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Sample records for ii hfir target

  1. Status of U.S./Japan collaborative program phase II HFIR target and RB{sup *} capsules

    Energy Technology Data Exchange (ETDEWEB)

    Pawel, J.E.; Lenox, K.E.; Longest, A.W. [Oak Ridge National Laboratory, TN (United States)] [and others

    1995-04-01

    The objective of the HFIR irradiations is to determine the response of various U.S. and Japanese austenitic and ferritic steels with different pretreatments and alloy compositions to the combined effects of displacement damage and helium generation. Specimen temperatures during irradiation range from 60 to 600{degrees}C and fluences range up to 60 dpa. The RB{sup *} experiments are a continuation of the ORR spectrally tailored experiments in which the spectrum is modified with a hafnium shield to simulate the expected fusion helium to damage (He/dpa) ratio. In the HFIR target capsules, many specimens have been isotopically tailored in order to achieve fusion helium generation rates.

  2. Calculated irradiation response of materials using fission reactor (HFIR, ORR, and EBR-II) neutron spectra

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, T.A.; Bishop, B.L.; Wiffen, F.W.

    1979-08-01

    In order to plan radiation damage experiments in fission reactors keyed toward fusion reactor applications, it is necessary to have available for these facilities displacement per atom (dpa) and gas production rates for many potential materials. This report supplies such data for the elemental constituents of alloys of interest to the United States fusion reactor alloy development program. The calculations are presented for positions of interest in the HFIR, ORR, and EBR-II reactors. DPA and gas production rates in alloys of interest can be synthesized from these results.

  3. 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...

  4. HFIR spent fuel management alternatives

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-10-15

    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.

  5. Key metrics for HFIR HEU and LEU models

    Energy Technology Data Exchange (ETDEWEB)

    Ilas, Germina [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Betzler, Benjamin R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Chandler, David [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Renfro, David G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Davidson, Eva E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-10-25

    This report compares key metrics for two fuel design models of the High Flux Isotope Reactor (HFIR). The first model represents the highly enriched uranium (HEU) fuel currently in use at HFIR, and the second model considers a low-enriched uranium (LEU) interim design fuel. Except for the fuel region, the two models are consistent, and both include an experiment loading that is representative of HFIR's current operation. The considered key metrics are the neutron flux at the cold source moderator vessel, the mass of 252Cf produced in the flux trap target region as function of cycle time, the fast neutron flux at locations of interest for material irradiation experiments, and the reactor cycle length. These key metrics are a small subset of the overall HFIR performance and safety metrics. They were defined as a means of capturing data essential for HFIR's primary missions, for use in optimization studies assessing the impact of HFIR's conversion from HEU fuel to different types of LEU fuel designs.

  6. Neutron Dosimetry of the HFIR Hydraulic Facility

    CERN Document Server

    Mahmood, S T

    1995-01-01

    The total, fast, and thermal neutron fluxes at five axial positions in the High Flux Isotope Reactor (HFIR) hydraulic tube have been measured using bare and/or cadmium-covered activation, fission, and helium accumulation flux monitors. The spectrum-averaged, one-group cross sections over selected energy ranges for the reactions used in the measurements were obtained using cross sections from the ENDF/B-V file, and the target region volume-integrated spectrum was calculated with DORT, a two-dimensional discrete ordinates radiation transport code. The fluxes obtained from various monitors are in good agreement. The total and fast (>1 MeV) neutron fluxes vary from 1.6 x 10 sup 1 sup 9 n/m sup 2 centre dot s and 1.6 x 10 sup 1 sup 8 n/m sup 2 centre dot s, respectively, at the ends (HT-1 and -9) of the facility to 4.0 x 10 sup 1 sup 9 n/m sup 2 centre dot s and 4.6 x 10 sup 1 sup 8 n/m sup 2 centre dot s, respectively, at the center (HT-5) of the facility. The thermal-to-fast (> 1 MeV) flux ratio varies from abou...

  7. Neutron dosimetry and damage calculations for the HFIR-JP-23 irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R.; Ratner, R.T. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-04-01

    Neutron fluence measurements and radiation damage calculations are reported for the joint U.S. Japanese experiment JP-23, which was conducted in target position G6 of the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL). The maximum neutron fluence at midplanes was 4.4E+22 n/cm{sup 2} resulting in about 9.0 dpa in type 316 stainless steel.

  8. Neutron dosimetry and damage calculations for the HFIR-JP-23 irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R.; Ratner, R.T. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-10-01

    Neutron fluence measurements and radiation damage calculations are reported for the joint US-Japanese experiment JP-23, which was conducted in target position G6 of the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL). The maximum neutron fluence at midplane was 4.4E+22 n/cm{sup 2} resulting in about 9.0 dpa in type 316 stainless steel.

  9. Fracture toughness and Charpy impact properties of several RAFMS before and after irradiation in HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Sokolov, M.A. [Oak Ridge National Laboratory, Oak Ridge, TN 37831-6151 (United States)]. E-mail: sokolovm@ornl.gov; Tanigawa, H. [Japan Atomic Energy Agency, Tokai, Ibaraki 319-1195 (Japan); Odette, G.R. [University of California-Santa Barbara, Santa Barbara, CA 93106-5080 (United States); Shiba, K. [Japan Atomic Energy Agency, Tokai, Ibaraki 319-1195 (Japan); Klueh, R.L. [Oak Ridge National Laboratory, Oak Ridge, TN 37831-6151 (United States)

    2007-08-01

    As part of the development of candidate reduced-activation ferritic steels for fusion applications, several steels, namely F82H, 9Cr-2WVTa steels and F82H weld metal, are being investigated in the joint DOE-JAEA collaboration program. Within this program, three capsules containing a variety of specimen designs were irradiated at two design temperatures in the ORNL High Flux Isotope Reactor (HFIR). Two capsules, RB-11J and RB-12J, were irradiated in the HFIR removable beryllium positions with europium oxide (Eu{sub 2}O{sub 3}) thermal neutron shields in place. Specimens were irradiated up to 5 dpa. Capsule JP25 was irradiated in the HFIR target position to 20 dpa. The design temperatures were 300 {sup o}C and 500 {sup o}C. Precracked third-sized V-notch Charpy (3.3 x 3.3 x 25.4 mm) and 0.18 T DC(T) specimens were tested to determine transition and ductile shelf fracture toughness before and after irradiation. The master curve methodology was applied to evaluate the fracture toughness transition temperature, T {sub 0}. Irradiation induced shifts of T {sub 0} and reductions of J {sub Q} were compared with Charpy V-notch impact properties. Fracture toughness and Charpy shifts were also compared to hardening results.

  10. Small Specimen Data from a High Temperature HFIR Irradiation Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Burchell, Timothy D [ORNL; McDuffee, Joel Lee [ORNL; Thoms, Kenneth R [ORNL

    2014-01-01

    The HTV capsule is a High Flux Isotope Reactor (HFIR) target-rod capsule designed to operate at very high temperatures. The graphite containing section of the capsule (in core) is approximately 18 inches (457.2 mm) long and is separated into eight temperature zones. The specimen diameters within each zone are set to achieve the desired gas gap and hence design temperature (900 C, 1200 C or 1500 C). The capsule has five zones containing 0.400 inch (10.16 mm) diameter specimens, two zones containing 0.350 inch (8.89 mm) diameter specimens and one zone containing 0.300 inch (7.62 mm) diameter specimens. The zones have been distributed within the experiment to optimize the gamma heating from the HFIR core as well as minimize the axial heat flow in the capsule. Consequently, there are two 900 C zones, three 1200 C zones, and three 1500 C zones within the HTV capsule. Each zone contains nine specimens 0.210 0.002 inches (5.334 mm) in length. The capsule will be irradiated to a peak dose of 3.17 displacements per atom. The HTV specimens include samples of the following graphite grades: SGL Carbon s NBG-17 and NBG-18, GrafTech s PCEA, Toyo Tanso s IG-110, Mersen s 2114 and the reference grade H-451 (SGL Carbon). As part of the pre-irradiation program the specimens were characterized using ASTM Standards C559 for bulk density, and ASTM C769 for approximate Young s modulus from the sonic velocity. The probe frequency used for the determination of time of flight of the ultrasonic signal was 2.25 MHz. Marked volume (specimen diameter) effects were noted for both bulk density (increased with increasing specimen volume or diameter) and Dynamic Young s modulus (decreased with increasing specimen volume or diameter). These trends are extended by adding the property vs. diameter data for unirradiated AGC-1 creep specimens (nominally 12.5 mm-diameter x 25.4 mm-length). The relatively large reduction in Dynamic Young s Modulus was surprising given the trend for increasing density

  11. Neutron dosimetry and damage calculations for the HFIR-JP-20 irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R. [Pacific Northwest National Lab., Richland, WA (United States); Baldwin, C.A. [Oak Ridge National Lab., TN (United States)

    1998-03-01

    Neutron fluence measurements and radiation damage calculations are reported for the joint US-Japanese experiment JP-20, which was conducted in a target position of the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL). The maximum total neutron fluence at midplane was 4.2 {times} 10{sup 22} n/cm{sup 2} (1.0 {times} 10{sup 22} n/cm{sup 2} above 0.1 MeV), resulting in about 8.4 dpa and 388 appm helium in type 316 stainless steel.

  12. Neutron dosimetry and damage calculations for the HFIR-JP-9, -12, and -15 irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R. [Pacific Northwest National Lab., Richland, WA (United States); Baldwin, C.A. [Oak Ridge National Lab., TN (United States)

    1998-03-01

    Neutron fluence measurements and radiation damage calculations are reported for the joint US-Japanese experiments JP-9, -12, and -15. These experiments were conducted in target positions of the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL) for a period of nearly four years. The maximum neutron fluence at midplane was 2.6 {times} 10{sup 23} n/cm{sup 2} (7.1 {times} 10{sup 22} n/cm{sup 2} above 0.1 MeV), resulting in about 60 dpa and 3900 appm helium in type 316 stainless steel.

  13. Neutron dosimetry and damage calculation for the JP-10, 11, 13, and 16 experiments in HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R.; Ratner, R.T.

    1996-04-01

    Neutron fluence measurements and radiation damage calculations are reported for the joint U.S./Japanese experiments JP-10, 11, 13, and 16 in the target of the High Flux Isotope Reactor (HFIR) at Oak Ridge National Lab (ORNL). These experiments were irradiated at 85 MW for 238.5 EFPD. The maximum fast neutron fluence >0.1 MeV was about 2.1E + 22 n/cm{sup 2} for all of the experiments resulting in about 17.3 dpa in 316 stainless steel.

  14. Neutron dosimetry and damage calculations for the JP-17, 18 and 19 experiments in HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R.; Baldwin, C.A.

    1996-04-01

    Neutron fluence measurements and radiation damage calculations are reported for the joint US-Japanese experiments JP-17, 18, and 19 in the target of the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL). These experiments were irradiated at 85 MW for two cycles resulting in 43.55 EFPD for JP-17 and 42.06 EFPD for JP-18 and 19. The maximum fast neutron fluence > 0.1 MeV was about 3.7E + 21 n/cm{sup 2} for all three irradiations, resulting in about 3 dpa in 316 stainless steel.

  15. Production of Medical Radioisotopes in the ORNL High Flux Isotope Reactor (HFIR) for Cancer Treatment and Arterial Restenosis Therapy after PTCA

    Science.gov (United States)

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

    1998-06-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-06-01

    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.

  17. 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.

  18. Evaluation of HFIR LEU Fuel Using the COMSOL Multiphysics Platform

    Energy Technology Data Exchange (ETDEWEB)

    Primm, Trent [ORNL; Ruggles, Arthur [ORNL; Freels, James D [ORNL

    2009-03-01

    A finite element computational approach to simulation of the High Flux Isotope Reactor (HFIR) Core Thermal-Fluid behavior is developed. These models were developed to facilitate design of a low enriched core for the HFIR, which will have different axial and radial flux profiles from the current HEU core and thus will require fuel and poison load optimization. This report outlines a stepwise implementation of this modeling approach using the commercial finite element code, COMSOL, with initial assessment of fuel, poison and clad conduction modeling capability, followed by assessment of mating of the fuel conduction models to a one dimensional fluid model typical of legacy simulation techniques for the HFIR core. The model is then extended to fully couple 2-dimensional conduction in the fuel to a 2-dimensional thermo-fluid model of the coolant for a HFIR core cooling sub-channel with additional assessment of simulation outcomes. Finally, 3-dimensional simulations of a fuel plate and cooling channel are presented.

  19. Microstructural observations of HFIR-irratiated austenitic stainless steels including welds from JP9-16

    Energy Technology Data Exchange (ETDEWEB)

    Sawai, T.; Shiba, K.; Hishinuma, A.

    1996-04-01

    Austenitic stainless steels, including specimens taken from various electron beam (EB) welds, have been irradiated in HFIR Phase II capsules, JP9-16. Fifteen specimens irradiated at 300, 400, and 500{degrees}C up to 17 dpa are so far examined by a transmission electron microscope (TEM). In 300{degrees}C irradiation, cavities were smaller than 2nm and different specimens showed little difference in cavity microstructure. At 400{degrees}C, cavity size was larger, but still very small (<8 nm). At 500{degrees}C, cavity size reached 30 nm in weld metal specimens of JPCA, while cold worked JPCA contained a small (<5 nm) cavities. Inhomogeneous microstructural evolution was clearly observed in weld-metal specimens irradiated at 500{degrees}C.

  20. Production of medical radioisotopes in the ORNL high flux isotope reactor (HFIR) for cancer treatment and arterial restenosis therapy after PICA

    Science.gov (United States)

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

    1999-01-01

    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. First beginning operation in 1965, the high thermal neutron flux (2.5×1015 neutrons/cm2/sec at 85 MW) and versatile target irradiation and handling facilities provide the opportunity for production of a wide variety of neutron-rich medical radioisotopes of current interest for therapy. 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-117 m 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 (22-24 days) 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-117 m 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.

  1. 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.

  2. Design and simulation of the CG1 beamline at HFIR

    Science.gov (United States)

    Nagler, S. E.; Lee, W.-T.; Moon, R. M.

    In the near future a super-critical hydrogen cold source will be installed in the HB4 beam tube of the High Flux Isotope Reactor (HFIR), Oak Ridge National Laboratory. The cold source will illuminate four neutron guides. Here we discuss the design and simulation of the guide CG1, dedicated to a new triple axis spectrometer. The conceptual design for the HFIR guides, including CG1, was aided by numerical calculations of neutron trajectories and acceptance diagrams. The CG1 guide consists of a partially trumpeting two-channel bender and a straight guide section. The design was subsequently modeled in detail from source to specimen, utilizing the McStas program. The lessons learned from the McStas simulations resulted in some minor but important changes in the design, and these were also verified using the original method of calculation. The resulting combination of guide and vertically focusing monochromator should deliver a beam with excellent spatial and angular distributions in and out of the scattering plane. The available intensity will enable the construction of a powerful spectrometer for incident energies as large as 20-25 meV.

  3. Design and simulation of the CG1 beamline at HFIR

    CERN Document Server

    Nagler, S E; Moon, R M

    2002-01-01

    In the near future a super-critical hydrogen cold source will be installed in the HB4 beam tube of the High Flux Isotope Reactor (HFIR), Oak Ridge National Laboratory. The cold source will illuminate four neutron guides. Here we discuss the design and simulation of the guide CG1, dedicated to a new triple axis spectrometer. The conceptual design for the HFIR guides, including CG1, was aided by numerical calculations of neutron trajectories and acceptance diagrams. The CG1 guide consists of a partially trumpeting two-channel bender and a straight guide section. The design was subsequently modeled in detail from source to specimen, utilizing the McStas program. The lessons learned from the McStas simulations resulted in some minor but important changes in the design, and these were also verified using the original method of calculation. The resulting combination of guide and vertically focusing monochromator should deliver a beam with excellent spatial and angular distributions in and out of the scattering plan...

