into the hepatic artery. In our study of five patients, we combined hepatic arterial perfusion scintigraphy (HAPS) and SPECT to assess the localization of approximately 1 X 10(5) labelled microspheres of human serum albumin (99Tcm MSA) in tumour. In addition, in three patients, we assessed the effect of an intra-arterial infusion of the vasoactive agent angiotension II during HAPS. Results were interpreted by comparing transaxial slices with corresponding slices of a tin colloid liver-spleen scan. Two of five patients showed good localization of 99Tcm MSA in tumour without an angiotensin II infusion. Of the three patients receiving angiotensin II, all showed good tumour targetting with the vasoconstrictor compared with only one of these three before its use. Thus, hepatic arterial infusion of angiotensin II greatly improves microsphere localization in tumour in some patients with colorectal liver metastases. This technique may be useful in the assessment of tumour targetting before and during locoregional therapy.

  3. Comparison of the effects of long-term thermal aging and HFIR irradiation on the microstructural evolution of 9Cr-1MoVNb steel

    International Nuclear Information System (INIS)

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

    1990-01-01

    Both thermal aging at 482--704 degree C for up to 25,000h and HFIR irradiation at 300--600 degree C for up to 39 dpa produce substantial changes in the as-tempered microstructure of 9Cr-1MoVNb martensitic/ferritic steel. However, the changes in the dislocation/subgrain boundary and the precipitate structures caused by thermal aging or neutron irradiation are quite different in nature. During thermal aging, the as-tempered lath/subgrain boundary and carbide precipitate structures remain stable below 650 degree C, but coarsen and recover somewhat at 650--704 degree C. The formation of abundant intergranular Laves phase, intra-lath dislocation networks, and fine dispersions of VC needles are thermal aging effects that are superimposed upon the as-tempered microstructure at 482--593 degree C. HFIR irradiation produces dense dispersions of very small ''black'' dislocations loops at 300 degree C and produces helium bubbles and voids at 400 degree C At 300--500 degree C, there is considerable recovery of the as-tempered lath/subgrain boundary structure and microstructural/microcompositional instability of the as-tempered carbide precipitates during irradiation. By contrast, the as-tempered microstructure remains essentially unchanged during irradiation at 600 degree C. Comparison of thermally aged with irradiation material suggests that the instabilities of the as-tempered lath/subgrain boundary and precipitate structures at lower irradiation temperatures are radiation-induced effects, whereas the absence of both Laves phase and fine VC needles during irradiation is a radiation-retarded thermal effect

  4. Biotechnological applications of mobile group II introns and their reverse transcriptases: gene targeting, RNA-seq, and non-coding RNA analysis.

    Science.gov (United States)

    Enyeart, Peter J; Mohr, Georg; Ellington, Andrew D; Lambowitz, Alan M

    2014-01-13

    Mobile group II introns are bacterial retrotransposons that combine the activities of an autocatalytic intron RNA (a ribozyme) and an intron-encoded reverse transcriptase to insert site-specifically into DNA. They recognize DNA target sites largely by base pairing of sequences within the intron RNA and achieve high DNA target specificity by using the ribozyme active site to couple correct base pairing to RNA-catalyzed intron integration. Algorithms have been developed to program the DNA target site specificity of several mobile group II introns, allowing them to be made into 'targetrons.' Targetrons function for gene targeting in a wide variety of bacteria and typically integrate at efficiencies high enough to be screened easily by colony PCR, without the need for selectable markers. Targetrons have found wide application in microbiological research, enabling gene targeting and genetic engineering of bacteria that had been intractable to other methods. Recently, a thermostable targetron has been developed for use in bacterial thermophiles, and new methods have been developed for using targetrons to position recombinase recognition sites, enabling large-scale genome-editing operations, such as deletions, inversions, insertions, and 'cut-and-pastes' (that is, translocation of large DNA segments), in a wide range of bacteria at high efficiency. Using targetrons in eukaryotes presents challenges due to the difficulties of nuclear localization and sub-optimal magnesium concentrations, although supplementation with magnesium can increase integration efficiency, and directed evolution is being employed to overcome these barriers. Finally, spurred by new methods for expressing group II intron reverse transcriptases that yield large amounts of highly active protein, thermostable group II intron reverse transcriptases from bacterial thermophiles are being used as research tools for a variety of applications, including qRT-PCR and next-generation RNA sequencing (RNA-seq). The

  5. Apolipoprotein A-II Plus Lipid Emulsion Enhance Cell Growth via SR-B1 and Target Pancreatic Cancer In Vitro and In Vivo

    Science.gov (United States)

    Thanh LE, Thao N.; Gill, Anthony J.; Bulanadi, Jerikho C.; Patel, Mili; Waddington, Lynne J.; Rye, Kerry-Anne; Moghaddam, Minoo J.; Smith, Ross C.

    2016-01-01

    Background Apolipoprotein A-II (ApoA-II) is down regulated in the sera of pancreatic ductal adenocarcinoma (PDAC) patients, which may be due to increase utilization of high density lipoprotein (HDL) lipid by pancreatic cancer tissue. This study examined the influence of exogenous ApoA-II on lipid uptake and cell growth in pancreatic cancer (PC) both in vitro and in vivo. Methods Cryo transmission electron microscopy (TEM) examined ApoA-II’s influence on morphology of SMOFLipid emulsion. The influence of ApoA-II on proliferation of cancer cell lines was determined by incubating them with lipid+/-ApoA-II and anti-SR-B1 antibody. Lipid was labeled with the fluorophore, DiD, to trace lipid uptake by cancer cells in vitro by confocal microscopy and in vivo in PDAC patient derived xenograft tumours (PDXT) by fluorescence imaging. Scavenger receptor class B type-1(SR-B1) expression in PDAC cell lines and in PDAC PDXT was measured by western blotting and immunohistochemistry, respectively. Results ApoA-II spontaneously converted lipid emulsion into very small unilamellar rHDL like vesicles (rHDL/A-II) and enhanced lipid uptake in PANC-1, CFPAC-1 and primary tumour cells as shown by confocal microscopy. SR-B1 expression was 13.2, 10.6, 3.1 and 2.3 fold higher in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cell lines than the normal pancreatic cell line (HPDE6) and 3.7 fold greater in PDAC tissue than in normal pancreas. ApoA-II plus lipid significantly increased the uptake of labeled lipid and promoted cell growth in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cells which was inhibited by anti SR-B1 antibody. Further, ApoA-II increased the uptake of lipid in xenografts by 3.4 fold. Conclusion Our data suggest that ApoA-II enhance targeting potential of lipid in pancreatic cancer which may have imaging and drug delivery potentialities. PMID:27002321

  6. Comparing the Suitability of Autodock, Gold and Glide for the Docking and Predicting the Possible Targets of Ru(II-Based Complexes as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Adebayo A. Adeniyi

    2013-03-01

    Full Text Available In cancer chemotherapy, metal-based complexes have been recognized as the most promising means of inhibiting cancer growth due to the successful application of cis-platin and its derivatives above many of the existing organic anticancer agents. The limitations in their rational design can be traced to the complexity of the mechanism of their operations, lack of proper knowledge of their targets and lack of force fields in docking packages to appropriately define the metal centre of the organometallic complexes. In this paper, some of the promising anticancer complexes of Ru(II such as the rapta-based complexes formulated as [Ru(η6-p-cymeneL2(pta] and those with unusual ligands are considered. CatB and kinases which have been experimentally confirmed as possible targets of the complexes are also predicted by the three methods as one of the most targeted receptors while TopII and HDAC7 are predicted by two and one of the methods as best targets. The interesting features of the binding of the complexes show that some of the complexes preferentially target specific macromolecules than the others, which is an indication of their specificity and possibility of their therapeutic combination without severe side effects that may come from competition for the same target. Also, introduction of unusual ligands is found to significantly improve the activities of most of the complexes studied. Strong correlations are observed for the predicted binding sites and the orientation of the complexes within the binding site by the three methods of docking. However there are disparities in the ranking of the complexes by the three method of docking, especially that of Glide.

  7. Synthesis and Biological Evaluation of Ru(II) and Pt(II) Complexes Bearing Carboxyl Groups as Potential Anticancer Targeted Drugs.

    Science.gov (United States)

    Martínez, Ma Ángeles; Carranza, M Pilar; Massaguer, Anna; Santos, Lucia; Organero, Juan A; Aliende, Cristina; de Llorens, Rafael; Ng-Choi, Iteng; Feliu, Lidia; Planas, Marta; Rodríguez, Ana M; Manzano, Blanca R; Espino, Gustavo; Jalón, Félix A

    2017-11-20

    The synthesis and characterization of Pt(II) (1 and 2) and Ru(II) arene (3 and 4) or polypyridine (5 and 6) complexes is described. With the aim of having a functional group to form bioconjugates, one uncoordinated carboxyl group has been introduced in all complexes. Some of the complexes were selected for their potential in photodynamic therapy (PDT). The molecular structures of complexes 2 and 5, as well as that of the sodium salt of the 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine ligand (cptpy), were determined by X-ray diffraction. Different techniques were used to evaluate the binding capacity to model DNA molecules, and MTT cytotoxicity assays were performed against four cell lines. Compounds 3, 4, and 5 showed little tendency to bind to DNA and exhibited poor biological activity. Compound 2 behaves as bonded to DNA probably through a covalent interaction, although its cytotoxicity was very low. Compound 1 and possibly 6, both of which contain a cptpy ligand, were able to intercalate with DNA, but toxicity was not observed for 6. However, compound 1 was active in all cell lines tested. Clonogenic assays and apoptosis induction studies were also performed on the PC-3 line for 1. The photodynamic behavior for complexes 1, 5, and 6 indicated that their nuclease activity was enhanced after irradiation at λ = 447 nm. The cell viability was significantly reduced only in the case of 5. The different behavior in the absence or presence of light makes complex 5 a potential prodrug of interest in PDT. Molecular docking studies followed by molecular dynamics simulations for 1 and the counterpart without the carboxyl group confirmed the experimental data that pointed to an intercalation mechanism. The cytotoxicity of 1 and the potential of 5 in PDT make them good candidates for subsequent conjugation, through the carboxyl group, to "selected peptides" which could facilitate the selective vectorization of the complex toward receptors that are overexpressed in

  8. Chitosan encapsulation of essential oil "cocktails" with well-defined binary Zn(II)-Schiff base species targeting antibacterial medicinal nanotechnology.

    Science.gov (United States)

    Halevas, Eleftherios; Nday, Christiane M; Chatzigeorgiou, Evanthia; Varsamis, Vasileios; Eleftheriadou, Despoina; Jackson, Graham E; Litsardakis, Georgios; Lazari, Diamanto; Ypsilantis, Konstantinos; Salifoglou, Athanasios

    2017-11-01

    The advent of biodegradable nanomaterials with enhanced antibacterial activity stands as a challenge to the global research community. In an attempt to pursue the development of novel antibacterial medicinal nanotechnology, we herein a) synthesized ionic-gelated chitosan nanoparticles, b) compared and evaluated the antibacterial activity of essential oils extracted from nine different herbs (Greek origin) and their combinations with a well-defined antibacterial Zn(II)-Schiff base compound, and c) encapsulated the most effective hybrid combination of Zn(II)-essential oils inside the chitosan matrix, thereby targeting well-formulated nanoparticles of distinct biological impact. The empty and loaded chitosan nanoparticles were physicochemically characterized by FT-IR, Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), with the entrapment and drug release studies being conducted through UV-Visible and atomic absorption techniques. The antimicrobial properties of the novel hybrid materials were demonstrated against Gram positive (S. aureus, B. subtilis, and B. cereus) and Gram negative (E. coli and X. campestris) bacteria using modified agar diffusion methods. The collective physicochemical profile of the hybrid Zn(II)-essential oil cocktails, formulated so as to achieve optimal activity when loaded to chitosan nanoparticles, signifies the importance of design in the development of efficient nanomedicinal pharmaceuticals a) based on both natural products and biogenic metal ionic cofactors, and b) targeting bacterial infections and drug resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. An integrated Drosophila model system reveals unique properties for F14512, a novel polyamine-containing anticancer drug that targets topoisomerase II.

    Directory of Open Access Journals (Sweden)

    Sonia Chelouah

    Full Text Available F14512 is a novel anti-tumor molecule based on an epipodophyllotoxin core coupled to a cancer-cell vectoring spermine moiety. This polyamine linkage is assumed to ensure the preferential uptake of F14512 by cancer cells, strong interaction with DNA and potent inhibition of topoisomerase II (Topo II. The antitumor activity of F14512 in human tumor models is significantly higher than that of other epipodophyllotoxins in spite of a lower induction of DNA breakage. Hence, the demonstrated superiority of F14512 over other Topo II poisons might not result solely from its preferential uptake by cancer cells, but could also be due to unique effects on Topo II interactions with DNA. To further dissect the mechanism of action of F14512, we used Drosophila melanogaster mutants whose genetic background leads to an easily scored phenotype that is sensitive to changes in Topo II activity and/or localization. F14512 has antiproliferative properties in Drosophila cells and stabilizes ternary Topo II/DNA cleavable complexes at unique sites located in moderately repeated sequences, suggesting that the drug specifically targets a select and limited subset of genomic sequences. Feeding F14512 to developing mutant Drosophila larvae led to the recovery of flies expressing a striking phenotype, "Eye wide shut," where one eye is replaced by a first thoracic segment. Other recovered F14512-induced gain- and loss-of-function phenotypes similarly correspond to precise genetic dysfunctions. These complex in vivo results obtained in a whole developing organism can be reconciled with known genetic anomalies and constitute a remarkable instance of specific alterations of gene expression by ingestion of a drug. "Drosophila-based anticancer pharmacology" hence reveals unique properties for F14512, demonstrating the usefulness of an assay system that provides a low-cost, rapid and effective complement to mammalian models and permits the elucidation of fundamental mechanisms of

  10. Dysregulated miR-127-5p contributes to type II collagen degradation by targeting matrix metalloproteinase-13 in human intervertebral disc degeneration.

    Science.gov (United States)

    Hua, Wen-Bin; Wu, Xing-Huo; Zhang, Yu-Kun; Song, Yu; Tu, Ji; Kang, Liang; Zhao, Kang-Cheng; Li, Shuai; Wang, Kun; Liu, Wei; Shao, Zeng-Wu; Yang, Shu-Hua; Yang, Cao

    2017-08-01

    Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  11. Targeting hexokinase II to mitochondria to modulate energy metabolism and reduce ischaemia-reperfusion injury in heart

    NARCIS (Netherlands)

    Nederlof, Rianne; Eerbeek, Otto; Hollmann, Markus W.; Southworth, Richard; Zuurbier, Coert J.

    2014-01-01

    Mitochondrially bound hexokinase II (mtHKII) has long been known to confer cancer cells with their resilience against cell death. More recently, mtHKII has emerged as a powerful protector against cardiac cell death. mtHKII protects against ischaemia-reperfusion (IR) injury in skeletal muscle and

  12. Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation

    OpenAIRE

    Balamurugan, Appakalai N.; Green, Michael L.; Breite, Andrew G.; Loganathan, Gopalakrishnan; Wilhelm, Joshua J.; Tweed, Benjamin; Vargova, Lenka; Lockridge, Amber; Kuriti, Manikya; Hughes, Michael G.; Williams, Stuart K.; Hering, Bernhard J.; Dwulet, Francis E.; McCarthy, Robert C.

    2015-01-01

    Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation.

  13. Mitocans as anti-cancer agents targeting mitochondria: lessons from studies with vitamin E analogues, inhibitors of complex II

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Dyason, J.C.; Freeman, R.; Dong, L.F.; Procházka, L.; Wang, X. F.; Scheffler, I.; Ralph, S.J.

    2007-01-01

    Roč. 39, č. 1 (2007), s. 65-72 ISSN 0145-479X Institutional research plan: CEZ:AV0Z50520701; CEZ:AV0Z50520514 Keywords : mitocans * mitochondria * complex II Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.634, year: 2007

  14. Department of Energy's High Flux Isotope Reactor (HFIR), October 20--24, 1980: A special report prepared for the Nuclear Facilities Personnel Qualification and Training Committee: An independent on-site safety review

    International Nuclear Information System (INIS)

    1981-02-01

    The intent of this on-site safety review was to make a broad management assessment of HFIR operations, rather than conduct a detailed in-depth audit. The result of the review should only be considered as having identified trends or indications. The Team's observations and recommendations are based upon licensed reactor facility practices used to meet industry standards. For the most part, these standards form the basis for many of the comments in this report. The Team believes that a uniform minimum standard of performance should be achieved in the operation of DOE reactors. In order to assure that this is accomplished, clear standards are necessary. Consistent with the provisions of past AEC and ERDA policy, the Team has used the standards of the commercial nuclear power industry. It is recognized that this approach is conservative in that the HFIR reactor has a significantly greater degree of inherent safety (low temperature, low pressure, low power) than a licensed reactor

  15. Characterization of the minimum domain required for targeting budding yeast myosin II to the site of cell division

    Directory of Open Access Journals (Sweden)

    Tolliday Nicola J

    2006-06-01

    Full Text Available Abstract Background All eukaryotes with the exception of plants use an actomyosin ring to generate a constriction force at the site of cell division (cleavage furrow during mitosis and meiosis. The structure and filament forming abilities located in the C-terminal or tail region of one of the main components, myosin II, are important for localising the molecule to the contractile ring (CR during cytokinesis. However, it remains poorly understood how myosin II is recruited to the site of cell division and how this recruitment relates to myosin filament assembly. Significant conservation between species of the components involved in cytokinesis, including those of the CR, allows the use of easily genetically manipulated organisms, such as budding yeast (Saccharomyces cerevisiae, in the study of cytokinesis. Budding yeast has a single myosin II protein, named Myo1. Unlike most other class II myosins, the tail of Myo1 has an irregular coiled coil. In this report we use molecular genetics, biochemistry and live cell imaging to characterize the minimum localisation domain (MLD of budding yeast Myo1. Results We show that the MLD is a small region in the centre of the tail of Myo1 and that it is both necessary and sufficient for localisation of Myo1 to the yeast bud neck, the pre-determined site of cell division. Hydrodynamic measurements of the MLD, purified from bacteria or yeast, show that it is likely to exist as a trimer. We also examine the importance of a small region of low coiled coil forming probability within the MLD, which we call the hinge region. Removal of the hinge region prevents contraction of the CR. Using fluorescence recovery after photobleaching (FRAP, we show that GFP-tagged MLD is slightly more dynamic than the GFP-tagged full length molecule but less dynamic than the GFP-tagged Myo1 construct lacking the hinge region. Conclusion Our results define the intrinsic determinant for the localization of budding yeast myosin II and show

  16. Anti-Inflammatory Inhibitors Targeting Jak and Ikk Have An Anabolic Effect on Type II Collagen Turnover ex Vivo

    DEFF Research Database (Denmark)

    Kjelgaard-Petersen, Cecilie Freja; Bay-Jensen, Anne-Christine; Karsdal, M.A.

    2016-01-01

    be beneficial for the selection of novel anti-inflammatory treatments for RA and iOA. Objectives The aim of this study was to investigate the direct effect of the anti-inflammatory inhibitors R406 (the active metabolite of Fostamatinib), Tofacitinib, TPCA-1 and SB203580 on the cartilage ECM turnover. Methods...... Full depth bovine cartilage ex vivo cultures were cultured for 3 weeks with OSM [10 ng/mL] and TNFα [2 ng/mL] (O+T) or together with R406, Tofacitinib or TPCA-1 at 10 μM and a two-fold dilution to 0.16 μM. SB203580 was tested at 3 μM, 1 μM and 0.3 μM. As negative control, untreated explants were...... R406, the Jak inhibitor Tofacitinib, and the IKK inhibitor TPCA-1 inhibited the release of ARGS or AGNx1, while the p38 inhibitor, SB203580, had no effect. The turnover of type II collagen was measured by the formation of type II collagen (ProC2) and MMP-mediated degradation of type II collagen (C2M...

  17. An Integrated Approach to Change the Outcome Part II: Targeted Neuromuscular Training Techniques to Reduce Identified ACL Injury Risk Factors

    Science.gov (United States)

    Myer, Gregory D.; Ford, Kevin R.; Brent, Jensen L.; Hewett, Timothy E.

    2014-01-01

    Prior reports indicate that female athletes who demonstrate high knee abduction moments (KAMs) during landing are more responsive to neuromuscular training designed to reduce KAM. Identification of female athletes who demonstrate high KAM, which accurately identifies those at risk for noncontact anterior cruciate ligament (ACL) injury, may be ideal for targeted neuromuscular training. Specific neuromuscular training targeted to the underlying biomechanical components that increase KAM may provide the most efficient and effective training strategy to reduce noncontact ACL injury risk. The purpose of the current commentary is to provide an integrative approach to identify and target mechanistic underpinnings to increased ACL injury in female athletes. Specific neuromuscular training techniques will be presented that address individual algorithm components related to high knee load landing patterns. If these integrated techniques are employed on a widespread basis, prevention strategies for noncontact ACL injury among young female athletes may prove both more effective and efficient. PMID:22580980

  18. Intercomparison of ILAS-II version 1.4 and version 2 target parameters with MIPAS-Envisat measurements

    Directory of Open Access Journals (Sweden)

    A. Griesfeller

    2008-02-01

    Full Text Available This paper assesses the mean differences between the two ILAS-II data versions (1.4 and 2 by comparing them with MIPAS measurements made between May and October 2003. For comparison with ILAS-II results, MIPAS data processed at the Institut für Meteorologie und Klimaforschung, Karlsruhe, Germany (IMK in cooperation with the Instituto de Astrofísica de Andalucía (IAA in Granada, Spain, were used. The coincidence criteria of ±300 km in space and ±12 h in time for H2O, N2O, and CH4 and the coincidence criteria of ±300 km in space and ±6 h in time for ClONO2, O3, and HNO3 were used. The ILAS-II data were separated into sunrise (= Northern Hemisphere and sunset (= Southern Hemisphere. For the sunrise data, a clear improvement from version 1.4 to version 2 was observed for H2O, CH4, ClONO2, and O3. In particular, the ILAS-II version 1.4 mixing ratios of H2O and CH4 were unrealistically small, and those of ClONO2 above altitudes of 30 km unrealistically large. For N2O and HNO3, there were no large differences between the two versions. Contrary to the Northern Hemisphere, where some exceptional profiles deviated significantly from known climatology, no such outlying profiles were found in the Southern Hemisphere for both versions. Generally, the ILAS-II version 2 data were in better agreement with the MIPAS data than the version 1.4, and are recommended for quantitative analysis in the stratosphere. For H2O data in the Southern Hemisphere, further data quality evaluation is necessary.

  19. Benefits and Sustainability of a Learning Collaborative for Implementation of Treat to Target in Rheumatoid Arthritis: Results of the TRACTION Trial Phase II.

    Science.gov (United States)

    Solomon, Daniel H; Lu, Bing; Yu, Zhi; Corrigan, Cassandra; Harrold, Leslie R; Smolen, Josef S; Fraenkel, Liana; Katz, Jeffrey N; Losina, Elena

    2018-01-05

    We conducted a two-phase randomized controlled trial of a Learning Collaborative (LC) to facilitate implementation of treat to target (TTT) to manage rheumatoid arthritis (RA). We found substantial improvement in implementation of TTT in Phase I. Herein, we report on a second 9 months (Phase II) where we examined maintenance of response in Phase I and predictors of greater improvement in TTT adherence. We recruited 11 rheumatology sites and randomized them to either receive the LC during Phase I or to a wait-list control group that received the LC intervention during Phase II. The outcome was change in TTT implementation score (0 to 100, 100 is best) from pre- to post-intervention. TTT implementation score is defined as a percent of components documented in visit notes. Analyses examined: 1) the extent that the Phase I intervention teams sustained improvement in TTT; and, 2) predictors of TTT improvement. The analysis included 636 RA patients. At baseline, mean TTT implementation score was 11% in Phase I intervention sites and 13% in Phase II sites. After the intervention, TTT implementation score improved to 57% in the Phase I intervention sites and to 58% in the Phase II sites. Intervention sites from Phase I sustained the improvement during the Phase II (52%). Predictors of greater TTT improvement included only having rheumatologist providers at the site, academic affiliation of the site, fewer providers per site, and the rheumatologist provider being a trainee. Improvement in TTT remained relatively stable over a post-intervention period. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Targeting mitochondria by Zn(II)N-alkylpyridylporphyrins: the impact of compound sub-mitochondrial partition on cell respiration and overall photodynamic efficacy.

    Science.gov (United States)

    Odeh, Ahmad M; Craik, James D; Ezzeddine, Rima; Tovmasyan, Artak; Batinic-Haberle, Ines; Benov, Ludmil T

    2014-01-01

    Mitochondria play a key role in aerobic ATP production and redox control. They harness crucial metabolic pathways and control cell death mechanisms, properties that make these organelles essential for survival of most eukaryotic cells. Cancer cells have altered cell death pathways and typically show a shift towards anaerobic glycolysis for energy production, factors which point to mitochondria as potential culprits in cancer development. Targeting mitochondria is an attractive approach to tumor control, but design of pharmaceutical agents based on rational approaches is still not well established. The aim of this study was to investigate which structural features of specially designed Zn(II)N-alkylpyridylporphyrins would direct them to mitochondria and to particular mitochondrial targets. Since Zn(II)N-alkylpyridylporphyrins can act as highly efficient photosensitizers, their localization can be confirmed by photodamage to particular mitochondrial components. Using cultured LS174T adenocarcinoma cells, we found that subcellular distribution of Zn-porphyrins is directed by the nature of the substituents attached to the meso pyridyl nitrogens at the porphyrin ring. Increasing the length of the aliphatic chain from one carbon (methyl) to six carbons (hexyl) increased mitochondrial uptake of the compounds. Such modifications also affected sub-mitochondrial distribution of the Zn-porphyrins. The amphiphilic hexyl derivative (ZnTnHex-2-PyP) localized in the vicinity of cytochrome c oxidase complex, causing its inactivation during illumination. Photoinactivation of critical cellular targets explains the superior efficiency of the hexyl derivative in causing mitochondrial photodamage, and suppressing cellular respiration and survival. Design of potent photosensitizers and redox-active scavengers of free radicals should take into consideration not only selective organelle uptake and localization, but also selective targeting of critical macromolecular structures.

  1. Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development.

    Science.gov (United States)

    Kim, Seonwook; Yang, Lihua; Kim, Seongu; Lee, Richard G; Graham, Mark J; Berliner, Judith A; Lusis, Aldons J; Cai, Lei; Temel, Ryan E; Rateri, Debra L; Lee, Sangderk

    2017-01-01

    The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin II (AngII, 1,000ng/kg/min) for the last 4 weeks of ASO administration. We confirmed that the HB-EGF ASO administration significantly downregulated HB-EGF expression in multiple tissues including the liver. Importantly, the HB-EGF ASO administration significantly suppressed development of aortic aneurysms including thoracic and abdominal types. Interestingly, the HB-EGF ASO administration induced a remarkable anti-hyperlipidemic effect by suppressing very low density lipoprotein (VLDL) level in the blood. Mechanistically, the HB-EGF targeting suppressed hepatic VLDL secretion rate without changing heparin-releasable plasma triglyceride (TG) hydrolytic activity or fecal neutral cholesterol excretion rate. This result suggested that the HB-EGF targeting induced protection against aneurysm development through anti-hyperlipidemic effects. Suppression of hepatic VLDL production process appears to be a key mechanism for the anti-hyperlipidemic effects by the HB-EGF targeting.

  2. The exosome component Rrp6 is required for RNA polymerase II termination at specific targets of the Nrd1-Nab3 pathway.

    Science.gov (United States)

    Fox, Melanie J; Gao, Hongyu; Smith-Kinnaman, Whitney R; Liu, Yunlong; Mosley, Amber L

    2015-01-01

    The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (Polymerase II (RNAPII) localization. Deletion of RRP6 promotes hyper-elongation of multiple NNS-dependent transcripts resulting from both improperly processed 3' RNA ends and faulty transcript termination at specific target genes. The defects in RNAPII termination cause transcriptome-wide changes in mRNA expression through transcription interference and/or antisense repression, similar to previously reported effects of depleting Nrd1 from the nucleus. Elongated transcripts were identified within all classes of known NNS targets with the largest changes in transcription termination occurring at CUTs. Interestingly, the extended transcripts that we have detected in our studies show remarkable similarity to Nrd1-unterminated transcripts at many locations, suggesting that Rrp6 acts with the NNS complex globally to promote transcription termination in addition to 3' end RNA processing and/or degradation at specific targets.

  3. Photoactive platinum(II) complexes of nonsteroidal anti-inflammatory drug naproxen: Interaction with biological targets, antioxidant activity and cytotoxicity.

    Science.gov (United States)

    Srivastava, Payal; Singh, Khushbu; Verma, Madhu; Sivakumar, Sri; Patra, Ashis K

    2018-01-20

    The effect on the therapeutic efficacy of Pt(II) complexes on combining non-steroidal anti-inflammatory drugs (NSAIDs) is an attractive strategy to circumvent chronic inflammation mediated by cancer and metastasis. Two square-planar platinum(II) complexes: [Pt(dach)(nap)Cl] (1) and [Pt(dach)(nap) 2 ] (2), where dach = (1R,2R)-dichloro(cyclohexane-1,2-diamine) and NSAID drug naproxen (nap), have been designed for studying their biological activity. The naproxen bound to the Pt(II) centre get released upon photoirradiation with low-power UV-A light as confirmed by the significant enhancement in emission intensities of the complexes. The compounds were evaluated for their photophysical properties, photostability, reactivity with 5'-guanosine monophophosphate (5'-GMP), interactions with CT-DNA and BSA, antioxidant activity and reactive oxygen species mediated photo-induced DNA damage properties. ESI-MS studies demonstrated the formation of bis-adduct with 5'-GMP and the formation of Pt II -DNA crosslinks by gel electrophoretic mobility shift assay and ITC studies. The interaction of the complexes 1 and 2 with the CT-DNA exhibits potential binding affinity (K b  ∼ 10 4  M -1 , K app ∼ 10 5  M -1 ), implying intercalation to CT-DNA through planar naphthyl ring of the complexes. Both the complexes also exhibit strong binding affinity towards BSA (K BSA ∼ 10 5  M -1 ). The complexes exhibit efficient DNA damage activity on irradiation at 365 nm via formation of singlet oxygen ( 1 O 2 ) and hydroxyl radical ( • OH) under physiological conditions. Both the complexes were cytotoxic in dark and exhibit significant enhancement of cytotoxicity upon photo-exposure against HeLa and HepG2 cancer cells giving IC 50 values ranging from 8 to 12 μM for 1 and 2. The cellular internalization data showed cytosolic and nuclear localization of the complexes in the HeLa cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Human CD4+ T cells lyse target cells via granzyme/perforin upon circumvention of MHC class II restriction by an antibody-like immunoreceptor.

    Science.gov (United States)

    Hombach, Andreas; Köhler, Heike; Rappl, Gunter; Abken, Hinrich

    2006-10-15

    Immune elimination of tumor cells requires the close cooperation between CD8+ CTL and CD4+ Th cells. We circumvent MHC class II-restriction of CD4+ T cells by expression of a recombinant immunoreceptor with an Ab-derived binding domain redirecting specificity. Human CD4+ T cells grafted with an immunoreceptor specific for carcinoembryonic Ag (CEA) are activated to proliferate and secrete cytokines upon binding to CEA+ target cells. Notably, redirected CD4+ T cells mediate cytolysis of CEA+ tumor cells with high efficiencies. Lysis by redirected CD4+ T cells is independent of death receptor signaling via TNF-alpha or Fas, but mediated by perforin and granzyme because cytolysis is inhibited by blocking the release of cytotoxic granules, but not by blocking of Fas ligand or TNF-alpha. CD4+ T cells redirected by Ab-derived immunoreceptors in a MHC class II-independent fashion substantially extend the power of an adoptive, Ag-triggered immunotherapy not only by CD4+ T cell help, but also by cytolytic effector functions. Because cytolysis is predominantly mediated via granzyme/perforin, target cells that are resistant to death receptor signaling become sensitive to a cytolytic attack by engineered CD4+ T cells.

  5. Self-similarity of hard cumulative processes in fixed target experiment for BES-II at STAR

    International Nuclear Information System (INIS)

    Tokarev, M.V.; Aparin, A.A.; Zborovsky, I.

    2014-01-01

    Search for signatures of phase transition in Au + Au collisions is in the heart of the heavy ion program at RHIC. Systematic study of particle production over a wide range of collision energy revealed new phenomena such as the nuclear suppression effect expressed by nuclear modification factor, the constituent quark number scaling for elliptic flow, the 'ridge effect' in - fluctuations, etc. To determine the phase boundaries and location of the critical point of nuclear matter, the Beam Energy Scan (BES-I) program at RHIC has been suggested and performed by STAR and PHENIX Collaborations. The obtained results have shown that the program (BES-II) should be continued. In this paper a proposal to use hard cumulative processes in BES Phase-II program is outlined. Selection of the cumulative events is assumed to enrich data sample by a new type of collisions characterized by higher energy density and more compressed matter. This would allow finding clearer signatures of phase transition, location of a critical point and studying extreme conditions in heavy ion collisions.

  6. Rational design of urea-based glutamate carboxypeptidase II (GCPII) inhibitors as versatile tools for specific drug targeting and delivery

    Czech Academy of Sciences Publication Activity Database

    Tykvart, Jan; Schimer, Jiří; Bařinková, Jitka; Pachl, Petr; Poštová Slavětínská, Lenka; Majer, Pavel; Konvalinka, Jan; Šácha, Pavel

    2014-01-01

    Roč. 22, č. 15 (2014), s. 4099-4108 ISSN 0968-0896 R&D Projects: GA ČR GBP208/12/G016 Grant - others:OPPK(CZ) CZ.2.16/3.1.00/24016 Institutional support: RVO:61388963 Keywords : GCPII * PSMA * structure-aided drug design * specific drug targeting Subject RIV: CE - Biochemistry Impact factor: 2.793, year: 2014

  7. Cholesterol target value attainment and lipid-lowering therapy in patients with stable or acute coronary heart disease: Results from the Dyslipidemia International Study II.

    Science.gov (United States)

    Gitt, Anselm K; Lautsch, Dominik; Ferrières, Jean; De Ferrari, Gaetano M; Vyas, Ami; Baxter, Carl A; Bash, Lori D; Ashton, Veronica; Horack, Martin; Almahmeed, Wael; Chiang, Fu-Tien; Poh, Kian Keong; Brudi, Philippe; Ambegaonkar, Baishali

    2017-11-01

    Low-density lipoprotein cholesterol (LDL-C) is a major contributor to cardiovascular disease. In the Dyslipidemia International Study II (DYSIS II), we determined LDL-C target value attainment, use of lipid-lowering therapy (LLT), and cardiovascular outcomes in patients with stable coronary heart disease (CHD) and those suffering from an acute coronary syndrome (ACS). DYSIS II included patients from 18 countries. Patients with either stable CHD or an ACS were enrolled if they were ≥18 years old and had a full lipid profile available. Data were collected at a physician visit (CHD cohort) or at hospital admission and 120 days later (ACS cohort). A total of 10,661 patients were enrolled, 6794 with stable CHD and 3867 with an ACS. Mean LDL-C levels were low at 88 mg/dl and 108 mg/dl for the CHD and ACS cohorts respectively, with only 29.4% and 18.9% displaying a level below 70 mg/dl. LLT was utilized by 93.8% of the CHD cohort, with a mean daily statin dosage of 25 ± 18 mg. The proportion of the ACS cohort treated with LLT rose from 65.2% at admission to 95.6% at follow-up. LLT-treated patients, who were female, obese, or current smokers, were less likely to achieve an LDL-C level of <70 mg/dl, while those with type 2 diabetes, chronic kidney disease, or those taking a higher statin dosage were more likely. Few of these very high-risk patients achieved the LDL-C target, indicating huge potential for improving cardiovascular outcome by use of more intensive LLT. Copyright © 2017. Published by Elsevier B.V.

  8. Time resolved, 2-D hard X-ray imaging of relativistic electron-beam target interactions on ETA-II

    International Nuclear Information System (INIS)

    Crist, C.E.; Sampayan, S.; Westenskow, G.; Caporaso, G.; Houck, T.; Weir, J.; Trimble, D.; Krogh, M.

    1998-01-01

    Advanced radiographic applications require a constant source size less than 1 mm. To study the time history of a relativistic electron beam as it interacts with a bremsstrahlung converter, one of the diagnostics they use is a multi-frame time-resolved hard x-ray camera. They are performing experiments on the ETA-II accelerator at Lawrence Livermore National Laboratory to investigate details of the electron beam/converter interactions. The camera they are using contains 6 time-resolved images, each image is a 5 ns frame. By starting each successive frame 10 ns after the previous frame, they create a 6-frame movie from the hard x-rays produced from the interaction of the 50-ns electron beam pulse

  9. Ru(II)-polypyridyl surface functionalised gold nanoparticles as DNA targeting supramolecular structures and luminescent cellular imaging agents.

    Science.gov (United States)

    Martínez-Calvo, Miguel; Orange, Kim N; Elmes, Robert B P; la Cour Poulsen, Bjørn; Williams, D Clive; Gunnlaugsson, Thorfinnur

    2016-01-07

    The development of Ru(II) functionalized gold nanoparticles 1–3·AuNP is described. These systems were found to be mono-disperse with a hydrodynamic radius of ca. 15 nm in water but gave rise to the formation of higher order structures in buffered solution. The interaction of 1–3·AuNP with DNA was also studied by spectroscopic and microscopic methods and suggested the formation of large self-assembly structures in solution. The uptake of 1–3·AuNP by cancer cells was studied using both confocal fluorescence as well as transmission electron microscopy (TEM), with the aim of investigating their potential as tools for cellular biology. These systems displaying a non-toxic profile with favourable photophysical properties may have application across various biological fields including diagnostics and therapeutics.

  10. Differential detection of type II methanotrophic bacteria in acidic peatlands using newly developed 16S rRNA-targeted fluorescent oligonucleotide probes.

    Science.gov (United States)

    Dedysh, Svetlana N; Dunfield, Peter F; Derakshani, Manigee; Stubner, Stephan; Heyer, Jürgen; Liesack, Werner

    2003-04-01

    Abstract Based on an extensive 16S rRNA sequence database for type II methanotrophic bacteria, a set of 16S rRNA-targeted oligonucleotide probes was developed for differential detection of specific phylogenetic groups of these bacteria by fluorescence in situ hybridisation (FISH). This set of oligonucleotides included a genus-specific probe for Methylocystis (Mcyst-1432) and three species-specific probes for Methylosinus sporium (Msins-647), Methylosinus trichosporium (Msint-1268) and the recently described acidophilic methanotroph Methylocapsa acidiphila (Mcaps-1032). These novel probes were applied to further characterise the type II methanotroph community that was detected in an acidic Sphagnum peat from West Siberia in a previous study (Dedysh et al. (2001) Appl. Environ. Microbiol. 67, 4850-4857). The largest detectable population of indigenous methanotrophs simultaneously hybridised with a group-specific probe targeting all currently known Methylosinus/Methylocystis spp. (M-450), with a genus-specific probe for Methylocystis spp. (Mcyst-1432), and with an additional probe (Mcyst-1261) that had been designed to target a defined phylogenetic subgroup of Methylocystis spp. The same subgroup of Methylocystis was also detected in acidic peat sampled from Sphagnum-dominated wetland in northern Germany. The population size of this peat-inhabiting Methylocystis subgroup was 2.0+/-0.1x10(6) cells g(-1) (wet weight) of peat from Siberia and 5.5+/-0.5x10(6) cells g(-1) of peat from northern Germany. This represented 60 and 95%, respectively, of the total number of methanotroph cells detected by FISH in these two wetland sites. Other major methanotroph populations were M. acidiphila and Methylocella palustris. Type I methanotrophs accounted for not more than 1% of total methanotroph cells. Neither M. trichosporium nor M. sporium were detected in acidic Sphagnum peat.

  11. Deeply inelastic transfer reactions induced by heavy ions in rare earth targets. II. Interpretation of experimental data

    International Nuclear Information System (INIS)

    Rivet, M.F.; Bimbot, R.; Ngo, C.

    1979-01-01

    The experimental angular distributions and cross sections for a series of deeply inelastic transfer reactions induced by various projectiles in rare earth targets have been interpreted using a model which includes a dynamical coupling between relative motion and mass asymmetry and treats statistical fluctuations. As the transfer reactions considered correspond to an increase of the potential energy of the composite system their observation is mainly due to fluctuations. The calculation reproduces correctly the angular distributions, but the cross sections are underestimated. Several effects are discussed which may increase these cross sections and are neglected in the calculation

  12. Microstructural evolution of austenitic stainless steels irradiated to 17 dpa in spectrally tailored experiment of the ORR and HFIR at 400{degrees}C

    Energy Technology Data Exchange (ETDEWEB)

    Wakai, E.; Hashimoto, N.; Gibson, L.T. [Oak Ridge National Lab., TN (United States)] [and others

    1997-08-01

    The microstructural evolution of austenitic JPCA aged and solution annealed JPCA, 316R, C, K, and HP steels irradiated at 400{degrees}C in spectrally tailored experiments of the ORR and HFIR has been investigated. The helium generation rates were about 12-16 appm He/dpa on the average up to 17.3 dpa. The number densities and average diameters of dislocation loops in the steels have ranges of 3.3 x 10{sup 21} m{sup -3} and 15.2-26.3 nm, respectively, except for HP steel for which they are 1.1 x 10{sup 23} m{sup -3} and 8.0 nm. Precipitates are formed in all steels except for HP steel, and the number densities and average diameters have ranges of 5.2 x 10{sup 20} - 7.7 x 10{sup 21} m{sup -3} and 3.4- 19.3 nm, respectively. In the 216R, C, and K steels, the precipitates are also formed at grain boundaries, and the mean sizes of these are about 110, 50, and 50 nm, respectively. The number densities of cavities are about 1 x 10{sup 22} m{sup -3} in all the steels. The swelling is low in the steels which form the precipitates.

  13. TP Atlas: integration and dissemination of advances in Targeted Proteins Research Program (TPRP)-structural biology project phase II in Japan.

    Science.gov (United States)

    Iwayanagi, Takao; Miyamoto, Sei; Konno, Takeshi; Mizutani, Hisashi; Hirai, Tomohiro; Shigemoto, Yasumasa; Gojobori, Takashi; Sugawara, Hideaki

    2012-09-01

    The Targeted Proteins Research Program (TPRP) promoted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan is the phase II of structural biology project (2007-2011) following the Protein 3000 Project (2002-2006) in Japan. While the phase I Protein 3000 Project put partial emphasis on the construction and maintenance of pipelines for structural analyses, the TPRP is dedicated to revealing the structures and functions of the targeted proteins that have great importance in both basic research and industrial applications. To pursue this objective, 35 Targeted Proteins (TP) Projects selected in the three areas of fundamental biology, medicine and pharmacology, and food and environment are tightly collaborated with 10 Advanced Technology (AT) Projects in the four fields of protein production, structural analyses, chemical library and screening, and information platform. Here, the outlines and achievements of the 35 TP Projects are summarized in the system named TP Atlas. Progress in the diversified areas is described in the modules of Graphical Summary, General Summary, Tabular Summary, and Structure Gallery of the TP Atlas in the standard and unified format. Advances in TP Projects owing to novel technologies stemmed from AT Projects and collaborative research among TP Projects are illustrated as a hallmark of the Program. The TP Atlas can be accessed at http://net.genes.nig.ac.jp/tpatlas/index_e.html .

  14. Small organic compounds enhance antigen loading of class II major histocompatibility complex proteins by targeting the polymorphic P1 pocket

    DEFF Research Database (Denmark)

    Höpner, Sabine; Dickhaut, Katharina; Hofstätter, Maria

    2006-01-01

    the peptide loading rate. The effect was evident only for an allelic subset and strictly correlated with the presence of glycine at the dimorphic position beta86 of the HLA-DR molecule. The residue forms the floor of the conserved pocket P1, located in the peptide binding site of MHC molecule. Apparently......, transient occupation of this pocket by the organic compound stabilizes the peptide-receptive conformation permitting rapid antigen loading. This interaction appeared restricted to the larger Gly(beta86) pocket and allowed striking enhancements of T cell responses for antigens presented by these "adamantyl......-susceptible" MHC molecules. As catalysts of antigen loading, compounds targeting P1 may be useful molecular tools to amplify the immune response. The observation, however, that the ligand repertoire can be affected through polymorphic sites form the outside may also imply that environmental factors could induce...

  15. REAL TIME PCR IDENTIFICATION FOR TARGET ADJUNCTIVE ANTIBIOTIC THERAPY OF SEVERE CHRONIC PERIODONTITIS. PART II - MICROBIOLOGICAL EFFECTIVENESS.

    Directory of Open Access Journals (Sweden)

    Kamen Kotsilkov

    2014-10-01

    Full Text Available INTRODUCTION: Antibiotic use in chronic periodontitis may result in improvement in periodontal status, although many questions regarding the indications for this therapy remain unanswered. The polymicrobial etiology of the periodontal infection hinders the choice of the proper antibiotic agent. Furthermore the indiscriminate use of antibiotics could lead to high levels of resistance and to various adverse reactions. In the recent years a various molecular diagnostics protocols were proposed in order to facilitate the decision for adjunctive antibiotic administration. OBJECTIVE: The aim of this study is to compare the microbiological effectiveness of adjunctive antibiotic administration with the mechanical periodontal therapy. METHODS: 30 patients with severe chronic periodontitis were enrolled in this study and were divided in 3 groups: Control group – with mechanical debridement only. Test group 1 – with combined adjunctive antibiotic administration using Amoxicillin+ Metronidazole. Test group 2 – with target antibiotic administration according to the resuts from the Real Time PCR identification. RESULTS: The prevalence of all the isolated microorganisms (exept. E.nodatum and C.gingivalis in Test Group 2 demonstrates statistically significant reduction compared with the other treatment approaches. Almost complete elimination was registered for the consensus pathogens from the red and orange complexes (above 99% and 100% for P.intemedia. CONCLUSION: The adjunct antibiotic treatment targeted with Real-Time PCR identification demonstrates almost complete elimination of the putative periodontal pathogens in the deep periodontal pockets in patients with severe chronic periodontitis. This result suggests slower recolonisation of these habitats thus limiting the risk for progression of the periodontal destruction.

  16. Parallaxes of southern extremely cool objects (parsec). II. Spectroscopic follow-up and parallaxes of 52 targets

    Energy Technology Data Exchange (ETDEWEB)

    Marocco, F.; Andrei, A. H.; Jones, H. R. A.; Pinfield, D. J.; Clarke, J. R. A.; Lucas, P. W. [Centre for Astrophysics Research, Science and Technology Research Institute, University of Hertfordshire, Hatfield AL10 9AB (United Kingdom); Smart, R. L.; Sozzetti, A.; Bucciarelli, B. [INAF/Osservatorio Astrofisico di Torino, Strada Osservatorio 20, I-10025 Pino Torinese (Italy); Day-Jones, A. C. [Departamento de Astronomia, Universidad de Chile, Camino del Observatorio 1515, Santiago (Chile); Penna, J. L. [Observatório Nacional/MCT, R. Gal. José Cristino 77, CEP20921-400 RJ (Brazil)

    2013-12-01

    We present near-infrared spectroscopy for 52 ultracool dwarfs, including two newly discovered late-M dwarfs, one new late-M subdwarf candidate, three new L, and four new T dwarfs. We also present parallaxes and proper motions for 21 of them. Four of the targets presented here have previous parallax measurements, while all the others are new values. This allow us to populate further the spectral sequence at early types (L0-L4). Combining the astrometric parameters with the new near-infrared spectroscopy presented here, we are able to investigate further the nature of some of the objects. In particular, we find that the peculiar blue L1 dwarf SDSS J133148.92–011651.4 is a metal-poor object, likely a member of the galactic thick disk. We discover a new M subdwarf candidate, 2MASS J20115649–6201127. We confirm the low-gravity nature of EROS-MP J0032–4405, DENIS-P J035726.9–441730, and 2MASS J22134491–2136079. We present two new metal-poor dwarfs: the L4pec 2MASS J19285196–4356256 and the M7pec SIPS2346–5928. We also determine the effective temperature and bolometric luminosity of the 21 targets with astrometric measurements, and we obtain a new polynomial relation between effective temperature and near-infrared spectral type. The new fit suggests a flattening of the sequence at the transition between M and L spectral types. This could be an effect of dust formation, which causes a more rapid evolution of the spectral features as a function of the effective temperature.

  17. Preclinical assessment of viral vectored and protein vaccines targeting the Duffy-binding protein region II of Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    Simone C de Cassan

    2015-07-01

    Full Text Available Malaria vaccine development has largely focused on Plasmodium falciparum; however a reawakening to the importance of P. vivax has spurred efforts to develop vaccines against this difficult to treat and at times severe form of relapsing malaria, which constitutes a significant proportion of human malaria cases worldwide. The almost complete dependence of P. vivax red blood cell invasion on the interaction of the P. vivax Duffy-binding protein region II (PvDBP_RII with the human Duffy antigen receptor for chemokines (DARC, makes this antigen an attractive vaccine candidate against blood-stage P. vivax. Here, we generated both preclinical and clinically-compatible adenoviral and poxviral vectored vaccine candidates expressing the Salvador I allele of PvDBP_RII – including human adenovirus serotype 5 (HAdV5, chimpanzee adenovirus serotype 63 (ChAd63 and modified vaccinia virus Ankara (MVA vectors. We report on the antibody and T cell immunogenicity of these vaccines in mice or rabbits, either used alone in a viral vectored prime-boost regime, or in ‘mixed-modality’ adenovirus prime – protein-in-adjuvant boost regimes (using a recombinant protein PvDBP_RII protein antigen formulated in Montanide®ISA720 or Abisco®100 adjuvants. Antibodies induced by these regimes were found to bind to native parasite antigen from P. vivax infected Thai patients and were capable of inhibiting the binding of PvDBP_RII to its receptor DARC using an in vitro binding inhibition assay. In recent years, recombinant ChAd63 and MVA vectors have been quickly translated into human clinical trials for numerous antigens from P. falciparum as well as a growing number of other pathogens. The vectors reported here are immunogenic in small animals, elicit antibodies against PvDBP_RII and have recently entered clinical trials which will provide the first assessment of the safety and immunogenicity of the PvDBP_RII antigen in humans.

  18. SU-E-J-88: Margin Reduction of Level II/III Planning Target Volume for Image-Guided Simultaneous Integrated Boost Head-And-Neck Treatment

    International Nuclear Information System (INIS)

    Can, S; Neylon, J; Qi, S; Santhanam, A; Low, D

    2014-01-01

    Purpose: To investigate the feasibility of improved normal tissue sparing for head-and-neck (H'N) image-guided radiotherapy (IGRT) by employing tighter CTV-to-PTV margins for target level II/III though a GPU-based deformable image registration and dose accumulation framework. Methods: Ten H'N simultaneous integrated boost cases treated on TomoTherapy were retrospectively analyzed. Weekly kVCT scans in addition to daily MVCT scans were acquired for each patient. Reduced margin plans were generated with 0- mm margin for level II and III PTV (while 3-5 mm margin for PTV1) and compared with the standard margin plan using 3-5mm margin to all CTV1-3 (reference plan). An in-house developed GPU-based 3D image deformation tool was used to register and deform the weekly KVCTs with the planning CT and determine the delivered mean/minimum/maximum dose, dose volume histograms (DVHs), etc. Results: Compared with the reference plans, the averaged cord maximum, the right and left parotid doses reduced by 22.7 %, 16.5 %, and 9 % respectively in the reduced margin plans. The V95 for PTV2 and PTV3 were found within 2 and 5% between the reference and tighter margin plans. For the reduced margin plans, the averaged cumulative mean doses were consistent with the planned dose for PTV1, PTV2 and PTV3 within 1.5%, 1.7% and 1.4%. Similar dose variations of the delivered dose were seen for the reference and tighter margin plans. The delivered maximum and mean doses for the cord were 3.55 % and 2.37% higher than the planned doses; a 5 % higher cumulative mean dose for the parotids was also observed for the delivered dose than the planned doses in both plans. Conclusion: By imposing tighter CTV-to-PTV margins for level II and III targets for H'N irradiation, acceptable cumulative doses were achievable when coupled with weekly kVCT guidance while improving normal structure sparing

  19. Treatment outcomes regarding the addition of targeted agents in the therapeutic portfolio for stage II-III rectal cancer undergoing neoadjuvant chemoradiation.

    Science.gov (United States)

    Liang, Jin-Tung; Chen, Tzu-Chun; Huang, John; Jeng, Yung-Ming; Cheng, Jason Chia-Hsien

    2017-11-24

    To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT). A retrospective study was performed in 124 consecutive patients with clinically T 3 N 0-2 M 0 -staged rectal cancer incorporating targeted agents in CCRT. Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, panalysis within bevacizumab+FOLFOX-treated patients with either wild-type (n=36) or mutant (n=40) K-ras status indicated K-ras status did not significantly influence the treatment outcomes. The addition of bevacizumab instead of cetuximab to FOLFOX in the neoadjuvant settings for T 3 N 0-2 M 0 -staged rectal cancer could induce a promising rate of pathologic complete response and lesser hepatotoxicity.

  20. The Gpn3 Q279* cancer-associated mutant inhibits Gpn1 nuclear export and is deficient in RNA polymerase II nuclear targeting.

    Science.gov (United States)

    Barbosa-Camacho, Angel A; Méndez-Hernández, Lucía E; Lara-Chacón, Bárbara; Peña-Gómez, Sonia G; Romero, Violeta; González-González, Rogelio; Guerra-Moreno, José A; Robledo-Rivera, Angélica Y; Sánchez-Olea, Roberto; Calera, Mónica R

    2017-11-01

    Gpn3 is required for RNA polymerase II (RNAPII) nuclear targeting. Here, we investigated the effect of a cancer-associated Q279* nonsense mutation in Gpn3 cellular function. Employing RNAi, we replaced endogenous Gpn3 by wt or Q279* RNAi-resistant Gpn3R in epithelial model cells. RNAPII nuclear accumulation and transcriptional activity were markedly decreased in cells expressing only Gpn3R Q279*. Wild-type Gpn3R localized to the cytoplasm but a fraction of Gpn3R Q279* entered the cell nucleus and inhibited Gpn1-EYFP nuclear export. This property and the transcriptional deficit in Gpn3R Q279*-expressing cells required a PDZ-binding motif generated by the Q279* mutation. We conclude that an acquired PDZ-binding motif in Gpn3 Q279* caused Gpn3 nuclear entry, and inhibited Gpn1 nuclear export and Gpn3-mediated RNAPII nuclear targeting. © 2017 Federation of European Biochemical Societies.

  1. Revised ANL-reported tensile data for unirradiated and irradiated (FFTF, HFIR) V-Ti and V-Cr-Ti alloys

    International Nuclear Information System (INIS)

    Billone, M.C.

    1998-01-01

    The tensile data for all unirradiated and irradiated vanadium alloys samples tested at Argonne National Laboratory (ANL) have been critically reviewed and, when necessary, revised. The review and revision are based on reanalyzing the original load-displacement strip chart recordings by a methodology consistent with current ASTM standards. For unirradiated alloys (162 samples), the revised values differ from the previous values as follows: -11±19 MPa (-4±6%) for yield strength (YS), -3±15 MPa (-1±3%) for ultimate tensile strength (UTS), -5±2% strain for uniform elongation (UE), and -4±2% strain for total elongation (TE). Of these changes, the decrease in -1±6 MPa (0±1%) for UTS, -5±2% for UE, and -4±2% for TE. Of these changes, the decrease in UE values for alloys irradiated and tested at 400--435 C is the most significant. This decrease results from the proper subtraction of nongauge-length deformation from measured crosshead deformation. In previous analysis of the tensile curves, the nongauge-length deformation was not correctly determined and subtracted from the crosshead displacement. The previously reported and revised tensile values for unirradiated alloys (20--700 C) are tabulated in Appendix A. The revised tensile values for the FFTF-irradiated (400--600 C) and HFIR-irradiated (400 C) alloys are tabulated in Appendix B, along with the neutron damage and helium levels. Appendix C compares the revised values to the previously reported values for irradiated alloys. Appendix D contains previous and revised values for the tensile properties of unirradiated V-5Cr-5Ti (BL-63) alloy exposed to oxygen

  2. The exosome component Rrp6 is required for RNA polymerase II termination at specific targets of the Nrd1-Nab3 pathway.

    Directory of Open Access Journals (Sweden)

    Melanie J Fox

    Full Text Available The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs and unstable transcripts. Known targets of the nuclear exosome include short (<1000 bp RNAPII transcripts such as small noncoding RNAs (snRNAs, cryptic unstable transcripts (CUTs, and some stable unannotated transcripts (SUTs that are terminated by an Nrd1, Nab3, and Sen1 (NNS dependent mechanism. NNS-dependent termination is coupled to RNA 3' end processing and/or degradation by the Rrp6/exosome in yeast. Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity. It remains unclear whether Rrp6 is directly involved in termination; however, Rrp6 has been implicated in the 3' end processing and degradation of ncRNA transcripts including CUTs. To determine the role of Rrp6 in NNS termination globally, we performed RNA sequencing (RNA-Seq on total RNA and perform ChIP-exo analysis of RNA Polymerase II (RNAPII localization. Deletion of RRP6 promotes hyper-elongation of multiple NNS-dependent transcripts resulting from both improperly processed 3' RNA ends and faulty transcript termination at specific target genes. The defects in RNAPII termination cause transcriptome-wide changes in mRNA expression through transcription interference and/or antisense repression, similar to previously reported effects of depleting Nrd1 from the nucleus. Elongated transcripts were identified within all classes of known NNS targets with the largest changes in transcription termination occurring at CUTs. Interestingly, the extended transcripts that we have detected in our studies show remarkable similarity to Nrd1-unterminated transcripts at many locations, suggesting that Rrp6 acts with the NNS complex globally to promote

  3. Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes.

    Science.gov (United States)

    Zhao, Lue Ping; Carlsson, Annelie; Larsson, Helena Elding; Forsander, Gun; Ivarsson, Sten A; Kockum, Ingrid; Ludvigsson, Johnny; Marcus, Claude; Persson, Martina; Samuelsson, Ulf; Örtqvist, Eva; Pyo, Chul-Woo; Bolouri, Hamid; Zhao, Michael; Nelson, Wyatt C; Geraghty, Daniel E; Lernmark, Åke

    2017-11-01

    It is of interest to predict possible lifetime risk of type 1 diabetes (T1D) in young children for recruiting high-risk subjects into longitudinal studies of effective prevention strategies. Utilizing a case-control study in Sweden, we applied a recently developed next generation targeted sequencing technology to genotype class II genes and applied an object-oriented regression to build and validate a prediction model for T1D. In the training set, estimated risk scores were significantly different between patients and controls (P = 8.12 × 10 -92 ), and the area under the curve (AUC) from the receiver operating characteristic (ROC) analysis was 0.917. Using the validation data set, we validated the result with AUC of 0.886. Combining both training and validation data resulted in a predictive model with AUC of 0.903. Further, we performed a "biological validation" by correlating risk scores with 6 islet autoantibodies, and found that the risk score was significantly correlated with IA-2A (Z-score = 3.628, P < 0.001). When applying this prediction model to the Swedish population, where the lifetime T1D risk ranges from 0.5% to 2%, we anticipate identifying approximately 20 000 high-risk subjects after testing all newborns, and this calculation would identify approximately 80% of all patients expected to develop T1D in their lifetime. Through both empirical and biological validation, we have established a prediction model for estimating lifetime T1D risk, using class II HLA. This prediction model should prove useful for future investigations to identify high-risk subjects for prevention research in high-risk populations. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Secondary metabolites of Cynodon dactylon as an antagonist to angiotensin II type1 receptor: Novel in silico drug targeting approach for diabetic retinopathy

    Science.gov (United States)

    Jananie, R. K.; Priya, V.; Vijayalakshmi, K.

    2012-01-01

    Objectives: To study the ability of the secondary metabolites of Cynodon dactylon to serve as an antagonist to angiotensin II type 1 receptor (AT1); activation of this receptor plays a vital role in diabetic retinopathy (DR). Materials and Methods: In silico methods are mainly harnessed to reduce time, cost and risk associated with drug discovery. Twenty-four compounds were identified as the secondary metabolites of hydroalcoholic extract of C. dactylon using the GCMS technique. These were considered as the ligands or inhibitors that would serve as an antagonist to the AT1. The ACD/Chemsketch tool was used to generate 3D structures of the ligands. A molecular file format converter tool was used to convert the generated data to the PDB format (Protein Data Bank) and was used for docking studies. The AT1 structure was retrieved from the Swissprot data base and PDB and visualized using the Rasmol tool. Domain analysis was carried from the Pfam data base; following this, the active site of the target protein was identified using a Q-site finder tool. The ability of the ligands to bind with the active site of AT1 was studied using the Autodocking tool. The docking results were analyzed using the WebLab viewer tool. Results: Sixteen ligands showed effective binding with the target protein; diazoprogesteron, didodecyl phthalate, and 9,12-octadecadienoyl chloride (z,z) may be considered as compounds that could be used to bind with the active site sequence of AT1. Conclusions: The present study shows that the metabolites of C. dactylon could serve as a natural antagonist to AT1 that could be used to treat diabetic retinopathy. PMID:22368412

  5. Thermal-hydraulic simulation of natural convection decay heat removal in the High Flux Isotope Reactor (HFIR) using RELAP5 and TEMPEST: Part 2, Interpretation and validation of results

    International Nuclear Information System (INIS)

    Ruggles, A.E.; Morris, D.G.

    1989-01-01

    The RELAP5/MOD2 code was used to predict the thermal-hydraulic behavior of the HFIR core during decay heat removal through boiling natural circulation. The low system pressure and low mass flux values associated with boiling natural circulation are far from conditions for which RELAP5 is well exercised. Therefore, some simple hand calculations are used herein to establish the physics of the results. The interpretation and validation effort is divided between the time average flow conditions and the time varying flow conditions. The time average flow conditions are evaluated using a lumped parameter model and heat balance. The Martinelli-Nelson correlations are used to model the two-phase pressure drop and void fraction vs flow quality relationship within the core region. Systems of parallel channels are susceptible to both density wave oscillations and pressure drop oscillations. Periodic variations in the mass flux and exit flow quality of individual core channels are predicted by RELAP5. These oscillations are consistent with those observed experimentally and are of the density wave type. The impact of the time varying flow properties on local wall superheat is bounded herein. The conditions necessary for Ledinegg flow excursions are identified. These conditions do not fall within the envelope of decay heat levels relevant to HFIR in boiling natural circulation. 14 refs., 5 figs., 1 tab

  6. Development of a quantitative assay amenable for high-throughput screening to target the type II secretion system for new treatments against plant-pathogenic bacteria.

    Science.gov (United States)

    Tran, Nini; Zielke, Ryszard A; Vining, Oliver B; Azevedo, Mark D; Armstrong, Donald J; Banowetz, Gary M; McPhail, Kerry L; Sikora, Aleksandra E

    2013-09-01

    Plant-pathogenic bacteria are the causative agents of diseases in important agricultural crops and ornamental plants. The severe economic burden of these diseases requires seeking new approaches for their control, particularly because phytopathogenic bacteria are often resistant to available treatments. The type II secretion (T2S) system is a key virulence factor used by major groups of phytopathogenic bacteria. The T2S machinery transports many hydrolytic enzymes responsible for degradation of the plant cell wall, thus enabling successful colonization and dissemination of the bacteria in the plant host. The genetic inactivation of the T2S system leads to loss of virulence, which strongly suggests that targeting the T2S could enable new treatments against plant-pathogenic bacteria. Accordingly, we have designed and optimized an assay to identify small-molecule inhibitors of the T2S system. This assay uses a double parametric output: measurement of bacterial growth and the enzymatic activity of cellulase, which is secreted via the T2S pathway in our model organism Dickeya dadantii. The assay was evaluated by screening natural extracts, culture filtrates isolated from rhizosphere bacteria, and a collection of pharmaceutically active compounds in LOPAC(1280). The calculated Z' values of 0.63, 0.63, and 0.58, respectively, strongly suggest that the assay is applicable for a high-throughput screening platform.

  7. QSAR, docking and ADMET studies of artemisinin derivatives for antimalarial activity targeting plasmepsin II, a hemoglobin-degrading enzyme from P. falciparum.

    Science.gov (United States)

    Qidwai, Tabish; Yadav, Dharmendra K; Khan, Feroz; Dhawan, Sangeeta; Bhakuni, R S

    2012-01-01

    This work presents the development of quantitative structure activity relationship (QSAR) model to predict the antimalarial activity of artemisinin derivatives. The structures of the molecules are represented by chemical descriptors that encode topological, geometric, and electronic structure features. Screening through QSAR model suggested that compounds A24, A24a, A53, A54, A62 and A64 possess significant antimalarial activity. Linear model is developed by the multiple linear regression method to link structures to their reported antimalarial activity. The correlation in terms of regression coefficient (r(2)) was 0.90 and prediction accuracy of model in terms of cross validation regression coefficient (rCV(2)) was 0.82. This study indicates that chemical properties viz., atom count (all atoms), connectivity index (order 1, standard), ring count (all rings), shape index (basic kappa, order 2), and solvent accessibility surface area are well correlated with antimalarial activity. The docking study showed high binding affinity of predicted active compounds against antimalarial target Plasmepsins (Plm-II). Further studies for oral bioavailability, ADMET and toxicity risk assessment suggest that compound A24, A24a, A53, A54, A62 and A64 exhibits marked antimalarial activity comparable to standard antimalarial drugs. Later one of the predicted active compound A64 was chemically synthesized, structure elucidated by NMR and in vivo tested in multidrug resistant strain of Plasmodium yoelii nigeriensis infected mice. The experimental results obtained agreed well with the predicted values.

  8. TAL effectors target the C-terminal domain of RNA polymerase II (CTD by inhibiting the prolyl-isomerase activity of a CTD-associated cyclophilin.

    Directory of Open Access Journals (Sweden)

    Mariane Noronha Domingues

    Full Text Available Transcriptional activator-like (TAL effectors of plant pathogenic bacteria function as transcription factors in plant cells. However, how TAL effectors control transcription in the host is presently unknown. Previously, we showed that TAL effectors of the citrus canker pathogen Xanthomonas citri, named PthAs, targeted the citrus protein complex comprising the thioredoxin CsTdx, ubiquitin-conjugating enzymes CsUev/Ubc13 and cyclophilin CsCyp. Here we show that CsCyp complements the function of Cpr1 and Ess1, two yeast cyclophilins that regulate transcription by the isomerization of proline residues of the regulatory C-terminal domain (CTD of RNA polymerase II. We also demonstrate that CsCyp, CsTdx, CsUev and four PthA variants interact with the citrus CTD and that CsCyp co-immunoprecipitate with the CTD in citrus cell extracts and with PthA2 transiently expressed in sweet orange epicotyls. The interactions of CsCyp with the CTD and PthA2 were inhibited by cyclosporin A (CsA, a cyclophilin inhibitor. Moreover, we present evidence that PthA2 inhibits the peptidyl-prolyl cis-trans isomerase (PPIase activity of CsCyp in a similar fashion as CsA, and that silencing of CsCyp, as well as treatments with CsA, enhance canker lesions in X. citri-infected leaves. Given that CsCyp appears to function as a negative regulator of cell growth and that Ess1 negatively regulates transcription elongation in yeast, we propose that PthAs activate host transcription by inhibiting the PPIase activity of CsCyp on the CTD.

  9. Analysis of 6912 unselected somatic hypermutations in human VDJ rearrangements reveals lack of strand specificity and correlation between phase II substitution rates and distance to the nearest 3' activation-induced cytidine deaminase target

    DEFF Research Database (Denmark)

    Ohm-Laursen, Line; Barington, Torben

    2007-01-01

    -23*01) from blood B lymphocytes enriched for CD27-positive memory cells. Analyses of 6,912 unique, unselected substitutions showed that in vivo hot and cold spots for the SHM of C and G residues corresponded closely to the target preferences reported for AID in vitro. A detailed analysis of all possible four......-nucleotide motifs present on both strands of the V(H) gene showed significant correlations between the substitution frequencies in reverse complementary motifs, suggesting that the SHM machinery targets both strands equally well. An analysis of individual J(H) and D gene segments showed that the substitution...... rates in G and T residues correlated inversely with the distance to the nearest 3' WRC AID hot spot motif on both the nontranscribed and transcribed strands. This suggests that phase II SHM takes place 5' of the initial AID deamination target and primarily targets T and G residues or, alternatively...

  10. Interaction of the tylosin-resistance methyltransferase RlmA II at its rRNA target differs from the orthologue RlmA I

    DEFF Research Database (Denmark)

    Douthwaite, Stephen; Jakobsen, Lene; Yoshizawa, Satoko

    2008-01-01

    of Gram-positive bacteria, including the tylosin-producer Streptomyces fradiae and the pathogen Streptococcus pneumoniae. Recombinant S. pneumoniae RlmA(II) was purified and shown to retain its activity and specificity in vitro when tested on unmethylated 23 S rRNA substrates. RlmA(II) makes multiple......RlmA(II) methylates the N1-position of nucleotide G748 in hairpin 35 of 23 S rRNA. The resultant methyl group extends into the peptide channel of the 50 S ribosomal subunit and confers resistance to tylosin and other mycinosylated macrolide antibiotics. Methylation at G748 occurs in several groups...

  11. The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.

    Science.gov (United States)

    Katayama, Seiichi; Ashizawa, Koji; Gohma, Hiroshi; Fukuhara, Tadahiro; Narumi, Kazunori; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Nakada, Tadashi; Nagai, Kenji

    2006-12-15

    The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17alpha-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ERalpha-selective agonist), diarylpropionitrile (DPN, an ERbeta-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ERalpha-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ERbeta-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.

  12. The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats

    International Nuclear Information System (INIS)

    Katayama, Seiichi; Ashizawa, Koji; Gohma, Hiroshi; Fukuhara, Tadahiro; Narumi, Kazunori; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Nakada, Tadashi; Nagai, Kenji

    2006-01-01

    The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17α-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ERα-selective agonist), diarylpropionitrile (DPN, an ERβ-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ERα-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ERβ-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats

  13. cobalt (ii), nickel (ii)

    African Journals Online (AJOL)

    DR. AMINU

    Department of Chemistry Bayero University, P. M. B. 3011, Kano, Nigeria. E-mail: hnuhu2000@yahoo.com. ABSTRACT. The manganese (II), cobalt (II), nickel (II) and .... water and common organic solvents, but are readily soluble in acetone. The molar conductance measurement [Table 3] of the complex compounds in.

  14. Shielding experiments by the JASMIN collaboration at Fermilab (II) - Radioactivity measurement induced by secondary particles from the anti-proton production target

    Energy Technology Data Exchange (ETDEWEB)

    Yashima, Hiroshi; /Kyoto U., KURRI; Matsuda, Norihiro; Kasugai, Yoshimi; /JAEA, Ibaraki; Matsumura, Hiroshi; Iwase, Hiroshi; /KEK, Tsukuba; Kinoshita, Norikazu; /KEK, Tsukuba /Tsukuba U.; Boehnlein, David; Lauten, Gary; Leveling, Anthony; Mokhov, Nikolai; Vaziri, Kamran; /Fermilab /Shimizu, Tokyo /JAEA, Ibaraki

    2011-01-01

    The JASMIN Collaboration has performed an experiment to conduct measurements of nuclear reaction rates around the anti-proton production (Pbar) target at the Fermi National Accelerator Laboratory (FNAL). At the Pbar target station, the target, consisting an Inconel 600 cylinder, was irradiated by a 120 GeV/c proton beam from the FNAL Main Injector. The beam intensity was 3.6 x 10{sub 12} protons per second. Samples of Al, Nb, Cu, and Au were placed near the target to investigate the spatial and energy distribution of secondary particles emitted from it. After irradiation, the induced activities of the samples were measured by studying their gamma ray spectra using HPGe detectors. The production rates of 30 nuclides induced in Al, Nb, Cu, Au samples were obtained. These rates increase for samples placed in a forward (small angle) position relative to the target. The angular dependence of these reaction rates becomes larger for increasing threshold energy. These experimental results are compared with Monte Carlo calculations. The calculated results generally agree with the experimental results to within a factor of 2 to 3.