  4. Status of lithium-filled specimen subcapsules for the HFIR-MFE-RB10J experiment

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, J.P.; Howell, M.; Lenox, K.E. [Oak Ridge National Lab., TN (United States)

    1998-09-01

    The HFIR-MFE-RB-10J experiment will be irradiated in a Removable Beryllium position in the HFIR for 10 reactor cycles, accumulating approximately 5 dpa in steel. The upper region of the capsule contains two lithium-filled subcapsules containing vanadium specimens. This report describes the techniques developed to achieve a satisfactory lithium fill with a specimen occupancy of 26% in each subcapsule.

  5. Design Analyses and Shielding of HFIR Cold Neutron Scattering Instruments

    Energy Technology Data Exchange (ETDEWEB)

    Gallmeier, F.X.; Selby, D.L.; Winn, B.; Stoica, D.; Jones, A.B.; Crow, L. [Neutron Sciences Directorate, Oak Ridge National Laboratory (United States)

    2011-07-01

    Research reactor geometries and special characteristics present unique dosimetry analysis and measurement issues. The introduction of a cold neutron moderator and the production of cold neutron beams at the Oak Ridge National Laboratory High Flux Isotope Reactor have created the need for modified methods and devices for analyzing and measuring low energy neutron fields (0.01 to 100 meV). These methods include modifications to an MCNPX version to provide modeling of neutron mirror reflection capability. This code has been used to analyze the HFIR cold neutron beams and to design new instrument equipment that will use the beams. Calculations have been compared with time-of-flight measurements performed at the start of the neutron guides and at the end of one of the guides. The results indicate that we have a good tool for analyzing the transport of these low energy beams through neutron mirror and guide systems for distance up to 60 meters from the reactor. (authors)

  6. Impact of HFIR LEU Conversion on Beryllium Reflector Degradation Factors

    Energy Technology Data Exchange (ETDEWEB)

    Ilas, Dan [ORNL

    2013-10-01

    An assessment of the impact of low enriched uranium (LEU) conversion on the factors that may cause the degradation of the beryllium reflector is performed for the High Flux Isotope Reactor (HFIR). The computational methods, models, and tools, comparisons with previous work, along with the results obtained are documented and discussed in this report. The report documents the results for the gas and neutronic poison production, and the heating in the beryllium reflector for both the highly enriched uranium (HEU) and LEU HFIR configurations, and discusses the impact that the conversion to LEU may have on these quantities. A time-averaging procedure was developed to calculate the isotopic (gas and poisons) production in reflector. The sensitivity of this approach to different approximations is gauged and documented. The results show that the gas is produced in the beryllium reflector at a total rate of 0.304 g/cycle for the HEU configuration; this rate increases by ~12% for the LEU case. The total tritium production rate in reflector is 0.098 g/cycle for the HEU core and approximately 11% higher for the LEU core. A significant increase (up to ~25%) in the neutronic poisons production in the reflector during the operation cycles is observed for the LEU core, compared to the HEU case, for regions close to the core s horizontal midplane. The poisoning level of the reflector may increase by more than two orders of magnitude during long periods of downtime. The heating rate in the reflector is estimated to be approximately 20% lower for the LEU core than for the HEU core. The decrease is due to a significantly lower contribution of the heating produced by the gamma radiation for the LEU core. Both the isotopic (gas and neutronic poisons) production and the heating rates are spatially non-uniform throughout the beryllium reflector volume. The maximum values typically occur in the removable reflector and close to the midplane.

  7. Conceptual Design Parameters for HFIR LEU U-Mo Fuel Conversion Experimental Irradiations

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-03-01

    The High Flux Isotope Reactor (HFIR) is a versatile research reactor that is operated at the Oak Ridge National Laboratory (ORNL). The HFIR core is loaded with high-enriched uranium (HEU) and operates at a power level of 85 MW. The primary scientific missions of the HFIR include cold and thermal neutron scattering, materials irradiation, and isotope production. An engineering design study of the conversion of the HFIR from HEU to low-enriched uranium (LEU) fuel is ongoing at the Oak Ridge National Laboratory. The LEU fuel considered is based on a uranium-molybdenum alloy that is 10 percent by weight molybdenum (U-10Mo) with a 235U enrichment of 19.75 wt %. The LEU core design discussed in this report is based on the design documented in ORNL/TM-2010/318. Much of the data reported in Sections 1 and 2 of this document was derived from or taken directly out of ORNL/TM-2010/318. The purpose of this report is to document the design parameters for and the anticipated normal operating conditions of the conceptual HFIR LEU fuel to aid in developing requirements for HFIR irradiation experiments.

  8. 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

  9. Materials Selection for the HFIR Cold Neutron Source

    Energy Technology Data Exchange (ETDEWEB)

    Farrell, K.

    2001-08-24

    In year 2002 the High Flux Isotope Reactor (HFIR) will be fitted with a source of cold neutrons to upgrade and expand its existing neutron scattering facilities. The in-reactor components of the new source consist of a moderator vessel containing supercritical hydrogen gas moderator at a temperature of 20K and pressure of 15 bar, and a surrounding vacuum vessel. They will be installed in an enlarged beam tube located at the site of the present horizontal beam tube, HB-4; which terminates within the reactor's beryllium reflector. These components must withstand exceptional service conditions. This report describes the reasons and factors underlying the choice of 6061-T6 aluminum alloy for construction of the in-reactor components. The overwhelming considerations are the need to minimize generation of nuclear heat and to remove that heat through the flowing moderator, and to achieve a minimum service life of about 8 years coincident with the replacement schedule for the beryllium reflector. 6061-T6 aluminum alloy offers the best combination of low nuclear heating, high thermal conductivity, good fabricability, compatibility with hydrogen, superior cryogenic properties, and a well-established history of satisfactory performance in nuclear environments. These features are documented herein. An assessment is given of the expected performance of each component of the cold source.

  10. The SNS/HFIR Web Portal System for SANS

    Energy Technology Data Exchange (ETDEWEB)

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

    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

  11. Physics Design of the ETA-II/Snowtron Double Pulse Target Experiment

    CERN Document Server

    Chen, Y J; McCarrick, J F; Paul, A C; Sampayan, S E; Wang, L F; Weir, J T; Chen, Yu-Jiuan; Ho, Darwin D.-M.; Mccarrick, James F.; Paul, Arthur C.; Sampayan, Stephen; Wang, Li-Fang; Weir, John T.

    2000-01-01

    We have modified the single pulse target experimental facility[ ] on the Experimental Test Accelerator II (ETA-II) to perform the double pulse target experiments to validate the DARHT-II[, ] multi-pulse target concept. The 1.15 MeV, 2 kA Snowtron injector will provide the first electron pulse. The 6 MeV, 2 kA ETA-II beam will be used as the probe beam. Our modeling indicates that the ETA-II/Snowtron experiment is a reasonable scaling experiment.

  12. 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.

  13. Countercurrent flow limited (CCFL) heat flux in the high flux isotope reactor (HFIR) fuel element

    Energy Technology Data Exchange (ETDEWEB)

    Ruggles, A.E.

    1990-10-12

    The countercurrent flow (CCF) performance in the fuel element region of the HFIR is examined experimentally and theoretically. The fuel element consists of two concentric annuli filled with aluminum clad fuel plates of 1.27 mm thickness separated by 1.27 mm flow channels. The plates are curved as they go radially outward to accomplish constant flow channel width and constant metal-to-coolant ratio. A full-scale HFIR fuel element mock-up is studied in an adiabatic air-water CCF experiment. A review of CCF models for narrow channels is presented along with the treatment of CCFs in system of parallel channels. The experimental results are related to the existing models and a mechanistic model for the annular'' CCF in a narrow channel is developed that captures the data trends well. The results of the experiment are used to calculate the CCFL heat flux of the HFIR fuel assembly. It was determined that the HFIR fuel assembly can reject 0.62 Mw of thermal power in the CCFL situation. 31 refs., 17 figs.

  14. 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 ab

  15. 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.

  16. 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.

  17. Swelling of F82H irradiated at 673 K up to 51 dpa in HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Miwa, Y. E-mail: miway@popsvr.tokai.jaeri.go.jp; Wakai, E.; Shiba, K.; Hashimoto, N.; Robertson, J.P.; Rowcliffe, A.F.; Hishinuma, A

    2000-12-01

    Reduced-activation ferritic/martensitic steel, F82H (8Cr-2W-0.2V-0.04Ta-0.1C), and variants doped with isotopically tailored boron were irradiated at 673 K up to 51 dpa in the high flux isotope reactor (HFIR). The concentrations of {sup 10}B in these alloys were 4, 62, and 325 appm during HFIR irradiation which resulted in the production of 4, 62 and 325 appm He, respectively. After irradiation, transmission electron microscopy (TEM) was carried out. The number density of cavities increased and the average diameter of cavities decreased with increasing amounts of {sup 10}B. The number density decreased and the average diameter increased with increasing displacement damage. Swelling increased as a function of displacement damage and He concentration.

  18. Study of in-reactor creep of vanadium alloy in the HFIR RB-12J experiment

    Energy Technology Data Exchange (ETDEWEB)

    Strain, R.V.; Konicek, C.F.; Tsai, H. [Argonne National Lab., IL (United States)

    1996-10-01

    Biaxial creep specimens will be included in the HFIR RB-12J experiment to study in-reactor creep of the V-4Cr-4Ti alloy at {approx}500{degrees}C and 5 dpa. These specimens were fabricated with the 500-kg, heat (832665) material and pressurized to attain 0, 50, 100, 150, and 200 MPa mid-wall hoop stresses during the irradiation.

  19. 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.

  20. Preliminary report on the irradiation conditions of the HFIR JP-23 experiment

    Energy Technology Data Exchange (ETDEWEB)

    Ermi, A.M. [Westinghouse Hanford Company, Richland, WA (United States); Gelles, D.S. [Pacific Northwest Laboratory, Richland, WA (United States)

    1995-04-01

    The objective of this effort was to irradiate a series of alloys over the temperature range 300 to 600{degrees}C to approximately 10 dpa in the High Flux Isotope Reactor (HFIR). The alloys covered a wide range of materials and treatments. The Japanese specimen matrix consisted of ferritic steels, vanadium alloys, copper alloys, molybdenum alloys, and titanium-aluminum compounds. The US specimen matrix consisted of vanadium alloys, 316 stainless steels, and isotopically tailored ferritic and austenitic alloys.

  1. Identification of cellular targets of a series of boron heterocycles using TIPA II-A sensitive target identification platform.

    Science.gov (United States)

    Ward, Matthew S; Silva, Isba; Martinez, Walfre; Jefferson, Jameka; Rahman, Shakila; Garcia, Jeanie M; Kanichar, Divya; Roppiyakuda, Lance; Kosmowska, Ewa; Faust, Michelle A; Tran, Kim P; Chow, Felicia; Buglo, Elena; Zhou, Feimeng; Groziak, Michael P; Xu, H Howard

    2016-08-01

    One of the hurdles in the discovery of antibiotics is the difficulty of linking antibacterial compounds to their cellular targets. Our laboratory has employed a genome-wide approach of over-expressing essential genes in order to identify cellular targets of antibacterial inhibitors. Our objective in this project was to develop and validate a more sensitive disk diffusion based platform of target identification (Target Identification Platform for Antibacterials version 2; TIPA II) using a collection of cell clones in an Escherichia coli mutant (AS19) host with increased outer membrane permeability. Five known antibiotics/inhibitors and 28 boron heterocycles were tested by TIPA II assay, in conjunction with the original assay TIPA. The TIPA II was more sensitive than TIPA because eight boron heterocycles previously found to be inactive to AG1 cells in TIPA assays exhibited activity to AS19 cells. For 15 boron heterocycles, resistant colonies were observed within the zones of inhibition only on the inducing plates in TIPA II assays. DNA sequencing confirmed that resistant clones harbor plasmids with fabI gene as insert, indicating that these boron heterocycles all target enoyl ACP reductase. Additionally, cell-based assays and dose response curved obtained indicated that for two boron heterocycle inhibitors, the fabI cell clone in AG1 (wild-type) host cells exhibited at least 11 fold more resistance under induced conditions than under non-induced conditions. Moreover, TIPA II also identified cellular targets of known antibacterial inhibitors triclosan, phosphomycin, trimethoprim, diazaborine and thiolactomycin, further validating the utility of the new system.

  2. Analysis of HFIR Dosimetry Experiments Performed in Cycles 400 and 401

    Energy Technology Data Exchange (ETDEWEB)

    Remec, Igor [ORNL; Baldwin, Charles A [ORNL

    2008-09-01

    The High Flux Isotope Reactor (HFIR) has been in operation at Oak Ridge National Laboratory since 1966. To upgrade and enhance capabilities for neutron science research at the reactor, a larger HB-2 beam tube was installed in April of 2002. To assess, experimentally, the impact of this larger beam tube on radiation damage rates [i.e., displacement-per-atom (dpa) rates] used in vessel life extension studies, dosimetry experiments were performed from April to August 2004 during fuel cycles 400 and 401. This report documents the analysis of the dosimetry experiments and the determination of best-estimate dpa rates. These dpa rates are obtained by performing a least-squares adjustment of calculated neutron and gamma-ray fluxes and the measured responses of radiometric monitors and beryllium helium accumulation fluence monitors. The best-estimate dpa rates provided here will be used to update HFIR pressure vessel life extension studies, which determine the pressure/temperature limits for reactor operation and the HFIR pressure vessel's remaining life. All irradiation parameters given in this report correspond to a reactor power of 85 MW.

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

    Energy Technology Data Exchange (ETDEWEB)

    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/sub 3/O/sub 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/sub 3/O/sub 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.

  4. Plectasin, a Fungal Defensin, Targets the Bacterial Cell Wall Precursor Lipid II

    DEFF Research Database (Denmark)

    Schneider, Tanja; Kruse, Thomas; Wimmer, Reinhard

    2010-01-01

    that plectasin, a fungal defensin, acts by directly binding the bacterial cell-wall precursor Lipid II. A wide range of genetic and biochemical approaches identify cell-wall biosynthesis as the pathway targeted by plectasin. In vitro assays for cell-wall synthesis identified Lipid II as the specific cellular...

  5. Past and current perspective on new therapeutic targets for Type-II diabetes.

    Science.gov (United States)

    Patil, Pradip D; Mahajan, Umesh B; Patil, Kalpesh R; Chaudhari, Sandip; Patil, Chandragouda R; Agrawal, Yogeeta O; Ojha, Shreesh; Goyal, Sameer N

    2017-01-01

    Loss of pancreatic β-cell function is a hallmark of Type-II diabetes mellitus (DM). It is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Recently, United Kingdom Prospective Diabetes Study reported that Type-II DM is a progressive disorder. Although, DM can be treated initially by monotherapy with oral agent; eventually, it may require multiple drugs. Additionally, insulin therapy is needed in many patients to achieve glycemic control. Pharmacological approaches are unsatisfactory in improving the consequences of insulin resistance. Single therapeutic approach in the treatment of Type-II DM is unsuccessful and usually a combination therapy is adopted. Increased understanding of biochemical, cellular and pathological alterations in Type-II DM has provided new insight in the management of Type-II DM. Knowledge of underlying mechanisms of Type-II DM development is essential for the exploration of novel therapeutic targets. Present review provides an insight into therapeutic targets of Type-II DM and their role in the development of insulin resistance. An overview of important signaling pathways and mechanisms in Type-II DM is provided for the better understanding of disease pathology. This review includes case studies of drugs that are withdrawn from the market. The experience gathered from previous studies and knowledge of Type-II DM pathways can guide the anti-diabetic drug development toward the discovery of clinically viable drugs that are useful in Type-II DM.