  15. Target and beam-target spin asymmetries in exclusive pion electroproduction for Q2>1 GeV2. II. e p →e π0p

    Science.gov (United States)

    Bosted, P. E.; Kim, A.; Adhikari, K. P.; Adikaram, D.; Akbar, Z.; Amaryan, M. J.; Anefalos Pereira, S.; Avakian, H.; Badui, R. A.; Ball, J.; Balossino, I.; Battaglieri, M.; Bedlinskiy, I.; Biselli, A. S.; Boiarinov, S.; Briscoe, W. J.; Brooks, W. K.; Bültmann, S.; Burkert, V. D.; Cao, T.; Carman, D. S.; Celentano, A.; Chandavar, S.; Charles, G.; Chetry, T.; Ciullo, G.; Clark, L.; Colaneri, L.; Cole, P. L.; Contalbrigo, M.; Cortes, O.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Dupre, R.; Egiyan, H.; El Alaoui, A.; El Fassi, L.; Elouadrhiri, L.; Eugenio, P.; Fanchini, E.; Fedotov, G.; Fegan, S.; Fersch, R.; Filippi, A.; Fleming, J. A.; Forest, T. A.; Fradi, A.; Ghandilyan, Y.; Gilfoyle, G. P.; Girod, F. X.; Glazier, D. I.; Gohn, W.; Golovatch, E.; Gothe, R. W.; Griffioen, K. A.; Guidal, M.; Guler, N.; Hakobyan, H.; Guo, L.; Hafidi, K.; Hakobyan, H.; Hanretty, C.; Harrison, N.; Hattawy, M.; Heddle, D.; Hicks, K.; Hollis, G.; Holtrop, M.; Hughes, S. M.; Ireland, D. G.; Isupov, E. L.; Jenkins, D.; Jiang, H.; Jo, H. S.; Joo, K.; Keller, D.; Khachatryan, G.; Khandaker, M.; Kim, W.; Klei, A.; Klein, F. J.; Koirala, S.; Kubarovsky, V.; Kuhn, S. E.; Lanza, L.; Lenisa, P.; Livingston, K.; Lu, H. Y.; MacGregor, I. J. D.; Markov, N.; Mayer, M.; McCracken, M. E.; McKinnon, B.; Mineeva, T.; Mirazita, M.; Mokeev, V. I.; Montgomery, R. A.; Movsisyan, A.; Munoz Camacho, C.; Murdoch, G.; Nadel-Turonski, P.; Ni, A.; Niccolai, S.; Niculescu, G.; Osipenko, M.; Ostrovidov, A. I.; Paolone, M.; Paremuzyan, R.; Park, K.; Pasyuk, E.; Phelps, W.; Pisano, S.; Pogorelko, O.; Price, J. W.; Prok, Y.; Protopopescu, D.; Puckett, A. J. R.; Raue, B. A.; Ripani, M.; Rizzo, A.; Rosner, G.; Rossi, P.; Roy, P.; Sabatié, F.; Saini, M. S.; Schumacher, R. A.; Seder, E.; Sharabian, Y. G.; Skorodumina, Iu.; Smith, G. D.; Sokhan, D.; Sparveris, N.; Stankovic, I.; Stepanyan, S.; Stoler, P.; Strakovsky, I. I.; Strauch, S.; Taiuti, M.; Tian, Ye; Torayev, B.; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Wei, X.; Weinstein, L. B.; Zachariou, N.; Zhang, J.; Zhao, Z. W.; Zonta, I.; CLAS Collaboration

    2017-03-01

    Beam-target double-spin asymmetries and target single-spin asymmetries were measured for the exclusive π0 electroproduction reaction γ*p →p π0 , expanding an analysis of the γ*p →n π+ reaction from the same experiment. The results were obtained from scattering of 6-GeV longitudinally polarized electrons off longitudinally polarized protons using the CEBAF Large Acceptance Spectrometer at Jefferson Laboratory. The kinematic ranges covered are 1.1 target asymmetries were found to generally be greater than zero, with relatively modest ϕ* dependence. The target asymmetries exhibit very strong ϕ* dependence, with a change in sign occurring between results at low W and high W , in contrast to π+ electroproduction. Reasonable agreement is found with phenomenological fits to previous data for W <1.6 GeV, but significant differences are seen at higher W . When combined with cross-sectional measurements, as well as π+ observables, the present results will provide powerful constraints on nucleon resonance amplitudes at moderate and large values of Q2, for resonances with masses as high as 2.4 GeV.

  16. Costs and benefits of industrial reporting and voluntary targets for energy efficiency. A report to the Congress of the United States. Volume II: Appendices

    Energy Technology Data Exchange (ETDEWEB)

    1994-02-01

    This part sets forth the regulations for the Industrial Energy conservation Program established under Part E of Title III of the Act. It includes criteria and procedures for the identification of reporting corporations, reporting requirements, criteria and procedures for exemption from filing reports directly with DOE, voluntary industrial energy efficiency improvement targets and voluntary recovered materials utilization targets. The purpose of the program is to promote increased energy conservation by American industry and, as it relates to the use of recovered materials, to conserve valuable energy and scarce natural resources.

  17. The adsorption of Tl(I), Au(III), Cu(II) and the separation of 199Tl from alpha bombardment of gold target with PDB-18C6

    International Nuclear Information System (INIS)

    Zhou Dehai; Zhou Jimeng

    1989-01-01

    The adsorptive behavior of polymer of methyl aldehyde of dibenzo-18-crown-6 (PDB-18C6) in hydrochloric acid medium is studied and it is shown that the adsorption of T1(I), Au(III), and Cu(II) depends on the particle size of the crown ether resins, hydrochloric acid concentration and amount of the crown ether resins used. The difference in the adsorption behavior of different particle sizes of crown ether resins may be used for separating Tl(I), Au(III), and Cu(II) ions. The best eluant of Tl(I) and Au(III) is 0.4 mol/l perchloric acid and 2-ethoxy-ethanol. The recovery for Tl(I) is 82-98.8%. The gold target is bombarded in a 1.2 m cyclotron with 25-27 MeV α-particle with a cumulative beam intensities of 27μA·h, and 199 Tl is separated from the gold target with PDB-18C6. γ-spectrometry has shown that the Tl obtained is 199 Tl of high purity containing only about 0.50% 200 Tl

  18. Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects

    Science.gov (United States)

    Morgan, William F.

    2003-01-01

    The goal of this review is to summarize the evidence for non-targeted and delayed effects of exposure to ionizing radiation in vivo. Currently, human health risks associated with radiation exposures are based primarily on the assumption that the detrimental effects of radiation occur in irradiated cells. Over the years a number of non-targeted effects of radiation exposure in vivo have been described that challenge this concept. These include radiation-induced genomic instability, bystander effects, clastogenic factors produced in plasma from irradiated individuals that can cause chromosomal damage when cultured with nonirradiated cells, and transgenerational effects of parental irradiation that can manifest in the progeny. These effects pose new challenges to evaluating the risk(s) associated with radiation exposure and understanding radiation-induced carcinogenesis.

  19. TNF Receptor Type II as an Emerging Drug Target for the Treatment of Cancer, Autoimmune Diseases, and Graft-Versus-Host Disease: Current Perspectives and In Silico Search for Small Molecule Binders

    Directory of Open Access Journals (Sweden)

    Faraz Shaikh

    2018-06-01

    Full Text Available There is now compelling evidence that TNF receptor type II (TNFR2 is predominantly expressed on CD4+Foxp3+ regulatory T cells (Tregs and myeloid-derived suppressor cells (MDSCs, and plays a major role in the expansion and function of Tregs and MDSCs. Consequently, targeting of TNFR2 by either antagonists or agonists may represent a novel strategy in the treatment of cancer and autoimmune diseases, by downregulating or upregulating suppressor cell activity. The advance in the understanding of complex structure of TNFR2 and its binding with TNF at molecular levels offers opportunity for structure-guided drug discovery. This article reviews the current evidences regarding the decisive role of TNFR2 in immunosuppressive function of Tregs and MDSCs, and the current effort to develop novel TNFR2-targeting therapeutic agents in the treatment of cancer, autoimmune diseases, and graft-versus-host disease. To shed light on the potential TNFR2-targeting small molecules, we for the first time performed virtual screening of 400,000 natural compounds against the two TNF-binding sites, regions 3 and 4, of TNFR2. Our result showed that the top hits at region 4 had slightly higher docking energies than those at region 3. Nevertheless, free energy calculation from the TNF–TNFR2 molecular dynamics simulation revealed that the binding strength of TNF in region 3 is only one-tenth of that in region 4. This suggests that region 3 is a potentially more viable binding site to be targeted by small molecules than region 4. Therefore, the effectiveness in targeting region 3 of TNFR2 deserves further investigation.

  20. Quantitative Proteome Analysis of Mouse Liver Lysosomes Provides Evidence for Mannose 6-phosphate-independent Targeting Mechanisms of Acid Hydrolases in Mucolipidosis II.

    Science.gov (United States)

    Markmann, Sandra; Krambeck, Svenja; Hughes, Christopher J; Mirzaian, Mina; Aerts, Johannes M F G; Saftig, Paul; Schweizer, Michaela; Vissers, Johannes P C; Braulke, Thomas; Damme, Markus

    2017-03-01

    The efficient receptor-mediated targeting of soluble lysosomal proteins to lysosomes requires the modification with mannose 6-phosphate (M6P) residues. Although the absence of M6P results in misrouting and hypersecretion of lysosomal enzymes in many cells, normal levels of lysosomal enzymes have been reported in liver of patients lacking the M6P-generating phosphotransferase (PT). The identity of lysosomal proteins depending on M6P has not yet been comprehensively analyzed. In this study we purified lysosomes from liver of PT-defective mice and 67 known soluble lysosomal proteins were identified that illustrated quantitative changes using an ion mobility-assisted data-independent label-free LC-MS approach. After validation of various differentially expressed lysosomal components by Western blotting and enzyme activity assays, the data revealed a small number of lysosomal proteins depending on M6P, including neuraminidase 1, cathepsin F, Npc2, and cathepsin L, whereas the majority reach lysosomes by alternative pathways. These data were compared with findings on cultured hepatocytes and liver sinusoid endothelial cells isolated from the liver of wild-type and PT-defective mice. Our findings show that the relative expression, targeting efficiency and lysosomal localization of lysosomal proteins tested in cultured hepatic cells resemble their proportion in isolated liver lysosomes. Hypersecretion of newly synthesized nonphosphorylated lysosomal proteins suggest that secretion-recapture mechanisms contribute to maintain major lysosomal functions in liver. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. T-cell memory responses elicited by yellow fever vaccine are targeted to overlapping epitopes containing multiple HLA-I and -II binding motifs.

    Directory of Open Access Journals (Sweden)

    Andréa Barbosa de Melo

    Full Text Available The yellow fever vaccines (YF-17D-204 and 17DD are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env and nonstructural (NS proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4(+ and CD8(+ T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines.

  2. Spallation Neutron Source Second Target Station Integrated Systems Update

    Energy Technology Data Exchange (ETDEWEB)

    Ankner, John Francis [ORNL; An, Ke [ORNL; Blokland, Willem [ORNL; Charlton, Timothy R. [ORNL; Coates, Leighton [ORNL; Dayton, Michael J. [ORNL; Dean, Robert A. [ORNL; Dominguez-Ontiveros, Elvis E. [ORNL; Ehlers, Georg [ORNL; Gallmeier, Franz X. [ORNL; Graves, Van B. [ORNL; Heller, William T. [ORNL; Holmes, Jeffrey A. [ORNL; Huq, Ashfia [ORNL; Lumsden, Mark D. [ORNL; McHargue, William M. [ORNL; McManamy, Thomas J. [ORNL; Plum, Michael A. [ORNL; Rajic, Slobodan [ORNL; Remec, Igor [ORNL; Robertson, Lee [ORNL; Sala, Gabriele [ORNL; Stoica, Alexandru Dan [ORNL; Trotter, Steven M. [ORNL; Winn, Barry L. [ORNL; Abudureyimu, Reheman [ORNL; Rennich, Mark J. [ORNL; Herwig, Kenneth W. [ORNL

    2017-04-01

    The Spallation Neutron Source (SNS) was designed from the beginning to accommodate both an accelerator upgrade to increase the proton power and a second target station (STS). Four workshops were organized in 2013 and 2014 to identify key science areas and challenges where neutrons will play a vital role [1-4]. Participants concluded that the addition of STS to the existing ORNL neutron sources was needed to complement the strengths of High Flux Isotope Reactor (HFIR) and the SNS first target station (FTS). To address the capability gaps identified in the workshops, a study was undertaken to identify instrument concepts that could provide the required new science capabilities. The study outlined 22 instrument concepts and presented an initial science case for STS [5]. These instrument concepts formed the basis of a planning suite of instruments whose requirements determined an initial site layout and moderator selection. An STS Technical Design Report (TDR) documented the STS concept based on those choices [6]. Since issue of the TDR, the STS concept has significantly matured as described in this document.

  3. Randomized phase II – study evaluating EGFR targeting therapy with Cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer – PARC: study protocol [ISRCTN56652283

    Directory of Open Access Journals (Sweden)

    Heeger S

    2005-10-01

    Full Text Available Abstract Background Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR. Methods/design The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrolment. Discussion The primary objective of this study is to evaluate the feasibility and the toxicity profile of

  4. Inhibition of iridovirus protein synthesis and virus replication by antisense morpholino oligonucleotides targeted to the major capsid protein, the 18 kDa immediate-early protein, and a viral homolog of RNA polymerase II

    International Nuclear Information System (INIS)

    Sample, Robert; Bryan, Locke; Long, Scott; Majji, Sai; Hoskins, Glenn; Sinning, Allan; Olivier, Jake; Chinchar, V. Gregory

    2007-01-01

    Frog virus 3 (FV3) is a large DNA virus that encodes ∼ 100 proteins. Although the general features of FV3 replication are known, the specific roles that most viral proteins play in the virus life cycle have not yet been elucidated. To address the question of viral gene function, antisense morpholino oligonucleotides (asMOs) were used to transiently knock-down expression of specific viral genes and thus infer their role in virus replication. We designed asMOs directed against the major capsid protein (MCP), an 18 kDa immediate-early protein (18K) that was thought to be a viral regulatory protein, and the viral homologue of the largest subunit of RNA polymerase II (vPol-IIα). All three asMOs successfully inhibited translation of the targeted protein, and two of the three asMOs resulted in marked phenotypic changes. Knock-down of the MCP resulted in a marked reduction in viral titer without a corresponding drop in the synthesis of other late viral proteins. Transmission electron microscopy (TEM) showed that in cells treated with the anti-MCP MO assembly sites were devoid of viral particles and contained numerous aberrant structures. In contrast, inhibition of 18K synthesis did not block virion formation, suggesting that the 18K protein was not essential for replication of FV3 in fathead minnow (FHM) cells. Finally, consistent with the view that late viral gene expression is catalyzed by a virus-encoded or virus-modified Pol-II-like protein, knock-down of vPol-IIα triggered a global decline in late gene expression and virus yields without affecting the synthesis of early viral genes. Collectively, these results demonstrate the utility of using asMOs to elucidate the function of FV3 proteins

  5. Copper (II)

    African Journals Online (AJOL)

    CLEMENT O BEWAJI

    Valine (2 - amino - 3 – methylbutanoic acid), is a chemical compound containing .... Stability constant (Kf). Gibb's free energy. ) (. 1. −. ∆. Mol. JG. [CuL2(H2O)2] ... synthesis and characterization of Co(ii), Ni(ii), Cu (II), and Zn(ii) complexes with ...

  6. A Selective Surface-Enhanced Raman Scattering Sensor for Mercury(II) Based on a Porous Polymer Material and the Target-Mediated Displacement of a T-Rich Strand

    Science.gov (United States)

    Kang, Y.; Zhang, L.; Zhang, H.; Wu, T.; Du, Y.

    2017-05-01

    A sensitive and selective surface-enhanced Raman scattering (SERS) sensor for mercury(II) was fabricated based on the target-mediated displacement of a T-rich oligonucleotide strand. A DNA/aptamer duplex was prepared by the hybridization between a tetramethylrhodamine(TMR)-labeled thymine(T)-rich Hg2+-specific aptamer (denoted as TMR-aptamer) and a thiolated adenine-rich capturing DNA. The duplex can be immobilized onto the SERS substrate of the Ag-moiety modified glycidyl methacrylate-ethylene dimethacrylate (denoted as Ag-GMA-EDMA) via self-assembly by the thiol anchor, in which the TMR-aptamer exists in a double-stranded chain. In this case, the label of the TMR moiety approaches the substrate surface and produces a strong SERS signal. Upon the addition of the target, a pair of TMR-aptamers could cooperatively coordinate with Hg2+ to form a stable duplex-like structure mediated by the T-Hg2+-T complex between two adjacent strands, which triggers the release of the TMR-aptamer from the SERS substrate surface, thus drawing the TMR tags away from the substrate with a significant decrease in the SERS signal. This optical sensor shows a sensitive response to Hg2+ in a concentration from 5 nM to 2.0 μM with a detection limit of 2.5 nM. The prepared sensor is negligibly responsive to other metal ions, can be easily regenerated, and shows good performance in real sample analysis.

  7. Structural optimization of SadA, an Fe(II)- and α-ketoglutarate-dependent dioxygenase targeting biocatalytic synthesis of N-succinyl-L-threo-3,4-dimethoxyphenylserine.

    Science.gov (United States)

    Qin, Hui-Min; Miyakawa, Takuya; Nakamura, Akira; Hibi, Makoto; Ogawa, Jun; Tanokura, Masaru

    2014-08-08

    L-threo-3,4-Dihydroxyphenylserine (l-DOPS, Droxidopa) is a psychoactive drug and synthetic amino acid precursor that acts as a prodrug to the neurotransmitters. SadA, a dioxygenase from Burkholderia ambifaria AMMD, is an Fe(II)- and α-ketoglutarate (KG)-dependent enzyme that catalyzes N-substituted branched-chain or aromatic l-amino acids. SadA is able to produce N-succinyl-l-threo-3,4-dimethoxyphenylserine (NSDOPS), which is a precursor of l-DOPS, by catalyzing the hydroxylation of N-succinyl-3,4-dimethoxyphenylalanine (NSDOPA). However, the catalytic activity of SadA toward NSDOPS is much lower than that toward N-succinyl branched-chain l-amino acids. Here, we report an improved biocatalytic synthesis of NSDOPS with SadA. Structure-based protein engineering was applied to improve the α-KG turnover activity for the synthesis of NSDOPS. The G79A, G79A/F261W or G79A/F261R mutant showed a more than 6-fold increase in activity compared to that of the wild-type enzyme. The results provide a new insight into the substrate specificity toward NSDOPA and will be useful for the rational design of SadA mutants as a target of industrial biocatalysts. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Mu2e-II Injection from PIP-II

    Energy Technology Data Exchange (ETDEWEB)

    Neuffer, David [Fermilab

    2018-04-26

    We discuss injection of 800 MeV proton beam from PIP-II into the production target for Mu2e-II, assuming a targeting and μ production scenario similar to mu2e. The incoming beam trajectory must be modified from the mu2e parameters to match the focusing fields. Adding a vertical deflection at injection enables the injected beam to reach the target. Other differences from the mu2e system must be considered, including changes in the target structure, the radiation shielding and beam dump/absorber. H- beam should be stripped to p+. Other variations are discussed.

  9. Around the laboratories: Rutherford: Successful tests on bubble chamber target technique; Stanford (SLAC): New storage rings proposal; Berkeley: The HAPPE project to examine cosmic rays with superconducting magnets; The 60th birthday of Professor N.N. Bogolyubov; Argonne: Performance of the automatic film measuring system POLLY II

    CERN Multimedia

    1969-01-01

    Around the laboratories: Rutherford: Successful tests on bubble chamber target technique; Stanford (SLAC): New storage rings proposal; Berkeley: The HAPPE project to examine cosmic rays with superconducting magnets; The 60th birthday of Professor N.N. Bogolyubov; Argonne: Performance of the automatic film measuring system POLLY II

  10. Studies on the separation of {sup 89}Sr(II) from irradiated yttria target using 4, 4{sup '}(5{sup '}) di-tert-butyl-cyclohexano-18-crown-6 (DtBuCH18C6) by solvent extraction technique

    Energy Technology Data Exchange (ETDEWEB)

    Saha, Debasish; Vithya, Jayagopal; Kumar, Ramalingam; Venkata Subramani, Canchipuram Ramamoorthy; Vasudeva Rao, Polur Ranga [Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam (India). Chemistry Group

    2016-07-01

    The radioisotope {sup 89}Sr as {sup 89}SrCl{sub 2} is medically useful for bone pain palliation and is produced in fast reactors using the {sup 89}Y(n, p){sup 89}Sr reaction. A procedure for isolation of the radionuclide {sup 89}Sr by chemical processing of the irradiated Y{sub 2}O{sub 3} target has been standardised and trial runs have been carried out at the Fast Breeder Test Reactor (FBTR), Kalpakkam. The chemical processing of the irradiated Y{sub 2}O{sub 3} target involves (i) the removal of target Y(III) by TBP extraction and (ii) further purification of the separated {sup 89}Sr fraction by cationic exchange chromatography. However a selective isolation of {sup 89}Sr by the Sr-specific crown ether makes the above chemical processing faster and relatively simple. This work presents a study on the selective removal of Sr from the irradiated target dissolver solution using the Sr-specific crown ether 4,4{sup '}(5{sup '}) di-tert-butyl-cyclohexano-18-crown-6 (DtBuCH18C6) in octanol medium. The separation behaviour of the other impurities such as Ce(IV), Y(III), Tb(III), Eu(III), Zn(II), Mn(II) and Rb(I) present along with Sr(II) in the irradiated sample was also investigated. The method of separation by using the crown ether DtBuCH18C6 is proved to be a potential tool for the purification of {sup 89}Sr(II) source produced from yttria target in fast reactors.

  11. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  12. CERN: Fixed target targets

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1993-03-15

    Full text: While the immediate priority of CERN's research programme is to exploit to the full the world's largest accelerator, the LEP electron-positron collider and its concomitant LEP200 energy upgrade (January, page 1), CERN is also mindful of its long tradition of diversified research. Away from LEP and preparations for the LHC proton-proton collider to be built above LEP in the same 27-kilometre tunnel, CERN is also preparing for a new generation of heavy ion experiments using a new source, providing heavier ions (April 1992, page 8), with first physics expected next year. CERN's smallest accelerator, the LEAR Low Energy Antiproton Ring continues to cover a wide range of research topics, and saw a record number of hours of operation in 1992. The new ISOLDE on-line isotope separator was inaugurated last year (July, page 5) and physics is already underway. The remaining effort concentrates around fixed target experiments at the SPS synchrotron, which formed the main thrust of CERN's research during the late 1970s. With the SPS and LEAR now approaching middle age, their research future was extensively studied last year. Broadly, a vigorous SPS programme looks assured until at least the end of 1995. Decisions for the longer term future of the West Experimental Area of the SPS will have to take into account the heavy demand for test beams from work towards experiments at big colliders, both at CERN and elsewhere. The North Experimental Area is the scene of larger experiments with longer lead times. Several more years of LEAR exploitation are already in the pipeline, but for the longer term, the ambitious Superlear project for a superconducting ring (January 1992, page 7) did not catch on. Neutrino physics has a long tradition at CERN, and this continues with the preparations for two major projects, the Chorus and Nomad experiments (November 1991, page 7), to start next year in the West Area. Delicate neutrino oscillation effects could become visible for the first

  13. CERN: Fixed target targets

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    Full text: While the immediate priority of CERN's research programme is to exploit to the full the world's largest accelerator, the LEP electron-positron collider and its concomitant LEP200 energy upgrade (January, page 1), CERN is also mindful of its long tradition of diversified research. Away from LEP and preparations for the LHC proton-proton collider to be built above LEP in the same 27-kilometre tunnel, CERN is also preparing for a new generation of heavy ion experiments using a new source, providing heavier ions (April 1992, page 8), with first physics expected next year. CERN's smallest accelerator, the LEAR Low Energy Antiproton Ring continues to cover a wide range of research topics, and saw a record number of hours of operation in 1992. The new ISOLDE on-line isotope separator was inaugurated last year (July, page 5) and physics is already underway. The remaining effort concentrates around fixed target experiments at the SPS synchrotron, which formed the main thrust of CERN's research during the late 1970s. With the SPS and LEAR now approaching middle age, their research future was extensively studied last year. Broadly, a vigorous SPS programme looks assured until at least the end of 1995. Decisions for the longer term future of the West Experimental Area of the SPS will have to take into account the heavy demand for test beams from work towards experiments at big colliders, both at CERN and elsewhere. The North Experimental Area is the scene of larger experiments with longer lead times. Several more years of LEAR exploitation are already in the pipeline, but for the longer term, the ambitious Superlear project for a superconducting ring (January 1992, page 7) did not catch on. Neutrino physics has a long tradition at CERN, and this continues with the preparations for two major projects, the Chorus and Nomad experiments (November 1991, page 7), to start next year in the West Area. Delicate neutrino oscillation effects could become

  14. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    International Nuclear Information System (INIS)

    Green, Mark A.

    2000-01-01

    Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy

  15. Structured cylindrical targets

    International Nuclear Information System (INIS)

    Arnold, R.

    1986-01-01

    A variety of experimental concepts using high-energy heavy-ion beams in cylindrical targets have been studied through numerical simulation. With an accelerator planned for GSl, plasma temperatures of 100 eV can be reached by cylindrical compression, using inhomogeneous hollow-shell targets. Magnetic insulation, using external fields, has been explored as an aid in reaching high core temperatures. Experiments on collision-pumped x-ray laser physics are also discussed. (ii) Two-dimensional PlC code simulations of homogeneous solid targets show hydrodynamic effects not found in previous 1-D calculations. (iii) Preliminary ideas for an experiment on non-equilibrium heavy-ion charge-states using an existing accelerator and a pre-formed plasma target are outlined. (author)

  16. Structured cylindrical targets

    International Nuclear Information System (INIS)

    Arnold, R.; Lackner-Russo, D.; Meyer-ter-Vehn, J.; Hoffmann, I.

    1986-01-01

    A variety of experimental concepts using high-energy heavy-ion beams in cylindrical targets have been studied through numerical simulation. With an accelerator planned for GSl, plasma temperatures of 100 eV can be reached by cylindrical compression, using inhomogenous hollow-shell targets. Magnetic insulation, using external fields, has been explored as an aid in reaching high core temperatures. Experiments on collision-pumped x-ray laser physics are also discussed. (ii) Two-dimensional PlC code simulations of homogeneous solid targets show hydrodynamic effects not found in previous l-D calculations. (iii) Preliminary ideas for an experiment on non-equilibrium heavy-ion charge-states using an existing accelerator and a pre-formed plasma target are outlined. (author)

  17. Target laboratory

    International Nuclear Information System (INIS)

    Ephraim, D.C.; Pednekar, A.R.

    1993-01-01

    A target laboratory to make stripper foils for the accelerator and various targets for use in the experiments is set up in the pelletron accelerator facility. The facilities available in the laboratory are: (1) D.C. glow discharge setup, (2) carbon arc set up, and (3) vacuum evaporation set up (resistance heating), electron beam source, rolling mill - all for target preparation. They are described. Centrifugal deposition technique is used for target preparation. (author). 3 figs

  18. Ice targets

    International Nuclear Information System (INIS)

    Pacheco, C.; Stark, C.; Tanaka, N.; Hodgkins, D.; Barnhart, J.; Kosty, J.

    1979-12-01

    This report presents a description of ice targets that were constructed for research work at the High Resolution Spectrometer (HRS) and at the Energetic Pion Channel and Spectrometer (EPICS). Reasons for using these ice targets and the instructions for their construction are given. Results of research using ice targets will be published at a later date

  19. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  20. Solar photocatalytic removal of Cu(II), Ni(II), Zn(II) and Pb(II): Speciation modeling of metal-citric acid complexes

    International Nuclear Information System (INIS)

    Kabra, Kavita; Chaudhary, Rubina; Sawhney, R.L.

    2008-01-01

    The present study is targeted on solar photocatalytic removal of metal ions from wastewater. Photoreductive deposition and dark adsorption of metal ions Cu(II), Ni(II), Pb(II) and Zn(II), using solar energy irradiated TiO 2 , has been investigated. Citric acid has been used as a hole scavenger. Modeling of metal species has been performed and speciation is used as a tool for discussing the photodeposition trends. Ninety-seven percent reductive deposition was obtained for copper. The deposition values of other metals were significantly low [nickel (36.4%), zinc (22.2%) and lead (41.4%)], indicating that the photocatalytic treatment process, using solar energy, was more suitable for wastewater containing Cu(II) ions. In absence of citric acid, the decreasing order deposition was Cu(II) > Ni(II) > Pb(II) > Zn(II), which proves the theoretical thermodynamic predictions about the metals

  1. The SafeBoosC Phase II Randomised Clinical Trial : A Treatment Guideline for Targeted Near-Infrared-Derived Cerebral Tissue Oxygenation versus Standard Treatment in Extremely Preterm Infants

    NARCIS (Netherlands)

    Pellicer, Adelina; Greisen, Gorm; Benders, Manon; Claris, Olivier; Dempsey, Eugene; Fumagalli, Monica; Gluud, Christian; Hagmann, Cornelia; Hellstroem-Westas, Lena; Hyttel-Sorensen, Simon; Lemmers, Petra; Naulaers, Gunnar; Pichler, Gerhard; Roll, Claudia; van Bel, Frank; van Oeveren, Wim; Skoog, Maria; Wolf, Martin; Austin, Topun

    2013-01-01

    Near-infrared spectroscopy-derived regional tissue oxygen saturation of haemoglobin (rSto(2)) reflects venous oxygen saturation. If cerebral metabolism is stable, rSto(2) can be used as an estimate of cerebral oxygen delivery. The SafeBoosC phase II randomised clinical trial hypothesises that the

  2. Retrospective Audit: Does Prior Assessment by Oral and Maxillofacial Surgeons Reduce the Risk of Osteonecrosis of The Jaw in Patients Receiving Bone-Targeted Therapies for Metastatic Cancers to the Skeleton?--Part II.

    Science.gov (United States)

    Turner, Bruce; Ali, Sacha; Pati, Jhumur; Nargund, Vinod; Ali, Enamul; Cheng, Leo; Wells, Paula

    2016-01-01

    Men who receive bone-targeted therapy for metastatic prostate cancer are at increased risk of osteonecrosis of the jaw (ONJ). Development of ONJ has been associated with the administration of bone-targeted therapies in association with other risk factors. ONJ can be distressing for a patient because it can cause pain, risk of jaw fracture, body image disturbance, difficultly eating, and difficulty maintaining good oral hygiene. The aim of this article is to report results of an audit of prior assessment by oral and maxillofacial surgeons (OMFS) before initiation of bone-targeted therapies and whether it may reduce the risk of ONJ in patients receiving bone-targeted therapies for advanced cancers.

  3. TBscore II

    DEFF Research Database (Denmark)

    Rudolf, Frauke; Lemvik, Grethe; Abate, Ebba

    2013-01-01

    Abstract Background: The TBscore, based on simple signs and symptoms, was introduced to predict unsuccessful outcome in tuberculosis patients on treatment. A recent inter-observer variation study showed profound variation in some variables. Further, some variables depend on a physician assessing...... them, making the score less applicable. The aim of the present study was to simplify the TBscore. Methods: Inter-observer variation assessment and exploratory factor analysis were combined to develop a simplified score, the TBscore II. To validate TBscore II we assessed the association between start...

  4. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  5. Target preparation

    International Nuclear Information System (INIS)

    Hinn, G.M.

    1984-01-01

    A few of the more interesting of the 210 targets prepared in the Laboratory last year are listed. In addition the author continues to use powdered silver mixed with /sup 9,10/BeO to produce sources for accelerator radio dating of Alaskan and South Polar snow. Currently, he is trying to increase production by multiple sample processing. Also the author routinely makes 3 μg/cm 2 cracked slacked carbon stripper foils and is continuing research with some degree of success in making enriched 28 Si targets starting with the oxide

  6. Pb II

    African Journals Online (AJOL)

    Windows User

    This investigation describes the use of non-living biomass of Aspergillus caespitosus for removal of ... Pb(II) production has exceeded 3.5 million tons per year. It has been used in the ... This biomass was selected after screening a wide range of microbes. .... prolonged, which proved better biopolymer in metal uptake (Gadd ...

  7. RTNS-II: present status

    International Nuclear Information System (INIS)

    Heikkinen, D.W.; Logan, C.M.

    1980-10-01

    The present status of the RTNS-II facility is described and typical operating parameters are given. A brief discussion is given of the methods used in production of the TiT 2 targets as well as their performance and tritium handling at RTNS-II. The various types of non-interactive beam diagnostics presently in use at the neutron sources are outlined. The on-line computer system which provides a time history of an irradiation and records target performance is described. Examples are listed of several representative experimental programs which have been carried out thus far at RTNS-II. These include both active and passive experiments. Finally, several of the major improvements to the facility made since the beginning of the experimental program are given

  8. Small Diameter Bomb Increment II (SDB II)

    Science.gov (United States)

    2015-12-01

    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-439 Small Diameter Bomb Increment II (SDB II) As of FY 2017 President’s Budget Defense... Bomb Increment II (SDB II) DoD Component Air Force Joint Participants Department of the Navy Responsible Office References SAR Baseline (Production...Mission and Description Small Diameter Bomb Increment II (SDB II) is a joint interest United States Air Force (USAF) and Department of the Navy

  9. What is LAMPF II

    International Nuclear Information System (INIS)

    Thiessen, H.A.

    1982-08-01

    The present conception of LAMPF II is a high-intensity 16-GeV synchrotron injected by the LAMPF 800-MeV H - beam. The proton beam will be used to make secondary beams of neutrinos, muons, pions, kaons, antiprotons, and hyperons more intense than those of any existing or proposed accelerator. For example, by taking maximum advantage of a thick target, modern beam optics, and the LAMPF II proton beam, it will be possible to make a negative muon beam with nearly 100% duty factor and nearly 100 times the flux of the existing Stopped Muon Channel (SMC). Because the unique features of the proposed machine are most applicable to beams of the same momentum as LAMPF (that is, < 2 GeV/c), it may be possible to use most of the experimental areas and some of the auxiliary equipment, including spectrometers, with the new accelerator. The complete facility will provide improved technology for many areas of physics already available at LAMPF and will allow expansion of medium-energy physics to include kaons, antiprotons, and hyperons. When LAMPF II comes on line in 1990 LAMPF will have been operational for 18 years and a major upgrade such as this proposal will be reasonable and prudent

  10. What is LAMPF II

    Energy Technology Data Exchange (ETDEWEB)

    Thiessen, H.A.

    1982-08-01

    The present conception of LAMPF II is a high-intensity 16-GeV synchrotron injected by the LAMPF 800-MeV H/sup -/ beam. The proton beam will be used to make secondary beams of neutrinos, muons, pions, kaons, antiprotons, and hyperons more intense than those of any existing or proposed accelerator. For example, by taking maximum advantage of a thick target, modern beam optics, and the LAMPF II proton beam, it will be possible to make a negative muon beam with nearly 100% duty factor and nearly 100 times the flux of the existing Stopped Muon Channel (SMC). Because the unique features of the proposed machine are most applicable to beams of the same momentum as LAMPF (that is, < 2 GeV/c), it may be possible to use most of the experimental areas and some of the auxiliary equipment, including spectrometers, with the new accelerator. The complete facility will provide improved technology for many areas of physics already available at LAMPF and will allow expansion of medium-energy physics to include kaons, antiprotons, and hyperons. When LAMPF II comes on line in 1990 LAMPF will have been operational for 18 years and a major upgrade such as this proposal will be reasonable and prudent.

  11. Hypoxia targeting copper complexes

    International Nuclear Information System (INIS)

    Dearling, J.L.

    1998-11-01

    The importance and incidence of tumour hypoxia, its measurement and current treatments available, including pharmacological and radiopharmacological methods of targeting hypoxia, are discussed. A variety of in vitro and in vivo methods for imposing hypoxia have been developed and are reviewed. Copper, its chemistry, biochemistry and radiochemistry, the potential for use of copper radionuclides and its use to date in this field is considered with particular reference to the thiosemicarbazones. Their biological activity, metal chelation, in vitro and in vivo studies of their radiocopper complexes and the potential for their use as hypoxia targeting radiopharmaceuticals is described. The reduction of the copper(II) complex to copper(l), its pivotal importance in their biological behaviour, and the potential for manipulation of this to effect hypoxia selectivity are described. An in vitro method for assessing the hypoxia selectivity of radiopharmaceuticals is reported. The rapid deoxygenation and high viability of a mammalian cell culture in this system is discussed and factors which may affect the cellular uptake of a radiopharmaceutical are described. The design, synthesis and complexation with copper and radiocopper of a range of bis(thiosemicarbazones) is reported. Synthesis of these compounds is simple giving high yields of pure products. The characteristics of the radiocopper complexes ( 64 Cu) including lipophilicity and redox activity are reported (reduction potentials in the range -0.314 - -0.590 V). High cellular uptakes of the radiocopper complexes of the ligands, in hypoxic and normoxic EMT6 and CHO320 cells, were observed. Extremes of selectivity are shown ranging from the hypoxia selective 64 Cu(II)ATSM to normoxic cell selective 64 Cu(II)GTS. The selectivities observed are compared with the physico chemical characteristics of the complexes. A good correlation exists between selectivity of the complex and its Cu(II)/Cu(I) reduction potential, with hypoxia

  12. Novel GABA receptor pesticide targets.

    Science.gov (United States)

    Casida, John E; Durkin, Kathleen A

    2015-06-01

    The γ-aminobutyric acid (GABA) receptor has four distinct but overlapping and coupled targets of pesticide action importantly associated with little or no cross-resistance. The target sites are differentiated by binding assays with specific radioligands, resistant strains, site-directed mutagenesis and molecular modeling. Three of the targets are for non-competitive antagonists (NCAs) or channel blockers of widely varied chemotypes. The target of the first generation (20th century) NCAs differs between the larger or elongated compounds (NCA-IA) including many important insecticides of the past (cyclodienes and polychlorocycloalkanes) or present (fiproles) and the smaller or compact compounds (NCA-IB) highly toxic to mammals and known as cage convulsants, rodenticides or chemical threat agents. The target of greatest current interest is designated NCA-II for the second generation (21st century) of NCAs consisting for now of isoxazolines and meta-diamides. This new and uniquely different NCA-II site apparently differs enough between insects and mammals to confer selective toxicity. The fourth target is the avermectin site (AVE) for allosteric modulators of the chloride channel. NCA pesticides vary in molecular surface area and solvent accessible volume relative to avermectin with NCA-IBs at 20-22%, NCA-IAs at 40-45% and NCA-IIs at 57-60%. The same type of relationship relative to ligand-docked length is 27-43% for NCA-IBs, 63-71% for NCA-IAs and 85-105% for NCA-IIs. The four targets are compared by molecular modeling for the Drosophila melanogaster GABA-R. The principal sites of interaction are proposed to be: pore V1' and A2' for NCA-IB compounds; pore A2', L6' and T9' for NCA-IA compounds; pore T9' to S15' in proximity to M1/M3 subunit interface (or alternatively an interstitial site) for NCA-II compounds; and M1/M3, M2 interfaces for AVE. Understanding the relationships of these four binding sites is important in resistance management and in the discovery and use

  13. Tomo II

    OpenAIRE

    Llano Zapata, José Eusebio

    2015-01-01

    Memorias, histórico, físicas, crítico, apologéticas de la América Meridional con unas breves advertencias y noticias útiles, a los que de orden de Su Majestad hubiesen de viajar y describir aquellas vastas regiones. Reino Vegetal, Tomo II. Por un anónimo americano en Cádiz por los años de 1757. Muy Señor mío, juzgo que los 20 artículos del libro que remití a Vuestra Merced le habrán hecho formar el concepto que merece la fecundidad de aquellos países en las producciones minerales. Y siendo es...