  6. 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.

  7. Targeting hexokinase II as a possible therapy for cholangiocarcinoma.

    Science.gov (United States)

    Thamrongwaranggoon, Ubonrat; Seubwai, Wunchana; Phoomak, Chatchai; Sangkhamanon, Sakkarn; Cha'on, Ubon; Boonmars, Thidarat; Wongkham, Sopit

    2017-03-04

    Overexpression of hexokinase 2 (HKII) has been demonstrated in various cancers. A number of in vitro and in vivo studies in several cancers show the significance of HKII in many cellular processes including proliferation, metastasis and apoptosis. However, the role of HKII in Opisthorchis viverrini (Ov) associated cholangiocarcinoma (CCA) is still unknown. In the present study, the expression and roles of HKII were determined in Ov associated CCA. The expression of HKII was investigated in 82 patients with histologically proven CCAs by immunohistochemistry. HKII was distinctively expressed in CCA tissues. It was rarely expressed in normal bile duct epithelium, but was expressed in hyperplastic/dysplastic and in 82% of CCA bile ducts. The observation was confirmed in the Ov associated hamster model. Suppression of HKII expression using siRNA significantly decreased cell proliferation, migration and invasion of CCA cell lines. Similar results were obtained using lonidamine (LND), an inhibitor of HK. LND significantly inhibited growth of 4 CCA cell lines tested in dose and time dependent fashion. Comparison the cytotoxic effects of LND and siRNA-HKII suggests the off target of LND above 100 μM. In addition, LND in non-cytotoxic doses could suppress migration and invasion of CCA cells. These results indicate the association of HKII in cholangiocarcinogenesis and progression and suggest the possibility of HKII as a therapeutic target for CCA.

  8. 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.

  9. Zn(II)-curc targets p53 in thyroid cancer cells.

    Science.gov (United States)

    Garufi, Alessia; D'Orazi, Valerio; Crispini, Alessandra; D'Orazi, Gabriella

    2015-10-01

    TP53 mutation is a common event in many cancers, including thyroid carcinoma. Defective p53 activity promotes cancer resistance to therapies and a more malignant phenotype, acquiring oncogenic functions. Rescuing the function of mutant p53 (mutp53) protein is an attractive anticancer therapeutic strategy. Zn(II)-curc is a novel small molecule that has been shown to target mutp53 protein in several cancer cells, but its effect in thyroid cancer cells remains unclear. Here, we investigated whether Zn(II)-curc could affect p53 in thyroid cancer cells with both p53 mutation (R273H) and wild-type p53. Zn(II)-curc induced mutp53H273 downregulation and reactivation of wild-type functions, such as binding to canonical target promoters and target gene transactivation. This latter effect was similar to that induced by PRIMA-1. In addition, Zn(II)-curc triggered p53 target gene expression in wild-type p53-carrying cells. In combination treatments, Zn(II)-curc enhanced the antitumor activity of chemotherapeutic drugs, in both mutant and wild-type-carrying cancer cells. Taken together, our data indicate that Zn(II)-curc promotes the reactivation of p53 in thyroid cancer cells, providing in vitro evidence for a potential therapeutic approach in thyroid cancers.

  10. A peptide vaccine targeting angiotensin II attenuates the cardiac dysfunction induced by myocardial infarction

    Science.gov (United States)

    Watanabe, Ryo; Suzuki, Jun-ichi; Wakayama, Kouji; Maejima, Yasuhiro; Shimamura, Munehisa; Koriyama, Hiroshi; Nakagami, Hironori; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Morishita, Ryuichi; Komuro, Issei; Isobe, Mitsuaki

    2017-01-01

    A peptide vaccine targeting angiotensin II (Ang II) was recently developed as a novel treatment for hypertension to resolve the problem of noncompliance with pharmacotherapy. Ang II plays a crucial role in the pathogenesis of cardiac remodeling after myocardial infarction (MI), which causes heart failure. In the present study, we examined whether the Ang II vaccine is effective in preventing heart failure. The injection of the Ang II vaccine in a rat model of MI attenuated cardiac dysfunction in association with an elevation in the serum anti-Ang II antibody titer. Furthermore, any detrimental effects of the Ang II vaccine were not observed in the rats that underwent sham operations. Treatment with immunized serum from Ang II vaccine-injected rats significantly suppressed post-MI cardiac dysfunction in MI rats and Ang II-induced remodeling-associated signaling in cardiac fibroblasts. Thus, our present study demonstrates that the Ang II vaccine may provide a promising novel therapeutic strategy for preventing heart failure. PMID:28266578

  11. 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.

  12. The Asteroid Identification Problem. II. Target Plane Confidence Boundaries

    Science.gov (United States)

    Milani, Andrea; Valsecchi, Giovanni B.

    1999-08-01

    The nominal orbit solution for an asteroid/comet resulting from a least squares fit to astrometric observations is surrounded by a region containing solutions equally compatible with the data, the confidence region. If the observed arc is not too short, and for an epoch close to the observations, the confidence region in the six-dimensional space of orbital elements is well approximated by an ellipsoid. This uncertainty of the orbital elements maps to a position uncertainty at close approach, which can be represented on a Modified Target Plane (MTP), a modification of the one used by Öpik. The MTP is orthogonal to the geocentric velocity at the closest approach point along the nominal orbit. In the linear approximation, the confidence ellipsoids are mapped on the MTP into concentric ellipses, computed by solving the variational equation. For an object observed at only one opposition, however, if the close approach is expected after many revolutions, the ellipses on the MTP become extremely elongated, therefore the linear approximation may fail, and the confidence boundaries on the MTP, by definition the nonlinear images of the confidence ellipsoids, may not be well approximated by the ellipses. In theory the Monte Carlo method by Muinonen and Bowell (1993, Icarus104, 255-279) can be used to compute the nonlinear confidence boundaries, but in practice the computational load is very heavy. We propose a new method to compute semilinear confidence boundaries on the MTP, based on the theory developed by Milani (1999, Icarus137, 269-292) to efficiently compute confidence boundaries for predicted observations. This method is a reasonable compromise between reliability and computational load, and can be used for real time risk assessment. These arguments can be applied to any small body approaching any planet, but in the case of a potentially hazardous object (PHO), either an asteroid or a comet whose orbit comes very close to that of the Earth, the application is most

  13. 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.

  14. Transmutation-induced embrittlement of V-Ti-Ni and V-Ni alloys in HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Ohnuki, S.; Takahashi, H. [Hokkaido Univ., Sapparo (Japan); Garner, F.A. [Pacific Northwest National Laboratory, Richland, WA (United States); Pawel, J.E. [Oak Ridge National Laboratory, TN (United States)] [and others

    1996-04-01

    Vanadium, V-1Ni, V-10Ti and V-10Ti-1Ni (at %) were irradiated in HFIR to doses ranging from 18 to 30 dpa and temperatures between 300 and 600C. Since the irradiation was conducted in a highly thermalized neutron spectrum without shielding against thermal neutrons, significant levels of chromium (15-22%) were formed by transmutation. The addition of such large chromium levels strongly elevated the ductile to brittle transition temperature. At higher irradiation temperatures radiation-induced segregation of transmutant Cr and solute Ti at specimen surfaces leads to strong increases in the density of the alloy.

  15. Neutron dosimetry and damage calculations for the HFIR-MFE-200J-1 irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R. [Pacific Northwest National Lab., Richland, WA (United States); Baldwin, C.A. [Oak Ridge National Lab., TN (United States)

    1998-03-01

    Neutron fluence measurements and radiation damage calculations are reported for the joint US-Japanese experiment MFE-200-J-, which was conducted in the removable beryllium (RB) position of the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL). The maximum neutron fluence at midplane was 4.1 {times} 10{sup 22} n/cm{sup 2} (1.9 {times} 10{sup 22} n/cm{sup 2} above 0.1 MeV), resulting in about 12 dpa and 28 appm helium in type 316 stainless steel.

  16. Target echo strength modelling at FOI, including results from the BeTSSi II workshop

    CERN Document Server

    Östberg, Martin

    2016-01-01

    An overview of the target echo strength (TS) modelling capacity at the Swedish Defense Research Agency (FOI) is presented. The modelling methods described range from approximate ones, such as raytracing and Kirchhoff approximation codes, to high accuracy full field codes including boundary integral equation methods and finite elements methods. Illustrations of the applicability of the codes are given for a few simple cases tackled during the BeTTSi II (Benchmark Target Echo Strength Simulation) workshop held in Kiel 2014.

  17. Targeting angiotensin II type 2 receptor pathways to treat neuropathic pain and inflammatory pain.

    Science.gov (United States)

    Smith, Maree T; Muralidharan, Arjun

    2015-01-01

    Neuropathic pain and chronic inflammatory pain are large unmet medical needs. Over the past two decades, numerous 'pain targets' have been identified for analgesic drug discovery. Despite promising results in rodent pain models, many compounds modulating such targets lacked efficacy in clinical trials. An exception is oral EMA401, a small-molecule angiotensin II type 2 receptor (AT2R) antagonist. Herein, angiotensin II/AT2R signaling-induced hyperexcitability and abnormal sprouting of cultured dorsal root ganglion neurons, together with radioligand binding, pharmacokinetics, analgesic efficacy and mode of action of small-molecule AT2R antagonists in rodent models of peripheral neuropathic and chronic inflammatory pain, are reviewed. The findings of a successful Phase IIa clinical trial of EMA401 in patients with neuropathic pain are presented in brief. The functional importance of angiotensin II/AT2R signaling has remained enigmatic for decades, and there are no clinically available medications that target the AT2R. However, on the basis of preclinical findings and recent clinical trial data showing that the peripherally restricted, small-molecule AT2R antagonist, EMA401, successfully alleviated neuropathic pain in a Phase II clinical trial, the AT2R is receiving considerable attention as a new therapeutic target with human validation for the relief of peripheral neuropathic and chronic inflammatory pain conditions.

  18. 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.

  19. TARGET ANALYSIS OF SUZHOU CREEK REHABILITATION PROJECT STAGE II:BASED ON WATER QUALITY MODEL

    Institute of Scientific and Technical Information of China (English)

    LIAO Zhen-liang; XU Zu-xin

    2004-01-01

    The Suzhou Creek is a seriously polluted tidal river in Shanghai. The Suzhou Creek Rehabilitation Project was launched in 1998, and the total investment will surpass 10 billion yuan RMB. It is important to assess the effectiveness of the project and ascertain its targets. In this study, by analyzing the achievements of Suzhou Creek Rehabilitation Project (Stage I) and its remaining problems, the main tasks of the Project Stage II are proposed. These works are wastewater interception, sediment dredging, bidirectional water diversion, and reconstruction of municipal pump stations. The water quality model established with USEPA's WASP is employed to analyze the quantitative targets of the Project Stage II. In the Project Stage II, the water quality of mainstream and tributaries will be improved continuously, the valus of CODCr, BOD5, DO in the mainstream will steadily attain Class IV according to the National Surface Water Quality Standard, and the ecological environment of Suzhou Creek with continuously recover.

  20. Accelerated 54{degree}C irradiated test of Shippingport neutron shield tank and HFIR vessel materials

    Energy Technology Data Exchange (ETDEWEB)

    Hawthorne, J.R. [Materials Engineering Associates, Inc., Lanham, MD (United States); Rosinski, S.T. [Sandia National Labs., Albuquerque, NM (United States)

    1993-01-01

    Charpy V-notch specimens (ASTM Type A) and 5.74-mm diameter tension test specimens of the Shippingport Reactor Neutron Shield Tank (NST) (outer wall material) were irradiated together with Charpy V-notch specimens of the Oak Ridge National Laboratory (ORNI), High,, Flux Isotope Reactor (HFIR) vessel (shell material), to 5.07 {times} 10{sup 17} n/cm{sup 2}, E > 1 MeV. The irradiation was performed in the Ford Nuclear Reactor (FNR), a test reactor, at a controlled temperature of 54{degrees}C (130{degrees}F) selected to approximate the prior service temperatures of the cited reactor structures. Radiation-induced elevations in the Charpy 41-J transition temperature and the ambient temperature yield strength were small and independent of specimen test orientation (ASTM LT vs. TL). The observations are consistent with prior findings for the two materials (A 212-B plate) and other like materials irradiated at low temperature (< 200{degrees}C) to low fluence. The high radiation embrittlement sensitivity observed in HFIR vessel surveillance program tests was not found in the present accelerated irradiation test. Response to 288{degrees}C-168 h postirradiation annealing was explored for the NST material. Notch ductility recovery was found independent of specimen test orientation but dependent on the temperature within the transition region at which the specimens were tested.

  1. Accelerated 54[degree]C irradiated test of Shippingport neutron shield tank and HFIR vessel materials

    Energy Technology Data Exchange (ETDEWEB)

    Hawthorne, J.R. (Materials Engineering Associates, Inc., Lanham, MD (United States)); Rosinski, S.T. (Sandia National Labs., Albuquerque, NM (United States))

    1993-01-01

    Charpy V-notch specimens (ASTM Type A) and 5.74-mm diameter tension test specimens of the Shippingport Reactor Neutron Shield Tank (NST) (outer wall material) were irradiated together with Charpy V-notch specimens of the Oak Ridge National Laboratory (ORNI), High,, Flux Isotope Reactor (HFIR) vessel (shell material), to 5.07 [times] 10[sup 17] n/cm[sup 2], E > 1 MeV. The irradiation was performed in the Ford Nuclear Reactor (FNR), a test reactor, at a controlled temperature of 54[degrees]C (130[degrees]F) selected to approximate the prior service temperatures of the cited reactor structures. Radiation-induced elevations in the Charpy 41-J transition temperature and the ambient temperature yield strength were small and independent of specimen test orientation (ASTM LT vs. TL). The observations are consistent with prior findings for the two materials (A 212-B plate) and other like materials irradiated at low temperature (< 200[degrees]C) to low fluence. The high radiation embrittlement sensitivity observed in HFIR vessel surveillance program tests was not found in the present accelerated irradiation test. Response to 288[degrees]C-168 h postirradiation annealing was explored for the NST material. Notch ductility recovery was found independent of specimen test orientation but dependent on the temperature within the transition region at which the specimens were tested.

  2. Ets-1 targeted by microrna-221 regulates angiotensin II-induced renal fibroblast activation and fibrosis.

    Science.gov (United States)

    Di, Jia; Jiang, Lei; Zhou, Yang; Cao, Hongdi; Fang, Li; Wen, Ping; Li, Xiurong; Dai, Chunsun; Yang, Junwei

    2014-01-01

    Fibroblast activation is one of the most important mechanisms for Angiotensin II (Ang II) in promoting renal fibrosis. Transcription factor Ets-1 is recognized to play a key role in kidney diseases. However, the role and mechanisms of Ets-1 in Ang-II induced fibroblast activation and kidney fibrosis are not fully understood. Mice were treated with Ang II via osmotic mini-pumps or Ang II expression plasmid (pAng II). Cultured normal rat kidney interstitial fibroblast (NRK-49F) cells were incubated with Ang II. Role of Ets-1 in renal fibrosis and fibroblast activation were assessed by Western blot, Immunohistochemical staining'MTT, Boyden chamber and Immunofluorescence staining. Effects of miR-221 on Ets-1 and fibroblast activation were investigated by MTT, Boyden chamber, Western blot and Q-PCR. We found that Ets-1 was up-regulated in fibrotic kidneys. Similarly, Ang II could activate NRK-49F cells as demonstrated by up-regulated α-SMA and fibronectin(FN) expression and enhanced cell proliferation and migration. Ang II also induced Ets-1 expression in NRK-49F cells in a dose and time dependent manner. Knock-down of Ets-1 by RNA interference attenuated Ang II-induced activation of NRK-49F cells. Ets-1 was previously reported as a target of microRNA-221 (miR-221). In Ang II-induced fibrotic kidney, miR-221 was down-regulated. Similar results were observed in Ang II treated NRK-49F cells. Ectopic expression of miR-221 mimic attenuated the up-regulation of Ets-1 by Ang II in NRK-49F cells, which further prevented the activation of NRK-49F cells. However, the inhibitor of miR-221 aggravated Ang II induced Ets-1 expression and NRK-49F cells activation. Our study suggests that miR-221/Ets-1 axis takes an important role in mediating AngII induced interstitial fibroblast activation and renal fibrosis. © 2014 S. Karger AG, Basel.