  14. Synthesis and characterization of Cu(II)-based anticancer chemotherapeutic agent targeting topoisomerase Iα: in vitro DNA binding, pBR322 cleavage, molecular docking studies and cytotoxicity against human cancer cell lines.

    Science.gov (United States)

    Tabassum, Sartaj; Zaki, Mehvash; Afzal, Mohd; Arjmand, Farukh

    2014-03-03

    New metal-based anticancer chemotherapeutic drug candidates [Cu(phen)L](NO₃)₂ (1) and [Zn(phen)L](NO₃)₂ (2) were synthesized from ligand L (derived from pharmacophore scaffold barbituric acid and pyrazole). In vitro DNA binding studies of the L, 1 and 2 were carried out by various biophysical techniques revealing electrostatic mode. Complex 1 cleaves pBR322 DNA via oxidative pathway and recognizes major groove of DNA double helix. The molecular docking study was carried out to ascertain the mode of action towards the molecular target DNA and enzymes. The complex 1 exhibited remarkably good anticancer activity on a panel of human cancer cell lines (GI₅₀ values < 10 μg/ml), and to elucidate the mechanism of cancer inhibition, Topo-I enzymatic activity was carried out. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. 9th International Symposium on the Biosafety of Genetically Modified Organisms. Session II: Identifying and defining hazards and potential consequences I: Concepts for problem formulation and non-target risk assessment.

    Science.gov (United States)

    Bigler, Franz

    2006-01-01

    The scientific organizers of the symposium put much emphasis on the identification and definition of hazard and the potential consequences thereof and three full sessions with a total of 13 presentations encompassing a wide range of related themes were planned for this topic. Unfortunately, one talk had to be cancelled because of illness of the speaker (BM Khadi, India). Some presentations covered conceptual approaches for environmental risk assessment (ERA) of GM plants (problem formulation in the risk assessment framework, familiarity approach, tiered and methodological frameworks, non-target risk assessment) and the use of models in assessing invasiveness and weediness of GM plants. Other presentations highlighted the lessons learned for future ERA from case studies and commercialized GM crops, and from monitoring of unintended releases to the environment. When the moderators of the three sessions came together after the presentations to align their summaries, there was an obvious need to restructure the 12 presentations in a way that allowed for a consistent summarizing discussion. The following new organization of the 12 talks was chosen: (1) Concepts for problem formulation and non-target risk assessment, (2) Modeling as a tool for predicting invasiveness of GM plants, (3) Case-studies of ERA of large-scale release, (4) Lessons learned for ERA from a commercialized GM plant, (5) Monitoring of unintended release of Bt maize in Mexico. The new thematic structure facilitates a more in-depth discussion of the presentations related to a specific topic, and the conclusions to be drawn are thus more consistent. Each moderator agreed to take responsibility for summarizing one or more themes and to prepare the respective report.

  16. Cd(II), Cu(II)

    African Journals Online (AJOL)

    user

    Depending on the way goethite was pretreated with oxalic acid, affinity for Cd(II) varied ...... Effects and mechanisms of oxalate on Cd(II) adsorption on goethite at different ... precipitation, surfactant mediation, hydrothermal and micro-emulsion.

  17. Cu(II) AND Zn(II)

    African Journals Online (AJOL)

    Preferred Customer

    SYNTHESIS OF 2,2-DIMETHYL-4-PHENYL-[1,3]-DIOXOLANE USING ZEOLITE. ENCAPSULATED Co(II), Cu(II) AND Zn(II) COMPLEXES. B.P. Nethravathi1, K. Rama Krishna Reddy2 and K.N. Mahendra1*. 1Department of Chemistry, Bangalore University, Bangalore-560001, India. 2Department of Chemistry, Government ...

  18. Elizabeth II uus kunstigalerii

    Index Scriptorium Estoniae

    1999-01-01

    Tähistamaks oma troonile asumise 50. aastapäeva, avab Elizabeth II 6. II 2002 Buckinghami palees uue kunstigalerii, mis ehitatakse palee tiibhoonena. Arhitekt John Simpson. Elizabeth II kunstikogust

  19. A Phase II Trial of SABR (Stereotactic Ablative Body Radiotherapy for Low-Risk Prostate Cancer Using a Non-Robotic Linear Accelerator and Real-Time Target Tracking: Report of Toxicity, Quality of Life and Disease Control Outcomes with 5-Year Minimum Followup

    Directory of Open Access Journals (Sweden)

    Constantine Anastasios Mantz

    2014-11-01

    Full Text Available Purpose/Objective(s: Herein, we report the results of an IRB-approved phase II trial of Varian Trilogy/TrueBeam-based SABR monotherapy for low-risk prostate cancer using the Calypso® System to provide real-time electromagnetic tracking of the prostate’s position during treatment delivery. Materials/Methods: A total of 102 low-risk patients completed protocol treatment between January 2007 and May 2009. A total dose of 40.0 Gy in 5 every-other-day fractions of 8.0 Gy was prescribed to the planning target volume. Target setup and tracking procedures were as follows: (1 the Calypso® System was used to achieve target setup prior to each fraction; (2 conebeam CT imaging was then used for correction of setup error and for assessment of target and Organs-at-Risk (OAR deformations; (3 after treatment delivery was initiated, the Calypso® System then provided real-time intrafractional target tracking. The NCI CTCAE v3.0 was used to assess urinary and rectal toxicity during treatment and at defined followup time points. Biochemical response and quality of life measurements were made at concurrent followup points.Results: Urinary toxicities were most common. At 6 months, 19.6%, 2.9% and 4.9% of patients reported grades 1 – 2 urinary frequency, dysuria and retention, respectively. Rectal toxicities were uncommon. By 12 months, 2.9% of patients reported painless rectal bleeding with subsequent symptom resolution without requiring invasive interventions. Quality of life measurements demonstrated a significant decline over baseline in urinary irritative/obstructive scores at 1 month following SABR but otherwise did not demonstrate any difference for bowel, bladder and sexual function scores at any other followup time point. One patient suffered biochemical recurrence at 6 years following SABR.Conclusions: At five years minimum followup for this favorable patient cohort, prostate SABR resulted in favorable toxicity, quality of life and biochemical

  20. BEPC II positron source

    International Nuclear Information System (INIS)

    Pei Guoxi; Sun Yaolin; Liu Jintong; Chi Yunlong; Liu Yucheng; Liu Nianzong

    2006-01-01

    BEPC II-an upgrade project of the Beijing Electron Positron Collider (BEPC) is a factory type of e + e - collider. The fundamental requirements for its injector linac are the beam energy of 1.89 GeV for on-energy injection and a 40 mA positron beam current at the linac end with a low beam emittance of 1.6 μm and a low energy spread of ±0.5% so as to guarantee a higher injection rate (≥50 mA/min) to the storage ring. Since the positron flux is proportional to the primary electron beam power on the target, the authors will increase the electron gun current from 4A to 10A by using a new electron gun system and increase the primary electron energy from 120 MeV to 240 MeV. The positron source itself is an extremely important system for producing more positrons, including a positron converter target chamber, a 12kA flux modulator, the 7m focusing module with DC power supplies and the support. The new positron production linac from the electron gun to the positron source has been installed into the tunnel. In what follows, the authors will emphasize the positron source design, manufacture and tests. (authors)

  1. Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II ...

    Indian Academy of Sciences (India)

    Unknown

    Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II) Schiff base complexes derived from o-phenylenediamine and acetoacetanilide. N RAMAN*, Y PITCHAIKANI RAJA and A KULANDAISAMY. Department of Chemistry, VHNSN College, Virudhunagar 626 001, India e-mail: ra_man@123india.com.

  2. International cooperation at RTNS-II

    International Nuclear Information System (INIS)

    Logan, C.M.

    1984-02-01

    The Rotating Target Neutron Source-II (RTNS-II) facility at LLNL is a unique materials-test facility. It provides the most intense source of 14-MeV neutrons in the world. Dedicated operation in support of the fusion-materials-research community began in early 1979. Three years later, the Japanese Ministry of Education, Science, and Culture (Monbusho) and the US Department of Energy agreed to jointly support the RTNS-II operation and to share in the use of the facility

  3. Heavy-ion targets

    International Nuclear Information System (INIS)

    Adair, H.L.; Kobisk, E.H.

    1985-01-01

    This chapter examines the characteristics of targets required in heavy-ion accelerator physics experiments. The effects of target parameters on heavy-ion experimental results are reviewed. The target fabrication and characterization techniques used to minimize experimental problems during heavy-ion bombardment are described. Topics considered include target thickness and uniformity, target lifetime, target purity, substrate materials, Doppler shift effects, metal preparations, and target preparation methods

  4. Bi-Spectral Method for Radar Target Recognition

    National Research Council Canada - National Science Library

    Yeo, Jiunn W

    2006-01-01

    .... Since World War II, the Identification of Friend or Foe (IFF) systems installed in radar systems have served as the primary cooperative target identification techniques based on the "question and answer" interrogation loop of unidentified aircraft...

  5. Stress calculations for RTNS-iI 50-cm targets

    International Nuclear Information System (INIS)

    Schumacher, B.J.; House, P.A.

    1981-04-01

    Structural calculations made during design of a 50-cm target for the Rotating Target Neutron Source (RTNS-II) are detailed. The limited ability of the current 23-cm diameter target to dissipate the additional beam power required for a yield increase from 2 x 10 13 to 4 x 10 13 neutrons/second has resulted in the need for a larger target. The stresses of several design configurations for a 50-cm target were calculated. The stress contours that would occur in several different target designs with and without various types of structural reinforcement that reduce stress and deflection are presented

  6. Spectroscopy of gluonic states at LAMPF II

    International Nuclear Information System (INIS)

    Chanowitz, M.S.

    1983-08-01

    The properties of QCD which imply the existence of gluonic states are reviewed. The problem of discovering the spectrum of gluonic states is discussed in general and illustrated with examples from current data. Higher statistics fixed target experiments, such as could be performed at LAMPF II, are essential for further progress

  7. (II) COMPLEX COMPOUND

    African Journals Online (AJOL)

    user

    electrochemical sensors, as well as in various chromatographic ... were carried out using Jenway pH meter Model 3320 and a conductivity ... Figure 1: the proposed molecular structure of the copper (II) Schiff base complex. M = Cu (II) or Mn (II).

  8. and copper(II)

    Indian Academy of Sciences (India)

    Unknown

    (II) and copper(II)–zinc(II) complexes. SUBODH KUMAR1, R N PATEL1*, P V KHADIKAR1 and. K B PANDEYA2. 1 Department of Chemistry, APS University, Rewa 486 003, India. 2 CSJM University, Kanpur 208 016, India e-mail: (R N Patel) ...

  9. LipidII : Just Another Brick in the Wall?

    NARCIS (Netherlands)

    Scheffers, Dirk-Jan; Tol, Menno B

    2015-01-01

    Nearly all bacteria contain a peptidoglycan cell wall. The peptidoglycan precursor molecule is LipidII, containing the basic peptidoglycan building block attached to a lipid. Although the suitability of LipidII as an antibacterial target has long been recognized, progress on elucidating the role(s)

  10. Organelle targeting: third level of drug targeting

    Directory of Open Access Journals (Sweden)

    Sakhrani NM

    2013-07-01

    Full Text Available Niraj M Sakhrani, Harish PadhDepartment of Cell and Molecular Biology, BV Patel Pharmaceutical Education and Research Development (PERD Centre, Gujarat, IndiaAbstract: Drug discovery and drug delivery are two main aspects for treatment of a variety of disorders. However, the real bottleneck associated with systemic drug administration is the lack of target-specific affinity toward a pathological site, resulting in systemic toxicity and innumerable other side effects as well as higher dosage requirement for efficacy. An attractive strategy to increase the therapeutic index of a drug is to specifically deliver the therapeutic molecule in its active form, not only into target tissue, nor even to target cells, but more importantly, into the targeted organelle, ie, to its intracellular therapeutic active site. This would ensure improved efficacy and minimize toxicity. Cancer chemotherapy today faces the major challenge of delivering chemotherapeutic drugs exclusively to tumor cells, while sparing normal proliferating cells. Nanoparticles play a crucial role by acting as a vehicle for delivery of drugs to target sites inside tumor cells. In this review, we spotlight active and passive targeting, followed by discussion of the importance of targeting to specific cell organelles and the potential role of cell-penetrating peptides. Finally, the discussion will address the strategies for drug/DNA targeting to lysosomes, mitochondria, nuclei and Golgi/endoplasmic reticulum.Keywords: intracellular drug delivery, cancer chemotherapy, therapeutic index, cell penetrating peptides

  11. Pius II. a utrakvismus

    OpenAIRE

    Šimek, Milan

    2009-01-01

    Milan Šimek Pius II. a utrakvismus Pius II. and utraquism Based on sources work - out, the thesis aims the description and analysis of the attitude alternation of Enea Sylvio Piccolomini - Pius II to the utraquism. The conclusions stress the postulate that Pius II. did not change that attitude, but just did not succed in quelling the utraquist movement. In the sense of political background that finally led to fatal dissention among both leaders, king Jiří of Poděbrady and pope Pius II.

  12. Complexes of cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II) and dioxouranium(II) with thiophene-2-aldehydethiosemicarbazone

    International Nuclear Information System (INIS)

    Singh, Balwan; Misra, Harihar

    1986-01-01

    Metal complexes of thiosemicarbazides have been known for their pharmacological applications. Significant antitubercular, fungicidal and antiviral activities have been reported for thiosemicarbazides and their derivatives. The present study describes the systhesis and characterisation of complexes of Co II , Cu II , Zn II ,Cd II and UO II with thiosemicarbazone obtained by condensing thiophene-2-aldehyde with thiosemicarbazide. 17 refs., 2 tables. (author)

  13. 48 CFR 16.403-2 - Fixed-price incentive (successive targets) contracts.

    Science.gov (United States)

    2010-10-01

    ... target cost plus the firm target profit as a guide. (ii) If negotiation of a firm fixed price is... pricing information is not sufficient to permit the negotiation of a realistic firm target cost and profit...; and (2) Cost or pricing information adequate for establishing a reasonable firm target cost is...

  14. CRISPRTarget: bioinformatic prediction and analysis of crRNA targets

    NARCIS (Netherlands)

    Biswas, A.; Gagnon, J.N.; Brouns, S.J.J.; Fineran, P.C.; Brown, C.M.

    2013-01-01

    The bacterial and archaeal CRISPR/Cas adaptive immune system targets specific protospacer nucleotide sequences in invading organisms. This requires base pairing between processed CRISPR RNA and the target protospacer. For type I and II CRISPR/Cas systems, protospacer adjacent motifs (PAM) are

  15. 42 CFR 457.310 - Targeted low-income child.

    Science.gov (United States)

    2010-10-01

    ... family income at or below 200 percent of the Federal poverty line for a family of the size involved; (ii... 42 Public Health 4 2010-10-01 2010-10-01 false Targeted low-income child. 457.310 Section 457.310... Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

  16. Deuterium pass through target

    International Nuclear Information System (INIS)

    Alger, D.L.

    1975-01-01

    A neutron emitting target is described for use in neutron generating apparatus including a deuteron source and an accelerator vacuum chamber. The target consists of a tritium-containing target layer, a deuteron accumulation layer, and a target support containing passages providing communication between the accumulation layer and portions of the surface of the support exposed to the accelerator vacuum chamber. With this arrangement, deuterons passing through the target layer and implanting in and diffusing through the accumulation layer, diffuse into the communicating passages and are returned to the accelerator vacuum chamber. The invention allows the continuous removal of deuterons from the target in conventional water cooled neutron generating apparatus. Preferably, the target is provided with thin barrier layers to prevent undesirable tritium diffusion out of the target layer, as well as deuteron diffusion into the target layer

  17. Correlation of mechanical property changes in neutron-irradiated pressure vessel steels on the basis of spectral effects

    International Nuclear Information System (INIS)

    Heinisch, H.L.

    1991-01-01

    Comparisons are made of tensile data on specimens of A212B and A302B pressure vessel steels irradiated at low temperatures (40-90degC) and to low doses (<0.1 dpa) with 14 MeV D-T fusion neutrons in the Rotating Target Neutron Source (RTNS-II), with fission reactor neutrons in the Omega West Reactor (OWR) and the Oak Ridge Research Reactor (ORR), and with the highly thermal spectrum at the pressure vessel surveillance positions of the High Flux Isotope Reactor (HFIR). For each neutron spectrum, damage cross sections are determined for several defect production functions derived from atomistic computer simulations of collision cascades. Displacements per atom (dpa) and the numbers of freely migrating defects are tested as damage correlation parameters for the tensile data. The data from RTNS-II, OWR and ORR correlate fairly well when compared on the basis of dpa, but the data from HFIR show only about one sixth as many dpa are needed to produce the same radiation-induced yield stress changes as in the other neutron spectra. In the HFIR surveillance position a significant fraction of the displacements is produced by recoils resulting from thermal neutron captures. Having energies of about 400 eV, these recoils are much more efficient per unit energy at producing freely migrating defects than the high energy recoils responsible for most of the displacements in the other neutron spectra considered. A significantly better correlation of data from HFIR with those from the other spectra is achieved when the property changes are compared on the basis of the production of freely migrating self-interstitial defects. (orig./MM)

  18. Molecular Targets for Targeted Radionuclide Therapy

    International Nuclear Information System (INIS)

    Mather, S.J.

    2009-01-01

    Molecular targeted radionuclide cancer therapy is becoming of increasing importance, especially for disseminated diseases. Systemic chemotherapies often lack selectivity while targeted radionuclide therapy has important advantages as the radioactive cytotoxic unit of the targeting vector is specifically directed to the cancer, sparing normal tissues. The principle strategy to improve cancer selectivity is to couple therapeutic agents to tumour-targeting vectors. In targeted radionuclide therapy (TRT), the cytotoxic portion of the conjugates normally contains a therapeutic radiometal immobilised by a bifunctional chelator. The aim is therefore to use as ligand-targeted therapeutics vectors coupled to Auger-, alpha- and/or beta-emitting radionuclides. An advantage of using radiation instead of chemotherapeutics as the cytotoxic agent is the so called 'crossfire effect'. This allows sterilisation of tumour cells that are not directly targeted due to heterogeneity in target molecule expression or inhomogeneous vector delivery. However, before the targeting ligands can be selected, the target molecule on the tumour has to be selected. It should be uniquely expressed, or at least highly overexpressed, on or in the target cells relative to normal tissues. The target should be easily accessible for ligand delivery and should not be shed or down- regulated after ligand binding. An important property of a receptor (or antigen) is its potential to be internalized upon binding of the ligand. This provides an active uptake mechanism and allows the therapeutic agent to be trapped within the tumour cells. Molecular targets of current interest include: Receptors: G-protein coupled receptors are overexpressed on many major human tumours. The prototype of these receptors are somatostatin receptors which show very high density in neuroendocrine tumours, but there are many other most interesting receptors to be applied for TRT. The targeting ligands for these receptors are

  19. Fixed Target Collisions at STAR

    Energy Technology Data Exchange (ETDEWEB)

    Meehan, Kathryn C.

    2016-12-15

    The RHIC Beam Energy Scan (BES) program was proposed to look for the turn-off of signatures of the quark gluon plasma (QGP), search for a possible QCD critical point, and study the nature of the phase transition between hadronic and partonic matter. Previous results have been used to claim that the onset of deconfinement occurs at a center-of-mass energy of 7 GeV. Data from lower energies are needed to test if this onset occurs. The goal of the STAR Fixed-Target Program is to extend the collision energy range in BES II to energies that are likely below the onset of deconfinement. Currently, STAR has inserted a gold target into the beam pipe and conducted test runs at center-of-mass energies of 3.9 and 4.5 GeV. Tests have been done with both Au and Al beams. First physics results from a Coulomb potential analysis of Au + Au fixed-target collisions are presented and are found to be consistent with results from previous experiments. Furthermore, the Coulomb potential, which is sensitive to the Z of the projectile and degree of baryonic stopping, will be compared to published results from the AGS.

  20. Targeting the Brain with Nanomedicine.

    Science.gov (United States)

    Rueda, Felix; Cruz, Luis J

    2017-01-01

    Herein, we review innovative nanomedicine-based approaches for treating, preventing and diagnosing neurodegenerative diseases. We focus on nanoscale systems such as polymeric nanoparticles (NPs), liposomes, micelles and other vehicles (e.g. dendrimers, nanogels, nanoemulsions and nanosuspensions) for targeted delivery of bioactive molecules to the brain. To ensure maximum selectivity for optimal therapeutic or diagnostic results, researchers must employ delivery systems that are non-toxic, biodegradable and biocompatible. This entails: (i) use of "safe" materials, such as polymers or lipids; (ii) targeting to the brain and, specifically, to the desired active site within the brain; (iii) controlled release of the loaded agent; and (iv) use of agents that, once released into the brain, will exhibit the desired pharmacologic activity. Here, we explore the design and preclinical use of representative delivery systems that have been proposed to date. We then analyze the principal challenges that have delayed clinical application of these and other approaches. Lastly, we look at future developments in this area, addressing the needs for increased penetration of the blood brain barrier (BBB), enhanced targeting of specific brain sites, improved therapeutic efficacy and lower neurotoxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Irradiation performance of HTGR fuel in HFIR capsule HT-31

    International Nuclear Information System (INIS)

    Tiegs, T.N.; Robbins, J.M.; Hamner, R.L.; Montgomery, B.H.; Kania, M.J.; Lindemer, T.B.; Morgan, C.S.

    1979-05-01

    The capsule was irradiated in the High Flux Isotope Reactor at ORNL to peak particle temperatures up to 1600 0 C, fast neutron fluences (0.18 MeV) up to 9 x 10 25 n/m 2 , and burnups up to 8.9% FIMA for ThO 2 particles. The oxygen release from plutonium fissions was less than calculated, possibly because of the solid solution of SrO and rare earth oxides in UO 2 . Tentative results show that pyrocarbon permeability decreases with increasing fast neutron fluence. Fission products in sol-gel UO 2 particles containing natural uranium mostly behaved similarly to those in particles containing highly enriched uranium (HEU). Thus, much of the data base collected on HEU fuel can be applied to low-enriched fuel. Fission product palladium penetrated into the SiC on Triso-coated particles. Also the SiC coating provided some retention of /sup 110m/Ag. Irradiation above about 1200 0 C without an outer pyrocarbon coating degraded the SiC coating on Triso-coated particles

  2. Acoustic emission monitoring of HFIR vessel during hydrostatic testing

    International Nuclear Information System (INIS)

    Friesel, M.A.; Dawson, J.F.

    1992-08-01

    This report discusses the results and conclusions reached from applying acoustic emission monitoring to surveillance of the High Flux Isotope Reactor vessel during pressure testing. The objective of the monitoring was to detect crack growth and/or fluid leakage should it occur during the pressure test. The report addresses the approach, acoustic emission instrumentation, installation, calibration, and test results

  3. Performance of HTGR fuel in HFIR capsule HT-33

    International Nuclear Information System (INIS)

    Tiegs, T.N.; Robbins, J.M.

    1979-06-01

    Irradiation capsule HT-33 was a cooperative effort between General Atomic Company (GA) and Oak Ridge National Laboratory (ORNL). In this capsule ThO 2 particles (fabricated by GA), low-enriched uranium particles, inert carbon particles, and various fuel rod matrices were tested under accelerated irradiation in the High-Flux Isotope Reactor. Visual examination showed good irradiation behavior for fuel rods with slug-injected matrices (using a pitch binder) and warm-molded matrices (using a thermosetting resin binder). Rod debonding improved somewhat with fuel rods that used GLCC H-451 ground graphite shim particles rather than Speer fluid coke shim particles. Measurements of permeability (by inert gas intrusion) of the pyrocarbon on the inert particles showed that the disorder created by the neutron flux did not increase the inert gas permeability. Metallographic examination of Triso-coated particles irradiated both with and without an outer pyrocarbon coating revealed that the outer coating is necessary to suppress SiC degradation at temperatures above approximately 1375 0 C. The fission product behavior (determined by the electron microprobe) was similar in both low-enriched and high-enriched uranium particles made from weak-acid resins. Furthermore, fission product palladium caused severe SiC corrosion at time-averaged temperatures above 1400 0 C

  4. The SNS/HFIR Web Portal System for SANS

    International Nuclear Information System (INIS)

    Campbell, Stuart I; Miller, Stephen D; Bilheux, Jean-Christophe; Reuter, Michael A; Peterson, Peter F; Kohl, James A; Trater, James R; Vazhkudai, Sudharshan S; Lynch, Vickie E; Green, Mark L

    2010-01-01

    The new generation of neutron scattering instruments being built are higher resolution and produce one or more orders of magnitude larger data than the previous generation of instruments. For instance, we have grown out of being able to perform some important tasks with our laptops. The data sizes are too big and the computational time would be too long. These large datasets can be problematic as facility users now begin to struggle with many of the same issues faced by more established computing communities. These issues include data access, management, and movement, data format standards, distributed computing, and collaboration with others. The Neutron Science Portal has been designed, and implemented to provide users with an easy-to-use interface for managing and processing data, while also keeping an eye on meeting modern computer security requirements that are currently being imposed on institutions. Users can browse or search for data which they are allowed to see, run data reduction and analysis applications, perform sample activation calculations and perform McStas simulations. Collaboration is facilitated by providing users a read/writeable common area, shared across all experiment team members. The portal currently has over 370 registered users; almost 7TB of experiment and user data, approximately 1,000,000 files cataloged, and had almost 10,000 unique visits last year. Future directions for enhancing portal robustness include examining how to mirror data and portal services, better facilitation of collaborations via virtual organizations, enhancing disconnected service via 'thick client' applications, and better inter-facility connectivity to support cross-cutting research.

  5. HFIR cold neutron source moderator vessel design analysis

    International Nuclear Information System (INIS)

    Chang, S.J.

    1998-04-01

    A cold neutron source capsule made of aluminum alloy is to be installed and located at the tip of one of the neutron beam tubes of the High Flux Isotope Reactor. Cold hydrogen liquid of temperature approximately 20 degree Kelvin and 15 bars pressure is designed to flow through the aluminum capsule that serves to chill and to moderate the incoming neutrons produced from the reactor core. The cold and low energy neutrons thus produced will be used as cold neutron sources for the diffraction experiments. The structural design calculation for the aluminum capsule is reported in this paper

  6. Monitoring production target thickness

    International Nuclear Information System (INIS)

    Oothoudt, M.A.

    1993-01-01

    Pion and muon production targets at the Clinton P. Anderson Meson Physics Facility consist of rotating graphite wheels. The previous target thickness monitoring Procedure scanned the target across a reduced intensity beam to determine beam center. The fractional loss in current across the centered target gave a measure of target thickness. This procedure, however, required interruption of beam delivery to experiments and frequently indicated a different fractional loss than at normal beam currents. The new monitoring Procedure compares integrated ups and downs toroid current monitor readings. The current monitors are read once per minute and the integral of readings are logged once per eight-hour shift. Changes in the upstream to downstream fractional difference provide a nonintrusive continuous measurement of target thickness under nominal operational conditions. Target scans are now done only when new targets are installed or when unexplained changes in the current monitor data are observed

  7. Quininium tetrachloridozinc(II

    Directory of Open Access Journals (Sweden)

    Li-Zhuang Chen

    2009-10-01

    Full Text Available The asymmetric unit of the title compound {systematic name: 2-[hydroxy(6-methoxyquinolin-1-ium-4-ylmethyl]-8-vinylquinuclidin-1-ium tetrachloridozinc(II}, (C20H26N2O2[ZnCl4], consists of a double protonated quininium cation and a tetrachloridozinc(II anion. The ZnII ion is in a slightly distorted tetrahedral coordination environment. The crystal structure is stabilized by intermolecular N—H...Cl and O—H...Cl hydrogen bonds.

  8. Burkina Faso - BRIGHT II

    Data.gov (United States)

    Millennium Challenge Corporation — Millennium Challenge Corporation hired Mathematica Policy Research to conduct an independent evaluation of the BRIGHT II program. The three main research questions...

  9. Charged particle fusion targets

    International Nuclear Information System (INIS)

    Bangerter, R.O.; Meeker, D.J.

    1977-01-01

    The power, voltage, energy and other requirements of electron and ion beam fusion targets are reviewed. Single shell, multiple shell and magnetically insulated target designs are discussed. Questions of stability are also considered. In particular, it is shown that ion beam targets are stabilized by an energy spread in the ion beam

  10. Liquid helium target

    International Nuclear Information System (INIS)

    Fujii, Y.; Kitami, T.; Torikoshi, M.

    1984-12-01

    A liquid helium target system has been built and used for the experiment on the reaction 4 He(γ, p). The target system has worked satisfactorily; the consumption rate of liquid helium is 360 ml/h and the cryogenic system retains liquid helium for about ten hours. The structure, operation and performance of the target system are reported. (author)

  11. Graphite targets at LAMPF

    International Nuclear Information System (INIS)

    Brown, R.D.; Grisham, D.L.

    1983-01-01

    Rotating polycrystalline and stationary pyrolytic graphite target designs for the LAMPF experimental area are described. Examples of finite element calculations of temperatures and stresses are presented. Some results of a metallographic investigation of irradiated pyrolytic graphite target plates are included, together with a brief description of high temperature bearings for the rotating targets

  12. Wake Shield Target Protection

    International Nuclear Information System (INIS)

    Valmianski, Emanuil I.; Petzoldt, Ronald W.; Alexander, Neil B.

    2003-01-01

    The heat flux from both gas convection and chamber radiation on a direct drive target must be limited to avoid target damage from excessive D-T temperature increase. One of the possibilities of protecting the target is a wake shield flying in front of the target. A shield will also reduce drag force on the target, thereby facilitating target tracking and position prediction. A Direct Simulation Monte Carlo (DSMC) code was used to calculate convection heat loads as boundary conditions input into ANSYS thermal calculations. These were used for studying the quality of target protection depending on various shapes of shields, target-shield distance, and protective properties of the shield moving relative to the target. The results show that the shield can reduce the convective heat flux by a factor of 2 to 5 depending on pressure, temperature, and velocity. The protective effect of a shield moving relative to the target is greater than the protective properties of a fixed shield. However, the protective effect of a shield moving under the drag force is not sufficient for bringing the heat load on the target down to the necessary limit. Some other ways of diminishing heat flux using a protective shield are discussed

  13. Development of distributed target

    CERN Document Server

    Yu Hai Jun; Li Qin; Zhou Fu Xin; Shi Jin Shui; Ma Bing; Chen Nan; Jing Xiao Bing

    2002-01-01

    Linear introduction accelerator is expected to generate small diameter X-ray spots with high intensity. The interaction of the electron beam with plasmas generated at the X-ray converter will make the spot on target increase with time and debase the X-ray dose and the imaging resolving power. A distributed target is developed which has about 24 pieces of thin 0.05 mm tantalum films distributed over 1 cm. due to the structure adoption, the distributed target material over a large volume decreases the energy deposition per unit volume and hence reduces the temperature of target surface, then reduces the initial plasma formalizing and its expansion velocity. The comparison and analysis with two kinds of target structures are presented using numerical calculation and experiments, the results show the X-ray dose and normalized angle distribution of the two is basically the same, while the surface of the distributed target is not destroyed like the previous block target

  14. Polarized targets and beams

    International Nuclear Information System (INIS)

    Meyer, W.

    1985-01-01

    First the experimental situation of the single-pion photoproduction and the photodisintegration of the deuteron is briefly discussed. Then a description of the Bonn polarization facilities is given. The point of main effort is put on the polarized target which plays a vital role in the program. A facility for photon induced double polarization experiments at ELSA will be presented in section 4. Properties of a tensor polarized deuteron target are discussed in section 5. The development in the field of polarized targets, especially on new target materials, enables a new generation of polarized target experiments with (polarized) electrons. Some comments on the use of a polarized target in combination with electron beams will be discussed in section 6. Electron deuteron scattering from a tensor polarized deuteron target is considered and compared with other experimental possibilities. (orig./HSI)

  15. cobalt(II), nickel(II)

    Indian Academy of Sciences (India)

    Unknown

    procedures. The supporting electrolyte, NaClO4 used in the voltammetric experiment was purchased from. Sigma. IR spectra were recorded in KBr medium on .... (13⋅6). L = Schiff base ligand form of one broad band envelope. The electronic spectra of Co(II) complex showed two spin-allowed transitions at 17856 and ...

  16. TargetSpy: a supervised machine learning approach for microRNA target prediction.

    Science.gov (United States)

    Sturm, Martin; Hackenberg, Michael; Langenberger, David; Frishman, Dmitrij

    2010-05-28

    Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila

  17. TargetSpy: a supervised machine learning approach for microRNA target prediction

    Directory of Open Access Journals (Sweden)

    Langenberger David

    2010-05-01

    Full Text Available Abstract Background Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. Results We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences. In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I no seed match requirement, II seed match requirement, and III conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Conclusion Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on

  18. Nuclear physics II

    International Nuclear Information System (INIS)

    Elze, T.

    1988-01-01

    This script consisting of two parts contains the matter of the courses Nuclear Pyhsics I and II, as they were presented in the winter term 1987/88 and summer term 1988 for students of physics at Frankfurt University. In the present part II the matter of the summer term is summarized. (orig.) [de

  19. World War II Homefront.

    Science.gov (United States)

    Garcia, Rachel

    2002-01-01

    Presents an annotated bibliography that provides Web sites focusing on the U.S. homefront during World War II. Covers various topics such as the homefront, Japanese Americans, women during World War II, posters, and African Americans. Includes lesson plan sources and a list of additional resources. (CMK)

  20. Some neutronic calculations for KENS-II

    International Nuclear Information System (INIS)

    Kiyanagi, Y.; Arai, M.; Watanabe, N.

    1989-01-01

    Proton energies of the intense spallation neutron sources currently in operation or designed are in the range Ep ≤ 1.1 GeV. Optimization studies of the target station have so far been performed for these proton energies. The KENS-II project has been included in the Japanese Hadron Facility Project where the proton accelerator, a so-called First Ring is shared with Meson Arena for nuclear physics and μSR experiments. The possible highest proton energy for this accelerator is 2 GeV, which is the highest among the world's spallation neutron sources. The authors, therefore, performed some neutronic calculations with 2 GeV protons in order to have a good knowledge of the neutronic characteristics and the optimal parameters of the target station for KENS-II. The fraction of slow neutron intensity versus the proton energy becomes 0.8 for 2 GeV compared to that for 0.8 GeV, and this is higher than 0.67 calculated for source neutrons. The uranium target has a higher neutron productivity, 1.5 times that of the tungsten target, even for 2 GeV protons. The target radius and the moderator axial position have definite optimal values for 2 GeV protons in spite of the broader distribution of the source neutrons in target, and these are essentially similar to the results for 0.8 GeV protons. The broad distribution with a little increase in the maximum luminosity of source neutrons for 2 GeV protons could make it easier to remove the heat load from the target than the case for the same beam-power with lower energy and higher proton current. Therefore, they could conclude that the 2 GeV protons for KENS-II do not have significant difficulties in producing slow neutrons, and that non-fissile material has higher advantages to produce neutrons for higher proton energies. Detailed neutronic calculations are now under way to design a neutron target station for KENS-II. 5 refs., 10 figs

  1. The Southern H ii Region Discovery Survey (SHRDS): Pilot Survey

    International Nuclear Information System (INIS)

    Brown, C.; Dickey, John M.; Jordan, C.; Anderson, L. D.; Armentrout, W. P.; Balser, Dana S.; Wenger, Trey V.; Bania, T. M.; Dawson, J. R.; Mc Clure-Griffiths, N. M.