  3. 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

  4. 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

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

    Directory of Open Access Journals (Sweden)

    Mert Yanik

    Full Text Available 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.

  6. Adenanthin targets peroxiredoxin I/II to kill hepatocellular carcinoma cells.

    Science.gov (United States)

    Hou, J-K; Huang, Y; He, W; Yan, Z-W; Fan, L; Liu, M-H; Xiao, W-L; Sun, H-D; Chen, G-Q

    2014-09-04

    Adenanthin, a natural diterpenoid isolated from the leaves of Isodon adenanthus, has recently been reported to induce leukemic cell differentiation by targeting peroxiredoxins (Prx) I and II. On the other hand, increasing lines of evidence propose that these Prx proteins would become potential targets to screen drugs for the prevention and treatment of solid tumors. Therefore, it is of significance to explore the potential activities of adenanthin on solid tumor cells. Here, we demonstrate that Prx I protein is essential for the survival of hepatocellular carcinoma (HCC) cells, and adenanthin can kill these malignant liver cells in vitro and xenografts. We also show that the cell death-inducing activity of adenanthin on HCC cells is mediated by the increased reactive oxygen species (ROS) levels. Furthermore, the silencing of Prx I or Prx II significantly enhances the cytotoxic activity of adenanthin on HCC, whereas the ectopic expression of Prx I and Prx II but not their mutants of adenanthin-bound cysteines can rescue adenanthin-induced cytotoxicity in Prxs-silenced HCC cells. Taken together, our results propose that adenanthin targets Prx I/II to kill HCC cells and its therapeutic significance warrants to be further explored in HCC patients.

  7. 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.

  8. 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

  9. Target recognition, resistance, immunity and genome mining of class II bacteriocins from Gram-positive bacteria.

    Science.gov (United States)

    Kjos, Morten; Borrero, Juan; Opsata, Mona; Birri, Dagim J; Holo, Helge; Cintas, Luis M; Snipen, Lars; Hernández, Pablo E; Nes, Ingolf F; Diep, Dzung B

    2011-12-01

    Due to their very potent antimicrobial activity against diverse food-spoiling bacteria and pathogens and their favourable biochemical properties, peptide bacteriocins from Gram-positive bacteria have long been considered promising for applications in food preservation or medical treatment. To take advantage of bacteriocins in different applications, it is crucial to have detailed knowledge on the molecular mechanisms by which these peptides recognize and kill target cells, how producer cells protect themselves from their own bacteriocin (self-immunity) and how target cells may develop resistance. In this review we discuss some important recent progress in these areas for the non-lantibiotic (class II) bacteriocins. We also discuss some examples of how the current wealth of genome sequences provides an invaluable source in the search for novel class II bacteriocins.

  10. High average power CO II laser MOPA system for Tin target LPP EUV light source

    Science.gov (United States)

    Ariga, Tatsuya; Hoshino, Hideo; Endo, Akira

    2007-02-01

    Extreme ultraviolet lithography (EUVL) is the candidate for next generation lithography to be introduced by the semiconductor industry to HVM (high volume manufacturing) in 2013. The power of the EUVL light source has to be at least 115W at a wavelength of 13.5nm. A laser produced plasma (LPP) is the main candidate for this light source but a cost effective laser driver is the key requirement for the realization of this concept. We are currently developing a high power and high repetition rate CO II laser system to achieve 50 W intermediate focus EUV power with a Tin droplet target. We have achieved CE of 2.8% with solid Tin wire target by a transversely excited atmospheric (TEA) CO II laser MOPA system with pulse width, pulse energy and pulse repetition rate as 10~15 ns, 30 mJ and 10 Hz, respectively. A CO II laser system with a short pulse length less than 15 ns, a nominal average power of a few kW, and a repetition rate of 100 kHz, based on RF-excited, fast axial flow CO II laser amplifiers is under development. Output power of about 3 kW has been achieved with a pulse length of 15 ns at 130 kHz repletion rate in a small signal amplification condition with P(20) single line. The phase distortion of the laser beam after amplification is negligible and the beam can be focused to about 150μm diameter in 1/e2. The CO II laser system is reported on short pulse amplification performance using RF-excited fast axial flow lasers as amplifiers. And the CO II laser average output power scaling is shown towards 5~10 kW with pulse width of 15 ns from a MOPA system.

  11. 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.

  12. 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)

  13. Efficient vaccine against pandemic influenza: combining DNA vaccination and targeted delivery to MHC class II molecules.

    Science.gov (United States)

    Grødeland, Gunnveig; Bogen, Bjarne

    2015-06-01

    There are two major limitations to vaccine preparedness in the event of devastating influenza pandemics: the time needed to generate a vaccine and rapid generation of sufficient amounts. DNA vaccination could represent a solution to these problems, but efficacy needs to be enhanced. In a separate line of research, it has been established that targeting of vaccine molecules to antigen-presenting cells enhances immune responses. We have combined the two principles by constructing DNA vaccines that encode bivalent fusion proteins; these target hemagglutinin to MHC class II molecules on antigen-presenting cells. Such DNA vaccines rapidly induce hemagglutinin-specific antibodies and T cell responses in immunized mice. Responses are long-lasting and protect mice against challenge with influenza virus. In a pandemic situation, targeted DNA vaccines could be produced and tested within a month. The novel DNA vaccines could represent a solution to pandemic preparedness in the advent of novel influenza pandemics.

  14. Description and status of the U.S./JAERI HFIR-MFE-RB-10J irradiation capsule

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, J.P.; Lenox, K.E.; Grossbeck, M.L.; Rowcliffe, A.F. [Oak Ridge National Lab., TN (United States); Jitsukawa, S.; Shiba, K. [Japan Atomic Energy Research Inst. (Japan)

    1998-03-01

    This report describes the HFIR-MFE-RB-10J experiment conducted under the US DOE/Japan Atomic Energy Research Institute Collaborative Testing Program. The irradiation will take place in a Removable Beryllium (RB) position in the High Flux Isotope Reactor (HFIR) for approximately 8 cycles (about 4 dpa in steel). The experiment consists of two distinct parts: the upper region of the capsule will contain vanadium specimens operating at either 420 or 480 C and the lower region will contain austenitic and ferritic/martensitic steel specimens operating at 250 C. The capsule will be surrounded by a Eu{sub 2}O{sub 3} shield in order to harden the spectrum and prevent unwanted transmutations.

  15. A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II

    Science.gov (United States)

    Cui, Guozhen; Chan, Judy Yuet-Wa; Wang, Li; Li, Chuwen; Shan, Luchen; Xu, Changjiang; Zhang, Qingwen; Wang, Yuqiang; Di, Lijun; Lee, Simon Ming-Yuen

    2016-01-01

    The mitochondrial respiratory chain, including mitochondrial complex II, has emerged as a potential target for cancer therapy. In the present study, a novel conjugate of danshensu (DSS) and tetramethylpyrazine (TMP), DT-010, was synthesized. Our results showed that DT-010 is more potent than its parental compounds separately or in combination, in inhibiting the proliferation of MCF-7 and MDA-MB-231 cells by inducing cytotoxicity and promoting cell cycle arrest. It also inhibited the growth of 4T1 breast cancer cells in vivo. DT-010 suppressed the fundamental parameters of mitochondrial function in MCF-7 cells, including basal respiration, ATP turnover, maximal respiration. Treatment with DT-010 in MCF-7 and MDA-MB-231 cells resulted in the loss of mitochondrial membrane potential and decreased ATP production. DT-010 also promoted ROS generation, while treatment with ROS scavenger, NAC (N-acetyl-L-cysteine), reversed DT-010-induced cytotoxicity. Further study showed that DT-010 suppressed succinate-induced mitochondrial respiration and impaired mitochondrial complex II enzyme activity indicating that DT-010 may inhibit mitochondrial complex II. Overall, our results suggested that the antitumor activity of DT-010 is associated with inhibition of mitochondrial complex II, which triggers ROS generation and mitochondrial dysfunction in breast cancer cells. PMID:27081033

  16. 2-Deoxyglucose conjugated platinum (II) complexes for targeted therapy: design, synthesis, and antitumor activity.

    Science.gov (United States)

    Mi, Qian; Ma, Yuru; Gao, Xiangqian; Liu, Ran; Liu, Pengxing; Mi, Yi; Fu, Xuegang; Gao, Qingzhi

    2016-11-01

    Malignant neoplasms exhibit an elevated rate of glycolysis over normal cells. To target the Warburg effect, we designed a new series of 2-deoxyglucose (2-DG) conjugated platinum (II) complexes for glucose transporter 1 (GLUT1)-mediated anticancer drug delivery. The potential GLUT1 transportability of the complexes was investigated through a comparative molecular docking analysis utilizing the latest GLUT1 protein crystal structure. The key binding site for 2-DG as GLUT1's substrate was identified with molecular dynamics simulation, and the docking study demonstrated that the 2-DG conjugated platinum (II) complexes can be recognized by the same binding site as potential GLUT1 substrate. The conjugates were synthesized and evaluated for in vitro cytotoxicity study with seven human cancer cell lines. The results of this study revealed that 2-DG conjugated platinum (II) complexes are GLUT1 transportable substrates and exhibit improved cytotoxicities in cancer cell lines that over express GLUT1 when compared to the clinical drug, Oxaliplatin. The correlation between GLUT1 expression and antitumor effects are also confirmed. The study provides fundamental information supporting the potential of the 2-DG conjugated platinum (II) complexes as lead compounds for further pharmaceutical R&D.

  17. Glutathione reductase targeted to type II cells does not protect mice from hyperoxic lung injury.

    Science.gov (United States)

    Heyob, Kathryn M; Rogers, Lynette K; Welty, Stephen E

    2008-12-01

    Exposure of the lung epithelium to reactive oxygen species without adequate antioxidant defenses leads to airway inflammation, and may contribute to lung injury. Glutathione peroxidase catalyzes the reduction of peroxides by oxidation of glutathione (GSH) to glutathione disulfide (GSSG), which can in turn be reduced by glutathione reductase (GR). Increased levels of GSSG have been shown to correlate negatively with outcome after oxidant exposure, and increased GR activity has been protective against hyperoxia in lung epithelial cells in vitro. We tested the hypothesis that increased GR expression targeted to type II alveolar epithelial cells would improve outcome in hyperoxia-induced lung injury. Human GR with a mitochondrial targeting sequence was targeted to mouse type II cells using the SPC promoter. Two transgenic lines were identified, with Line 2 having higher lung GR activities than Line 1. Both transgenic lines had lower lung GSSG levels and higher GSH/GSSG ratios than wild-type. Six-week-old wild-type and transgenic mice were exposed to greater than 95% O2 or room air (RA) for 84 hours. After exposure, Line 2 mice had higher right lung/body weight ratios and lavage protein concentrations than wild-type mice, and both lines 1 and 2 had lower GSSG levels than wild-type mice. These findings suggest that GSSG accumulation in the lung may not play a significant role in the development of hyperoxic lung injury, or that compensatory responses to unregulated GR expression render animals more susceptible to hyperoxic lung injury.

  18. 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.

  19. Hollow glass microsphere production for laser direct-driven fusion targets on Shen Guang II

    Institute of Scientific and Technical Information of China (English)

    QIU; Longhui(邱龙会); FU; Yibei(傅依备); TANG; Yongjian(唐永建); WEI; Yun(魏芸); ZHENG; Yongming(郑永铭); SHI; Tao(师韬); YAO; Shujiu(姚书久)

    2002-01-01

    A liquid-droplet technique was investigated to fabricate thin wall hollow glass microspheres (HGM) used in laser fusion experiments on Shen Guang II. Glass-forming compositions, operating conditions of the droplet generator and the vertical multiple-zone furnace were optimized. Thin wall HGM with diameters of about 100, 200, and 520 μm were fabricated, whose failure pressures, gas retention properties for D2, and chemical durability were all characterized. The results of the fusion experiments show that the HGM targets are quite satisfactory and the highest neutron yields obtained are 4x 109.

  20. Targeting GH-1 splicing as a novel pharmacological strategy for growth hormone deficiency type II.

    Science.gov (United States)

    Miletta, Maria Consolata; Flück, Christa E; Mullis, Primus-E

    2017-01-15

    Isolated growth hormone deficiency type II (IGHD II) is a rare genetic splicing disorder characterized by reduced growth hormone (GH) secretion and short stature. It is mainly caused by autosomal dominant-negative mutations within the growth hormone gene (GH-1) which results in missplicing at the mRNA level and the subsequent loss of exon 3, producing the 17.5-kDa GH isoform: a mutant and inactive GH protein that reduces the stability and the secretion of the 22-kDa GH isoform, the main biologically active GH form. At present, patients suffering from IGHD II are treated with daily injections of recombinant human GH (rhGH) in order to reach normal height. However, this type of replacement therapy, although effective in terms of growth, does not prevent the toxic effects of the 17.5-kDa mutant on the pituitary gland, which may eventually lead to other hormonal deficiencies. As the severity of the disease inversely correlates with the 17.5-kDa/22-kDa ratio, increasing the inclusion of exon 3 is expected to ameliorate disease symptoms. This review focuses on the recent advances in experimental and therapeutic strategies applicable to treat IGHD II in clinical and preclinical contexts. Several avenues for alternative IGHD II therapy will be discussed including the use of small interfering RNA (siRNA) and short hairpin RNA (shRNA) constructs that specifically target the exon 3-deleted transcripts as well as the application of histone deacetylase inhibitors (HDACi) and antisense oligonucleotides (AONs) to enhance full-length GH-1 transcription, correct GH-1 exon 3 splicing and manipulate GH pathway.

  1. 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.

  2. Glutathione Reductase Targeted to Type II Cells Does Not Protect Mice from Hyperoxic Lung Injury

    Science.gov (United States)

    Heyob, Kathryn M.; Rogers, Lynette K.; Welty, Stephen E.

    2008-01-01

    Exposure of the lung epithelium to reactive oxygen species without adequate antioxidant defenses leads to airway inflammation, and may contribute to lung injury. Glutathione peroxidase catalyzes the reduction of peroxides by oxidation of glutathione (GSH) to glutathione disulfide (GSSG), which can in turn be reduced by glutathione reductase (GR). Increased levels of GSSG have been shown to correlate negatively with outcome after oxidant exposure, and increased GR activity has been protective against hyperoxia in lung epithelial cells in vitro. We tested the hypothesis that increased GR expression targeted to type II alveolar epithelial cells would improve outcome in hyperoxia-induced lung injury. Human GR with a mitochondrial targeting sequence was targeted to mouse type II cells using the SPC promoter. Two transgenic lines were identified, with Line 2 having higher lung GR activities than Line 1. Both transgenic lines had lower lung GSSG levels and higher GSH/GSSG ratios than wild-type. Six-week-old wild-type and transgenic mice were exposed to greater than 95% O2 or room air (RA) for 84 hours. After exposure, Line 2 mice had higher right lung/body weight ratios and lavage protein concentrations than wild-type mice, and both lines 1 and 2 had lower GSSG levels than wild-type mice. These findings suggest that GSSG accumulation in the lung may not play a significant role in the development of hyperoxic lung injury, or that compensatory responses to unregulated GR expression render animals more susceptible to hyperoxic lung injury. PMID:18566333

  3. 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.

  4. Embrittlement of Cr-Mo steels after low fluence irradiation in HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Klueh, R.L.; Alexander, D.J.

    1995-04-01

    The goal of this work is the determination of the possible effect of the simultaneous formation of helium and displacement damage during irradiation on the Charpy impact behavior. Subsize Charpy impact specimens of 9Cr-1MoVNb (modified 9Cr-1Mo) and 12Cr-1MoVW (Sandvik HT9) steels and 12Cr-1MoVW with 2%Ni (12Cr-1MOVW-2Ni) were irradiated in the High Flux Isotope Reactor (HFIR) at 300 and 400{degree}C to damage levels up to 2.5 dpa. The objective was to study the effect of the simultaneous formation of displacement damage and transmutation helium on impact toghness. Despite the low fluence relative to previous irradiations of these steels, significant increases in the ductile-brittle transition temperature (DBTT) occurred. The 12Cr-1MoVW-2Ni steel irradiated at 400{degree}C had the largest increase in DBTT and displayed indications of intergranular fracture. A mechanism is proposed to explain how helium can affect the fracture behaviour of this latter steel in the present tests, and how it affected all three steels in previous experiments, where the steels were irradiated to higher fluences.

  5. Effect of helium production on swelling of F82H irradiated in HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Wakai, E. E-mail: wakai@realab01.tokai.jaeri.go.jp; Hashimoto, N.; Miwa, Y.; Robertson, J.P.; Klueh, R.L.; Shiba, K.; Jistukawa, S

    2000-12-01

    The effects of helium production and heat treatment on the swelling of F82H steel irradiated in the HFIR to 51 dpa have been investigated using {sup 10}B, {sup 58}Ni and {sup 60}Ni-doped specimens. The swelling of tempered F82H-std and F82H doped with {sup 10}B irradiated at 400 deg. C ranged from 0.52% to 1.2%, while the swelling of the non-tempered F82H doped with {sup 58}Ni or {sup 60}Ni was less than 0.02%. At 300 deg. C the swelling in all steels was insignificant. In the F82H + Ni, a high number of density carbides formed in the matrix at these temperatures. The production of helium atoms enhanced the swelling of the F82H steel. However, the non-tempered treatment for the F82H + Ni suppressed remarkably the swelling. The cause of low swelling in the F82H + Ni may be due to the occurrence of the high density of carbides acting as sinks or the decrease of mobility of vacancies interacting with carbon atoms in matrix.

  6. 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.

  7. Hexokinase II-derived cell-penetrating peptide targets mitochondria and triggers apoptosis in cancer cells.

    Science.gov (United States)

    Woldetsadik, Abiy D; Vogel, Maria C; Rabeh, Wael M; Magzoub, Mazin

    2017-05-01

    Overexpression of mitochondria-bound hexokinase II (HKII) in cancer cells plays an important role in their metabolic reprogramming and protects them against apoptosis, thereby facilitating their growth and proliferation. Here, we show that covalently coupling a peptide corresponding to the mitochondrial membrane-binding N-terminal 15 aa of HKII (pHK) to a short, penetration-accelerating sequence (PAS) enhances the cellular uptake, mitochondrial localization, and cytotoxicity of the peptide in HeLa cells. Further analysis revealed that pHK-PAS depolarized mitochondrial membrane potential, inhibited mitochondrial respiration and glycolysis, and depleted intracellular ATP levels. The effects of pHK-PAS were correlated with dissociation of endogenous full-length HKII from mitochondria and release of cytochrome c Of significance, pHK-PAS treatment of noncancerous HEK293 cells resulted in substantially lower cytotoxicity. Thus, pHK-PAS effectively disrupted the mitochondria-HKII association in cancer cells, which led to mitochondrial dysfunction and, finally, apoptosis. Our results demonstrate the potential of the pHK-PAS cell-penetrating peptide as a novel therapeutic strategy in cancer.-Woldetsadik, A. D., Vogel, M. C., Rabeh, W. M., Magzoub, M. Hexokinase II-derived cell-penetrating peptide targets mitochondria and triggers apoptosis in cancer cells. © The Author(s).

  8. 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

    , signalling molecules and transcription factors. Subsequent comprehensive in silico analysis identified 24 target genes, of which 22 genes were qPCR validated. We identified seven genes involved in AngII signalling pathways. CONCLUSION: We here report novel insight of an extensive network of molecular......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...... function including regulation of cardiac hypertrophy, heart failure and blood pressure possibly through AT1R signalling. However, the miR-132/212 targets in the heart remain unknown. MATERIALS AND METHODS: To understand the role of these miRNAs in cardiac signalling networks, we undertook comprehensive...

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

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J. [Oak Ridge National Lab., TN (United States)

    1998-03-01

    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 {approximately}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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-01-01

    Abstract. 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

  11. 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.

  12. Project Plan Remote Target Fabrication Refurbishment Project

    Energy Technology Data Exchange (ETDEWEB)

    Bell, Gary L [ORNL; Taylor, Robin D [ORNL

    2009-08-01

    In early FY2009, the DOE Office of Science - Nuclear Physics Program reinstated a program for continued production of {sup 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 {sup 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 {sup 252}Cf; the average irradiation period is {approx}10 HFIR cycles, requiring about 1.5 calendar years. The strategy for continued production of {sup 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

  13. 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%.

  14. Analysis of dpa rates in the HFIR reactor vessel using a hybrid Monte Carlo/deterministic method

    Energy Technology Data Exchange (ETDEWEB)

    Blakeman, Edward [Retired

    2016-01-01

    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 below to approximately 12 above the axial extent 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%.

  15. 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.

  16. Defect annealing and thermal desorption of deuterium in low dose HFIR neutron-irradiated tungsten

    Energy Technology Data Exchange (ETDEWEB)

    Masashi Shimada; M. Hara; T. Otsuka; Y. Oya; Y. Hatano

    2014-05-01

    for the sample exposed to TPE at 500 °C. Tritium Migration Analysis Program (TMAP) analysis reveals that the detrapping energy decreases from 1.8 eV to 1.4 eV, indicating the changes in trapping mechanisms. This paper also summarizes deuterium behavior studies in HFIR neutron-irradiated tungsten under US-Japan TITAN program.

  17. 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

  18. 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

  19. Hypoxia-Targeted Drug Q6 Induces G2-M Arrest and Apoptosis via Poisoning Topoisomerase II under Hypoxia.

    Directory of Open Access Journals (Sweden)

    Linlin Chang

    Full Text Available In spite of the tremendous efforts dedicated to developing hypoxia-activated prodrugs, no agents yet have been approved for clinical therapy. In the present study, the hypoxic selective anti-cancer activity as well as the cellular target of a novel tirapazamine (TPZ analogue, 7-methyl-3-(3-chlorophenyl-quinoxaline-2-carbonitrile 1,4-dioxide (Q6 were investigated. Q6 implemented anti-cancer effects via poisoning topoisomerase II (topo II under hypoxia. Modified trapped in agarose DNA immunostaining (TARDIS assay showed more topo II-DNA cleavage complexes trapped by Q6 than TPZ at even lower concentration. In addition, by introducing ataxia-telangiectasia-mutated (ATM kinase inhibitors caffeine and KU-60019, we displayed that Q6-triggered apoptosis was attributed, at least partially, to DNA double-strand breaks generated by the topo II-targeting effect. Collectively, Q6 stood out for its better hypoxia-selectivity and topo II-poisoning than the parental compound TPZ. All these data shed light on the research of Q6 as a promising hypoxia-activated prodrug candidate for human hepatocellular carcinoma therapy.

  20. Final Environmental Impact Statement for the Strategic Target System. Volume II

    Science.gov (United States)

    1992-05-01

    mm 110 Deranken, Marchelle 111 Guerra, Raquel mm 112 Kolder, Teri mim 113 Nakahara, Joyce m<-- 115 Gulliksen, Gary mm 116 Byrd, Jaime <mlm 117...1:| ii iis 13J 111 :W : ::::I| ill 497 Alvarez , Patrick mfm 499 Granda, Chia mim 501 Hilbonson, M. 1 iii 502 Damron, Mark H. 111 504 Stayton

  1. Targeting and germ-line transmission of a null mutation at the metallothionein I and II loci in mouse.

    OpenAIRE

    Michalska, A E; Choo, K. H.

    1993-01-01

    We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals...

  2. 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.

  3. Tensile properties of V-(4-15)Cr-5Ti alloys irradiated at 400{degrees}C in the HFIR

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-10-01

    V-(4-15)Cr-5Ti alloys were irradiated in a helium environment to {approx}10 dpa at {approx}400{degrees}C in the High Flux Isotope Reactor (HFIR). This report presents results of postirradiation tests of tensile properties of V-4Cr-4Ti, V-8Cr-6Ti, V-10Cr-5Ti, and V-15Cr-5Ti. Despite concerns on the effects of transmutation of vanadium to Cr and impurity pickup from the helium environment, all of the alloys exhibited ductile tensile behavior. However, the alloys exhibited ductilities somewhat lower than those of the specimens irradiated to a similar dose and at a similar temperature in an Li environment in fast reactors. Uniform plastic strain in the V-Cr-(4-5)Ti alloys decreased monotonically with increasing Cr content.

  4. Seismic hazard evaluation for the high-flux isotope reactor (HFIR) Oak Ridge National Laboratory, Oak Ridge, Tennessee

    Energy Technology Data Exchange (ETDEWEB)

    McGuire, R.K.; Toro, G.R. (Risk Engineering, Inc., Golden, CO (United States))

    1991-09-01

    This study investigates the probabilistic hazard of earthquake-induced ground shaking at the HFIR facility, Oak Ridge, Tennessee. These results will be used to calculate plant response and potential effects in a Probabilistic Risk Assessment (PRA). For this purpose, several guidelines apply to this work. First, both the frequency of exceedance and the uncertainty in frequency of exceedance of various ground motion levels must be represented. These are required by the PRA so that the frequency and uncertainty of various possible plant states can be expressed. Second, there is a deliberate attempt to provide an unbiased distribution of frequencies of exceedance, i.e. to present results that are neither conservative nor unconservative. This is consistent with the goals of a PRA, to provide unbiased estimates of plant effects from which appropriate decisions (for instance about evaluating existing levels of seismic design) can be reached. Recent intensive studies of seismic hazard in the central and eastern United States (CEUS) have been completed by the Electric Power Research Institute (EPRI). These studies represent major efforts to characterize the seismic hazard for nuclear power plants in the CEUS, and use the most recent, up-to-date understandings of seismicity and ground motion relations for the region. With these studies as a resource, the current effort relies exclusively on the seismicity and ground motion assumptions therein to formulate seismic hazard curves for the HFIR facility. The interpretation of these studies to derive seismic hazard curves in a format suitable for input to a PRA is described in this report. 29 refs., 40 figs., 22 tabs.

  5. EpsinR, a target for pyrenocine B, role in endogenous MHC-II-restricted antigen presentation.

    Science.gov (United States)

    Shishido, Tatsuya; Hachisuka, Masami; Ryuzaki, Kai; Miura, Yuko; Tanabe, Atsushi; Tamura, Yasuaki; Kusayanagi, Tomoe; Takeuchi, Toshifumi; Kamisuki, Shinji; Sugawara, Fumio; Sahara, Hiroeki

    2014-11-01

    While the presentation mechanism of antigenic peptides derived from exogenous proteins by MHC class II molecules is well understood, relatively little is known about the presentation mechanism of endogenous MHC class II-restricted antigens. We therefore screened a chemical library of 200 compounds derived from natural products to identify inhibitors of the presentation of endogenous MHC class II-restricted antigens. We found that pyrenocine B, a compound derived from the fungus Pyrenochaeta terrestris, inhibits presentation of endogenous MHC class II-restricted minor histocompatibility antigen IL-4 inducible gene 1 (IL4I1) by primary dendritic cells (DCs). Phage display screening and surface plasmon resonance (SPR) analysis were used to investigate the mechanism of suppressive action by pyrenocine B. EpsinR, a target molecule for pyrenocine B, mediates endosomal trafficking through binding of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Lentiviral-mediated short hairpin (sh) RNA downregulation of EpsinR expression in DCs resulted in a decrease in the responsiveness of CD4+ T cells. Our data thus suggest that EpsinR plays a role in antigen presentation, which provides insight into the mechanism of presentation pathway of endogenous MHC class II-restricted antigen.

  6. 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%.

  7. Molecular targeting therapy with angiotensin II receptor blocker for prostatic cancer

    Directory of Open Access Journals (Sweden)

    Hiroji Uemura

    2011-12-01

    Full Text Available Angiotensin II (Ang-II plays a key role as a vasoconstrictor in controlling blood pressure and electrolyte/fluid homeostasis. Recently it has also been shown that this peptide is a cytokine, acting as a growth factor in cardiovascular and stromal cells. In addition, the physiological function of Ang-II seems to be similar in prostate cancer and stromal cells. It is widely assumed that Ang-II facilitates the growth of both cells, and its receptor blockers (ARBs have the potential to inhibit the growth of various cancer cells and tumors through the Ang-II receptor type 1 (AT1 receptor. The mechanism of cell growth inhibition by ARBs has been considered to be that of suppression of the signal transduction systems activated by growth factors or cytokines in prostate cancer cells, and suppression of angiogenesis. This review highlights the possible use of ARBs as novel agents for prostatic diseases including prostate cancer and benign hypertrophy, and covers related literature.

  8. Molecular targeting therapy with angiotensin II receptor blocker for prostatic cancer

    Directory of Open Access Journals (Sweden)

    Hiroji Uemura

    2011-12-01

    Full Text Available Angiotensin II (Ang-II plays a key role as a vasoconstrictor in controlling blood pressure and electrolyte/fluid homeostasis. Recently it has also been shown that this peptide is a cytokine, acting as a growth factor in cardiovascular and stromal cells. In addition, the physiological function of Ang-II seems to be similar in prostate cancer and stromal cells. It is widely assumed that Ang-II facilitates the growth of both cells, and its receptor blockers (ARBs have the potential to inhibit the growth of various cancer cells and tumors through the Ang-II receptor type 1 (AT1 receptor. The mechanism of cell growth inhibition by ARBs has been considered to be that of suppression of the signal transduction systems activated by growth factors or cytokines in prostate cancer cells, and suppression of angiogenesis. This review highlights the possible use of ARBs as novel agents for prostatic diseases including prostate cancer and benign hypertrophy, and covers related literature.

  9. Targeting the MHC Class II antigen presentation pathway in cancer immunotherapy.

    Science.gov (United States)

    Thibodeau, Jacques; Bourgeois-Daigneault, Marie-Claude; Lapointe, Réjean

    2012-09-01

    The success of immunotherapy relies on the participation of all arms of the immune system and the role of CD4+ T lymphocytes in preventing tumor growth is now well established. Understanding how tumors evade immune responses holds the key to the development of cancer immunotherapies. In this review, we discuss how MHC Class II expression varies in cancer cells and how this influences antitumor immune responses. We also discuss the means that are currently available for harnessing the MHC Class II antigen presentation pathway for the development of efficient vaccines to activate the immune system against cancer.