    2017-01-01

    The Southern H ii Region Discovery Survey is a survey of the third and fourth quadrants of the Galactic plane that will detect radio recombination line (RRL) and continuum emission at cm-wavelengths from several hundred H ii region candidates using the Australia Telescope Compact Array. The targets for this survey come from the WISE Catalog of Galactic H ii Regions and were identified based on mid-infrared and radio continuum emission. In this pilot project, two different configurations of the Compact Array Broad Band receiver and spectrometer system were used for short test observations. The pilot surveys detected RRL emission from 36 of 53 H ii region candidates, as well as seven known H ii regions that were included for calibration. These 36 recombination line detections confirm that the candidates are true H ii regions and allow us to estimate their distances.

  2. The Southern H ii Region Discovery Survey (SHRDS): Pilot Survey

    Energy Technology Data Exchange (ETDEWEB)

    Brown, C.; Dickey, John M. [School of Physical Sciences, Private Bag 37, University of Tasmania, Hobart, TAS, 7001 (Australia); Jordan, C. [International Centre for Radio Astronomy Research, Curtin University, Perth, WA, 6845 (Australia); Anderson, L. D.; Armentrout, W. P. [Department of Physics and Astronomy, West Virginia University, P.O. Box 6315, Morgantown, WV 26506 (United States); Balser, Dana S.; Wenger, Trey V. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22904 (United States); Bania, T. M. [Institute for Astrophysical Research, Department of Astronomy, Boston University, 725 Commonwealth Avenue, Boston, MA 02215 (United States); Dawson, J. R. [Department of Physics and Astronomy and MQ Research Centre in Astronomy, Astrophysics and Astrophotonics, Macquarie University, NSW, 2109 (Australia); Mc Clure-Griffiths, N. M. [Research School of Astronomy and Astrophysics, The Australian National University, Canberra ACT 2611 (Australia)

    2017-07-01

    The Southern H ii Region Discovery Survey is a survey of the third and fourth quadrants of the Galactic plane that will detect radio recombination line (RRL) and continuum emission at cm-wavelengths from several hundred H ii region candidates using the Australia Telescope Compact Array. The targets for this survey come from the WISE Catalog of Galactic H ii Regions and were identified based on mid-infrared and radio continuum emission. In this pilot project, two different configurations of the Compact Array Broad Band receiver and spectrometer system were used for short test observations. The pilot surveys detected RRL emission from 36 of 53 H ii region candidates, as well as seven known H ii regions that were included for calibration. These 36 recombination line detections confirm that the candidates are true H ii regions and allow us to estimate their distances.

  3. Biologically active new Fe(II, Co(II, Ni(II, Cu(II, Zn(II and Cd(II complexes of N-(2-thienylmethylenemethanamine

    Directory of Open Access Journals (Sweden)

    C. SPÎNU

    2008-04-01

    Full Text Available Iron(II, cobalt(II, nickel (II, copper (II, zinc(II and cadmium(II complexes of the type ML2Cl2, where M is a metal and L is the Schiff base N-(2-thienylmethylenemethanamine (TNAM formed by the condensation of 2-thiophenecarboxaldehyde and methylamine, were prepared and characterized by elemental analysis as well as magnetic and spectroscopic measurements. The elemental analyses suggest the stoichiometry to be 1:2 (metal:ligand. Magnetic susceptibility data coupled with electronic, ESR and Mössbauer spectra suggest a distorted octahedral structure for the Fe(II, Co(II and Ni(II complexes, a square-planar geometry for the Cu(II compound and a tetrahedral geometry for the Zn(II and Cd(II complexes. The infrared and NMR spectra of the complexes agree with co-ordination to the central metal atom through nitrogen and sulphur atoms. Conductance measurements suggest the non-electrolytic nature of the complexes, except for the Cu(II, Zn(II and Cd(II complexes, which are 1:2 electrolytes. The Schiff base and its metal chelates were screened for their biological activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and the metal chelates were found to possess better antibacterial activity than that of the uncomplexed Schiff base.

  4. Nova target experiments

    International Nuclear Information System (INIS)

    Drake, R.P.

    1985-11-01

    The Nova laser, at the Lawrence Livermore National Laboratory, provides unique opportunities for target experiments. It has unprecedented energy on target and significant flexibility. The paper presented by John Hunt described the capabilities and the status of Nova. This paper discusses plans for future experiments using Nova, and the present status of target experiments. We plan to perform high-quality physics experiments that exploit the unique capabilities of Nova. Because this is our goal, we are fielding an extensive array of well-characterized target diagnostics to measure the emissions from the target. The first section of this paper discusses the basic target diagnostics. We are also taking care to quantify the performance of the laser

  5. Recent progress at RTNS-II

    International Nuclear Information System (INIS)

    Heikkinen, D.W.; Logan, C.M.

    1984-01-01

    The Rotating Target Neutron Source (RTNS-II) facility produces 14-MeV neutrons for materials damage studies. Initial operation for irradiations, which occurred in 1979, began with a neutron source strength of 10 13 n/s utilizing one of the accelerator-based neutron sources. Details are given on improvements which have resulted in both increased neutron production and neutron source strength and improved control and monitoring. 8 references

  6. Targeting and Persuasive Advertising

    OpenAIRE

    Egli, Alain (Autor/in)

    2015-01-01

    Firms face a prisoner's dilemma when advertising in a competitive environment. In a Hotelling framework with persuasive advertisingfirms counteract this prisoner's dilemma with targeting. The firms even solve the prisoner's problem if targeted advertising is effective enough. Advertising turns from wasteful competition into profits. This is in contrast to wasteful competition as argument for regulations. A further result is maximum advertising differentiation: thefirms target their advertisin...

  7. The ISOLDE target robots

    CERN Multimedia

    Maximilein Brice

    2002-01-01

    ISOLDE targets need to be changed frequently, around 80 times per year. The high radiation levels do not permit this to be done by human hands and the target changes are effected by 2 industrial robots (picture _01). On the left, in the distance, the front-end of the GPS (General Purpose Separator) is seen, while the HRS (High Resolution Separator) is at the right. Also seen are the doors to the irradiated-target storage.

  8. Deuterium high pressure target

    International Nuclear Information System (INIS)

    Perevozchikov, V.V.; Yukhimchuk, A.A.; Vinogradov, Yu.I.

    2001-01-01

    The design of the deuterium high-pressure target is presented. The target having volume of 76 cm 3 serves to provide the experimental research of muon catalyzed fusion reactions in ultra-pure deuterium in the temperature range 80-800 K under pressures of up to 150 MPa. The operation of the main systems of the target is described: generation and purification of deuterium gas, refrigeration, heating, evacuation, automated control system and data collection system

  9. Evolved H II regions

    International Nuclear Information System (INIS)

    Churchwell, E.

    1975-01-01

    A probable evolutionary sequence of H II regions based on six distinct types of observed objects is suggested. Two examples which may deviate from this idealized sequence, are discussed. Even though a size-mean density relation of H II regions can be used as a rough indication of whether a nebula is very young or evolved, it is argued that such a relation is not likely to be useful for the quantitative assignment of ages to H II regions. Evolved H II regions appear to fit into one of four structural types: rings, core-halos, smooth structures, and irregular or filamentary structures. Examples of each type are given with their derived physical parameters. The energy balance in these nebulae is considered. The mass of ionized gas in evolved H II regions is in general too large to trace the nebula back to single compact H II regions. Finally, the morphological type of the Galaxy is considered from its H II region content. 2 tables, 2 figs., 29 refs

  10. Targeted Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    David Cheng

    2011-10-01

    Full Text Available Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

  11. Targeted Radionuclide Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ersahin, Devrim, E-mail: devrimersahin@yahoo.com; Doddamane, Indukala; Cheng, David [Department of Diagnostic Radiology, School of Medicine, Yale University, 333 Cedar St., New Haven, CT 06520 (United States)

    2011-10-11

    Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

  12. Target Assembly Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Target Assembly Facility integrates new armor concepts into actual armored vehicles. Featuring the capability ofmachining and cutting radioactive materials, it...

  13. Targeted Radionuclide Therapy

    International Nuclear Information System (INIS)

    Ersahin, Devrim; Doddamane, Indukala; Cheng, David

    2011-01-01

    Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose

  14. Targeting the tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

    2006-11-07

    Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

  15. Gene silencing in Tribolium castaneum as a tool for the targeted identification of candidate RNAi targets in crop pests.

    Science.gov (United States)

    Knorr, Eileen; Fishilevich, Elane; Tenbusch, Linda; Frey, Meghan L F; Rangasamy, Murugesan; Billion, Andre; Worden, Sarah E; Gandra, Premchand; Arora, Kanika; Lo, Wendy; Schulenberg, Greg; Valverde-Garcia, Pablo; Vilcinskas, Andreas; Narva, Kenneth E

    2018-02-01

    RNAi shows potential as an agricultural technology for insect control, yet, a relatively low number of robust lethal RNAi targets have been demonstrated to control insects of agricultural interest. In the current study, a selection of lethal RNAi target genes from the iBeetle (Tribolium castaneum) screen were used to demonstrate efficacy of orthologous targets in the economically important coleopteran pests Diabrotica virgifera virgifera and Meligethes aeneus. Transcript orthologs of 50 selected genes were analyzed in D. v. virgifera diet-based RNAi bioassays; 21 of these RNAi targets showed mortality and 36 showed growth inhibition. Low dose injection- and diet-based dsRNA assays in T. castaneum and D. v. virgifera, respectively, enabled the identification of the four highly potent RNAi target genes: Rop, dre4, ncm, and RpII140. Maize was genetically engineered to express dsRNA directed against these prioritized candidate target genes. T 0 plants expressing Rop, dre4, or RpII140 RNA hairpins showed protection from D. v. virgifera larval feeding damage. dsRNA targeting Rop, dre4, ncm, and RpII140 in M. aeneus also caused high levels of mortality both by injection and feeding. In summary, high throughput systems for model organisms can be successfully used to identify potent RNA targets for difficult-to-work with agricultural insect pests.

  16. The TRUPACT-II Matrix Depleton Program

    International Nuclear Information System (INIS)

    Connolly, M.J.; Djordjevic, S.M.; Loehr, C.A.; Smith, M.C.; Banjac, V.; Lyon, W.F.

    1995-01-01

    Contact-handled transuranic (CH-TRU) wastes will be shipped and disposed at the Waste Isolation Pilot Plant (WIPP) repository in the Transuranic Package Transporter-II (TRUPACT-II) shipping package. A primary transportation requirement for the TRUPACT-II is that the concentration of potentially flammable gases (i.e., hydrogen and methane) must not exceed 5 percent by volume in the package or the payload during a 60-day shipping period. Decomposition of waste materials by radiation, or radiolysis, is the predominant mechanism of gas generation during transport. The gas generation potential of a target waste material is characterized by a G-value, which is the number of molecules of gas generated per 100 eV of ionizing radiation absorbed by the target material. To demonstrate compliance with the flammable gas concentration requirement, theoretical worst-case calculations were performed to establish allowable wattage (decay heat) limits for waste containers. The calculations were based on the G-value for the waste material with the highest potential for flammable gas generation. The calculations also made no allowances for decreases of the G-value over time due to matrix depletion phenomena that have been observed by many experimenters. Matrix depletion occurs over time when an alpha-generating source particle alters the target material (by evaporation, reaction, or decomposition) into a material of lower gas generating potential. The net effect of these alterations is represented by the ''effective G-value.''

  17. Preliminary PBFA II design

    International Nuclear Information System (INIS)

    Johnson, D.L.; VanDevender, J.P.; Martin, T.H.

    1980-01-01

    The upgrade of Sandia National Laboratories particle beam fusion accelerator, PBFA I, to PBFA II presents several interesting and challenging pulsed power design problems. PBFA II requires increasing the PBFA I output parameters from 2 MV, 30 TW, 1 MJ to 4 MV, 100 TW, 3.5 MJ with the constraint of using much of the same PBFA I hardware. The increased PBFA II output will be obtained by doubling the number of modules (from 36 to 72), increasing the primary energy storage (from 4 MJ to 15 MJ), lowering the pulse forming line (PFL) output impedance, and adding a voltage doubling network

  18. Mn(II), Zn(II) and VO(II) Schiff

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 113; Issue 3. Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II) Schiff base complexes derived from o-phenylenediamine and acetoacetanilide. N Raman Y Pitchaikani Raja A Kulandaisamy. Inorganic Volume 113 Issue 3 June 2001 pp 183-189 ...

  19. The Belle II Experiment

    CERN Document Server

    Kahn, J

    2017-01-01

    Set to begin data taking at the end of 2018, the Belle II experiment is the next-generation B-factory experiment hosted at KEK in Tsukuba, Japan. The experiment represents the cumulative effort from the collaboration of experimental and detector physics, computing, and software development. Taking everything learned from the previous Belle experiment, which ran from 1998 to 2010, Belle II aims to probe deeper than ever before into the field of heavy quark physics. By achieving an integrated luminosity of 50 ab−1 and accumulating 50 times more data than the previous experiment across its lifetime, along with a rewritten analysis framework, the Belle II experiment will push the high precision frontier of high energy physics. This paper will give an overview of the key components and development activities that make the Belle II experiment possible.

  20. Factor II assay

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003674.htm Factor II assay To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  1. Factor II deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000549.htm Factor II deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  2. Ni(II

    African Journals Online (AJOL)

    Preferred Customer

    analytical chemistry, catalysis, electrochemistry, ring-opening metathesis ... Ethanol was dried over anhydrous copper(II) sulfate and distilled over metallic sodium. ... All bacteria were inoculated into Nutrient Broth (Difco) and incubated for 24 h ...

  3. NNDSS - Table II. Vibriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Vibriosis - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year), and selected...

  4. Disruption Rose Tinted II

    OpenAIRE

    Livingstone, Andrew

    2009-01-01

    'Disruption - Rose Tinted II' continues to engage narratives of historical English china as previously explored in the work 'Rose Tinted'. This work engages the sleepy rural idyll which is overlaid with visual contemporary social commentary.

  5. NNDSS - Table II. Vibriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Vibriosis - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year), and selected...

  6. Gamble II Facility

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Gamble II produces a high-voltage (2 MV), high-current (1 MA), short (100 ns) pulse of energy of either positive or negative polarity. This terawatt power...

  7. Leo II PC

    Data.gov (United States)

    Kansas Data Access and Support Center — LEO II is a second-generation software system developed for use on the PC, which is designed to convert location references accurately between legal descriptions and...

  8. Tokapole II device

    International Nuclear Information System (INIS)

    Sprott, J.G.

    1978-05-01

    A discussion is given of the design and operation of the Tokapole II device. The following topics are considered: physics considerations, vacuum vessel, poloidal field, ring and support design, toroidal field, vacuum system, initial results, and future plans

  9. copper(II)

    Indian Academy of Sciences (India)

    Unknown

    bis(2,2,6,6-tetramethyl-3,5-heptadionato)copper(II) ... Abstract. Equilibrium concentrations of various condensed and gaseous phases have been thermodyna- ... phere, over a wide range of substrate temperatures and total reactor pressures.

  10. Digital optical computer II

    Science.gov (United States)

    Guilfoyle, Peter S.; Stone, Richard V.

    1991-12-01

    OptiComp is currently completing a 32-bit, fully programmable digital optical computer (DOC II) that is designed to operate in a UNIX environment running RISC microcode. OptiComp's DOC II architecture is focused toward parallel microcode implementation where data is input in a dual rail format. By exploiting the physical principals inherent to optics (speed and low power consumption), an architectural balance of optical interconnects and software code efficiency can be achieved including high fan-in and fan-out. OptiComp's DOC II program is jointly sponsored by the Office of Naval Research (ONR), the Strategic Defense Initiative Office (SDIO), NASA space station group and Rome Laboratory (USAF). This paper not only describes the motivational basis behind DOC II but also provides an optical overview and architectural summary of the device that allows the emulation of any digital instruction set.

  11. Target reactor development problems

    International Nuclear Information System (INIS)

    Lathrop, K.D.; Vigil, J.C.

    1977-01-01

    Target-blanket design studies are discussed for an accelerator-breeder concept employing a linear accelerator in conjunction with a modified conventional power reactor to produce both fissile fuel and power. The following problems in target and blanket system design are discussed: radiation damage, heat removal, neutronic design, and economics

  12. The CNGS target

    CERN Multimedia

    Patrice Loïez

    2005-01-01

    The CERN Neutrinos to Gran Sasso (CNGS) target ‘magazine’ of five target units. Each unit contains a series of 10-cm long graphite rods distributed over a length of 2 m. It is designed to maximize the number of secondary particles produced and hence the number of neutrinos. One unit is used at a time to prevent over heating.

  13. Targeted radionuclide therapy

    African Journals Online (AJOL)

    target for which a speci c treatment/drug is intended (Fig. 1). eranostics .... Using an anti-CD20 antibody as a delivery device to target the follicular ... systems combine diagnostic imaging (Ga-68-DOTATATE PET/CT) .... Intra-articular injected ...

  14. Modelling Recycling Targets

    DEFF Research Database (Denmark)

    hill, amanda; Leinikka Dall, Ole; Andersen, Frits Møller

    2014-01-01

    % for household waste, and sets an ambitious goal of a 50% recycling rate by 2020. This study integrates the recycling target into the FRIDA model to project how much waste and from which streams should be diverted from incineration to recycling in order to achieve the target. Furthermore, it discusses how...

  15. Strategic Targeted Advertising

    NARCIS (Netherlands)

    A. Galeotti; J.L. Moraga-Gonzalez (José Luis)

    2003-01-01

    textabstractWe present a strategic game of pricing and targeted-advertising. Firms can simultaneously target price advertisements to different groups of customers, or to the entire market. Pure strategy equilibria do not exist and thus market segmentation cannot occur surely. Equilibria exhibit

  16. Seedling root targets

    Science.gov (United States)

    Diane L. Haase

    2011-01-01

    Roots are critical to seedling performance after outplanting. Although root quality is not as quick and simple to measure as shoot quality, target root characteristics should be included in any seedling quality assessment program. This paper provides a brief review of root characteristics most commonly targeted for operational seedling production. These are: root mass...

  17. Internal targets for LEAR

    International Nuclear Information System (INIS)

    Kilian, K.; Gspann, J.; Mohl, D.; Poth, H.

    1984-01-01

    This chapter considers the use of thin internal targets in conjunction with phase-space cooling at the Low-Energy Antiproton Ring (LEAR). Topics considered include the merits of internal target operation; the most efficient use of antiprotons and of proton synchrotron (PS) protons, highest center-of-mass (c.m.) energy resolution; highest angular resolution and access to extreme angles; the transparent environment for all reaction products; a windowless source and pure targets; highest luminosity and count rates; access to lowest energies with increasing resolution; internal target thickness and vacuum requirements; required cooling performance; and modes of operation. It is demonstrated that an internal target in conjunction with phase-space cooling has the potential of better performance in terms of the economic use of antiprotons and consequently of PS protons; energy resolution; angular resolution; maximum reaction rate capability (statistical precision); efficient parasitic operation; transparency of the target for reaction products; access to low energies; and the ease of polarized target experiments. It is concluded that all p - experiments which need high statistics and high p - flux, such as studies of rare channels or broad, weak resonance structures, would profit from internal targets

  18. Fusion target design

    International Nuclear Information System (INIS)

    Bangerter, R.O.

    1978-01-01

    Most detailed fusion target design is done by numerical simulation using large computers. Although numerical simulation is briefly discussed, this lecture deals primarily with the way in which basic physical arguments, driver technology considerations and economical power production requirements are used to guide and augment the simulations. Physics topics discussed include target energetics, preheat, stability and symmetry. A specific design example is discussed

  19. SPEAR II performance

    International Nuclear Information System (INIS)

    Paterson, J.M.

    1975-01-01

    The single beam and colliding beam performance of the SLAC electron-positron storage ring SPEAR II is described. The sevenfold increase in harmonic number in SPEAR II in comparison to SPEAR I has made significant changes in single beam behavior. Strong synchrobetatron resonances and a new transverse instability are observed, and our first studies of these phenomena are described. Measurements on current dependent bunch lengthening are presented. (auth)

  20. Computing at Belle II

    International Nuclear Information System (INIS)

    Kuhr, Thomas

    2012-01-01

    Belle II, a next-generation B-factory experiment, will search for new physics effects in a data sample about 50 times larger than the one collected by its predecessor, the Belle experiment. To match the advances in accelerator and detector technology, the computing system and the software have to be upgraded as well. The Belle II computing model is presented and an overview of the distributed computing system and the offline software framework is given.

  1. Nsls-II Boster

    Science.gov (United States)

    Gurov, S. M.; Akimov, A. V.; Akimov, V. E.; Anashin, V. V.; Anchugov, O. V.; Baranov, G. N.; Batrakov, A. M.; Belikov, O. V.; Bekhtenev, E. A.; Blum, E.; Bulatov, A. V.; Burenkov, D. B.; Cheblakov, P. B.; Chernyakin, A. D.; Cheskidov, V. G.; Churkin, I. N.; Davidsavier, M.; Derbenev, A. A.; Erokhin, A. I.; Fliller, R. P.; Fulkerson, M.; Gorchakov, K. M.; Ganetis, G.; Gao, F.; Gurov, D. S.; Hseuh, H.; Hu, Y.; Johanson, M.; Kadyrov, R. A.; Karnaev, S. E.; Karpov, G. V.; Kiselev, V. A.; Kobets, V. V.; Konstantinov, V. M.; Kolmogorov, V. V.; Korepanov, A. A.; Kramer, S.; Krasnov, A. A.; Kremnev, A. A.; Kuper, E. A.; Kuzminykh, V. S.; Levichev, E. B.; Li, Y.; Long, J. De; Makeev, A. V.; Mamkin, V. R.; Medvedko, A. S.; Meshkov, O. I.; Nefedov, N. B.; Neyfeld, V. V.; Okunev, I. N.; Ozaki, S.; Padrazo, D.; Petrov, V. V.; Petrichenkov, M. V.; Philipchenko, A. V.; Polyansky, A. V.; Pureskin, D. N.; Rakhimov, A. R.; Rose, J.; Ruvinskiy, S. I.; Rybitskaya, T. V.; Sazonov, N. V.; Schegolev, L. M.; Semenov, A. M.; Semenov, E. P.; Senkov, D. V.; Serdakov, L. E.; Serednyakov, S. S.; Shaftan, T. V.; Sharma, S.; Shichkov, D. S.; Shiyankov, S. V.; Shvedov, D. A.; Simonov, E. A.; Singh, O.; Sinyatkin, S. V.; Smaluk, V. V.; Sukhanov, A. V.; Tian, Y.; Tsukanova, L. A.; Vakhrushev, R. V.; Vobly, P. D.; Utkin, A. V.; Wang, G.; Wahl, W.; Willeke, F.; Yaminov, K. R.; Yong, H.; Zhuravlev, A.; Zuhoski, P.

    The National Synchrotron Light Source II is a third generation light source, which was constructed at Brookhaven National Laboratory. This project includes a highly-optimized 3 GeV electron storage ring, linac preinjector, and full-energy synchrotron injector. Budker Institute of Nuclear Physics built and delivered the booster for NSLS-II. The commissioning of the booster was successfully completed. This paper reviews fulfilled work by participants.

  2. Electron beam fusion targets

    International Nuclear Information System (INIS)

    Clauser, M.J.; Sweeney, M.A.

    1975-01-01

    R The behavior of the DT filled gold shells when irradiated by a variety of pulse shapes was studied. In these pulses the power (and beam current) was varied, but the voltage was kept constant at 1 MeV. In general the performance of the target, for a given peak power, was not significantly affected by the pulse shape. Pulses with rise times of up to half the implosion time do not significantly degrade the target performance. The use of the ''optimal pulse'' of laser fusion with a fixed peak power does not appear to improve the performance of these targets. The main function of the ''optimal pulse'' is to produce a large rho r of the target during the thermonuclear burn. In e-beam targets a total rho r of 5--10 g/cm 2 can be obtained without pulse shaping; the problem here is one of achieving high enough temperatures to ignite the DT. (U.S.)

  3. The PIP-II Conceptual Design Report

    Energy Technology Data Exchange (ETDEWEB)

    Ball, M. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Burov, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Chase, B. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Chakravarty, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Chen, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Dixon, S. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Edelen, J. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Grassellino, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Johnson, D. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Holmes, S. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Kazakov, S. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Klebaner, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Kourbanis, I. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Leveling, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Melnychuk, O. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Neuffer, D. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Nicol, T. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Ostiguy, J. -F. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Pasquinelli, R. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Passarelli, D. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Ristori, L. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Pellico, W. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Patrick, J. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Prost, L. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Rakhno, I. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Saini, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Schappert, W. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Shemyakin, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Steimel, J. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Scarpine, V. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Vivoli, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Warner, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Yakovlev, V. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Ostroumov, P. [Argonne National Lab. (ANL), Argonne, IL (United States); Conway, Z. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2017-03-01

    The Proton Improvement Plan-II (PIP-II) encompasses a set of upgrades and improvements to the Fermilab accelerator complex aimed at supporting a world-leading neutrino program over the next several decades. PIP-II is an integral part of the strategic plan for U.S. High Energy Physics as described in the Particle Physics Project Prioritization Panel (P5) report of May 2014 and formalized through the Mission Need Statement approved in November 2015. As an immediate goal, PIP-II is focused on upgrades to the Fermilab accelerator complex capable of providing proton beam power in excess of 1 MW on target at the initiation of the Long Baseline Neutrino Facility/Deep Underground Neutrino Experiment (LBNF/DUNE) program, currently anticipated for the mid- 2020s. PIP-II is a part of a longer-term goal of establishing a high-intensity proton facility that is unique within the world, ultimately leading to multi-MW capabilities at Fermilab....

  4. 26 CFR 1.338-6 - Allocation of ADSP and AGUB among target assets.

    Science.gov (United States)

    2010-04-01

    ... allocated among Class II acquisition date assets of target in proportion to the fair market values of such... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Allocation of ADSP and AGUB among target assets... among target assets. (a) Scope—(1) In general. This section prescribes rules for allocating ADSP and...

  5. RTNS-II status

    International Nuclear Information System (INIS)

    Short, D.W.; Heikkinen, D.W.

    1987-01-01

    This report presents operational information about the Rotating Target Neutron Source (RTNS). Data presented include neutrons produced by year, availability, productivity, and staff radiation doses. 4 figs

  6. The Water Maser in II Zw 96: Scientific Justification

    Energy Technology Data Exchange (ETDEWEB)

    Wiggins, Brandon Kerry [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-08-06

    We propose a VLBI search to image and locate the water emission in II Zw 96. We propose 3 sites within II Zw 96 for VLBI followup (see the proposed target listing below). We request 2.5 hours of on-source integration time with the VLBA per source. The array will achieve ~ 65µJy sensitivity in K band in this time which will be sufficient to detect luminous water maser features.

  7. AA antiproton production target

    CERN Multimedia

    CERN PhotoLab

    1979-01-01

    The first version of the antiproton production target was a tungsten rod, 11 cm long and 3 mm in diameter. The rod was embedded in graphite, pressure-seated into an outer casing of stainless steel. At the entrance to the target assembly was a scintillator screen, imprinted with circles every 5 mm in radius, which allowed to precisely aim the 26 GeV high-intensity proton beam from the PS onto the centre of the target rod. The scintillator screen was a 1 mm thick plate of Cr-doped alumina. See also 7903034 and 7905091.

  8. Shiva target irradiation facility

    International Nuclear Information System (INIS)

    Manes, K.R.; Ahlstrom, H.G.; Coleman, L.W.; Storm, E.K.; Glaze, J.A.; Hurley, C.A.; Rienecker, F.; O'Neal, W.C.

    1977-01-01

    The first laser/plasma studies performed with the Shiva laser system will be two sided irradiations extending the data obtained by other LLL lasers to higher powers. The twenty approximately 1 TW laser pulses will reach the target simultaneously from above and below in nested pentagonal clusters. The upper and lower clusters of ten beams each are radially polarized so that they strike the target in p-polarization and maximize absorption. This geometry introduces laser system isolation problems which will be briefly discussed. The layout and types of target diagnostics will be described and a brief status report on the facility given

  9. STANFORD: Internal targets

    Energy Technology Data Exchange (ETDEWEB)

    Riordan, Michael

    1989-05-15

    Of burgeoning interest to many nuclear and particle physicists is a storage ring technique for fixed target experiments. It hinges on the use of gas-jet targets, shooting a narrow stream of atoms through a circulating beam of electrons or protons. Pioneered at CERN and the Soviet Novosibirsk Laboratory, more such 'internal targets' are being built or contemplated for storage rings in Europe, the Soviet Union, and the United States. From 9-12 January, physicists from around the world met at the Stanford Linear Accelerator Center (SLAC) to discuss prospects and problems in this expanding field.

  10. TARGET Research Goals

    Science.gov (United States)

    TARGET researchers use various sequencing and array-based methods to examine the genomes, transcriptomes, and for some diseases epigenomes of select childhood cancers. This “multi-omic” approach generates a comprehensive profile of molecular alterations for each cancer type. Alterations are changes in DNA or RNA, such as rearrangements in chromosome structure or variations in gene expression, respectively. Through computational analyses and assays to validate biological function, TARGET researchers predict which alterations disrupt the function of a gene or pathway and promote cancer growth, progression, and/or survival. Researchers identify candidate therapeutic targets and/or prognostic markers from the cancer-associated alterations.

  11. Target Price Accuracy

    Directory of Open Access Journals (Sweden)

    Alexander G. Kerl

    2011-04-01

    Full Text Available This study analyzes the accuracy of forecasted target prices within analysts’ reports. We compute a measure for target price forecast accuracy that evaluates the ability of analysts to exactly forecast the ex-ante (unknown 12-month stock price. Furthermore, we determine factors that explain this accuracy. Target price accuracy is negatively related to analyst-specific optimism and stock-specific risk (measured by volatility and price-to-book ratio. However, target price accuracy is positively related to the level of detail of each report, company size and the reputation of the investment bank. The potential conflicts of interests between an analyst and a covered company do not bias forecast accuracy.

  12. Autonomous Target Ranging Techniques

    DEFF Research Database (Denmark)

    Jørgensen, Peter Siegbjørn; Jørgensen, John Leif; Denver, Troelz

    2003-01-01

    of this telescope, a fast determination of the range to and the motion of the detected targets are important. This is needed in order to prepare the future observation strategy for each target, i.e. when is the closest approach where imaging will be optimal. In order to quickly obtain such a determination two...... ranging strategies are presented. One is an improved laser ranger with an effective range with non-cooperative targets of at least 10,000 km, demonstrated in ground tests. The accuracy of the laser ranging will be approximately 1 m. The laser ranger may furthermore be used for trajectory determination...... of nano-gravity probes, which will perform direct mass measurements of selected targets. The other is triangulation from two spacecraft. For this method it is important to distinguish between detection and tracking range, which will be different for Bering since different instruments are used...

  13. Targeted Cancer Therapies

    Science.gov (United States)

    ... are sometimes referred to as the product of "rational" drug design.) One approach to identify potential targets ... molecules that stimulate new blood vessel growth. Immunotherapies trigger the immune system to destroy cancer cells. Some ...

  14. Targeting radiation to tumours

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Greater Glasgow Health Board, Glasgow

    1994-01-01

    Biologically targeted radiotherapy entails the preferential delivery of radiation to solid tumours or individual tumour cells by means of tumour-seeking delivery vehicles to which radionuclides can be conjugated. Monoclonal antibodies have attracted attention for some years as potentially selective targeting agents, but advances in tumour and molecular biology are now providing a much wider choice of molecular species. General radiobiological principles may be derived which are applicable to most forms of targeted radiotherapy. These principles provide guidelines for the appropriate choice of radionuclide in specific treatment situations and its optimal combination with other treatment modalities. In future, the availability of gene targeting agents will focus attention on the use of Auger electron emitters whose high potency and short range selectivity makes them attractive choices for specific killing of cancer cells whose genetic peculiarities are known. (author)

  15. Probing HeII Reionization at z>3.5 with Resolved HeII Lyman Alpha Forest Spectra

    Science.gov (United States)

    Worseck, Gabor

    2017-08-01

    The advent of GALEX and COS have revolutionized our view of HeII reionization, the final major phase transition of the intergalactic medium. COS spectra of the HeII Lyman alpha forest have confirmed with high confidence the high HeII transmission that signifies the completion of HeII reionization at z 2.7. However, the handful of z>3.5 quasars observed to date show a set of HeII transmission 'spikes' and larger regions with non-zero transmission that suggest HeII reionization was well underway by z=4. This is in striking conflict with predictions from state-of-the-art radiative transfer simulations of a HeII reionization driven by bright quasars. Explaining these measurements may require either faint quasars or more exotic sources of hard photons at z>4, with concomitant implications for HI reionization. However, many of the observed spikes are unresolved in G140L spectra and are significantly impacted by Poisson noise. Current data cannot reliably probe the ionization state of helium at z>3.5.We request 41 orbits to obtain science-grade G130M spectra of the two UV-brightest HeII-transmitting QSOs at z>3.5 to confirm and resolve their HeII transmission spikes as an unequivocal test of early HeII reionization. These spectra are complemented by recently obtained data from 8m telescopes: (1) Echelle spectra of the coeval HI Lya forest to map the underlying density field that modulates the HeII absorption, and (2) Our dedicated survey for foreground QSOs that may source the HeII transmission. Our recent HST programs revealed the only two viable targets to resolve the z>3.5 HeII Lyman alpha forest, and to conclusively solve this riddle.

  16. Radioimmunotherapy (II): clinical application

    International Nuclear Information System (INIS)

    Cheon, Gi Jeong; Kang, Hye Jin; Lim, Sang Moo

    2006-01-01

    Molecular targeting may be defined as the specific concentration of a diagnostic or therapeutic tracer by its interaction with a molecular species that is distinctly present or absent in a disease state. Monoclonal antibody (mAb) is one of the successful agents for targeted therapy in cancer. To enhance the therapeutic effect. the concept of targeting radionuclides to tumors using radiolabeled mAbs against tumor-associated antigens, radioimmunotherapy, was proposed. The efficacy of radioimmunotherapy, however, has to be further optimized. Several strategies to improve targeting of tumors with radiolabeled mAbs have been developed, such as the use of mAb fragments, the use of high-affinity mAbs, the use of labeling techniques that are stable in vivo, active removal of the radiolabeled mAb from the circulation, and pretargeting strategies. Until now, however, there are many kinds of obstacles to be solved in the use of mAb for the targeted therapy. Major technical challenges to molecular targeting are related to the rapid and specific delivery of tracers to the target, the elimination of unwanted background activity, and the development of more specific targets to create a cytocidal effect. Further development of this field will be determined by success in solving these challenges

  17. Strategic Targeted Advertising

    OpenAIRE

    Andrea Galeotti; Jose Luis Moraga

    2003-01-01

    textabstractWe present a strategic game of pricing and targeted-advertising. Firms can simultaneously target price advertisements to different groups of customers, or to the entire market. Pure strategy equilibria do not exist and thus market segmentation cannot occur surely. Equilibria exhibit random advertising --to induce an unequal distribution of information in the market-- and random pricing --to obtain profits from badly informed buyers--. We characterize a positive profits equilibrium...

  18. Targets and teamwork

    DEFF Research Database (Denmark)

    Skinner, Timothy C.; Lange, Karin S.; Hoey, Hilary

    2017-01-01

    differences in mean HbA1c between centers ranging from 7.3±0.8% (53mmol/mol±8.7) to 8.9±1.1% (74mmol/mol±12.0). Centers with lower mean HbA1c had (1) parents who reported lower targets for their children, (2) health-care professionals that reported lower targets and more frequent testing, and (3) teams...

  19. Targets and special materials

    International Nuclear Information System (INIS)

    Blanc, R.; Bouriant, M.; Richaud, J.P.

    1997-01-01

    The target preparation group supplied a large number of samples to nuclear physicists for experiments using SARA and also other accelerators throughout the world. Particular preparation and projects include: 208 Pb, 116 Cd, 6 LiF, 123 Sb, In and Ta targets, strippers for SARA and GANIL, optical silicone disks for POLDER and GRAAL experiments, active participations for the AMS project and finally filament preparation for the GENEPI project. (authors)

  20. The ISIS target

    International Nuclear Information System (INIS)

    Carne, A.; Broome, T.A.; Hogston, J.R.; Holding, M.

    1989-01-01

    This presentation discusses the two target failures that have occurred, gives the understanding of the causes and indicates the steps being taken to alleviate the problems. At the outset of the design it was understood that the target would have a finite lifetime, due to radiation damage effects, exacerbated by mechanical damage due to thermal cycling and fatigue. Estimates of target lifetime at full intensity are about 2 years for radiation damage swelling and about 10E4 gross thermal excursions. The latter number is the one which gives uncertainty in defining the life of the target, since it is dependent on the reliability of the accelerator and quality of the proton beam. The commissioning of an accelerator system and bringing it up to high beam intensities have their own special problems. There must be protection of components against uncontrolled beam loss, which produces thermal damage, prompt radiation and induced activity. Fast beam trips for beam loss protection, or equipment failures, result in quenches from high temperature in the target which get bigger with increasing beam intensity. But the target itself is a difficult device to make, taking about 12 months to manufacture. Further, changing one is a complex and time consuming task, not without its hazards. There is thus something of a balancing act to bring the accelerator towards specification before the target fails due to thermal cycling fatigue. In the early days of ISIS beam loss protection was the dominant consideration and the target was regarded somewhat as a sacrificial lamb to the goddess of machine reliability. 2 refs., 6 figs

  1. II-VI semiconductor compounds

    CERN Document Server

    1993-01-01

    For condensed matter physicists and electronic engineers, this volume deals with aspects of II-VI semiconductor compounds. Areas covered include devices and applications of II-VI compounds; Co-based II-IV semi-magnetic semiconductors; and electronic structure of strained II-VI superlattices.