  10. TARGET:?

    National Research Council Canada - National Science Library

    James M Acton

    2014-01-01

      By 2003. as military planners had become worried that the country's long-range conventional weapons, such as cruise missiles, might be too slow to reach hypothetical distant targets that needed to be struck urgently...

  11. Targeting kynurenine aminotransferase II in psychiatric diseases: promising effects of an orally active enzyme inhibitor.

    Science.gov (United States)

    Wu, Hui-Qiu; Okuyama, Masahiro; Kajii, Yasushi; Pocivavsek, Ana; Bruno, John P; Schwarcz, Robert

    2014-03-01

    Increased brain levels of the tryptophan metabolite kynurenic acid (KYNA) have been linked to cognitive dysfunctions in schizophrenia and other psychiatric diseases. In the rat, local inhibition of kynurenine aminotransferase II (KAT II), the enzyme responsible for the neosynthesis of readily mobilizable KYNA in the brain, leads to a prompt reduction in extracellular KYNA levels, and secondarily induces an increase in extracellular glutamate, dopamine, and acetylcholine levels in several brain areas. Using microdialysis in unanesthetized, adult rats, we now show that the novel, systemically active KAT II inhibitor BFF-816, applied orally at 30 mg/kg in all experiments, mimics the effects of local enzyme inhibition. No tolerance was seen when animals were treated daily for 5 consecutive days. Behaviorally, daily injections of BFF-816 significantly decreased escape latency in the Morris water maze, indicating improved performance in spatial and contextual memory. Thus, systemically applied BFF-816 constitutes an excellent tool for studying the neurobiology of KYNA and, in particular, for investigating the mechanisms linking KAT II inhibition to changes in glutamatergic, dopaminergic, and cholinergic function in brain physiology and pathology.

  12. Neutron dosimetry, damage calculations, and helium measurements for the HFIR-MFE-60J-1 and MFE-330J-1 spectral tailoring experiments

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R. [Pacific Northwest Laboratory, Richland, WA (United States); Baldwin, C.A. [Oak Ridge National Lab., TN (United States); Oliver, B.M.

    1995-04-01

    The objective is to provide dosimetry and damage analysis for fusion materials irradiation experiments. Neutron fluence measurements and radiation damage calculations are reported for the joint US -Japanese MFE-60J-1 and MFE-330J-1 experiments in the hafnium-lined removable beryllium (RB{sup *}) position of the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory. These experiments were continuations of the ORR-6J and 7J irradiations performed in the Oak Ridge Research Reactor. The combination of irradiations was designed to tailor the neutron spectrum in order to achieve fusion reactor helium/dpa levels in stainless steel. These experiments produced maximum helium (appm)/dpa(displacement per atom) levels of 10.2 at 18.5 dpa for the ORR-6J and HFIR-MFE-60J-1 combination and 11.8 at 19.0 dpa for the ORR-7J and HFIR-MFE-330J-1 combination. A helium measurement in one JPCA sample was in good agreement with helium calculations.

  13. Targeting and germ-line transmission of a null mutation at the metallothionein I and II loci in mouse.

    Science.gov (United States)

    Michalska, A E; Choo, K H

    1993-09-01

    We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4 indicated their greater susceptibility to cadmium toxicity than wild-type animals. These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II.

  14. Compression of infrared imagery sequences containing a slow-moving point target, part II.

    Science.gov (United States)

    Huber-Shalem, Revital; Hadar, Ofer; Rotman, Stanley R; Huber-Lerner, Merav

    2013-03-10

    Infrared (IR) imagery sequences are commonly used for detecting moving targets in the presence of evolving cloud clutter or background noise. This research concentrates on slow-moving point targets that are less than one pixel in size, such as aircraft at long ranges from a sensor. Because transmitting IR imagery sequences to a base unit or storing them consumes considerable time and resources, a compression method that maintains the point-target detection capabilities is highly desirable. In our previous work, we introduced two temporal compression methods that preserve the temporal profile properties of the point target in the form of discrete cosine transform (DCT) quantization and parabola fit. In the present work, we extend the compression task method of DCT quantization by applying spatial compression over the temporally compressed coefficients, which is followed by bit encoding. We evaluate the proposed compression method using a signal-to-noise ratio (SNR)-based measure for point target detection and find that it yields better results than the compression standard H.264. Furthermore, we introduce an automatic detection algorithm that extracts the target location from the SNR scores image, which is acquired during the evaluation process and has a probability of detection and a probability of false alarm close to those of the original sequences. We previously determined that it is necessary to establish a minimal noise level in the SNR-based measure to compensate for smoothing that is induced by the compression. Here, the noise level calculation process is modified in order to allow detection of targets traversing all background types.

  15. Hypothesis: Targeted Ikkβ deletion upregulates MIF signaling responsiveness and MHC class II expression in mouse hepatocytes

    Directory of Open Access Journals (Sweden)

    Katherine S Koch

    2010-03-01

    Full Text Available Katherine S Koch, Hyam L LeffertHepatocyte Growth Control and Stem Cell Laboratory, Department of Pharmacology, School of Medicine, University of California, San Diego, CA, USAAbstract: Macrophage migration inhibitory factor (MIF is causally related to the pathogenesis of chronic liver disease but its hepatocellular mechanisms of action are largely unknown. Scattered reports in the literature hint at functional connections between the expression of MIF and major histocompatibility complex (MHC Class II molecules. Not surprisingly, these relationships have not yet been explored in hepatocytes because MIF and MHC Class II cell surface receptors are commonly expressed by other cell types including various antigen presenting cells of the immune system. On the other hand, mounting evidence suggests that heteromeric MIF receptors share a common molecule with intracellular MHC Class II complexes, viz., CD74, which also serves as the MHC Class II chaperone; and, while it is unclear what cancer-related role(s MHC Class II receptors might play, increasing evidence suggests that MIF and CD74 are also implicated in the biology of hepatocellular carcinoma. These reports are provocative for two reasons: firstly, Ikkβ Δhep mice carrying hepatocyte-targeted deletions of Ikkβ, an IκB kinase complex subunit required for the activation of the transcription factor NF-κB (nuclear factor-κB, have been shown to display heightened susceptibilities to hepatotoxins and chemical hepatocarcinogens; secondly, microarray profiling observations indicate that Ikkβ Δhep hepatocytes constitutively and “ectopically” overexpress genes, particularly CD74, CD44 (a MIF-receptor subunit and MHC Class II I-A/E β and I-A α chains, and gene families that regulate host immune process and immune defense responses. These findings together suggest that Ikkβ Δhep mice might express functional MIF and MHC Class II receptors, leading to increased hepatocellular sensitivity to

  16. The miR-200 family and its targets regulate type II cell differentiation in human fetal lung.

    Science.gov (United States)

    Benlhabib, Houda; Guo, Wei; Pierce, Brianne M; Mendelson, Carole R

    2015-09-11

    Type II cell differentiation and expression of the major surfactant protein, SP-A, in mid-gestation human fetal lung (HFL) are induced by cAMP and inhibited by TGF-β. cAMP induction of SP-A promoter activity is mediated by increased phosphorylation and DNA binding of thyroid transcription factor-1 (TTF-1/Nkx2.1), a master regulator of lung development. To further define mechanisms for developmental induction of surfactant synthesis in HFL, herein, we investigated the potential roles of microRNAs (miRNAs, miRs). To identify and characterize differentially regulated miRNAs in mid-gestation HFL explants during type II pneumocyte differentiation in culture, we performed miRNA microarray of RNA from epithelial cells isolated from mid-gestation HFL explants before and after culture with or without Bt2cAMP. Interestingly, the miR-200 family was significantly up-regulated during type II cell differentiation; miR-200 induction was inversely correlated with expression of known targets, transcription factors ZEB1/2 and TGF-β2. miR-200 antagonists inhibited TTF-1 and surfactant proteins and up-regulated TGF-β2 and ZEB1 expression in type II cells. Overexpression of ZEB1 in type II cells decreased DNA binding of endogenous TTF-1, blocked cAMP stimulation of surfactant proteins, and inhibited miR-200 expression, whereas cAMP markedly inhibited ZEB1/2 and TGF-β. Importantly, overexpression of ZEB1 or miR-200 antagonists in HFL type II cells also inhibited LPCAT1 and ABCA3, enzymes involved in surfactant phospholipid synthesis and trafficking, and blocked lamellar body biogenesis. Our findings suggest that the miR-200 family and ZEB1, which exist in a double-negative feedback loop regulated by TGF-β, serve important roles in the developmental regulation of type II cell differentiation and function in HFL. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. 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.

  18. The Berlin Exoplanet Search Telescope II. Catalog of Variable Stars. I. Characterization of Three Southern Target Fields

    CERN Document Server

    Fruth, T; Chini, R; Csizmadia, Sz; Dreyer, C; Eigmüller, P; Erikson, A; Kabath, P; Kirste, S; Lemke, R; Murphy, M; Pasternacki, T; Rauer, H; Titz-Weider, R

    2013-01-01

    A photometric survey of three Southern target fields with BEST II yielded the detection of 2,406 previously unknown variable stars and an additional 617 stars with suspected variability. This study presents a catalog including their coordinates, magnitudes, light curves, ephemerides, amplitudes, and type of variability. In addition, the variability of 17 known objects is confirmed, thus validating the results. The catalog contains a number of known and new variables that are of interest for further astrophysical investigations, in order to, e.g., search for additional bodies in eclipsing binary systems, or to test stellar interior models. Altogether, 209,070 stars were monitored with BEST II during a total of 128 nights in 2009/2010. The overall variability fraction of 1.2-1.5% in these target fields is well comparable to similar ground-based photometric surveys. Within the main magnitude range of $R\\in\\left[11,17\\right]$, we identify 0.67(3)% of all stars to be eclipsing binaries, which indicates a completen...

  19. THE BERLIN EXOPLANET SEARCH TELESCOPE II CATALOG OF VARIABLE STARS. I. CHARACTERIZATION OF THREE SOUTHERN TARGET FIELDS

    Energy Technology Data Exchange (ETDEWEB)

    Fruth, T.; Cabrera, J.; Csizmadia, Sz.; Dreyer, C.; Eigmüller, P.; Erikson, A.; Kabath, P.; Kirste, S.; Pasternacki, T.; Rauer, H.; Titz-Weider, R. [Institut für Planetenforschung, Deutsches Zentrum für Luft- und Raumfahrt, Rutherfordstr. 2, D-12489 Berlin (Germany); Chini, R.; Lemke, R. [Astronomisches Institut, Ruhr-Universität Bochum, D-44780 Bochum (Germany); Murphy, M., E-mail: thomas.fruth@dlr.de [Departamento de Física, Universidad Católica del Norte, P.O. 1280, Antofagasta (Chile)

    2013-11-01

    A photometric survey of three southern target fields with BEST II yielded the detection of 2406 previously unknown variable stars and an additional 617 stars with suspected variability. This study presents a catalog including their coordinates, magnitudes, light curves, ephemerides, amplitudes, and type of variability. In addition, the variability of 17 known objects is confirmed, thus validating the results. The catalog contains a number of known and new variables that are of interest for further astrophysical investigations, in order to, e.g., search for additional bodies in eclipsing binary systems, or to test stellar interior models. Altogether, 209,070 stars were monitored with BEST II during a total of 128 nights in 2009/2010. The overall variability fraction of 1.2%-1.5% in these target fields is well comparable to similar ground-based photometric surveys. Within the main magnitude range of R in [11, 17], we identify 0.67(3)% of all stars to be eclipsing binaries, which indicates a completeness of about one third for this particular type in comparison to space surveys.

  20. Understanding physical developer (PD): Part I--Is PD targeting lipids?

    Science.gov (United States)

    de la Hunty, Mackenzie; Moret, Sébastien; Chadwick, Scott; Lennard, Chris; Spindler, Xanthe; Roux, Claude

    2015-12-01

    Physical developer (PD) is a fingermark development technique that involves the selective reduction of silver onto fingermark residue. PD can develop marks on porous substrates even if they have been wet, leading to the logical, long held belief that the reagent targets the water insoluble constituents in the fingermark residue. The present research has tested this hypothesis as part of a broader study that aims to identify the targets of physical developer. Spot tests of some fatty acids, cholesterol and squalene, treated with PD, showed that only cholesterol produced significant silver deposition. PD is known to be particularly effective on aged marks, however cholesterol degrades over time. These observations indicate that PD reactivity with fingermarks cannot solely be due to the presence of cholesterol. Fingermarks were deposited on paper and washed with various organic solvents before being treated with PD. PD effectiveness was intermittent on both solvent washed and unwashed sides of both natural and groomed marks; however, it was seen to effectively develop groomed samples that had been exposed to common lipid extraction solvents, shown to have removed the lipids by visualisation using the lipid stain Nile red. PD effectiveness was most affected by exposure of samples to solvents that could dissolve water soluble components, showing that the removal of these constituents (by either water, or other solvents) decreases the amount of silver deposited on the fingermark residue by the working solution. Close observation of PD developed samples showed variation in silver deposition uniformity when comparing a developed ridge to a pore site located on that ridge. Some samples showed an absence of silver, and other showed an increase of silver at pore locations. This indicates that the material excreted by the pores on the finger has an effect on silver deposition, suggesting that PD may be specifically targeting eccrine constituents that are present along the

  1. Understanding Physical Developer (PD): Part II--Is PD targeting eccrine constituents?

    Science.gov (United States)

    de la Hunty, Mackenzie; Moret, Sébastien; Chadwick, Scott; Lennard, Chris; Spindler, Xanthe; Roux, Claude

    2015-12-01

    Physical developer (PD) is a fingermark development technique that deposits silver onto fingermark ridges. It is the only technique currently in routine operational use that gives results on porous substrates that have been wet. There is a reasonable understanding of the working solution chemistry, but the chemical constituent(s) contained in fingermark residue that are specifically targeted by PD are largely unknown. A better understanding of the PD technique will permit a more informed selection of alternative or complementary detection methods, and greater usage in operational laboratories. Recent research by our group has shown that PD does not selectively target the lipids present in the residue. This research investigated the hypothesis that PD targets the eccrine constituents in fingermark residue. This was tested by comparison of PD and indanedione-zinc (Ind-Zn) treated natural fingermarks that had been deposited successively, and marks that had been deposited with a ten second interval in between depositions. Such an interval allows for the regeneration of secretions from the pores located on the ridges of the fingers. On fingermark depletions with no time interval between depositions, PD and Ind-Zn treated depletions successively (and comparatively) decreased in development intensity as the amount of residue diminished. Short time intervals in between successive depletions resulted in additional secretions from the pores intermittently occurring, the increased development of which was visualised by treatment with both PD and Ind-Zn. The changes in development intensity were seen with both techniques on the same split depletions in a series, comparably and proportionately. These results indicate that the components targeted by PD are contained in the material excreted by the friction ridge pores through its mirrored development with Ind-Zn. Repetition of the experiments on marks that only contained eccrine material showed good Ind-Zn development but poor

  2. MicroRNA-410 functions as a tumor suppressor by targeting angiotensin II type 1 receptor in pancreatic cancer.

    Science.gov (United States)

    Guo, Rende; Gu, Jianhua; Zhang, Zhibin; Wang, Yi; Gu, Chuan

    2015-01-01

    MicroRNAs (miRNAs) act as key regulators of gene expression in diverse biological processes and are intimately involved in tumorigenesis. However, the underlying molecular mechanisms of miR-410 in pancreatic cancer remain poorly understood. In this study, we found that miR-410 overexpression suppressed pancreatic cancer cell growth in vitro and in vivo as well as cell invasion and migration. miR-410 also resulted in G1/S cell-cycle arrest. We then showed that angiotensin II type 1 receptor (AGTR1) was a direct target of miR-410, with miR-410 suppressing AGTR1 expression levels. In contrast, inhibition of miR-410 increased the expression of AGTR1. Silencing of AGTR1 inhibited cell growth and invasion, similar to miR-410 overexpression. In addition, we found that the induction of vascular endothelial growth factor and the activation of the ERK signaling pathway by angiotensin II were blocked by miR-410, similar to the angiotensin II inhibitor losartan. miR-410 overexpression inhibited angiogenesis in mice through the repression of CD31 expression. ERK pathway knockdown suppressed pancreatic cancer cell proliferation, invasion, and angiogenesis. Finally, we found that miR-410 was downregulated in pancreatic cancer tissues compared to adjacent nontumor tissues, whereas AGTR1 was upregulated in pancreatic cancer tissues. Pearson correlation analysis showed that miR-410 and AGTR1 were inversely expressed. In conclusion, our data indicate that miR-410 suppresses pancreatic cancer growth, cell invasion, migration, and angiogenesis via the downregulation of AGTR1, acting as a tumor-suppressive miRNA. In addition, our results suggest that miR-410 is a potential diagnostic biomarker and therapeutic target for patients with pancreatic cancer. © 2015 International Union of Biochemistry and Molecular Biology.

  3. Targeting cytochrome C oxidase in mitochondria with Pt(II)-porphyrins for photodynamic therapy

    Science.gov (United States)

    Börsch, Michael

    2010-02-01

    Mitochondria are the power house of living cells, where the synthesis of the chemical "energy currency" adenosine triphosphate (ATP) occurs. Oxidative phosphorylation by a series of membrane protein complexes I to IV, that is, the electron transport chain, is the source of the electrochemical potential difference or proton motive force (PMF) of protons across the inner mitochondrial membrane. The PMF is required for ATP production by complex V of the electron transport chain, i.e. by FoF1-ATP synthase. Destroying cytochrome C oxidase (COX; complex IV) in Photodynamic Therapy (PDT) is achieved by the cationic photosensitizer Pt(II)-TMPyP. Electron microscopy revealed the disruption of the mitochondrial christae as a primary step of PDT. Time resolved phosphorescence measurements identified COX as the binding site for Pt(II)-TMPyP in living HeLa cells. As this photosensitizer competed with cytochrome C in binding to COX, destruction of COX might not only disturb ATP synthesis but could expedite the release of cytochrome C to the cytosol inducing apoptosis.

  4. Prevention of alcohol abuse-related birth effects--II. Targeting and pricing.

    Science.gov (United States)

    Abel, E L

    1998-01-01

    Current public health measures to reduce the occurrence of fetal alcohol abuse syndrome (FAAS) and alcohol abuse-related birth effects (AARBEs) have been ineffective, because they target alcohol consumption, rather than alcohol abuse. The present discussion contends that the most effective public health strategy for reducing FAAS and AARBEs is a combination of more specific public health messages that target alcohol abuse, coupled with higher taxes on alcohol beverages. Although alcohol consumption by alcohol abusers has been thought to be inelastic to price changes, recent studies have found that both heavy drinking and binge drinking are sensitive to alcohol price changes, and price elasticities are relatively high for heavy drinkers who are aware of the consequences of their drinking. Although price increases may have a disproportionate impact on lower socioeconomic groups, this article concludes that they are justifiable from both a utilitarian and a categorical imperative perspective.

  5. EFFECTIVNESS OF TARGET ANTIMICROBIAL THERAPY OF SEVERE CHRONIC PERIODONTITIS PART II: PREVALENCE OF RESIDUAL POCKETS

    Directory of Open Access Journals (Sweden)

    Kamen Kotsilkov

    2010-10-01

    Full Text Available Comprehensive treatment of periodontitis is very different from the treatment of most bacterial infections. While periodontitis is traditionally considered a bacterial infection, many variables influence treatment outcomes. The reduction of the probing depth of the periodontal pockets is one of the main criteria for the success of the periodontal treatment. The prevalence of the residual pockets with probing depth greater than 4 mm determines the risk of disease progression. The reduction of the periodontal sites with PD above 7mm with non-surgical periodontal treatment could limit the necessity of periodontal surgery. Aim: Evaluation of the effectiveness of treatment of severe chronic periodontitis with additional target antibiotic administration in comparison with the therapy with adjunctive antimicrobial combination amoxicillin+metronidazole and conventional mechanical periodontal treatment regarding the prevalence and the achieved mean reduction of PD of periodontal pockets with initial PPD below 3mm, from 3 to 5mm, from 5-7mm and above 7mm.Results: In all study groups a reduction of the mean PD has been achieved. The prevalence of periodontal sites with PD above 7mm after therapy is the lowest in the group with target antibiotic administration. These results advocate the effectiveness of the target adjunctive antimicrobial treatment in order to limit the extent of the surgical procedures in the therapy of the periodontal disease.

  6. 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

  7. DNA as a Target for Anticancer Phen-Imidazole Pd(II) Complexes.

    Science.gov (United States)

    Heydari, Maryam; Moghadam, Mahboube Eslami; Tarlani, AliAkbar; Farhangian, Hossein

    2017-05-01

    Imidazole ring is a known structure in many natural or synthetic drug molecules and its metal complexes can interact with DNA and do the cleavage. Hence, to study the influence of the structure and size of the ligand on biological behavior of metal complexes, two water-soluble Pd(II) complexes of phen and FIP ligands (where phen is 1,10-phenanthroline and FIP is 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1, 10]phenanthroline) with the formula of [Pd(phen)(FIP)](NO3)2 and [Pd(FIP)2]Cl2, that were activated against chronic myelogenous leukemia cell line, K562, were selected. Also, the interaction of these anticancer Pd(II) complexes with highly polymerized calf thymus DNA was extensively studied by means of electronic absorption, fluorescence, and circular dichroism in Tris-buffer. The results showed that the binding was positive cooperation and [Pd(phen)(FIP)](NO3)2 (K f = 127 M(-1) G = 1.2) exhibited higher binding constant and number of binding sites than [Pd(FIP)2]Cl2 (K f = 13 M(-1) G = 1.03) upon binding to DNA. The fluorescence data indicates that quenching effect for [Pd(phen)(FIP)](NO3)2 (K SV = 58 mM(-1)) was higher than [Pd(FIP)2]Cl2 (K SV = 12 mM(-1)). Also, [Pd(FIP)2]Cl2 interacts with ethidium bromide-DNA, as non-competitive inhibition, and can bind to DNA via groove binding and [Pd(phen)(FIP)](NO3)2 can intercalate in DNA. These results were confirmed by circular dichroism spectra. Docking data revealed that longer complexes have higher interaction energy and bind to DNA via groove binding. Graphical Abstract Two anticancer Pd(II) complexes of imidazole derivative have been synthesized and interacted with calf thymus DNA. Modes of binding have been studied by electronic absorption, fluorescence, and CD measurements. [Pd(FIP)2]Cl2 can bind to DNA via groove binding while intercalation mode of binding is observed for [Pd(phen)(FIP)](NO3)2.

  8. Capsule fabrication for in-situ measurement of radiation induced electrical degradation (RIED) of ceramics in HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Eatherly, W.S.; Heatherly, D.W.; Hurst, M.T.; Qualls, A.L. [and others

    1996-04-01

    A collaborative DOE/Monbusho series of irradiation experiments is being implemented to determine, in situ, the effects of irradiation on the electrical resistivity of ceramic materials. The first experiment, TRIST-ER1, has been designed to irradiate 15 Al{sub 2}O{sub 3} test specimens at 450{degrees}C in an RB position of the High Flux Isotope Reactor (HFIR). Each test specimen is located in a sealed vanadium subcapsule with instrumentation provided to each subcapsule to measure temperature and resistance, and to place a biasing voltage across the specimen. Twelve of the specimens will be biased with 200 V/mm across the sample at all times, while three will not be biased, but can be if so desired during the irradiation. The experiment design, component fabrication, and subcapsule assembly have been completed. A three cycle irradiation, to a fast neutron (E>0.1 MeV) fluence of about 3x10{sup 25}n/m{sup 2} ({approx}3 dpa in Al{sub 2}O{sub 3}), is expected to begin early in March 1996.

  9. Effect of boron on post irradiation tensile properties of reduced activation ferritic steel (F-82H) irradiated in HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Kiyoyuki; Suzuki, Masahide; Hishinuma, Akimichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Dept. of Materials Science and Engineering; Pawel, J.E. [Oak Ridge National Lab., TN (United States). Metals and Ceramics Div.

    1994-12-31

    Reduced activation ferritic/martensitic steel, F-82H (Fe-8Cr-2W-V-Ta), was irradiated in the High Flux Isotope Reactor (HFIR) to doses between 11 and 34 dpa at 400 and 500 C. Post irradiation tensile tests were performed at the nominal irradiation temperature in vacuum. Some specimens included {sup 10}B or natural boron (nB) to estimate the helium effect on tensile properties. Tensile properties including the 0.2% offset yield stress, the ultimate tensile strength, the uniform elongation and the total elongation were measured. The tensile properties were not dependent on helium content in specimens irradiated to 34 dpa, however {sup 10}B-doped specimens with the highest levels of helium showed slightly higher yield strength and less ductility than boron-free specimens. Strength appears to go through a peak, and ductility through a trough at about 11 dpa. The irradiation to more than 21 dpa reduced the strength and increased the elongation to the unirradiated levels. Ferritic steels are one of the candidate alloys for nuclear fusion reactors because of their good thermophysical properties, their superior swelling resistance, and the low corrosion rate in contact with potential breeder and coolant materials.

  10. Microstructural evolution of HFIR-irradiated low activation F82H and F82H-{sup 10}B steels

    Energy Technology Data Exchange (ETDEWEB)

    Wakai, E.; Shiba, K.; Sawai, T. [Japan Atomic Energy Research Inst. (Japan); Hashimoto, N.; Robertson, J.P.; Klueh, R.L. [Oak Ridge National Lab., TN (United States)

    1998-03-01

    Microstructures of reduced-activation F82H (8Cr-2W-0.2V-0.04Ta) and the F82H steels doped with {sup 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-{sup 10}B steel. Cavities were observed in the F82H-{sup 10}B steels, but the swelling value is insignificant. Small particles of M{sub 6}C formed on the M{sub 23}C{sub 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.

  11. Cancer Cell Mitochondria Targeting by Pancratistatin Analogs is Dependent on Functional Complex II and III

    Science.gov (United States)

    Ma, Dennis; Pignanelli, Christopher; Tarade, Daniel; Gilbert, Tyler; Noel, Megan; Mansour, Fadi; Adams, Scott; Dowhayko, Alexander; Stokes, Kyle; Vshyvenko, Sergey; Hudlicky, Tomas; McNulty, James; Pandey, Siyaram

    2017-01-01

    Enhanced mitochondrial stability and decreased dependence on oxidative phosphorylation confer an acquired resistance to apoptosis in cancer cells, but may present opportunities for therapeutic intervention. The compound pancratistatin (PST) has been shown to selectively induce apoptosis in cancer cells. However, its low availability in nature has hindered its clinical advancement. We synthesized PST analogs and a medium-throughput screen was completed. Analogs SVTH-7, -6, and -5 demonstrated potent anti-cancer activity greater than PST and several standard chemotherapeutics. They disrupted mitochondrial function, activated the intrinsic apoptotic pathway, and reduced growth of tumor xenografts in vivo. Interestingly, the pro-apoptotic effects of SVTH-7 on cancer cells and mitochondria were abrogated with the inhibition of mitochondrial complex II and III, suggesting mitochondrial or metabolic vulnerabilities may be exploited by this analog. This work provides a scaffold for characterizing distinct mitochondrial and metabolic features of cancer cells and reveals several lead compounds with high therapeutic potential. PMID:28220885

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

    CERN Document Server

    Moskovitz, Nicholas; 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 association due to a lack of any prominent absorption features in our data. We have also conducted a series of high signal-to-noise visible-wavelength observations to investigate the reported surface heterogeneity. Our time series of visible spectra do not show evidence for variability at a precision level of a few percent. This result suggests two most likely possibilities. One, that the surface of 1999 JU3 is homogenous and that unaccounted for systematic effects are causing spectral variation across epochs. Or two, tha...

  13. Ungeremine effectively targets mammalian as well as bacterial type I and type II topoisomerases.

    Science.gov (United States)

    Casu, Laura; Cottiglia, Filippo; Leonti, Marco; De Logu, Alessandro; Agus, Emanuela; Tse-Dinh, Yuk-Ching; Lombardo, Valentina; Sissi, Claudia

    2011-12-01

    From the methanol extract of the bulbs of Pancratium illyricum L., three phenanthridine type alkaloids, ungeremine (1), (-)-lycorine (2) and (+)-vittatine (3) were isolated. For the evaluation of their anticancer and antibacterial potential, compounds 1-3 were tested against human (I, IIα) and bacterial (IA, IV) topoisomerases. Our data demonstrated that ungeremine impairs the activity of both, human and bacterial topoisomerases. Remarkably, ungeremine was found to largely increments the DNA cleavage promoted by bacterial topoisomerase IA, a new target in antimicrobial chemotherapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. AGS SUPER NEUTRINO BEAM FACILITY ACCELERATOR AND TARGET SYSTEM DESIGN (NEUTRINO WORKING GROUP REPORT-II).

    Energy Technology Data Exchange (ETDEWEB)

    DIWAN,M.; MARCIANO,W.; WENG,W.; RAPARIA,D.

    2003-04-21

    This document describes the design of the accelerator and target systems for the AGS Super Neutrino Beam Facility. Under the direction of the Associate Laboratory Director Tom Kirk, BNL has established a Neutrino Working Group to explore the scientific case and facility requirements for a very long baseline neutrino experiment. Results of a study of the physics merit and detector performance was published in BNL-69395 in October 2002, where it was shown that a wide-band neutrino beam generated by a 1 MW proton beam from the AGS, coupled with a half megaton water Cerenkov detector located deep underground in the former Homestake mine in South Dakota would be able to measure the complete set of neutrino oscillation parameters: (1) precise determination of the oscillation parameters {Delta}m{sub 32}{sup 2} and sin{sup 2} 2{theta}{sub 32}; (2) detection of the oscillation of {nu}{sub {mu}}-{nu}{sub e} and measurement of sin{sup 2} 2{theta}{sub 13}; (3) measurement of {Delta}m{sub 21}{sup 2} sin 2{theta}{sub 12} in a {nu}{sub {mu}} {yields} {nu}{sub e} appearance mode, independent of the value of {theta}{sub 13}; (4) verification of matter enhancement and the sign of {Delta}m{sub 32}{sup 2}; and (5) determination of the CP-violation parameter {delta}{sub CP} in the neutrino sector. This report details the performance requirements and conceptual design of the accelerator and the target systems for the production of a neutrino beam by a 1.0 MW proton beam from the AGS. The major components of this facility include a new 1.2 GeV superconducting linac, ramping the AGS at 2.5 Hz, and the new target station for 1.0 MW beam. It also calls for moderate increase, about 30%, of the AGS intensity per pulse. Special care is taken to account for all sources of proton beam loss plus shielding and collimation of stray beam halo particles to ensure equipment reliability and personal safety. A preliminary cost estimate and schedule for the accelerator upgrade and target system are also

  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. Electromagnetic Pulses Generated From Laser Target Interactions at Shenguang II Laser Facility

    Science.gov (United States)

    Yang, Jinwen; Li, Tingshuai; Yi, Tao; Wang, Chuanke; Yang, Ming; Yang, Weiming; Liu, Shenye; Jiang, Shaoen; Ding, Yongkun

    2016-10-01

    Significant electromagnetic pulses (EMP) can be generated by the intensive laser irradiating solid targets in inertial confinement fusion (ICF). To evaluate the EMP intensity and distribution in and outside the laser chamber, we designed and fabricated a discone antenna with ultra-wide bands of over 10 GHz. The return loss (S11 parameter) of this antenna was below -10 dB and could even achieve under -30 dB at 3.1 GHz. The EMP intensity in this study at 80 cm and 40 cm away from the target chamber center (TCC) reached 400 kV/m and 2000 kV/m. The current results are expected to offer preliminary information to study physics regarding laser plasma interactions and will also lay experimental foundation for EMI shielding design to protect various diagnostics. supported by the Fundamental Research Funds for the Central Universities of China (No. ZYGX2015J108) and National Natural Science Foundation of China (Nos. 11575166 and 51581140)

  17. 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.