  2. An ISOLDE target unit

    CERN Multimedia

    Maximilien Brice

    2002-01-01

    A good dozen different targets are available for ISOLDE, made of different materials and equipped with different kinds of ion-sources, according to the needs of the experiments. Each separator (GPS: general purpose; HRS: high resolution) has its own target. Because of the high radiation levels, robots effect the target changes, about 80 times per year. In the standard unit shown in picture _01, the target is the cylindrical object in the front. It contains uranium-carbide kept at a temperature of 2200 deg C, necessary for the isotopes to be able to escape. At either end, one sees the heater current leads, carrying 700 A. The Booster beam, some 3E13 protons per pulse, enters the target from left. The evaporated isotope atoms enter a hot-plasma ion source (the black object behind the target). The whole unit sits at 60 kV potential (pulsed in synchronism with the arrival of the Booster beam) which accelerates the ions (away from the viewer) towards one of the 2 separators.

  3. Laser targets: introduction

    International Nuclear Information System (INIS)

    Rosen, M.D.

    1985-01-01

    The laser target design group was engaged in three main tasks in 1984: (1) analyzing Novette implosion and hohlraum-scaling data, (2) planning for the first experiments on Nova, and (3) designing laboratory x-ray laser targets and experiments. The Novette implosion and hohlraum scaling data are mostly classified and are therefore not discussed in detail here. The authors achieved average final/initial pusher pr ratios of about 50, some 3 times higher than the value achieved in the best Shiva shots. These pr values imply a fuel compression to 100 times liquid density, although this figure and other aspects of the experiments are subject to further interpretation because of detailed questions of target symmetry and stability. Their main long-term goal for Nova is to produce a so-called hydrodynamically equivalent target (HET) - that is, a target whose hydrodynamic behavior (implosion velocity, convergence ratio, symmetry and stability requirements, etc.) is very much like that of a high-gain target, but one that is scaled down in size to match the energy available from Nova and is too small to achieve enough hot-spot pr to ignite the cold, near-Fermi-degenerate fuel around it. Their goal for Nova's first year is to do experiments that will teach them how to achieve the symmetry and stability conditions required by an HET

  4. Argus target chamber

    International Nuclear Information System (INIS)

    Rienecker, F. Jr.; Glaros, S.S.; Kobierecki, M.

    1975-01-01

    A target chamber for application in the laser fusion program must satisfy some very basic requirements. (1) Provide a vacuum on the order of 10 -6 torr. (2) Support a microscopically small target in a fixed point in space and verify its location within 5 micrometers. (3) Contain an adjustable beam focusing system capable of delivering a number of laser beams onto the target simultaneously, both in time and space. (4) Provide access for diagnostics to evaluate the results of target irradiation. (5) Have flexibility to allow changes in targets, focusing optics and number of beams. The ARGUS laser which is now under construction at LLL will have a target chamber which meets these requirements in a simple economic manner. The chamber and auxiliary equipment are described, with reference to two double beam focusing systems; namely, lenses and ellipsoidal mirrors. Provision is made for future operation with four beams, using ellipsoidal mirrors for two-sided illumination and lens systems for tetragonal and tetrahedral irradiation

  5. About APPLE II Operation

    International Nuclear Information System (INIS)

    Schmidt, T.; Zimoch, D.

    2007-01-01

    The operation of an APPLE II based undulator beamline with all its polarization states (linear horizontal and vertical, circular and elliptical, and continous variation of the linear vector) requires an effective description allowing an automated calculation of gap and shift parameter as function of energy and operation mode. The extension of the linear polarization range from 0 to 180 deg. requires 4 shiftable magnet arrrays, permitting use of the APU (adjustable phase undulator) concept. Studies for a pure fixed gap APPLE II for the SLS revealed surprising symmetries between circular and linear polarization modes allowing for simplified operation. A semi-analytical model covering all types of APPLE II and its implementation will be presented

  6. VATICANO II CONCILIO DOCTRINAL?

    Directory of Open Access Journals (Sweden)

    Horacio Bojorge

    1970-01-01

    Full Text Available It is a century since the army of Victor Manuel invaded Rome and put an end to Vatican I. In this article we try to understand Vatican II linking it to the previous circumtances and binding it to its doctrinal and pastoral character. Vatican II omitted many subjects that seemed important, e. g. not giving any dogmatic definitions. Contrasting with the Tridentine and Vatican I, that were mostly doctrinal, Vatican II was pastoral. But it was also doctrinal as were the two previous also pastoral. The Constitution "Dei Verbum" brings forth the intentions that led John XXIII to summon the Council in 5-8-1962. The world looked confused and agitated. What could the Church do?

  7. Progress in light ion beam fusion research on PBFA II

    International Nuclear Information System (INIS)

    Cook, D.L.; Allshouse, G.O.; Bailey, J.

    1986-01-01

    PBFA II is a 100 TW pulsed power accelerator constructed at Sandia National Laboratories for use in the Light Ion Fusion Program. The objective of PBFA II is to accelerate and focus upon an inertial confinement fusion (ICF) target a lithium beam with sufficient energy, power, and power density to perform ignition scaling experiments. The technologies used in PBFA II include: (1) primary energy storage and compression with 6 MV, low-inductance Marx generators, (2) pulse forming in water-insulated, water-dielectric lines with self-closing water switches, (4) voltage addition in vacuum using self-magnetically-insulated biconic transmission lines, (5) inductive energy storage and pulse compression using a fast-opening plasma erosion switch, (6) beam formation using a magnetically-insulated ion diode, and (7) space-charge and current-neutralized beam propagation to the target in a gas-filled cell. The first multimodule shot was on December 11, 1985. The plans for PBFA II include development and demonstration of the pulse-shaping techniques which are necessary for high-gain target compressions. Following a modification of the accelerator which will probably include an ''extraction'' ion diode, a 4- to 5-meter plasma channel for beam bunching during propagation, and a target chamber located beneath the accelerator, temporally-shaped ion beam pulses will be available for pulse-shaped target experiments. (author)

  8. Targeted therapy using nanotechnology: focus on cancer.

    Science.gov (United States)

    Sanna, Vanna; Pala, Nicolino; Sechi, Mario

    2014-01-01

    Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication.

  9. Datalogger usando nios ii

    OpenAIRE

    Campoverde Rugel, Luis Enrique; Velásquez Vargas, Washington Adrián; Ponguillo, Ronald

    2013-01-01

    El presente proyecto consiste en la implementación de un Datalogger utilizando el microprocesador NIOS II el cual fue embebido en el FPGA CYCLONE II que se encuentra integrada en la tarjeta de desarrollo ALTERA DE2, el cual obtiene datos de distintos sensores y los almacena en una tarjeta SD Card. Para la realización del proyecto se aplican cuatro etapas. La primera etapa está basada en obtener los datos mediante el uso de sensores y la transmisión usando un PIC, la siguiente etapa se basa...

  10. Results from SAGE II

    International Nuclear Information System (INIS)

    Nico, J.S.

    1994-01-01

    The Russian-American Gallium solar neutrino Experiment (SAGE) began the second phase of operation (SAGE II) in September of 1992. Monthly measurements of the integral flux of solar neutrinos have been made with 55 tonnes of gallium. The K-peak results of the first nine runs of SAGE II give a capture rate of 66 -13 +18 (stat) -7 +5 (sys) SNU. Combined with the SAGE I result of 73 -16 +18 (stat) -7 5 (sys) SNU, the capture rate is 69 -11 +11 (stat) -7 +5 (sys) SNU. This represents only 52%--56% of the capture rate predicted by different Standard Solar Models

  11. Information on Asse II

    International Nuclear Information System (INIS)

    2014-01-01

    The brochure published by BfS describes the actual situation of Asse II with respect to the debate on an interim storage and the status of the realization of a final repository search law. During the visit of the new environment minister Hendricks in the underground facility repository Asse II the issue interim storage site and the retrieval of the corroded casks with radioactive waste were discussed. The challenges for BFS include the acceleration of the retrieval process and the safety of the procedure.

  12. TJ-II project

    International Nuclear Information System (INIS)

    Alejaldre, C.; Gozalo, J.J.A.; Perez, J.B.; Magaria, F.C.; Diaz, J.R.C.; Perez, J.G.; Lopez-Fraguas, A.; Garcia, L.; Krivenski, V.I.; Martin, R.; Navarro, A.P.; Perea, A.; Rodriguez-Yunta, A.; Ayza, M.S.; Varias, A.

    1990-01-01

    The TJ-II device is a medium-size helical-axis stellarator to be built in Madrid. Its main characteristics are potential for high-beta operation; flexibility, i.e., its rotational transform can be varied over a wide range and its shear to some extent; and bean-shaped plasma cross section. The latest understanding of TJ-II physics in the fields of electron cyclotron resonance heating, transport, and magneto-hydrodynamics, and the engineering solutions introduced in its final design are discussed

  13. ECLESIOLOGIA DO VATICANO II

    Directory of Open Access Journals (Sweden)

    Víctor Codina

    2013-01-01

    Full Text Available Não se pode compreender a eclesiologia do Vaticano II sem conhecer a vida, o estilo pastoral e o carisma de João XXIII, que convocou o Concílio e abriu o caminho em direção a uma nova configuração eclesial que acabava com séculos de uma Igreja de Cristandade. O Vaticano II implica uma transição de uma Igreja clerical a uma Igreja Povo de Deus, povo de batizados. A passagem de uma Igreja juridicista e legalista a uma Igreja Mistério de comunhão em Cristo. Mudar de uma Igreja triunfalista e ligada ao poder mundano a uma Igreja vivificada pela força renovadora do Espírito. A Igreja está a caminho rumo ao Reino de Deus juntamente com todos os cristãos e com toda a humanidade. A recepção do Vaticano II supõe uma conversão pastoral: voltar ao Evangelho e abrir-se aos novos sinais dos tempos seguindo o Espírito que inspirou João XXIII. ABSTRACT: You cannot understand the Ecclesiology of Vatican II without knowing the life, the pastoral style and the charisma of John XXIII, who convened the Council and opened the way toward a new ecclesial setting that ended centuries of a church of Christendom. The Vatican II involves a transition from a clerical Church to a “People (baptized people of God” Church. The Vatican II implies the passage from a juridical and legalistic Church to a Church as the Mystery of the communion in Christ. The Vatican II implies the change from a triumphalistic Church and connected to worldly power to a Church vivified by the renewing force of the Spirit. The Church is on its way toward the Kingdom of God together with all Christians and all mankind. The reception of the Vatican II supposes a pastoral conversion: a return to the Gospel and openness to new signs of the times following the Spirit that inspired John XXIII.

  14. Galaxy S II

    CERN Document Server

    Gralla, Preston

    2011-01-01

    Unlock the potential of Samsung's outstanding smartphone with this jargon-free guide from technology guru Preston Gralla. You'll quickly learn how to shoot high-res photos and HD video, keep your schedule, stay in touch, and enjoy your favorite media. Every page is packed with illustrations and valuable advice to help you get the most from the smartest phone in town. The important stuff you need to know: Get dialed in. Learn your way around the Galaxy S II's calling and texting features.Go online. Browse the Web, manage email, and download apps with Galaxy S II's 3G/4G network (or create you

  15. Calculus II For Dummies

    CERN Document Server

    Zegarelli, Mark

    2012-01-01

    An easy-to-understand primer on advanced calculus topics Calculus II is a prerequisite for many popular college majors, including pre-med, engineering, and physics. Calculus II For Dummies offers expert instruction, advice, and tips to help second semester calculus students get a handle on the subject and ace their exams. It covers intermediate calculus topics in plain English, featuring in-depth coverage of integration, including substitution, integration techniques and when to use them, approximate integration, and improper integrals. This hands-on guide also covers sequences and series, wit

  16. Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage

    OpenAIRE

    Barker, Catherine R.; McNamara, Anne V.; Rackstraw, Stephen A.; Nelson, David E.; White, Mike R.; Watson, Alastair J. M.; Jenkins, John R.

    2006-01-01

    Topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and meiosis and is a highly attractive target for chemotherapeutic agents. We have identified previously topoisomerase II and heat shock protein 90 (Hsp90) as part of a complex. In this paper we demonstrate that drug combinations targeting these two enzymes cause a synergistic increase in apoptosis. The objective of our study was to identify the mode of cell killing and the mechanism behind the inc...

  17. DARHT-II Downstream Transport Beamline

    International Nuclear Information System (INIS)

    Westenskow, G A; Bertolini, L R; Duffy, P T; Paul, A C

    2001-01-01

    This paper describes the mechanical design of the downstream beam transport line for the second axis of the Dual Axis Radiographic Hydrodynamic Test (DARHT II) Facility. The DARHT-II project is a collaboration between LANL, LBNL and LLNL. DARHT II is a 18.4-MeV, 2000-Amperes, 2-(micro)sec linear induction accelerator designed to generate short bursts of x-rays for the purpose of radiographing dense objects. The downstream beam transport line is approximately 22-meter long region extending from the end of the accelerator to the bremsstrahlung target. Within this proposed transport line there are 12 conventional solenoid, quadrupole and dipole magnets; as well as several specialty magnets, which transport and focus the beam to the target and to the beam dumps. There are two high power beam dumps, which are designed to absorb 80-kJ per pulse during accelerator start-up and operation. Aspects of the mechanical design of these elements are presented

  18. An updated Type II supernova Hubble diagram

    Science.gov (United States)

    Gall, E. E. E.; Kotak, R.; Leibundgut, B.; Taubenberger, S.; Hillebrandt, W.; Kromer, M.; Burgett, W. S.; Chambers, K.; Flewelling, H.; Huber, M. E.; Kaiser, N.; Kudritzki, R. P.; Magnier, E. A.; Metcalfe, N.; Smith, K.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.

    2018-03-01

    We present photometry and spectroscopy of nine Type II-P/L supernovae (SNe) with redshifts in the 0.045 ≲ z ≲ 0.335 range, with a view to re-examining their utility as distance indicators. Specifically, we apply the expanding photosphere method (EPM) and the standardized candle method (SCM) to each target, and find that both methods yield distances that are in reasonable agreement with each other. The current record-holder for the highest-redshift spectroscopically confirmed supernova (SN) II-P is PS1-13bni (z = 0.335-0.012+0.009), and illustrates the promise of Type II SNe as cosmological tools. We updated existing EPM and SCM Hubble diagrams by adding our sample to those previously published. Within the context of Type II SN distance measuring techniques, we investigated two related questions. First, we explored the possibility of utilising spectral lines other than the traditionally used Fe IIλ5169 to infer the photospheric velocity of SN ejecta. Using local well-observed objects, we derive an epoch-dependent relation between the strong Balmer line and Fe IIλ5169 velocities that is applicable 30 to 40 days post-explosion. Motivated in part by the continuum of key observables such as rise time and decline rates exhibited from II-P to II-L SNe, we assessed the possibility of using Hubble-flow Type II-L SNe as distance indicators. These yield similar distances as the Type II-P SNe. Although these initial results are encouraging, a significantly larger sample of SNe II-L would be required to draw definitive conclusions. Tables A.1, A.3, A.5, A.7, A.9, A.11, A.13, A.15 and A.17 are also available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/611/A25

  19. Computational design of binding proteins to EGFR domain II.

    Directory of Open Access Journals (Sweden)

    Yoon Sup Choi

    Full Text Available We developed a process to produce novel interactions between two previously unrelated proteins. This process selects protein scaffolds and designs protein interfaces that bind to a surface patch of interest on a target protein. Scaffolds with shapes complementary to the target surface patch were screened using an exhaustive computational search of the human proteome and optimized by directed evolution using phage display. This method was applied to successfully design scaffolds that bind to epidermal growth factor receptor (EGFR domain II, the interface of EGFR dimerization, with high reactivity toward the target surface patch of EGFR domain II. One potential application of these tailor-made protein interactions is the development of therapeutic agents against specific protein targets.

  20. Photoreactions of ruthenium(II) and osmium(II) complexes with deoxyribonucleic acid (DNA).

    Science.gov (United States)

    Moucheron, C; Kirsch-De Mesmaeker, A; Kelly, J M

    1997-09-01

    The design of Ru(II) and Os(II) complexes which are photoreactive with deoxyribonucleic acid (DNA) represents one of the main targets for the development of novel molecular tools for the study of DNA and, in the future, for the production of new, metal-based, anti-tumor drugs. In this review, we explain how it is possible to make a complex photoreactive with nucleobases and nucleic acids. According to the photophysical behaviour of the Ru(II) compounds, two types of photochemistry are expected: (1) photosubstitution of a ligand by a nucleobase and another monodentate ligand, which takes place from the triplet, metal-centred (3MC) state; this state is populated thermally from the lowest lying triplet metal to ligand charge transfer (3MLCT) state; (2) photoreaction from the 3MLCT state, corresponding to photoredox processes with DNA bases. The two photoreactivities are in competition. By modulating appropriately the redox properties of the 3MLCT state, an electron transfer process from the base to the excited complex takes place, and is directly correlated with DNA cleavage or the formation of an adduct of the complex to DNA. In this adduct, guanine is linked by N2 to the alpha-position of a non-chelating nitrogen of the polyazaaromatic ligand without destruction of the complex. Different strategies are explained which increase the affinity of the complexes for DNA and direct the complex photoreactivity to sites of special DNA topology or targeted sequences of bases. Moreover, the replacement of the Ru(II) ion by the Os(II) ion in the photoreactive complexes leads to an increased specificity of photoreaction. Indeed, only one type of photoreactivity (from the 3MLCT state) is present for the Os(II) complexes because the 3MC state is too high in energy to be populated at room temperature.

  1. Burglar Target Selection

    Science.gov (United States)

    Townsley, Michael; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

    2015-01-01

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments. PMID:25866418

  2. LANSCE target system performance

    International Nuclear Information System (INIS)

    Russell, G.J.; Gilmore, J.S.; Robinson, H.; Legate, G.L.; Bridge, A.; Sanchez, R.J.; Brewton, R.J.; Woods, R.; Hughes, H.G. III

    1989-01-01

    We measured neutron beam fluxes at LANSCE using gold foil activation techniques. We did an extensive computer simulation of the as-built LANSCE Target/Moderator/Reflector/Shield geometry. We used this mockup in a Monte Carlo calculation to predict LANSCE neutronic performance for comparison with measured results. For neutron beam fluxes at 1 eV, the ratio of measured data to calculated varies from ∼0.6-0.9. The computed 1 eV neutron leakage at the moderator surface is 3.9 x 10 10 n/eV-sr-s-μA for LANSCE high-intensity water moderators. The corresponding values for the LANSCE high-resolution water moderator and the liquid hydrogen moderator are 3.3 and 2.9 x 10 10 , respectively. LANSCE predicted moderator intensities (per proton) for a tungsten target are essentially the same as ISIS predicted moderator intensities for a depleted uranium target. The calculated LANSCE steady state unperturbed thermal (E 13 n/cm 2 -s. The unique LANSCE split-target/flux-trap-moderator system is performing exceedingly well. The system has operated without a target or moderator change for over three years at nominal proton currents of ∼25 μA of 800-MeV protons. (author)

  3. Periodontics II: Course Proposal.

    Science.gov (United States)

    Dordick, Bruce

    A proposal is presented for Periodontics II, a course offered at the Community College of Philadelphia to give the dental hygiene/assisting student an understanding of the disease states of the periodontium and their treatment. A standardized course proposal cover form is given, followed by a statement of purpose for the course, a list of major…

  4. Workshop 96. Part II

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    Part II of the seminar proceedings contains contributions in various areas of science and technology, among them materials science in mechanical engineering, materials science in electrical, chemical and civil engineering, and electronics, measuring and communication engineering. In those areas, 6 contributions have been selected for INIS. (P.A.).

  5. Experiment CATETO II

    International Nuclear Information System (INIS)

    Hendriks, J.A.; Freudenreich, W.E.

    1994-03-01

    In the irradiation experiment CATETO II different reduced activation (RA) steels will be irradiated up to 2.5 dpa at a temperature of 300 C. The results of the calculation of the nuclear constants, the reactivity effect, and the activity of the steel samples are presented. (orig.)

  6. Amorphous iron (II) carbonate

    DEFF Research Database (Denmark)

    Sel, Ozlem; Radha, A.V.; Dideriksen, Knud

    2012-01-01

    Abstract The synthesis, characterization and crystallization energetics of amorphous iron (II) carbonate (AFC) are reported. AFC may form as a precursor for siderite (FeCO3). The enthalpy of crystallization (DHcrys) of AFC is similar to that of amorphous magnesium carbonate (AMC) and more...

  7. Workshop 96. Part II

    International Nuclear Information System (INIS)

    1995-12-01

    Part II of the seminar proceedings contains contributions in various areas of science and technology, among them materials science in mechanical engineering, materials science in electrical, chemical and civil engineering, and electronics, measuring and communication engineering. In those areas, 6 contributions have been selected for INIS. (P.A.)

  8. UNISIST II: Special Report.

    Science.gov (United States)

    Hattery, Lowell H., Ed.

    1979-01-01

    The major part of this report of the Intergovernmental Conference on Scientific and Technical Information (UNISIST II), held in Paris May 28-June 1, 1979, focuses on three sets of recommendations which were unanimously approved after combining the recommendations proposed by various groups and blocs: (1) recommendations to the United Nations…

  9. Photosystem II and photoinhibition

    NARCIS (Netherlands)

    Feikema, Willem Onno

    2006-01-01

    Plants harvest light energy and convert it into chemical energy. Light absorption by photosystems I and II (PSI and PSII) results in charge separations in their reaction centers (RCs), initiating a chain of redox reactions with PSI generating the reducing power for CO2 assimilation into sugars, and

  10. Status of the Gerda phase II experiment

    Energy Technology Data Exchange (ETDEWEB)

    Lazzaro, Andrea [Physik-Department and Excellence Cluster Universe, Technische Universitaet Muenchen (Germany); Collaboration: GERDA-Collaboration

    2016-07-01

    The Gerda experiment searches for the neutrinoless double beta decay (0νββ) in {sup 76}Ge. The first phase of the experiment collected 21.6 kg. yr of exposure with a background index (BI) of 0.01 cts/(keV . kg . yr). No signal was observed and a lower limit for the 0νββ half-life was set to T{sup 0νββ}{sub 1/2} < 2.1 . 10{sup 25} yr (90% C.L). The apparatus has now been upgraded to the Phase II configuration. In Phase II 38 kg of HPGe detectors will be operated to reach an exposure of 100 kg . yr. The goal of Gerda Phase II is to lower the BI to 10{sup -3} cts/(keV . kg . y), in order to reach the sensitivity for T{sup 0νββ}{sub 1/2} = O(10{sup 26}) yr. The additional target mass is constituted of 30 custom made BEGe detectors with higher energy resolution and better pulse shape discrimination performance. The detectors are operated in new radio-pure low-mass holders. The liquid argon surrounding the detectors has been instrumented to veto the background events which produce scintillation light. In this talk the current status and the performance of the Gerda Phase II are presented.

  11. Late-onset Bartter syndrome type II.

    Science.gov (United States)

    Gollasch, Benjamin; Anistan, Yoland-Marie; Canaan-Kühl, Sima; Gollasch, Maik

    2017-10-01

    Mutations in the ROMK1 potassium channel gene ( KCNJ1 ) cause antenatal/neonatal Bartter syndrome type II (aBS II), a renal disorder that begins in utero , accounting for the polyhydramnios and premature delivery that is typical in affected infants, who develop massive renal salt wasting, hypokalaemic metabolic alkalosis, secondary hyperreninaemic hyperaldosteronism, hypercalciuria and nephrocalcinosis. This BS type is believed to represent a disorder of the infancy, but not in adulthood. We herein describe a female patient with a remarkably late-onset and mild clinical manifestation of BS II with compound heterozygous KCNJ1 missense mutations, consisting of a novel c.197T > A (p.I66N) and a previously reported c.875G > A (p.R292Q) KCNJ1 mutation. We implemented and evaluated the performance of two different bioinformatics-based approaches of targeted massively parallel sequencing [next generation sequencing (NGS)] in defining the molecular diagnosis. Our results demonstrate that aBS II may be suspected in patients with a late-onset phenotype. Our experimental approach of NGS-based mutation screening combined with Sanger sequencing proved to be a reliable molecular approach for defining the clinical diagnosis in our patient, and results in important differential diagnostic and therapeutic implications for patients with BS. Our results could have a significant impact on the diagnosis and methodological approaches of genetic testing in other patients with clinical unclassified phenotypes of nephrocalcinosis and congenital renal electrolyte abnormalities.

  12. Neuroprotective Effects and Mechanisms of Curcumin–Cu(II and –Zn(II Complexes Systems and Their Pharmacological Implications

    Directory of Open Access Journals (Sweden)

    Fa-Shun Yan

    2017-12-01

    Full Text Available Alzheimer’s disease (AD is the main form of dementia and has a steadily increasing prevalence. As both oxidative stress and metal homeostasis are involved in the pathogenesis of AD, it would be interesting to develop a dual function agent, targeting the two factors. Curcumin, a natural compound isolated from the rhizome of Curcuma longa, is an antioxidant and can also chelate metal ions. Whether the complexes of curcumin with metal ions possess neuroprotective effects has not been evaluated. Therefore, the present study was designed to investigate the protective effects of the complexes of curcumin with Cu(II or Zn(II on hydrogen peroxide (H2O2-induced injury and the underlying molecular mechanisms. The use of rat pheochromocytoma (PC12 cells, a widely used neuronal cell model system, was adopted. It was revealed that curcumin–Cu(II complexes systems possessed enhanced O2·–-scavenging activities compared to unchelated curcumin. In comparison with unchelated curcumin, the protective effects of curcumin–Cu(II complexes systems were stronger than curcumin–Zn(II system. Curcumin–Cu(II or –Zn(II complexes systems significantly enhanced the superoxide dismutase, catalase, and glutathione peroxidase activities and attenuated the increase of malondialdehyde levels and caspase-3 and caspase-9 activities, in a dose-dependent manner. The curcumin–Cu(II complex system with a 2:1 ratio exhibited the most significant effect. Further mechanistic study demonstrated that curcumin–Cu(II or –Zn(II complexes systems inhibited cell apoptosis via downregulating the nuclear factor κB (NF-κB pathway and upregulating Bcl-2/Bax pathway. In summary, the present study found that curcumin–Cu(II or –Zn(II complexes systems, especially the former, possess significant neuroprotective effects, which indicates the potential advantage of curcumin as a promising agent against AD and deserves further study.

  13. Neuroprotective Effects and Mechanisms of Curcumin-Cu(II) and -Zn(II) Complexes Systems and Their Pharmacological Implications.

    Science.gov (United States)

    Yan, Fa-Shun; Sun, Jian-Long; Xie, Wen-Hai; Shen, Liang; Ji, Hong-Fang

    2017-12-28

    Alzheimer's disease (AD) is the main form of dementia and has a steadily increasing prevalence. As both oxidative stress and metal homeostasis are involved in the pathogenesis of AD, it would be interesting to develop a dual function agent, targeting the two factors. Curcumin, a natural compound isolated from the rhizome of Curcuma longa , is an antioxidant and can also chelate metal ions. Whether the complexes of curcumin with metal ions possess neuroprotective effects has not been evaluated. Therefore, the present study was designed to investigate the protective effects of the complexes of curcumin with Cu(II) or Zn(II) on hydrogen peroxide (H₂O₂)-induced injury and the underlying molecular mechanisms. The use of rat pheochromocytoma (PC12) cells, a widely used neuronal cell model system, was adopted. It was revealed that curcumin-Cu(II) complexes systems possessed enhanced O₂ ·- -scavenging activities compared to unchelated curcumin. In comparison with unchelated curcumin, the protective effects of curcumin-Cu(II) complexes systems were stronger than curcumin-Zn(II) system. Curcumin-Cu(II) or -Zn(II) complexes systems significantly enhanced the superoxide dismutase, catalase, and glutathione peroxidase activities and attenuated the increase of malondialdehyde levels and caspase-3 and caspase-9 activities, in a dose-dependent manner. The curcumin-Cu(II) complex system with a 2:1 ratio exhibited the most significant effect. Further mechanistic study demonstrated that curcumin-Cu(II) or -Zn(II) complexes systems inhibited cell apoptosis via downregulating the nuclear factor κB (NF-κB) pathway and upregulating Bcl-2/Bax pathway. In summary, the present study found that curcumin-Cu(II) or -Zn(II) complexes systems, especially the former, possess significant neuroprotective effects, which indicates the potential advantage of curcumin as a promising agent against AD and deserves further study.

  14. Modelling Recycling Targets

    DEFF Research Database (Denmark)

    Hill, Amanda Louise; Leinikka Dall, Ole; Andersen, Frits M.

    2014-01-01

    Within the European Union (EU) a paradigm shift is currently occurring in the waste sector, where EU waste directives and national waste strategies are placing emphasis on resource efficiency and recycling targets. The most recent Danish resource strategy calculates a national recycling rate of 22......% for household waste, and sets an ambitious goal of a 50% recycling rate by 2020. This study integrates the recycling target into the FRIDA model to project how much waste and from which streams should be diverted from incineration to recycling in order to achieve the target. Furthermore, it discusses how...... the existing technological, organizational and legislative frameworks may affect recycling activities. The results of the analysis show that with current best practice recycling rates, the 50% recycling rate cannot be reached without recycling of household biowaste. It also shows that all Danish municipalities...

  15. Targeted Phototherapy (newer phototherapy

    Directory of Open Access Journals (Sweden)

    Zonunsanga

    2015-04-01

    Full Text Available Conventional phototherapy uses a whole body cabinet or body part machine such as hand, foot or scalp machines. They have many disadvantages due to which new phototherapy technique was then developed to overcome this situation. This new technique is called targeted phototherapy which includes excimer laser, intense pulse light system (IPL, photodynamic therapy and ultraviolet (UV light source with a sophisticated delivery system which is easy to be operated by hands. The mechanisms of action of targeted phototherapy systems are similar to those in conventional UVB/UVA therapy. They have many advantages like less chances of side effects, avoidance of exposure of unnecessary sites, faster response, shortening of the duration of treatments. But they have disadvantages like high costs and inability to use for extensive areas. This review article discusses targeted phototherapy in considerable to the mechanism of actions and advantages and disadvantages in comparison to the conventional phototherapy.

  16. Setting reference targets

    International Nuclear Information System (INIS)

    Ruland, R.E.

    1997-04-01

    Reference Targets are used to represent virtual quantities like the magnetic axis of a magnet or the definition of a coordinate system. To explain the function of reference targets in the sequence of the alignment process, this paper will first briefly discuss the geometry of the trajectory design space and of the surveying space, then continue with an overview of a typical alignment process. This is followed by a discussion on magnet fiducialization. While the magnetic measurement methods to determine the magnetic centerline are only listed (they will be discussed in detail in a subsequent talk), emphasis is given to the optical/mechanical methods and to the task of transferring the centerline position to reference targets

  17. Zodiac II: Debris Disk Science from a Balloon

    Science.gov (United States)

    Bryden, Geoffrey; Traub, Wesley; Roberts, Lewis C., Jr.; Bruno, Robin; Unwin, Stephen; Backovsky, Stan; Brugarolas, Paul; Chakrabarti, Supriya; Chen, Pin; Hillenbrand, Lynne; hide

    2011-01-01

    Zodiac II is a proposed balloon-borne science investigation of debris disks around nearby stars. Debris disks are analogs of the Asteroid Belt (mainly rocky) and Kuiper Belt (mainly icy) in our Solar System. Zodiac II will measure the size, shape, brightness, and color of a statistically significant sample of disks. These measurements will enable us to probe these fundamental questions: what do debris disks tell us about the evolution of planetary systems; how are debris disks produced; how are debris disks shaped by planets; what materials are debris disks made of; how much dust do debris disks make as they grind down; and how long do debris disks live? In addition, Zodiac II will observe hot, young exoplanets as targets of opportunity. The Zodiac II instrument is a 1.1-m diameter SiC (Silicone carbide) telescope and an imaging coronagraph on a gondola carried by a stratospheric balloon. Its data product is a set of images of each targeted debris disk in four broad visible-wavelength bands. Zodiac II will address its science questions by taking high-resolution, multi-wavelength images of the debris disks around tens of nearby stars. Mid-latitude flights are considered: overnight test flights in the US followed by half-global flights in the Southern Hemisphere. These longer flights are required to fully explore the set of known debris disks accessible only to Zodiac II. On these targets, it will be 100 times more sensitive than the Hubble Space Telescope's Advanced Camera for Surveys (HST/ACS); no existing telescope can match the Zodiac II contrast and resolution performance. A second objective of Zodiac II is to use the near-space environment to raise the Technology Readiness Level (TRL) of SiC mirrors, internal coronagraphs, deformable mirrors, and wavefront sensing and control, all potentially needed for a future space-based telescope for high-contrast exoplanet imaging.

  18. Fine target of deuterium

    International Nuclear Information System (INIS)

    Diaz Diaz, J.; Granados Gonzalez, C. E.; Gutierrez Bernal, R.

    1959-01-01

    A fine target of deuterium on a tantalum plate by the absorption method is obtained. In order to obtain the de gasification temperature an induction generator of high frequency is used and the deuterium pass is regulated by means of a palladium valve. Two vacuum measures are available, one to measure the high vacuum in the de gasification process of the tantalum plate and the other, for low vacuum, to measure the deuterium inlet in the installation and the deuterium pressure change in the installation after the absorption in the tantalum plate. A target of 48 μ gr/cm 2 thick is obtained. (Author) 1 refs

  19. Targeting the right journal.

    Science.gov (United States)

    Piterman, L; McCall, L

    1999-07-01

    While research is scientific, publication is a mixture of science and political pragmatism. Targeting the right journal is influenced by the following factors: the discipline that best represents the subject; the purpose of the message; the audience who are to be recipients of the message; the realities of geographic parochialism; the desire of authors to maximise personal and professional opportunities. If the originally targeted journal rejects the article, authors should have alternative publication strategies that give them professional recognition without requiring them to compromise the message or their ethics.

  20. AA antiproton production target

    CERN Multimedia

    CERN PhotoLab

    1979-01-01

    The first version of the antiproton production target was a tungsten rod, 11 cm long (actually a row of 11 rods, each 1 cm long) and 3 mm in diameter. The rod was embedded in graphite, pressure-seated into an outer casing made of stainless steel. The casing had fins for forced-air cooling. In this picture, the 26 GeV high-intensity beam from the PS enters from the right, where a scintillator screen, with circles every 5 mm in radius, permits precise aim at the target centre. See also 7903034 and 7905094.

  1. Targets and tactics

    DEFF Research Database (Denmark)

    Woo, V; Shestakova, M V; Ørskov, C

    2008-01-01

    BACKGROUND: The incidence of type 2 diabetes is reaching pandemic proportions, impacting patients and healthcare systems across the globe. Evidence suggests that a majority of patients are not achieving recommended blood glucose targets resulting in an increased risk of micro- and macro-vascular ......BACKGROUND: The incidence of type 2 diabetes is reaching pandemic proportions, impacting patients and healthcare systems across the globe. Evidence suggests that a majority of patients are not achieving recommended blood glucose targets resulting in an increased risk of micro- and macro...... diabetes has never been more compelling; with a clear focus on strategies for glycaemic control, the impact of the diabetes pandemic can be limited....

  2. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available -of-evidence (WofE) method logistic regression canonical favorability analysis neural networks evidential belief functions Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study... for the following equation: n∑ i=r ( n i ) pi(1− p)n−i = 0.95 . (1) Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study Methodology Results METHODS (cont. . . ): FITNESS FUNCTION...

  3. Target station design for a 1 MW pulsed spallation neutron source

    International Nuclear Information System (INIS)

    Russell, G.J.; Baker, G.D.; Brewton, R.J.

    1993-01-01

    Target stations are vital components of the 1 MW, next generation spallation neutron source proposed for LANSCE. By and large, target stations design determines the overall performance of the facility. Many traditional concepts will probably have to be rethought, and many new concepts will have to be put forward to meet the 1 MW challenge. This article gives a brief overview of the proposed neutron spallation source from the target station viewpoint, as well as the general philosophy adopted for the design of the LANSCE-II target stations. Some of the saliant concepts and features envisioned for LANSCE-II are briefly described

  4. First results from GERDA Phase II

    Science.gov (United States)

    Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevchik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

    2017-09-01

    Gerda is designed for a background-free search of 76Ge neutrinoless double-β decay, using bare Ge detectors in liquid Ar. The experiment was upgraded after the successful completion of Phase I to double the target mass and further reduce the background. Newly-designed Ge detectors were installed along with LAr scintillation sensors. Phase II of data-taking started in Dec 2015 with approximately 36 kg of Ge detectors and is currently ongoing. The first results based on 10.8 kg· yr of exposure are presented. The background goal of 10-3 cts/(keV· kg· yr) is achieved and a search for neutrinoless double-β decay is performed by combining Phase I and II data. No signal is found and a new limit is set at T1/20ν > 5.3 \\cdot {1025} yr (90% C.L.).

  5. The Gerda Phase II detector assembly

    Energy Technology Data Exchange (ETDEWEB)

    Bode, Tobias; Schoenert, Stefan [Physik-Department E15, Technische Universitaet Muenchen (Germany); Schwingenheuer, Bernhard [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); Collaboration: GERDA-Collaboration

    2013-07-01

    Phase II of the Gerda (Germanium Detector Array) experiment will continue the search for the neutrinoless double beta decay (0νββ) of {sup 76}Ge. Prerequisites for Phase II are an increased target mass and a reduced background index of < 10 {sup -3} cts/(keV.kg.yr). Major hardware upgrades to achieve these requirements are scheduled for 2013. They include the deployment of a new radio pure low mass detector assembly. The structural properties of available radio-pure materials and reduction of mass necessitate a change of the electrical contacting used to bias and read-out the detectors. The detector assembly design and the favored contacting solution are presented.

  6. The metacompiler system META-II/X

    International Nuclear Information System (INIS)

    Kneis, W.

    1975-03-01

    It is the objective of this work to demonstrate by the properties of the META-II/X system and concrete compiler implementation for IML that a simple and universally applicable symbol processor allows to develop in a very easy manner precompilers for problem oriented languages. The main feature consists in the fact that no auxiliary routines coded manually had to be added for special implementation. The translation of IML is exclusively defined by the compiler description written in the META language. As a whole, META-II/X proves to be a system which is relatively convenient to handle in automating the translation of explicit languages. The decisive point is the choise of an assembler language as target language allowing to transfer to the assembler level references not completely resolved. Implementation includes the possibility of an uncomplicated transfer of the whole system inclusive of the internal compiler representations. (orig.) [de

  7. Heysham II/Torness AGR core integrity

    International Nuclear Information System (INIS)

    Birch, A.L.; Hampson, J.D.

    1985-01-01

    The design and construction process for the Heysham II/Torness AGR core structures is presented. The design intent utilizing all past experience in designing and building AGR core structures is described. The major aspects of the design criteria and the design conditions are outlined to demonstrate how the integrity of the Heysham II/Torness core is assured. Since no recognized codes of practice for graphite core design exist, the National Nuclear Corporation (NNC) have conceived design criteria utilizing reserve factors based on their design experience. Target reserve factors are defined for particular loading conditions including the ultimate 'safe-shutdown earthquake'. The substantial programme of computer analysis and RandD work to substantiate the design, including seismic qualification, is described. In keeping with their responsibility for the detailed core structure design and the fuel path geometry (guide tube system), NNC attach great importance to design/manufacture/construction liaison, which is demonstrated in the quality assurance section. (author)

  8. Global track finder for Belle II experiment

    Energy Technology Data Exchange (ETDEWEB)

    Trusov, Viktor; Feindt, Michael; Heck, Martin; Kuhr, Thomas; Goldenzweig, Pablo [Karlsruhe Institute of Technology, IEKP (Germany); Collaboration: Belle II-Collaboration

    2015-07-01

    We present an implementation of a method based on the Legendre transformation for reconstruction charged particle tracks in the central drift chamber of the Belle II experiment. The method is designed for fast track finding and restoring circular patterns of track hits in transverse plane. It is done by searching for common tangents to drift circles of hits in the conformal space. With known transverse trajectories longitudinal momentum estimation performed by assigning stereo hits followed by determination of the track parameters. The method includes algorithms responsible for track quality estimation and reduction of rate of fakes. The work is targeting at increasing the efficiency and reducing the execution time because the computing power available to the experiment is limited. The algorithm is developed within the Belle II software environment with using Monte-Carlo simulation for probing its efficiency.

  9. TFOS DEWS II pathophysiology report.

    Science.gov (United States)

    Bron, Anthony J; de Paiva, Cintia S; Chauhan, Sunil K; Bonini, Stefano; Gabison, Eric E; Jain, Sandeep; Knop, Erich; Markoulli, Maria; Ogawa, Yoko; Perez, Victor; Uchino, Yuichi; Yokoi, Norihiko; Zoukhri, Driss; Sullivan, David A

    2017-07-01

    The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of both epithelial and goblet cells. The consequent decrease in surface wettability leads to early tear film breakup and amplifies hyperosmolarity via a Vicious Circle. Pain in dry eye is caused by tear hyperosmolarity, loss of lubrication, inflammatory mediators and neurosensory factors, while visual symptoms arise from tear and ocular surface irregularity. Increased friction targets damage to the lids and ocular surface, resulting in characteristic punctate epithelial keratitis, superior limbic keratoconjunctivitis, filamentary keratitis, lid parallel conjunctival folds, and lid wiper epitheliopathy. Hybrid dry eye disease, with features of both aqueous deficiency and increased evaporation, is common and efforts should be made to determine the relative contribution of each form to the total picture. To this end, practical methods are needed to measure tear evaporation in the clinic, and similarly, methods are needed to measure osmolarity at the tissue level across the ocular surface, to better determine the severity of dry eye. Areas for future research include the role of genetic mechanisms in non-Sjögren syndrome dry eye, the targeting of the terminal duct in meibomian gland disease and the influence of gaze dynamics and the closed eye state on tear stability and ocular surface inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. PROSTVAC® targeted immunotherapy candidate for prostate cancer.

    Science.gov (United States)

    Shore, Neal D

    2014-01-01

    Targeted immunotherapies represent a valid strategy for the treatment of metastatic castrate-resistant prostate cancer. A randomized, double-blind, Phase II clinical trial of PROSTVAC® demonstrated a statistically significant improvement in overall survival and a large, global, Phase III trial with overall survival as the primary end point is ongoing. PROSTVAC immunotherapy contains the transgenes for prostate-specific antigen and three costimulatory molecules (designated TRICOM). Research suggests that PROSTVAC not only targets prostate-specific antigen, but also other tumor antigens via antigen cascade. PROSTVAC is well tolerated and has been safely combined with other cancer therapies, including hormonal therapy, radiotherapy, another immunotherapy and chemotherapy. Even greater benefits of PROSTVAC may be recognized in earlier-stage disease and low-disease burden settings where immunotherapy can trigger a long-lasting immune response.

  11. European Telecommunications Satellite II (EUTELSAT II)

    Science.gov (United States)

    Laemmel, G.; Brittinger, P.

    1991-01-01

    EUTELSAT II is a regional public telecommunications system for Europe. The services which will be provided are telephone and television. The satellites will be placed at a geostationary orbit within the arcs of 6 degrees east to 19 degrees east or 26 degrees to 36 degrees east. The designed lifetime is 7 years. After separation of the satellites from the launch vehicles, telemetry, telecommand, and ranging will be performed within the S-band frequencies. After positioning of the satellite at its final geostationary orbit, the Ku-band telecommunication equipment will be activated. From this time on, all satellite control operations will be performed in Ku-band. The Deep Space Network (DSN) will support the transfer and drift orbit mission phases. The coverage will consist of the 26-m antennas at Goldstone and Canberra as prime support for the transfer and drift orbits. Maximum support will consist of a 7-day period, plus 14 days of contingency support. Information is given in tabular form for DSN support, frequency assignments, telemetry, command, and tracking support responsibility.

  12. Resveratrol: A novel type of topoisomerase II inhibitor.

    Science.gov (United States)

    Lee, Joyce H; Wendorff, Timothy J; Berger, James M

    2017-12-22

    Resveratrol, a polyphenol found in various plant sources, has gained attention as a possible agent responsible for the purported health benefits of certain foods, such as red wine. Despite annual multi-million dollar market sales as a nutriceutical, there is little consensus about the physiological roles of resveratrol. One suggested molecular target of resveratrol is eukaryotic topoisomerase II (topo II), an enzyme essential for chromosome segregation and DNA supercoiling homeostasis. Interestingly, resveratrol is chemically similar to ICRF-187, a clinically approved chemotherapeutic that stabilizes an ATP-dependent dimerization interface in topo II to block enzyme activity. Based on this similarity, we hypothesized that resveratrol may antagonize topo II by a similar mechanism. Using a variety of biochemical assays, we find that resveratrol indeed acts through the ICRF-187 binding locus, but that it inhibits topo II by preventing ATPase domain dimerization rather than stabilizing it. This work presents the first comprehensive analysis of the biochemical effects of both ICRF-187 and resveratrol on the human isoforms of topo II, and reveals a new mode for the allosteric regulation of topo II through modulation of ATPase status. Natural polyphenols related to resveratrol that have been shown to impact topo II function may operate in a similar manner. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. EPOXYEICOSATRIENOIC ACID ANALOG ATTENUATES ANGIOTENSIN II HYPERTENSION AND KIDNEY INJURY

    Directory of Open Access Journals (Sweden)

    Md. Abdul Hye Khan

    2014-09-01

    Full Text Available Epoxyeicosatrienoic acids (EETs contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end-organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II-induced hypertension. EET-B was administered in drinking water for 14 days (10mg/kg/d and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

  14. ISOLDE back on target

    CERN Multimedia

    Anaïs Schaeffer

    2014-01-01

    Today, Friday 1 August, the ISOLDE installation, supplied by the beams of the PS Booster, restarted its physics programme. After a shutdown of almost a year and a half, there was a real buzz in the air as the first beam of protons hit the target of the first post-LS1 ISOLDE experiment.   One of the new target-handling robots installed by ISOLDE during LS1. Many improvements have been made to the ISOLDE installation during LS1. One of the main projects was the installation of new robots for handling the targets (see photo 1). “Our targets are bombarded by protons from the PS Booster’s beams and become very radioactive,” explains Maria Jose Garcia Borge, spokesperson for the ISOLDE collaboration. “They therefore need to be handled carefully, which is where the robots come in. The robots we had until now were already over 20 years old and were starting to suffer from the effects of radiation. So LS1 was a perfect opportunity to replace them with more moder...

  15. Targeted Therapy for Melanoma

    International Nuclear Information System (INIS)

    Quinn, Thomas; Moore, Herbert

    2016-01-01

    The research project, entitled ''Targeted Therapy for Melanoma,'' was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the "2"1"2"P"b"/"2"0"3Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg"1"1)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of "2"1"2Pb labeled DOTA-Re(Arg"1"1)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter "2"1"2Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  16. Targets of curcumin

    Science.gov (United States)

    Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

    2010-01-01

    Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

  17. Target-Rich Environment

    Science.gov (United States)

    Perna, Mark C.

    2005-01-01

    Target marketing is defining school enrollment goals and then developing a strategic plan to accomplish those goals through the use of specific communication vehicles and community focus. It is critical to reach the right audience, with the right message, at the right time, for the right cost. In this brief article, the author describes several…

  18. Targeted enzyme prodrug therapies.

    Science.gov (United States)

    Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

    2010-09-01

    The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

  19. Targeting trichothecene biosynthetic genes

    NARCIS (Netherlands)

    Wei, Songhong; Lee, van der Theo; Verstappen, Els; Gent, van Marga; Waalwijk, Cees

    2017-01-01

    Biosynthesis of trichothecenes requires the involvement of at least 15 genes, most of which have been targeted for PCR. Qualitative PCRs are used to assign chemotypes to individual isolates, e.g., the capacity to produce type A and/or type B trichothecenes. Many regions in the core cluster

  20. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

    2016-12-05

    The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  1. The targets of curcumin.

    Science.gov (United States)

    Zhou, Hongyu; Beevers, Christopher S; Huang, Shile

    2011-03-01

    Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-kB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer's disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here.

  2. The PIP-II Reference Design Report

    Energy Technology Data Exchange (ETDEWEB)

    Lebedev, Valeri, [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); et al.

    2015-06-01

    The Proton Improvement Plan-II (PIP-II) is a high-intensity proton facility being developed to support a world-leading neutrino program over the next two decades at Fermilab. PIP-II is an integral part of the U.S. Intensity Frontier Roadmap as described in the Particle Physics Project Prioritization Panel (P5) report of May 2014 [1]. As an immediate goal PIP-II is focused on upgrades to the Fermilab accelerator complex capable of providing a beam power in excess of 1 MW on target at the initiation of LBNF [1,2] operations. PIP-II is a part of a longer-term concept for a sustained campaign of upgrades and improvements to achieve multi-MW capabilities at Fermilab. PIP-II is based on three major thrusts. They are (1) the recently completed upgrades to the Recycler and Main Injector (MI) for the NOvA experiment, (2) the Proton Improvement Plan [3] currently underway, and (3) the Project X Reference Design [4]. Note that: The Proton Improvement Plan (PIP) consolidates a set of improvements to the existing Linac, Booster, and Main Injector (MI) aimed at supporting 15 Hz Booster beam operation. In combination, the NOvA upgrades and PIP create a capability of delivering 700 kW beam power from the Main Injector at 120 GeV; The scope of the Project X Reference Design Report was aimed well beyond PIP. It described a complete concept for a multi-MW proton facility that could support a broad particle physics program based on neutrino, kaon, muon, and nucleon experiments [5,6]. The Project X conceptual design has evolved over a number of years, incorporating continuous input on physics research goals and advances in the underlying technology development programs [7,8,9]. PIP-II, to high degree, inherits these goals as the goals for future developments and upgrades. This document (PIP-II Reference Design Report) describes an initial step in the development of the Fermilab accelerating complex. The plan described in this Report balances the far-term goals of the Laboratory

  3. Ni (II) and Cu(II) complexes of

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: The objective of this study is to investigate the antimicrobial activity of novel. Schiff base metal complexes. The resistance of micro-organisms to classical antimicrobial compounds poses a challenge to effective management and treatment of some diseases. In line with this, copper (II), nickel (II) and cobalt (II) ...

  4. RTNS-II fusion materials irradiation facility

    International Nuclear Information System (INIS)

    Heikkinen, D.W.; Tuckerman, D.B.; Davis, J.C.; Massoletti, D.J.; Short, D.W.

    1986-01-01

    The Rotating Target Neutron Source (RTNS-II) facility provides an intense source of 14-MeV neutrons for the fusion energy programs of Japan and the United States. Each of the two identical accelerator-based neutron sources is capable of providing source strengths in excess of 3 x 10 13 n/s using deuteron beam currents up to 150 mA. The present status of the facility, as well as the various upgrade options, will be described in detail

  5. The NDCX-II engineering design

    Energy Technology Data Exchange (ETDEWEB)

    Waldron, W.L., E-mail: WLWaldron@lbl.gov [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Abraham, W.J.; Arbelaez, D. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Friedman, A. [Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States); Galvin, J.E. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Gilson, E.P. [Princeton Plasma Physics Laboratory, Princeton, NJ 08543 (United States); Greenway, W.G. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Grote, D.P. [Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States); Jung, J.-Y.; Kwan, J.W.; Leitner, M.; Lidia, S.M.; Lipton, T.M.; Reginato, L.L.; Regis, M.J.; Roy, P.K. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Sharp, W.M. [Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States); Stettler, M.W.; Takakuwa, J.H.; Volmering, J. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); and others

    2014-01-01

    The Neutralized Drift Compression Experiment (NDCX-II) is a user facility located at Lawrence Berkeley National Laboratory which is uniquely designed for ion-beam-driven high energy density laboratory physics and heavy ion fusion research. Construction was completed in March 2012 and the facility is now in the commissioning phase. A significant amount of engineering was carried out in order to meet the performance parameters required for a wide range of target heating experiments while making the most cost-effective use of high-value hardware available from a decommissioned high current electron induction accelerator. The technical challenges and design of this new ion induction accelerator facility are described.

  6. Luminosity Measurements at LHCb for Run II

    CERN Multimedia

    Coombs, George

    2018-01-01

    A precise measurement of the luminosity is a necessary component of many physics analyses, especially cross-section measurements. At LHCb two different direct measurement methods are used to determine the luminosity: the “van der Meer scan” (VDM) and the “Beam Gas Imaging” (BGI) methods. A combined result from these two methods gave a precision of less than 2% for Run I and efforts are ongoing to provide a similar result for Run II. Fixed target luminosity is determined with an indirect method based on the single electron scattering cross-section.

  7. F/H Area Effluent Treatment Facility. Phase II. CAC basic data

    International Nuclear Information System (INIS)

    Collins, W.W.; O'Leary, C.D.

    1984-01-01

    Project objectives and requirements are listed for both Phase I and II. Schedule is listed with startup targeted for 1989. Storage facilities will be provided for both chemical and radioactive effluents. 8 figs., 19 tabs

  8. New Therapeutic Targets in Soft Tissue Sarcoma

    Science.gov (United States)

    Demicco, Elizabeth G; Maki, Robert G; Lev, Dina C.; Lazar, Alexander J

    2012-01-01

    Soft tissue sarcomas are an uncommon and diverse group of more than 50 mesenchymal malignancies. The pathogenesis of many of these is poorly understood, but others have begun to reveal the secrets of their inner workings. With considerable effort over recent years, soft tissue sarcomas have increasingly been classified on the basis of underlying molecular alterations. In turn, this has allowed the development and application of targeted agents in several specific, molecularly defined, sarcoma subtypes. This review will focus the rationale for targeted therapy in sarcoma, with emphasis on the relevance of specific molecular factors and pathways in both translocation-associated sarcomas and in genetically complex tumors. In addition, we will address some of the early successes in sarcoma targeted therapy as well as a few challenges and disappointments in this field. Finally we will discuss several possible opportunities represented by poorly understood, but potentially promising new therapeutic targets, as well as several novel biologic agents currently in preclinical and early phase I/II trials. This will provide the reader with context for understanding the current state this field and a sense of where it may be headed in the coming years. PMID:22498582

  9. Transport phenomena II essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Transport Phenomena II covers forced convention, temperature distribution, free convection, diffusitivity and the mechanism of mass transfer, convective mass transfer, concentration

  10. Information on Asse II

    International Nuclear Information System (INIS)

    2015-01-01

    The information brochure on Asse II describes the situation in the repository for radioactive wastes that was closed by law due to the violations of safety standards. The discussed topics include the necessity of waste retrieval, the problems with public anxiety and public information, the hazard of an uncontrolled water ingress (worst case scenario), the work sites in the cavern, man-machine interactions and the cost of the project.

  11. Information on Asse II

    International Nuclear Information System (INIS)

    2014-01-01

    The information on Asse II include the following topics: The image and what is behind - the barrier building Dammjoch built 1914; Fact finding - underground explorations; concept for a site comparison; Learning from experiences - the final repository projects Asse, Gorleben and Morsleben show what should not be done; At first drilling - thereafter building - progress of the recovery duct; The retrieval can only go on in dialogue with the public.

  12. Heat transfer II essentials

    CERN Document Server

    REA, The Editors of

    1988-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Heat Transfer II reviews correlations for forced convection, free convection, heat exchangers, radiation heat transfer, and boiling and condensation.

  13. Numerical analysis II essentials

    CERN Document Server

    REA, The Editors of; Staff of Research Education Association

    1989-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Numerical Analysis II covers simultaneous linear systems and matrix methods, differential equations, Fourier transformations, partial differential equations, and Monte Carlo methods.

  14. Review on technology II

    International Nuclear Information System (INIS)

    Mroziewicz, B.

    1986-01-01

    The most important requirements for the spectral properties of photodetectors are reviewed with particular attention to the fiber optics applications. Data on a number of materials are collected and presented. Pros and cons are pointed out for each type of photodetector-photoconductor, p-i-n photodiode and APD. A review is given of the relevant papers presented in the poster session 'Technology II' of the Symposium

  15. Algebra & trigonometry II essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Algebra & Trigonometry II includes logarithms, sequences and series, permutations, combinations and probability, vectors, matrices, determinants and systems of equations, mathematica

  16. EASI graphics - Version II

    International Nuclear Information System (INIS)

    Allensworth, J.A.

    1984-04-01

    EASI (Estimate of Adversary Sequence Interruption) is an analytical technique for measuring the effectiveness of physical protection systems. EASI Graphics is a computer graphics extension of EASI which provides a capability for performing sensitivity and trade-off analyses of the parameters of a physical protection system. This document reports on the implementation of the Version II of EASI Graphics and illustrates its application with some examples. 5 references, 15 figures, 6 tables

  17. BeII** revisited

    International Nuclear Information System (INIS)

    Fischer, C.F.

    1982-01-01

    Doubly excited 1s2snl and 1s2pnl quartet states of BeII** are readily populated in beam-foil experiments and line-rich spectra have been obtained covering 600 to 5500 A wavelength range. In spite of several theoretical calculations a substantial number of observed lines have not been identified. The quartet system in BeII is an intersting one from a theoretical point of view. Three electron systems are simple enough that a fairly high level of accuracy is attainable without the calculations becoming horrendous. The important correlation effects are between the outer two electrons and, to a good approximation, the three-electrons system may be treated as a two-electron system outside a 1s-core. The multi-configuration Hartree-Fock (MCHF) method has been used successfully in a number of studies. Programs are under development that take into account the non-orthogonality of orbitals in the initial and final state, and allow for some non-orthogonal orbitals in a wavefunction expansion. LS dependent relativistic effects are also included. A study of BeII** was undertaken to evaluate the MCHF techniques being developed and to assit in the identification of observed lines. Most of the earlier calculations concentrated on the lower-lying levels. In this work particular attention was given to the more highly-excited states, though calculations for lower-lying states had to be repeated in order to predict life-times

  18. Voreloxin is an anticancer quinolone derivative that intercalates DNA and poisons topoisomerase II.

    Directory of Open Access Journals (Sweden)

    Rachael E Hawtin

    2010-04-01

    Full Text Available Topoisomerase II is critical for DNA replication, transcription and chromosome segregation and is a well validated target of anti-neoplastic drugs including the anthracyclines and epipodophyllotoxins. However, these drugs are limited by common tumor resistance mechanisms and side-effect profiles. Novel topoisomerase II-targeting agents may benefit patients who prove resistant to currently available topoisomerase II-targeting drugs or encounter unacceptable toxicities. Voreloxin is an anticancer quinolone derivative, a chemical scaffold not used previously for cancer treatment. Voreloxin is completing Phase 2 clinical trials in acute myeloid leukemia and platinum-resistant ovarian cancer. This study defined voreloxin's anticancer mechanism of action as a critical component of rational clinical development informed by translational research.Biochemical and cell-based studies established that voreloxin intercalates DNA and poisons topoisomerase II, causing DNA double-strand breaks, G2 arrest, and apoptosis. Voreloxin is differentiated both structurally and mechanistically from other topoisomerase II poisons currently in use as chemotherapeutics. In cell-based studies, voreloxin poisoned topoisomerase II and caused dose-dependent, site-selective DNA fragmentation analogous to that of quinolone antibacterials in prokaryotes; in contrast etoposide, the nonintercalating epipodophyllotoxin topoisomerase II poison, caused extensive DNA fragmentation. Etoposide's activity was highly dependent on topoisomerase II while voreloxin and the intercalating anthracycline topoisomerase II poison, doxorubicin, had comparable dependence on this enzyme for inducing G2 arrest. Mechanistic interrogation with voreloxin analogs revealed that intercalation is required for voreloxin's activity; a nonintercalating analog did not inhibit proliferation or induce G2 arrest, while an analog with enhanced intercalation was 9.5-fold more potent.As a first-in-class anticancer

  19. Parameter measurement of target

    International Nuclear Information System (INIS)

    Gao Dangzhong

    2001-01-01

    The progress of parameter measurement of target (ICF-15) in 1999 are presented, including the design and contract of the microsphere equator profiler, the precise air bearing manufacturing, high-resolution X-ray image of multi-layer shells and the X-ray photos processed with special image and data software, some plastic shells measured in precision of 0.3 μm, the high-resolution observation and photograph system of 'dew-point method', special fixture of target and its temperature distribution measuring, the dew-point temperature and fuel gas pressure of shells measuring with internal pressure of 5 - 15 (x10 5 ) Pa D 2 and wall thickness of 1.5∼3 μm

  20. Guilty Feelings, Targeted Actions

    Science.gov (United States)

    Cryder, Cynthia E.; Springer, Stephen; Morewedge, Carey K.

    2014-01-01

    Early investigations of guilt cast it as an emotion that prompts broad reparative behaviors that help guilty individuals feel better about themselves or about their transgressions. The current investigation found support for a more recent representation of guilt as an emotion designed to identify and correct specific social offenses. Across five experiments, guilt influenced behavior in a targeted and strategic way. Guilt prompted participants to share resources more generously with others, but only did so when those others were persons whom the participant had wronged and only when those wronged individuals could notice the gesture. Rather than trigger broad reparative behaviors that remediate one’s general reputation or self-perception, guilt triggers targeted behaviors intended to remediate specific social transgressions. PMID:22337764

  1. Inertial confinement fusion target

    International Nuclear Information System (INIS)

    Bourdier, A.

    2001-12-01

    A simple, zero-dimensional model describing the temporal behaviour of an imploding-shell, magnetized fuel inertial confinement fusion target is formulated. The addition of a magnetic field to the fuel reduces thermal conduction losses. As a consequence, it might lead to high gains and reduce the driver requirements. This beneficial effect of the magnetic field on thermonuclear gains is confirmed qualitatively by the zero-dimensional model results. Still, the extent of the initial-condition space for which significant gains can occur is not, by far, as large as previously reported. One-dimensional CEA code simulations which confirm this results are also presented. Finally, we suggest to study the approach proposed by Hasegawa. In this scheme, the laser target is not imploded, and the life-time of the plasma can be very much increased. (author)

  2. Hohlraum targets for HIDIF

    International Nuclear Information System (INIS)

    Ramis, R.; Ramirez, J.; Meyer-ter-Vehn, J.

    2000-01-01

    An optimized high gain IFE indirect target design is presented. Beam parameters (5 MJ of 5 GeV Bi + ions in 10-20 ns and focal spot of 3 mm radius) are in agreement to the ones considered recently for the European Study Group on Heavy Ion Driven Inertial Fusion (HIDIF). The energy yield is close to 530 MJ, giving a large enough gain appropriate for industrial energy production. Numerical and analytical modeling are described and discussed. (authors)

  3. Target Glint Suppression Technology.

    Science.gov (United States)

    1980-09-01

    Rayleigh for either horizontal or vertical polarization). 2.1.2 Spatial Characterization. Before the effects of diversity on target detection can be...ncs) dRCS T If the lower intergration limit is taken as zero for the Rayleigh targct model of interest, then this quantity is unbounded. In...port wing, inner section Trailing edge of starboard .:ing, inner section Leading edge of horizontal stabilizer, inner section, port side TLeal, -g

  4. Conditional targeting for communication

    International Nuclear Information System (INIS)

    Rodrigues, Anselmo; Caldas, Ibere L.; Baptista, Murilo S.; Piqueira, Jose Roberto C.

    2004-01-01

    In this work we propose the use of a targeting method applied to chaotic systems in order to reach special trajectories that encode arbitrary sources of messages. One advantage of this procedure is to overcome dynamical constraints which impose limits in the amount of information that the chaotic trajectories can encode. Another advantage is the message decoding, practically instantaneous and independent of any special technique or algorithm. Furthermore, with this procedure, information can be transmitted with no errors due to bounded noise

  5. Heterogeneous chromatin target model

    International Nuclear Information System (INIS)

    Watanabe, Makoto

    1996-01-01

    The higher order structure of the entangled chromatin fibers in a chromosome plays a key role in molecular control mechanism involved in chromosome mutation due to ionizing radiations or chemical mutagens. The condensed superstructure of chromatin is not so rigid and regular as has been postulated in general. We have proposed a rheological explanation for the flexible network system ('chromatin network') that consists of the fluctuating assembly of nucleosome clusters linked with supertwisting DNA in a chromatin fiber ('Supertwisting Particulate Model'). We have proposed a 'Heterosensitive Target Model' for cellular radiosensitivity that is a modification of 'Heterogeneous Target Model'. The heterogeneity of chromatin target is derived from the highly condensed organization of chromatin segments consist of unstable and fragile sites in the fluctuating assembly of nucleosome clusters, namely 'supranucleosomal particles' or 'superbeads'. The models have been principally supported by our electron microscopic experiments employing 'surface - spreading whole - mount technique' since 1967. However, some deformation and artifacts in the chromatin structure are inevitable with these electron microscopic procedures. On the contrary, the 'atomic force microscope (AFM)' can be operated in liquid as well as in the air. A living specimen can be examined without any preparative procedures. Micromanipulation of the isolated chromosome is also possible by the precise positional control of a cantilever on the nanometer scale. The living human chromosomes were submerged in a solution of culture medium and observed by AFM using a liquid immersion cell. The surface - spreading whole - mount technique was applicable for this observation. The particulate chromatin segments of nucleosome clusters were clearly observed within mitotic human chromosomes in a living hydrated condition. These findings support the heterogeneity of chromatin target in a living cell. (J.P.N.)

  6. Design and Demonstration of a Material-Plasma Exposure Target Station for Neutron Irradiated Samples

    Energy Technology Data Exchange (ETDEWEB)

    Rapp, Juergen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Aaron, A. M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bell, Gary L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Burgess, Thomas W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ellis, Ronald James [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Giuliano, D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Howard, R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kiggans, James O. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lessard, Timothy L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ohriner, Evan Keith [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Perkins, Dale E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Varma, Venugopal Koikal [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-10-20

    -state heat fluxes of 5–20 MW/m2 and ion fluxes up to 1024 m-2s-1. Since PFCs will have to withstand neutron irradiation displacement damage up to 50 dpa, the target station design must accommodate radioactive specimens (materials to be irradiated in HFIR or at SNS) to enable investigations of the impact of neutron damage on materials. Therefore, the system will have to be able to install and extract irradiated specimens using equipment and methods to avoid sample modification, control contamination, and minimize worker dose. Included in the design considerations will be an assessment of all the steps between neutron irradiation and post-exposure materials examination/characterization, as well as an evaluation of the facility hazard categorization. In particular, the factors associated with the acquisition of radioactive specimens and their preparation, transportation, experimental configuration at the plasma-specimen interface, post-plasma-exposure sample handling, and specimen preparation will be evaluated. Neutronics calculations to determine the dose rates of the samples were carried out for a large number of potential plasma-facing materials.

  7. Design and Demonstration of a Material-Plasma Exposure Target Station for Neutron Irradiated Samples

    International Nuclear Information System (INIS)

    Rapp, Juergen; Aaron, A. M.; Bell, Gary L.; Burgess, Thomas W.; Ellis, Ronald James; Giuliano, D.; Howard, R.; Kiggans, James O.; Lessard, Timothy L.; Ohriner, Evan Keith; Perkins, Dale E.; Varma, Venugopal Koikal

    2015-01-01

    5-20 MW/m"2 and ion fluxes up to 10"2"4 m"-"2s"-"1. Since PFCs will have to withstand neutron irradiation displacement damage up to 50 dpa, the target station design must accommodate radioactive specimens (materials to be irradiated in HFIR or at SNS) to enable investigations of the impact of neutron damage on materials. Therefore, the system will have to be able to install and extract irradiated specimens using equipment and methods to avoid sample modification, control contamination, and minimize worker dose. Included in the design considerations will be an assessment of all the steps between neutron irradiation and post-exposure materials examination/characterization, as well as an evaluation of the facility hazard categorization. In particular, the factors associated with the acquisition of radioactive specimens and their preparation, transportation, experimental configuration at the plasma-specimen interface, post-plasma-exposure sample handling, and specimen preparation will be evaluated. Neutronics calculations to determine the dose rates of the samples were carried out for a large number of potential plasma-facing materials.

  8. Implementing Target Value Design.

    Science.gov (United States)

    Alves, Thais da C L; Lichtig, Will; Rybkowski, Zofia K

    2017-04-01

    An alternative to the traditional way of designing projects is the process of target value design (TVD), which takes different departure points to start the design process. The TVD process starts with the client defining an allowable cost that needs to be met by the design and construction teams. An expected cost in the TVD process is defined through multiple interactions between multiple stakeholders who define wishes and others who define ways of achieving these wishes. Finally, a target cost is defined based on the expected profit the design and construction teams are expecting to make. TVD follows a series of continuous improvement efforts aimed at reaching the desired goals for the project and its associated target value cost. The process takes advantage of rapid cycles of suggestions, analyses, and implementation that starts with the definition of value for the client. In the traditional design process, the goal is to identify user preferences and find solutions that meet the needs of the client's expressed preferences. In the lean design process, the goal is to educate users about their values and advocate for a better facility over the long run; this way owners can help contractors and designers to identify better solutions. This article aims to inform the healthcare community about tools and techniques commonly used during the TVD process and how they can be used to educate and support project participants in developing better solutions to meet their needs now as well as in the future.

  9. The Bochum Polarized Target

    International Nuclear Information System (INIS)

    Reicherz, G.; Goertz, S.; Harmsen, J.; Heckmann, J.; Meier, A.; Meyer, W.; Radtke, E.

    2001-01-01

    The Bochum 'Polarized Target' group develops the target material 6 LiD for the COMPASS experiment at CERN. Several different materials like alcohols, alcanes and ammonia are under investigation. Solid State Targets are polarized in magnetic fields higher than B=2.5T and at temperatures below T=1K. For the Dynamic Nuclear Polarization process, paramagnetic centers are induced chemically or by irradiation with ionizing beams. The radical density is a critical factor for optimization of polarization and relaxation times at adequate magnetic fields and temperatures. In a high sensitive EPR--apparatus, an evaporator and a dilution cryostat with a continuous wave NMR--system, the materials are investigated and optimized. To improve the polarization measurement, the Liverpool NMR-box is modified by exchanging the fixed capacitor for a varicap diode which not only makes the tuning very easy but also provides a continuously tuned circuit. The dependence of the signal area upon the circuit current is measured and it is shown that it follows a linear function

  10. Average [O II] nebular emission associated with Mg II absorbers: dependence on Fe II absorption

    Science.gov (United States)

    Joshi, Ravi; Srianand, Raghunathan; Petitjean, Patrick; Noterdaeme, Pasquier

    2018-05-01

    We investigate the effect of Fe II equivalent width (W2600) and fibre size on the average luminosity of [O II] λλ3727, 3729 nebular emission associated with Mg II absorbers (at 0.55 ≤ z ≤ 1.3) in the composite spectra of quasars obtained with 3 and 2 arcsec fibres in the Sloan Digital Sky Survey. We confirm the presence of strong correlations between [O II] luminosity (L_{[O II]}) and equivalent width (W2796) and redshift of Mg II absorbers. However, we show L_{[O II]} and average luminosity surface density suffer from fibre size effects. More importantly, for a given fibre size, the average L_{[O II]} strongly depends on the equivalent width of Fe II absorption lines and found to be higher for Mg II absorbers with R ≡W2600/W2796 ≥ 0.5. In fact, we show the observed strong correlations of L_{[O II]} with W2796 and z of Mg II absorbers are mainly driven by such systems. Direct [O II] detections also confirm the link between L_{[O II]} and R. Therefore, one has to pay attention to the fibre losses and dependence of redshift evolution of Mg II absorbers on W2600 before using them as a luminosity unbiased probe of global star formation rate density. We show that the [O II] nebular emission detected in the stacked spectrum is not dominated by few direct detections (i.e. detections ≥3σ significant level). On an average, the systems with R ≥ 0.5 and W2796 ≥ 2 Å are more reddened, showing colour excess E(B - V) ˜ 0.02, with respect to the systems with R < 0.5 and most likely trace the high H I column density systems.

  11. Target definition for shipwreck hunting

    Directory of Open Access Journals (Sweden)

    Kim Paul Kirsner

    2015-10-01

    Full Text Available The research described in the present article was implemented to define the locations of two World War II shipwrecks, the German raider Kormoran, and the Australian light cruiser HMAS Sydney. The paper describes the long and complex trail that led through inefficient oceanographic prediction to ambiguous historical prediction involving a single report and on to precise cognitive prediction based on nine reports from more than 70 survivors, a process that yielded a single target position or ‘mean’ just 2.7 NM (nautical miles from the wreck of Kormoran. Prediction for the position of the wreck of Sydney opened with wishful thinking that she had somehow reached the coast more than 100 NM away when cognitive analysis of the survivor’s reports actually provided the basis for accurate prediction in a position near to the wreck of Kormoran. In the account provided below, the focus on cognitive procedures emerged from, first, a review of a sample of the shipwreck hunts, and, second, growing awareness of the extraordinarily rich database available for this search, and the extent to which it was open to cognitive analysis. This review touches on both the trans-disciplinary and the cognitive or intra-disciplinary issues that so challenged the political entities responsible for supervising of the search for the wrecks of Kormoran and Sydney. One of the theoretical questions that emerged from these debate concerns the model of expertise advanced by Collins (2013. The decomposability of alleged forms of expertise is revealed as a fundamental problem for research projects that might or might not benefit from trans-disciplinary research. Where expertise can be decomposed for operational purposes, the traditional dividing lines between experts and novices, and fools for that matter, are much harder to discern, and require advanced and scientifically informed review.

  12. Experience with MODSIM II

    International Nuclear Information System (INIS)

    Streets, J.; Berg, D.; Oleynik, G.; Pordes, R.; Slimmer, D.

    1992-02-01

    We present results of computer simulations for Data Acquisition systems for large fixed target experiments in an object oriented simulation language, MODSIM. This paper summarizes our experiences and presents preliminary results from the simulation already completed. We also indicate the resources required for this project

  13. Algebra II workbook for dummies

    CERN Document Server

    Sterling, Mary Jane

    2014-01-01

    To succeed in Algebra II, start practicing now Algebra II builds on your Algebra I skills to prepare you for trigonometry, calculus, and a of myriad STEM topics. Working through practice problems helps students better ingest and retain lesson content, creating a solid foundation to build on for future success. Algebra II Workbook For Dummies, 2nd Edition helps you learn Algebra II by doing Algebra II. Author and math professor Mary Jane Sterling walks you through the entire course, showing you how to approach and solve the problems you encounter in class. You'll begin by refreshing your Algebr

  14. Synthesis and spectroscopic studies of biologically active tetraazamacrocyclic complexes of Mn(II, Co(II, Ni(II, Pd(II and Pt(II

    Directory of Open Access Journals (Sweden)

    Monika Tyagi

    2014-01-01

    Full Text Available Complexes of Mn(II, Co(II, Ni(II, Pd(II and Pt(II were synthesized with the macrocyclic ligand, i.e., 2,3,9,10-tetraketo-1,4,8,11-tetraazacycoletradecane. The ligand was prepared by the [2 + 2] condensation of diethyloxalate and 1,3-diamino propane and characterized by elemental analysis, mass, IR and 1H NMR spectral studies. All the complexes were characterized by elemental analysis, molar conductance, magnetic susceptibility measurements, IR, electronic and electron paramagnetic resonance spectral studies. The molar conductance measurements of Mn(II, Co(II and Ni(II complexes in DMF correspond to non electrolyte nature, whereas Pd(II and Pt(II complexes are 1:2 electrolyte. On the basis of spectral studies an octahedral geometry has been assigned for Mn(II, Co(II and Ni(II complexes, whereas square planar geometry assigned for Pd(II and Pt(II. In vitro the ligand and its metal complexes were evaluated against plant pathogenic fungi (Fusarium odum, Aspergillus niger and Rhizoctonia bataticola and some compounds found to be more active as commercially available fungicide like Chlorothalonil.

  15. Removal of Ni (II), Co (II) and Pb (II) ions from aqueous media using ...

    African Journals Online (AJOL)

    Removal of Ni (II), Co (II) and Pb (II) ions from aqueous media using Starch ... The results showed that 0.025 % loaded SSMNPs gave the optimal sorption ... constants (Lagergren and Pseudo-2nd-order) for Ni2+ and Co2+ adsorption were ... Langmuir correlation coefficients showed a better fit for the adsorption isotherms.

  16. Inflation targeting and core inflation

    OpenAIRE

    Julie Smith

    2005-01-01

    This paper examines the interaction of core inflation and inflation targeting as a monetary policy regime. Interest in core inflation has grown because of inflation targeting. Core inflation is defined in numerous ways giving rise to many potential measures; this paper defines core inflation as the best forecaster of inflation. A cross-country study finds before the start of inflation targeting, but not after, core inflation differs between non-inflation targeters and inflation targeters. Thr...

  17. Getting sulfur on target

    Energy Technology Data Exchange (ETDEWEB)

    Halbert, T.R.; Brignac, G.B. [ExxonMobil Process Research Labs. (United States); Greeley, J.P.; Demmin, R.A.; Roundtree, E.M. [ExxonMobil Research and Engineering Co. (United States)

    2000-06-01

    The paper focuses on how the required reductions in sulfur levels in motor vehicle fuel may be achieved over about the next five years. It is said that broadly there are two possible approaches, they are: (a) to hydrotreat the feed to the FCC unit and (b) to treat the naphtha produced by the FCC unit. The difficulties associated with these processes are mentioned. The article is presented under the sub-headings of (i) technology options for cat naphtha desulfurisation; (ii) optimising fractionator design via improved VLE models; (iii) commercial experience with ICN SCANfining; (iv) mercaptan predictive models and (v) process improvements. It was concluded that the individual needs of the refiner can be addressed by ExxonMobil Research and Engineering (EMRE) and the necessary reductions in sulfur levels can be achieved.

  18. Targeting the bone marrow: applications in stem cell transplantation

    International Nuclear Information System (INIS)

    Orchard, K.; Cooper, M.

    2004-01-01

    Therapeutic doses of radiation cab be selectively directed to the bone marrow either directly using vectors that bind to myeloid and/or lymphoid specific antigens or indirectly by targeting bone matrix. The combination of an accessible target tissue and relatively radiation sensitive malignant cells favours the use of targeted radiotherapy in the treatment of haematopoietic malignancies. Dose escalation of targeted radiation can increase tumour cell destruction and has led to the use of myelosuppressive and possibly myeloablative doses of targeted radiation. A natural development has been the use of targeted radiation in conditioning prior to haematopoietic stem cell transplantation (HSCT). Several groups are actively exploring the use of targeted radiotherapy in the context of HSCT as treatment for haematological malignancies. Although no randomised trials using targeted radiotherapy in HSCT have been published, phase I and II trials have shown very encouraging results stimulating further clinical research in this field. After more than a decade of translational research the optimal combination of therapeutic radioisotope and vector has not been determined. This review summarises the clinical experience of targeted radiotherapy in HSCT and discusses the problems that still need to be solved to maximise the potential of this new treatment modality in HSCT

  19. Electronics II essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electronics II covers operational amplifiers, feedback and frequency compensation of OP amps, multivibrators, logic gates and families, Boolean algebra, registers, counters, arithmet

  20. Engineering mathematics-II

    CERN Document Server

    Ganesh, A

    2009-01-01

    About the Book: This book Engineering Mathematics-II is designed as a self-contained, comprehensive classroom text for the second semester B.E. Classes of Visveswaraiah Technological University as per the Revised new Syllabus. The topics included are Differential Calculus, Integral Calculus and Vector Integration, Differential Equations and Laplace Transforms. The book is written in a simple way and is accompanied with explanatory figures. All this make the students enjoy the subject while they learn. Inclusion of selected exercises and problems make the book educational in nature. It shou

  1. Thermodynamics II essentials

    CERN Document Server

    REA, The Editors of

    2013-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Thermodynamics II includes review of thermodynamic relations, power and refrigeration cycles, mixtures and solutions, chemical reactions, chemical equilibrium, and flow through nozzl

  2. Physics II for dummies

    CERN Document Server

    Holzner, Steven

    2010-01-01

    A plain-English guide to advanced physics. Does just thinking about the laws of motion make your head spin? Does studying electricity short your circuits? Physics II For Dummies walks you through the essentials and gives you easy-to-understand and digestible guidance on this often intimidating course. Thanks to this book, you don?t have to be Einstein to understand physics. As you learn about mechanical waves and sound, forces and fields, electric potential and electric energy, and much more, you?ll appreciate the For Dummies law: The easier we make it, the faster you'll understand it!

  3. Physical chemistry II essentials

    CERN Document Server

    REA, The Editors of

    1992-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Physical Chemistry II includes reaction mechanisms, theoretical approaches to chemical kinetics, gravitational work, electrical and magnetic work, surface work, kinetic theory, collisional and transport properties of gases, statistical mechanics, matter and waves, quantum mechanics, and rotations and vibrations of atoms and molecules.

  4. Graphics gems II

    CERN Document Server

    Arvo, James

    1991-01-01

    Graphics Gems II is a collection of articles shared by a diverse group of people that reflect ideas and approaches in graphics programming which can benefit other computer graphics programmers.This volume presents techniques for doing well-known graphics operations faster or easier. The book contains chapters devoted to topics on two-dimensional and three-dimensional geometry and algorithms, image processing, frame buffer techniques, and ray tracing techniques. The radiosity approach, matrix techniques, and numerical and programming techniques are likewise discussed.Graphics artists and comput

  5. Thin film processes II

    CERN Document Server

    Kern, Werner

    1991-01-01

    This sequel to the 1978 classic, Thin Film Processes, gives a clear, practical exposition of important thin film deposition and etching processes that have not yet been adequately reviewed. It discusses selected processes in tutorial overviews with implementation guide lines and an introduction to the literature. Though edited to stand alone, when taken together, Thin Film Processes II and its predecessor present a thorough grounding in modern thin film techniques.Key Features* Provides an all-new sequel to the 1978 classic, Thin Film Processes* Introduces new topics, and sever

  6. Statistics II essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Statistics II discusses sampling theory, statistical inference, independent and dependent variables, correlation theory, experimental design, count data, chi-square test, and time se

  7. Data structures II essentials

    CERN Document Server

    Smolarski, Dennis C

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Data Structures II includes sets, trees, advanced sorting, elementary graph theory, hashing, memory management and garbage collection, and appendices on recursion vs. iteration, alge

  8. Computer science II essentials

    CERN Document Server

    Raus, Randall

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Computer Science II includes organization of a computer, memory and input/output, coding, data structures, and program development. Also included is an overview of the most commonly

  9. Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage.

    Science.gov (United States)

    Barker, Catherine R; McNamara, Anne V; Rackstraw, Stephen A; Nelson, David E; White, Mike R; Watson, Alastair J M; Jenkins, John R

    2006-01-01

    Topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and meiosis and is a highly attractive target for chemotherapeutic agents. We have identified previously topoisomerase II and heat shock protein 90 (Hsp90) as part of a complex. In this paper we demonstrate that drug combinations targeting these two enzymes cause a synergistic increase in apoptosis. The objective of our study was to identify the mode of cell killing and the mechanism behind the increase in topoisomerase II mediated DNA damage. Importantly we demonstrate that Hsp90 inhibition results in an increased topoiosmerase II activity but not degradation of topoisomerase II and it is this, in the presence of a topoisomerase II poison that causes the increase in cell death. Our results suggest a novel mechanism of action where the inhibition of Hsp90 disrupts the Hsp90-topoisomerase II interaction leading to an increase in and activation of unbound topoisomerase II, which, in the presence of a topoisomerase II poison leads to the formation of an increased number of cleavable complexes ultimately resulting in rise in DNA damage and a subsequent increase cell death.

  10. Synthesis and spectral studies of manganese(II), cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II) and mercury(II) complexes of 4-oxo-4H-1-benzopyran-3-carboxaldehyde hydrazone derivatives

    International Nuclear Information System (INIS)

    Nawar, N.; Khattab, M.A.; Bekheit, M.M.; El-Kaddah, A.H.

    1996-01-01

    A few complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) with 4-oxo-4H-1-benzopyran-3-(carboxaldehyde-4-chlorobenzylhydrazone) (BCBH) and 4-oxo-4H-1-benzopyran-3-(carboxaldehyde-4-methylbenzylhydrazone) (BMBH) have been synthesised and characterized by elemental analysis, molar conductivities, magnetic measurements and infrared (IR) and visible spectral studies. The IR spectra show that BCBH and BMBH behave as bidentate ligands either in the keto or enol form. (author). 24 refs., 2 tabs

  11. Targeted therapy for sarcomas

    Directory of Open Access Journals (Sweden)

    Forscher C

    2014-03-01

    Full Text Available Charles Forscher,1 Monica Mita,2 Robert Figlin3 1Sarcoma Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Academic Development Program, Samuel Oschin Comprehensive Cancer Institute, and Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing's sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing's sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. Keywords: sarcoma, targeted agents, tyrosine kinase inhibitors, mTor inhibition

  12. SCORPION II persistent surveillance system update

    Science.gov (United States)

    Coster, Michael; Chambers, Jon

    2010-04-01

    This paper updates the improvements and benefits demonstrated in the next generation Northrop Grumman SCORPION II family of persistent surveillance and target recognition systems produced by the Xetron Campus in Cincinnati, Ohio. SCORPION II reduces the size, weight, and cost of all SCORPION components in a flexible, field programmable system that is easier to conceal and enables integration of over fifty different Unattended Ground Sensor (UGS) and camera types from a variety of manufacturers, with a modular approach to supporting multiple Line of Sight (LOS) and Beyond Line of Sight (BLOS) communications interfaces. Since 1998 Northrop Grumman has been integrating best in class sensors with its proven universal modular Gateway to provide encrypted data exfiltration to Common Operational Picture (COP) systems and remote sensor command and control. In addition to feeding COP systems, SCORPION and SCORPION II data can be directly processed using a common sensor status graphical user interface (GUI) that allows for viewing and analysis of images and sensor data from up to seven hundred SCORPION system gateways on single or multiple displays. This GUI enables a large amount of sensor data and imagery to be used for actionable intelligence as well as remote sensor command and control by a minimum number of analysts.

  13. Targeted mass spectrometry

    DEFF Research Database (Denmark)

    Osinalde, Nerea; Aloria, Kerman; Omaetxebarria, Miren J.

    2017-01-01

    Following the rapid expansion of the proteomics field, the investigation of post translational modifications (PTM) has become extremely popular changing our perspective of how proteins constantly fine tune cellular functions. Reversible protein phosphorylation plays a pivotal role in virtually all...... for becoming the method of choice to study with high precision and sensitivity already known site-specific phosphorylation events. This review summarizes the contribution of large-scale unbiased MS analyses and highlights the need of targeted MS-based approaches for follow-up investigation. Additionally...

  14. Angiotensin II Regulates Th1 T Cell Differentiation Through Angiotensin II Type 1 Receptor-PKA-Mediated Activation of Proteasome.

    Science.gov (United States)

    Qin, Xian-Yun; Zhang, Yun-Long; Chi, Ya-Fei; Yan, Bo; Zeng, Xiang-Jun; Li, Hui-Hua; Liu, Ying

    2018-01-01

    Naive CD4+ T cells differentiate into T helper cells (Th1 and Th2) that play an essential role in the cardiovascular diseases. However, the molecular mechanism by which angiotensin II (Ang II) promotes Th1 differentiation remains unclear. The aim of this study was to determine whether the Ang II-induced Th1 differentiation regulated by ubiquitin-proteasome system (UPS). Jurkat cells were treated with Ang II (100 nM) in the presence or absence of different inhibitors. The gene mRNA levels were detected by real-time quantitative PCR analysis. The protein levels were measured by ELISA assay or Western blot analysis, respectively. Ang II treatment significantly induced a shift from Th0 to Th1 cell differentiation, which was markedly blocked by angiotensin II type 1 receptor (AT1R) inhibitor Losartan (LST). Moreover, Ang II significantly increased the activities and the expression of proteasome catalytic subunits (β1, β1i, β2i and β5i) in a dose- and time-dependent manner. However, Ang II-induced proteasome activities were remarkably abrogated by LST and PKA inhibitor H-89. Mechanistically, Ang II-induced Th1 differentiation was at least in part through proteasome-mediated degradation of IκBα and MKP-1 and activation of STAT1 and NF-κB. This study for the first time demonstrates that Ang II activates AT1R-PKA-proteasome pathway, which promotes degradation of IκBα and MKP-1 and activation of STAT1 and NF-κB thereby leading to Th1 differentiation. Thus, inhibition of proteasome activation might be a potential therapeutic target for Th1-mediated diseases. © 2018 The Author(s). Published by S. Karger AG, Basel.

  15. SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Yang, Li; Weng, Wei; Sun, Zhi-Xin; Fu, Xian-Jie; Ma, Jun; Zhuang, Wen-Fang

    2015-01-01

    Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent. - Highlights: • SKI-II inhibits proliferation and survival of primary and transformed AML cells. • SKI-II induces apoptotic death of AML cells, but is safe to normal PBMCs. • SKI-II is more efficient than two known SphK1 inhibitors in inhibiting AML cells. • SKI-II inhibits SphK1 activity, while increasing ceramide production in AML cells. • SKI-II dose-dependently inhibits U937 xenograft growth in SCID mice

  16. SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Li; Weng, Wei; Sun, Zhi-Xin; Fu, Xian-Jie; Ma, Jun, E-mail: majuntongrensh1@126.com; Zhuang, Wen-Fang, E-mail: wenfangzhuangmd@163.com

    2015-05-15

    Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent. - Highlights: • SKI-II inhibits proliferation and survival of primary and transformed AML cells. • SKI-II induces apoptotic death of AML cells, but is safe to normal PBMCs. • SKI-II is more efficient than two known SphK1 inhibitors in inhibiting AML cells. • SKI-II inhibits SphK1 activity, while increasing ceramide production in AML cells. • SKI-II dose-dependently inhibits U937 xenograft growth in SCID mice.

  17. Targeted deficiency of the transcriptional activator Hnf1alpha alters subnuclear positioning of its genomic targets.

    Directory of Open Access Journals (Sweden)

    Reini F Luco

    2008-05-01

    Full Text Available DNA binding transcriptional activators play a central role in gene-selective regulation. In part, this is mediated by targeting local covalent modifications of histone tails. Transcriptional regulation has also been associated with the positioning of genes within the nucleus. We have now examined the role of a transcriptional activator in regulating the positioning of target genes. This was carried out with primary beta-cells and hepatocytes freshly isolated from mice lacking Hnf1alpha, an activator encoded by the most frequently mutated gene in human monogenic diabetes (MODY3. We show that in Hnf1a-/- cells inactive endogenous Hnf1alpha-target genes exhibit increased trimethylated histone H3-Lys27 and reduced methylated H3-Lys4. Inactive Hnf1alpha-targets in Hnf1a-/- cells are also preferentially located in peripheral subnuclear domains enriched in trimethylated H3-Lys27, whereas active targets in wild-type cells are positioned in more central domains enriched in methylated H3-Lys4 and RNA polymerase II. We demonstrate that this differential positioning involves the decondensation of target chromatin, and show that it is spatially restricted rather than a reflection of non-specific changes in the nuclear organization of Hnf1a-deficient cells. This study, therefore, provides genetic evidence that a single transcriptional activator can influence the subnuclear location of its endogenous genomic targets in primary cells, and links activator-dependent changes in local chromatin structure to the spatial organization of the genome. We have also revealed a defect in subnuclear gene positioning in a model of a human transcription factor disease.

  18. Fixed target beams

    CERN Document Server

    Kain, V; Cettour-Cave, S; Cornelis, K; Fraser, M A; Gatignon, L; Goddard, B; Velotti, F

    2017-01-01

    The CERN SPS (Super Proton Synchrotron) serves asLHC injector and provides beam for the North Area fixedtarget experiments. At low energy, the vertical acceptancebecomes critical with high intensity large emittance fixed tar-get beams. Optimizing the vertical available aperture is a keyingredient to optimize transmission and reduce activationaround the ring. During the 2016 run a tool was developed toprovide an automated local aperture scan around the entirering.The flux of particles slow extracted with the1/3inte-ger resonance from the Super Proton Synchrotron at CERNshould ideally be constant over the length of the extractionplateau, for optimum use of the beam by the fixed target ex-periments in the North Area. The extracted intensity is con-trolled in feed-forward correction of the horizontal tune viathe main SPS quadrupoles. The Mains power supply noiseat 50 Hz and harmonics is also corrected in feed-forwardby small amplitude tune modulation at the respective fre-quencies with a dedicated additional quad...

  19. Cardiotoxicity of novel HER2-targeted therapies.

    Science.gov (United States)

    Sendur, Mehmet A N; Aksoy, Sercan; Altundag, Kadri

    2013-08-01

    Trastuzumab, an anti-HER2 humanized monoclonal antibody, is the standard treatment for both early and metastatic HER2-positive breast cancer. In addition to other chemotherapeutic agents, trastuzumab significantly improves response rate and survival in HER2-positive early and metastatic breast cancer. Although it is well known that trastuzumab therapy is closely associated with both symptomatic and asymptomatic cardiotoxicity, less is known about novel HER2-targeted therapies. The aim of this review is to discuss the cardiac safety data from recent studies of novel anti-HER2 drugs other than trastuzumab. Novel HER2-targeted therapies showed favorable results in HER2 positive metastatic breast cancer patients. Pubmed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched until January 2013 using the following search keywords; 'trastuzumab, trastuzumab cardiotoxicity, HER-2 targeted therapies, lapatinib, pertuzumab, trastuzumab emtansine, afatinib and neratinib'; papers which were considered relevant for the aim of this review were selected by the authors. Lapatinib, pertuzumab, T-DM1, neratinib and afatinib molecules are evaluated in the study. In a comprehensive analysis, 3689 lapatinib treated patients enrolled in 49 trials; asymptomatic cardiac events were reported in 53 patients (1.4%) and symptomatic grade III and IV systolic dysfunction was observed only in 7 patients (0.2%) treated with lapatinib. In phase I-III trials of pertuzumab, cardiac dysfunction was seen in 4.5-14.5% of patients with pertuzumab treatment and cardiac dysfunction was usually grade I and II. Cardiotoxicity of pertuzumab was usually reported with the trastuzumab combination and no additive cardiotoxicity was reported with addition of pertuzumab to trastuzumab. T-DM1 had a better safety profile compared to trastuzumab, no significant cardiotoxicity was observed with T-DM1 in heavily pre-treated patients. In the EMILIA study, only in 1.7% of patients in the T

  20. Evaluation of the computerized procedures Manual II (COPMA II)

    International Nuclear Information System (INIS)

    Converse, S.A.

    1995-11-01

    The purpose of this study was to evaluate the effects of a computerized procedure system, the Computerized Procedure Manual II (COPMA-II), on the performance and mental workload of licensed reactor operators. To evaluate COPMA-II, eight teams of two operators were trained to operate a scaled pressurized water reactor facility (SPWRF) with traditional paper procedures and with COPMA-II. Following training, each team operated the SPWRF under normal operating conditions with both paper procedures and COPMA-II. The teams then performed one of two accident scenarios with paper procedures, but performed the remaining accident scenario with COPMA-II. Performance measures and subjective estimates of mental workload were recorded for each performance trial. The most important finding of the study was that the operators committed only half as many errors during the accident scenarios with COPMA-II as they committed with paper procedures. However, time to initiate a procedure was fastest for paper procedures for accident scenario trials. For performance under normal operating conditions, there was no difference in time to initiate or to complete a procedure, or in the number of errors committed with paper procedures and with COPMA-II. There were no consistent differences in the mental workload ratings operators recorded for trials with paper procedures and COPMA-II

  1. Aquaporin-2 membrane targeting

    DEFF Research Database (Denmark)

    Olesen, Emma T B; Fenton, Robert A

    2017-01-01

    The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic peptide hormone arginine vasopressin (AVP). This process is of crucial importance for the maintenance of body water homeostasis...... of aquaporin-2 (AQP2) to the apical plasma membrane of collecting duct (CD) principal cells (10, 20). This process is mainly regulated by the actions of AVP on the type 2 AVP receptor (V2R), although the V1a receptor may also play a minor role (26). The V2R is classified within the group of 7-transmembrane....... For example, 1) stimulation with the nonspecific AC activator forskolin increases AQP2 membrane accumulation in a mouse cortical collecting duct cell line [e.g., Norregaard et al. (16)]; 2) cAMP increases CD water permeability (15); 3) the cAMP-activated protein kinase A (PKA) can phosphorylate AQP2 on its...

  2. ORION laser target diagnostics

    International Nuclear Information System (INIS)

    Bentley, C. D.; Edwards, R. D.; Andrew, J. E.; James, S. F.; Gardner, M. D.; Comley, A. J.; Vaughan, K.; Horsfield, C. J.; Rubery, M. S.; Rothman, S. D.; Daykin, S.; Masoero, S. J.; Palmer, J. B.; Meadowcroft, A. L.; Williams, B. M.; Gumbrell, E. T.; Fyrth, J. D.; Brown, C. R. D.; Hill, M. P.; Oades, K.

    2012-01-01

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

  3. ORION laser target diagnostics.

    Science.gov (United States)

    Bentley, C D; Edwards, R D; Andrew, J E; James, S F; Gardner, M D; Comley, A J; Vaughan, K; Horsfield, C J; Rubery, M S; Rothman, S D; Daykin, S; Masoero, S J; Palmer, J B; Meadowcroft, A L; Williams, B M; Gumbrell, E T; Fyrth, J D; Brown, C R D; Hill, M P; Oades, K; Wright, M J; Hood, B A; Kemshall, P

    2012-10-01

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

  4. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available prospective map are the weights-of-evidence (WofE) method logistic regression canonical favorability analysis neural networks evidential belief functions Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer Introduction to Remote.... . . ): FITNESS FUNCTION φWMSD+V(Sn) = λ N(A) ∑ −→x ∈A P(−→x ) ∣ ∣ ∣ ∣−→x −QSn( −→x ) ∣ ∣ ∣ ∣ +(1− λ)s2(OSn) , (2) where QSn( −→x ) is the location vector of an optimal exploration focal point in Sn nearest to −→x , and s2(OSn) is the variance...

  5. RTNS-II utilization

    International Nuclear Information System (INIS)

    Doran, D.G.; Panayotou, N.F.; Powell, R.W.

    1979-12-01

    The objective of the several RTNS-II irradation programs is to maximize information gained from the small test volume available in this unique irradiation facility for application in the fusion materials program. While this facility provides the highest 14 MeV neutron flux available, the flux is generally too low and the irradiation volume too small for testing of engineering materials. Emphasis, therefore, is on identifying damage mechanisms of high energy neutrons and correlating them quantitatively with effects produced by fission neutrons. The information gained will be used to evaluate and calibrate damage and correlation models under development. The scope of the program includes in-situ experiments, postirradiation experiments, irradiation temperatures ranging from 4 0 K to 1,000 0 K, and fluences ranging from 3 x 10 16 to about 3 x 10 19 n/cm 2

  6. Belle II Software

    International Nuclear Information System (INIS)

    Kuhr, T; Ritter, M

    2016-01-01

    Belle II is a next generation B factory experiment that will collect 50 times more data than its predecessor, Belle. The higher luminosity at the SuperKEKB accelerator leads to higher background levels and requires a major upgrade of the detector. As a consequence, the simulation, reconstruction, and analysis software must also be upgraded substantially. Most of the software has been redesigned from scratch, taking into account the experience from Belle and other experiments and utilizing new technologies. The large amount of experimental and simulated data requires a high level of reliability and reproducibility, even in parallel environments. Several technologies, tools, and organizational measures are employed to evaluate and monitor the performance of the software during development. (paper)

  7. Inside ISIS II

    CERN Multimedia

    1981-01-01

    ISIS stands for Identification of Secondaries by Ionization Sampling. It was a drift chamber with an active volume of about 40 m3 built by Oxford University as a particle identifier for the European Hybrid Spectrometer (EHS). The photo shows the electrostatic grading structure and the central anode-wire plane, with Roger Giles standing just under it (Annual Report 1981 p. 57, Fig. 4). ISIS-II differed from the prototype ISIS-I only in the depth of the track (4 m instead of 1 m) thus extending the momentum range for particle identification to 50 GeV/c. See Nucl. Instr. and Meth. 224 (1984) 396, and Nucl. Instr. and Meth. 258 (1987) 26.

  8. Water radiological surveillance (II)

    International Nuclear Information System (INIS)

    Pablo San Martin de, M.

    2008-01-01

    This paper summarizes the characteristics of the Environmental Surveillance Radiological Networks (ESRN) currently operating in CEDEX. In the first part, the Spanish Continental Waters ESRN has been presented. This second one describes Spanish Costal Waters ESRN and the High Sensitivity Networks in Continental and Marine Waters. It also presents the Radiological Surveillance of Drinking Waters that CEDEX carries out in waters of public consumption management by the Canal de Isabel II (CYII) and by the Mancomunity of Canals Taibilla (M.C.T.). The legislation applicable in each case is reviewed as well. Due to its extension the article has been divided into two parts. As Spanish Continental Waters ESRN has been reviewed in the first part, the others ESRN are discussed in this second one. (Author) 10 refs

  9. PEP-II Alignment

    CERN Document Server

    Gaydosh, M

    2003-01-01

    The PEP-II Asymmetric B-factory consists of two independent storage rings, one located atop the other in the 2200m-circumference PEP tunnel. The high-energy ring, which stores a 9-GeV electron beam, is an upgrade of the existing PEP collider. It re-utilizes all of the PEP magnets and incorporates a state-of-the-art copper vacuum chamber and a new RF system capable of supporting a one-amp stored beam. The low-energy ring, which stores 3.1-GeV positrons, is new construction. Injection is achieved by extracting electrons and positrons at collision energies from the SLC and transporting them each in a dedicated bypass line. The low-emittance SLC beams will be used for the injection process.

  10. Stage II Seminoma

    International Nuclear Information System (INIS)

    Sagerman, R.H.; Kotlove, D.J.; Regine, W.; Chung, C.T.; King, G.A.; Dalai, P.S.

    1988-01-01

    Between 1966 and 1985, 32 patients with stage II (21 A,11 B) testicular seminoma were treated with postorchiectomy irradiation to the retroperitoneal and ipsilateral iliac nodes; 28 received elective mediastinal-supraclavicular irradiation. The median follow-up was 8 1/2 years; 29 patients were followed up for over 3 years and 24 for over 5 years. Twenty-eight patients remain alive and well and four have die, two of a second primary cancer. Two patients developed recurrent seminoma in the mediastinum; these patients showed a variant lymphangiographic pattern. Both remain well after further irradiation or irradiation plus chemotherapy. A third patient developed nonseminomatous ''recurrence'' in the radiation field and is well after chemotherapy

  11. Determining the cortical target of transcranial magnetic stimulation.

    Science.gov (United States)

    Thielscher, A; Wichmann, F A

    2009-10-01

    Determining the cortical region that is effectively targeted by TMS to induce a reproducible behavioral effect is a non-trivial problem. In mapping experiments, a grid of coil positions is used to systematically assess the TMS effect on, e.g. muscle responses or error rates. The center-of-mass (CoM) of the response distribution is projected onto the cortex to determine the likely target site, implicitly assuming the existence of a single, contiguous target. The mapping results, however, often contain several local maxima. These could either stem from measurement noise, or hint towards a distributed target region. Critically, the calculation of a CoM, by design, treats multiple maxima as if they were noise. Here, a stringent hierarchical sigmoidal model fitting approach is developed that determines the cortical target(s) from TMS mapping based on electric field calculations. Monte-Carlo simulations are used to assess the significance and the goodness-of-fit of the sigmoidal fits, and to obtain confidence regions around the calculated targets. The approach was applied to mapping data on visual suppression (N=7). In all subjects, we reliably identified two or three neighboring targets commonly contributing to the suppression effect (average distance+/-SD: 7.7+/-2.3 mm). This demonstrates that (i) the assumption of a single CoM is not generally valid and (ii) the combination of TMS mapping with the fitting approach has a cortical resolution of TMS.

  12. Phase II Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Schuknecht, Nate [Project Manager; White, David [Principle Investigator; Hoste, Graeme [Research Engineer

    2014-09-11

    The SkyTrough DSP will advance the state-of-the-art in parabolic troughs for utility applications, with a larger aperture, higher operating temperature, and lower cost. The goal of this project was to develop a parabolic trough collector that enables solar electricity generation in the 2020 marketplace for a 216MWe nameplate baseload power plant. This plant requires an LCOE of 9¢/kWhe, given a capacity factor of 75%, a fossil fuel limit of 15%, a fossil fuel cost of $6.75/MMBtu, $25.00/kWht thermal storage cost, and a domestic installation corresponding to Daggett, CA. The result of our optimization was a trough design of larger aperture and operating temperature than has been fielded in large, utility scale parabolic trough applications: 7.6m width x 150m SCA length (1,118m2 aperture), with four 90mm diameter × 4.7m receivers per mirror module and an operating temperature of 500°C. The results from physical modeling in the System Advisory Model indicate that, for a capacity factor of 75%: The LCOE will be 8.87¢/kWhe. SkyFuel examined the design of almost every parabolic trough component from a perspective of load and performance at aperture areas from 500 to 2,900m2. Aperture-dependent design was combined with fixed quotations for similar parts from the commercialized SkyTrough product, and established an installed cost of $130/m2 in 2020. This project was conducted in two phases. Phase I was a preliminary design, culminating in an optimum trough size and further improvement of an advanced polymeric reflective material. This phase was completed in October of 2011. Phase II has been the detailed engineering design and component testing, which culminated in the fabrication and testing of a single mirror module. Phase II is complete, and this document presents a summary of the comprehensive work.

  13. Bradycardia During Targeted Temperature Management

    DEFF Research Database (Denmark)

    Thomsen, Jakob Hartvig; Nielsen, Niklas; Hassager, Christian

    2016-01-01

    OBJECTIVES: Bradycardia is common during targeted temperature management, likely being a physiologic response to lower body temperature, and has recently been associated with favorable outcome following out-of-hospital cardiac arrest in smaller observational studies. The present study sought...... to confirm this finding in a large multicenter cohort of patients treated with targeted temperature management at 33°C and explore the response to targeted temperature management targeting 36°C. DESIGN: Post hoc analysis of a prospective randomized study. SETTING: Thirty-six ICUs in 10 countries. PATIENTS......: We studied 447 (targeted temperature management = 33°C) and 430 (targeted temperature management = 36°C) comatose out-of-hospital cardiac arrest patients with available heart rate data, randomly assigned in the targeted temperature management trial from 2010 to 2013. INTERVENTIONS: Targeted...

  14. Effect of Cu(II), Cd(II) and Zn(II) on Pb(II) biosorption by algae Gelidium-derived materials.

    Science.gov (United States)

    Vilar, Vítor J P; Botelho, Cidália M S; Boaventura, Rui A R

    2008-06-15

    Biosorption of Pb(II), Cu(II), Cd(II) and Zn(II) from binary metal solutions onto the algae Gelidium sesquipedale, an algal industrial waste and a waste-based composite material was investigated at pH 5.3, in a batch system. Binary Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II) solutions have been tested. For the same equilibrium concentrations of both metal ions (1 mmol l(-1)), approximately 66, 85 and 86% of the total uptake capacity of the biosorbents is taken by lead ions in the systems Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II), respectively. Two-metal results were fitted to a discrete and a continuous model, showing the inhibition of the primary metal biosorption by the co-cation. The model parameters suggest that Cd(II) and Zn(II) have the same decreasing effect on the Pb(II) uptake capacity. The uptake of Pb(II) was highly sensitive to the presence of Cu(II). From the discrete model it was possible to obtain the Langmuir affinity constant for Pb(II) biosorption. The presence of the co-cations decreases the apparent affinity of Pb(II). The experimental results were successfully fitted by the continuous model, at different pH values, for each biosorbent. The following sequence for the equilibrium affinity constants was found: Pb>Cu>Cd approximately Zn.

  15. Aerospace Systems Monitor, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Proposal Title: Aerospace Systems Monitor PHASE 1 Technical Abstract: This Phase II STTR project will continue development and commercialization of the Aerospace...

  16. Solid Polarized Targets and Applications

    International Nuclear Information System (INIS)

    Crabb, D. G.

    2008-01-01

    Examples are given of dynamically polarized targets in use today and how the subsystems have changed to meet the needs of todays experiments. Particular emphasis is placed on target materials such as ammonia and lithium deuteride. Recent polarization studies of irradiated materials such as butanol, deuterated butanol, polyethylene, and deuterated polyethylene are presented. The operation of two non-DNP target systems as well as applications of traditional DNP targets are briefly discussed

  17. Techniques for preparing isotopic targets

    International Nuclear Information System (INIS)

    Xu Guoji; Guan Shouren; Luo Xinghua; Sun Shuhua

    1987-12-01

    The techniques of making isotopic targets for nuclear physics experiments are introduced. Vacuum evaporation, electroplating, centrifugal precipitation, rolling and focused heavy-ion beam sputtering used to prepare various isotopic targets at IAE are described. Reduction-distillation with active metals and electrolytic reduction for converting isotope oxides to metals are mentioned. The stripping processes of producing self-supporting isotopic targets are summarized. The store methods of metallic targets are given

  18. Nova target diagnostics control system

    International Nuclear Information System (INIS)

    Severyn, J.R.

    1985-01-01

    During the past year the Nova target diagnostics control system was finished and put in service. The diagnostics loft constructed to the north of the target room provides the environmental conditions required to collect reliable target diagnostic data. These improvements include equipment cooling and isolation of the power source with strict control of instrumentation grounds to eliminate data corruption due to electromagnetic pulses from the laser power-conditioning system or from target implosion effects

  19. Stanford polarized atomic beam target

    International Nuclear Information System (INIS)

    Mavis, D.G.; Dunham, J.S.; Hugg, J.W.; Glavish, H.F.

    1976-01-01

    A polarized atomic beam source was used to produce an atomic hydrogen beam which was in turn used as a polarized proton target. A target density of 2 x 10'' atoms/cm 3 and a target polarization of 0.37 without the use of rf transitions were measured. These measurements indicate that a number of experiments are currently feasible with a variety of polarized target beams

  20. Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria

    Directory of Open Access Journals (Sweden)

    Daniel Ken Inaoka

    2015-07-01

    Full Text Available Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM. In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.