  18. Protein synthesis is the primary target of reactive oxygen species in the photoinhibition of photosystem II.

    Science.gov (United States)

    Nishiyama, Yoshitaka; Allakhverdiev, Suleyman I; Murata, Norio

    2011-05-01

    Photoinhibition of photosystem II (PSII) occurs when the rate of photodamage to PSII exceeds the rate of the repair of photodamaged PSII. Recent examination of photoinhibition by separate determinations of photodamage and repair has revealed that the rate of photodamage to PSII is directly proportional to the intensity of incident light and that the repair of PSII is particularly sensitive to the inactivation by reactive oxygen species (ROS). The ROS-induced inactivation of repair is attributable to the suppression of the synthesis de novo of proteins, such as the D1 protein, that are required for the repair of PSII at the level of translational elongation. Furthermore, molecular analysis has revealed that the ROS-induced suppression of protein synthesis is associated with the specific inactivation of elongation factor G via the formation of an intramolecular disulfide bond. Impairment of various mechanisms that protect PSII against photoinhibition, including photorespiration, thermal dissipation of excitation energy, and the cyclic transport of electrons, decreases the rate of repair of PSII via the suppression of protein synthesis. In this review, we present a newly established model of the mechanism and the physiological significance of repair in the regulation of the photoinhibition of PSII.

  19. Linker design for the modular assembly of multifunctional and targeted platinum(ii)-containing anticancer agents.

    Science.gov (United States)

    Ding, S; Bierbach, U

    2016-08-16

    A versatile and efficient modular synthetic platform was developed for assembling multifunctional conjugates and targeted forms of platinum-(benz)acridines, a class of highly cytotoxic DNA-targeted hybrid agents. The synthetic strategy involved amide coupling between succinyl ester-modified platinum compounds (P1, P2) and a set of 11 biologically relevant primary and secondary amines (N1-N11). To demonstrate the feasibility and versatility of the approach, a structurally and functionally diverse range of amines was introduced. These include biologically active molecules, such as rucaparib (a PARP inhibitor), E/Z-endoxifen (an estrogen receptor antagonist), and a quinazoline-based tyrosine kinase inhibitor. Micro-scale reactions in Eppendorf tubes or on 96-well plates were used to screen for optimal coupling conditions in DMF solution with carbodiimide-, uronium-, and phosphonium-based compounds, as well as other common coupling reagents. Reactions with the phosphonium-based coupling reagent PyBOP produced the highest yields and gave the cleanest conversions. Furthermore, it was demonstrated that the chemistry can also be performed in aqueous media and is amenable to parallel synthesis based on multiple consecutive reactions in DMF in a "one-tube" format. In-line LC-MS was used to assess the stability of the conjugates in physiologically relevant buffers. Hydrolysis of the conjugates occurs at the ester moiety and is facilitated by the aquated metal moiety under low-chloride ion conditions. The rate of ester cleavage greatly depends on the nature of the amine component. Potential applications of the linker technology are discussed.

  20. Experiments and analysis of gold disk targets irradiated by smoothing beams of Xingguang II facilities with 350 nm wavelength

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Gold disk targets were irradiated using focusing and beam smoothing methods on Xingguang (XG-II) laser facilities with 350 nm wavelength, 0.6 ns pulse width and 20-80 Joules energies. Laser absorption, light scattering and X-ray conversion were experimentally investigated. The experimental results showed that laser absorption and scattered light were about 90% and 10%, respectively, under focusing irradiation, but the laser absorption increased 5%-10% and the scattered light about 1% under the condition of beam smoothing. Compared with the case of focusing irradiation, the laser absorption was effectively improved and the scattered light remarkably dropped under uniform irradiation; then due to the decrease in laser intensity, X-ray conversion increased. This is highly advantageous to the inertial confinement fusion. However, X-ray conversion mechanism basically did not change and X-ray conversion efficiency under beam smoothing and focusing irradiation was basically the same.

  1. Experiments and analysis of gold disk targets irradiated by smoothing beams of Xingguang II facilities with 350 nm wavelength

    Institute of Scientific and Technical Information of China (English)

    JIANG; ShaoEn

    2007-01-01

    Gold disk targets were irradiated using focusing and beam smoothing methods on Xingguang (XG-II) laser facilities with 350 nm wavelength, 0.6 ns pulse width and 20-80 Joules energies. Laser absorption, light scattering and X-ray conversion were experimentally investigated. The experimental results showed that laser absorption and scattered light were about 90% and 10%, respectively, under focusing irradiation, but the laser absorption increased 5%-10% and the scattered light about 1% under the condition of beam smoothing. Compared with the case of focusing irradiation, the laser absorption was effectively improved and the scattered light remarkably dropped under uniform irradiation; then due to the decrease in laser intensity, X-ray conversion increased. This is highly advantageous to the inertial confinement fusion. However, X-ray conversion mechanism basically did not change and X-ray conversion efficiency under beam smoothing and focusing irradiation was basically the same.……

  2. Selective anticancer copper(II)-mixed ligand complexes: targeting of ROS and proteasomes.

    Science.gov (United States)

    Ng, Chew Hee; Kong, Siew Ming; Tiong, Yee Lian; Maah, Mohd Jamil; Sukram, Nurhazwani; Ahmad, Munirah; Khoo, Alan Soo Beng

    2014-04-01

    Copper compounds can be alternatives to platinum-based anticancer drugs. This study investigated the effects of a series of ternary copper(II) complexes, [Cu(phen)(aa)(H2O)]NO3·xH2O 1-4 (phen = 1,10-phenanthroline; aa = gly (1), DL-ala (2), sar (3), C-dmg (4)), on metastatic and cisplatin-resistant MDA-MB-231 breast cancer cells and MCF10A non-cancerous breast cells, and some aspects of the mechanisms. These complexes were distinctively more antiproliferative towards and induced greater apoptotic cell death in MDA-MB-231 than in MCF10A cells. 2 and 4 could induce cell cycle arrest only in cancer cells. Further evidence from DCFH-DA assay showed higher induction of reactive oxygen species (ROS) in treated cancer cells but minimal ROS increase in normal cells. DNA double-strand breaks, via a γ-H2AX assay, were only detected in cancer cells treated with 5 μM of the complexes. These complexes poorly inhibited chymotrypsin-like activity in the 20S rabbit proteasome while they did not inhibit the three proteolytic sites of MDA-MB-231 cells at 10 μM. However, the complexes could inhibit degradation of ubiquinated proteins of MDA-MB-231 cells. In addition, compound 4 was found to be effective against cervical (Hela), ovarian (SKOV3), lung (A549, PC9), NPC (Hone1, HK1, C666-1), breast (MCF7, T47D), lymphoma and leukemia (Nalmawa, HL60) and colorectal (SW480, SW48, HCT118) cancer cell lines with IC50 values (24 h) in the 1.7-19.0 μM range. Single dose NCI60 screening of 4 showed the complex to be highly cytotoxic to most cancer cell types and more effective than cisplatin.

  3. 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.

  4. Physical properties of the ESA Rosetta target asteroid (21) Lutetia. II. Shape and flyby geometry

    Science.gov (United States)

    Carry, B.; Kaasalainen, M.; Leyrat, C.; Merline, W. J.; Drummond, J. D.; Conrad, A.; Weaver, H. A.; Tamblyn, P. M.; Chapman, C. R.; Dumas, C.; Colas, F.; Christou, J. C.; Dotto, E.; Perna, D.; Fornasier, S.; Bernasconi, L.; Behrend, R.; Vachier, F.; Kryszczynska, A.; Polinska, M.; Fulchignoni, M.; Roy, R.; Naves, R.; Poncy, R.; Wiggins, P.

    2010-11-01

    Aims: We determine the physical properties (spin state and shape) of asteroid (21) Lutetia, target of the International Rosetta Mission of the European Space Agency, to help in preparing for observations during the flyby on 2010 July 10 by predicting the orientation of Lutetia as seen from Rosetta. Methods: We use our novel KOALA inversion algorithm to determine the physical properties of asteroids from a combination of optical lightcurves, disk-resolved images, and stellar occultations, although the last are not available for (21) Lutetia. Results: We find the spin axis of (21) Lutetia to lie within 5° of (λ = 52°, β = -6°) in the Ecliptic J2000 reference frame (equatorial α = 52°, δ = +12°), and determine an improved sidereal period of 8.168 270 ± 0.000 001 h. This pole solution implies that the southern hemisphere of Lutetia will be in “seasonal” shadow at the time of the flyby. The apparent cross-section of Lutetia is triangular when seen “pole-on” and more rectangular “equator-on”. The best-fit model suggests there are several concavities. The largest of these is close to the north pole and may be associated with strong impacts. Based on observations collected at the W. M. Keck Observatory and at European Southern Observatory Very Large Telescope (program ID: 079.C-0493, PI: E. Dotto). The W. M. Keck Observatory is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.Tables 1, 2, 4 and Figs. 3-5 are only available in electronic form at http://www.aanda.org

  5. Targeted gene transfer of hepatocyte growth factor to alveolar type II epithelial cells reduces lung fibrosis in rats.

    Science.gov (United States)

    Gazdhar, Amiq; Temuri, Almas; Knudsen, Lars; Gugger, Mathias; Schmid, Ralph A; Ochs, Matthias; Geiser, Thomas

    2013-01-01

    Inefficient alveolar wound repair contributes to the development of pulmonary fibrosis. Hepatocyte growth factor (HGF) is a potent growth factor for alveolar type II epithelial cells (AECII) and may improve repair and reduce fibrosis. We studied whether targeted gene transfer of HGF specifically to AECII improves lung fibrosis in bleomycin-induced lung fibrosis. A plasmid encoding human HGF expressed from the human surfactant protein C promoter (pSpC-hHGF) was designed, and extracorporeal electroporation-mediated gene transfer of HGF specifically to AECII was performed 7 days after bleomycin-induced lung injury in the rat. Animals were killed 7 days after hHGF gene transfer. Electroporation-mediated HGF gene transfer resulted in HGF expression specifically in AECII at biologically relevant levels. HGF gene transfer reduced pulmonary fibrosis as assessed by histology, hydroxyproline determination, and design-based stereology compared with controls. Our results indicate that the antifibrotic effect of HGF is due in part to a reduction of transforming growth factor-β(1), modulation of the epithelial-mesenchymal transition, and reduction of extravascular fibrin deposition. We conclude that targeted HGF gene transfer specifically to AECII decreases bleomycin-induced lung fibrosis and may therefore represent a novel cell-specific gene transfer technology to treat pulmonary fibrosis.

  6. 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.

  7. Embrittlement of reduced-activation ferritic/martensitic steels irradiated in HFIR at 300 deg. C and 400 deg. C

    Energy Technology Data Exchange (ETDEWEB)

    Klueh, R.L. E-mail: ku2@ornl.gov; Sokolov, M.A.; Shiba, K.; Miwa, Y.; Robertson, J.P

    2000-12-01

    Miniature tensile and Charpy specimens of four ferritic/martensitic steels were irradiated at 300 deg. C and 400 deg. C in the high flux isotope reactor (HFIR) to a maximum dose of {approx}12 dpa. The steels were standard F82H (F82H-Std), a modified F82H (F82H-Mod), ORNL 9Cr-2WVTa, and 9Cr-2WVTa-2Ni, the 9Cr-2WVTa containing 2% Ni to produce helium by (n,{alpha}) reactions with thermal neutrons. More helium was produced in the F82H-Std than the F82H-Mod because of the presence of boron. Irradiation embrittlement in the form of an increase in the ductile-brittle transition temperature ({delta}DBTT) and a decrease in the upper-shelf energy (USE) occurred for all the steels. The two F82H steels had similar {delta}DBTTs after irradiation at 300 deg. C, but after irradiation at 400 deg. C, the {delta}DBTT for F82H-Std was less than for F82H-Mod. Under these irradiation conditions, little effect of the extra helium in the F82H-Std could be discerned. Less embrittlement was observed for 9Cr-2WVTa steel irradiated at 400 deg. C than for the two F82H steels. The 9Cr-2WVTa-2Ni steel with {approx}115 appm He had a larger {delta}DBTT than the 9Cr-2WVTa with {approx}5 appm He, indicating a possible helium effect.

  8. An mRNA Capping Enzyme Targets FACT to the Active Gene To Enhance the Engagement of RNA Polymerase II into Transcriptional Elongation.

    Science.gov (United States)

    Sen, Rwik; Kaja, Amala; Ferdoush, Jannatul; Lahudkar, Shweta; Barman, Priyanka; Bhaumik, Sukesh R

    2017-07-01

    We have recently demonstrated that an mRNA capping enzyme, Cet1, impairs promoter-proximal accumulation/pausing of RNA polymerase II (Pol II) independently of its capping activity in Saccharomyces cerevisiae to control transcription. However, it is still unknown how Pol II pausing is regulated by Cet1. Here, we show that Cet1's N-terminal domain (NTD) promotes the recruitment of FACT (facilitates chromatin transcription that enhances the engagement of Pol II into transcriptional elongation) to the coding sequence of an active gene, ADH1, independently of mRNA-capping activity. Absence of Cet1's NTD decreases FACT targeting to ADH1 and consequently reduces the engagement of Pol II in transcriptional elongation, leading to promoter-proximal accumulation of Pol II. Similar results were also observed at other genes. Consistently, Cet1 interacts with FACT. Collectively, our results support the notion that Cet1's NTD promotes FACT targeting to the active gene independently of mRNA-capping activity in facilitating Pol II's engagement in transcriptional elongation, thus deciphering a novel regulatory pathway of gene expression. Copyright © 2017 American Society for Microbiology.

  9. The Acceptor Side of Photosystem II Is the Initial Target of Nitrite Stress in Synechocystis sp. Strain PCC 6803.

    Science.gov (United States)

    Zhang, Xin; Ma, Fei; Zhu, Xi; Zhu, Junying; Rong, Junfeng; Zhan, Jiao; Chen, Hui; He, Chenliu; Wang, Qiang

    2017-02-01

    Nitrite, a common form of inorganic nitrogen (N), can be used as a nitrogen source through N assimilation. However, high levels of nitrite depress photosynthesis in various organisms. In this study, we investigated which components of the photosynthetic electron transfer chain are targeted by nitrite stress in Synechocystis sp. strain PCC 6803 cells. Measurements of whole-chain and photosystem II (PSII)-mediated electron transport activities revealed that high levels of nitrite primarily impair electron flow in PSII. Changes in PSII activity in response to nitrite stress occurred in two distinct phases. During the first phase, which occurred in the first 3 h of nitrite treatment, electron transfer from the primary quinone acceptor (QA) to the secondary quinone acceptor (QB) was retarded, as indicated by chlorophyll (Chl) a fluorescence induction, S-state distribution, and QA(-) reoxidation tests. In the second phase, which occurred after 6 h of nitrite exposure, the reaction center was inactivated and the donor side of photosystem II was inhibited, as revealed by changes in Chl fluorescence parameters and thermoluminescence and by immunoblot analysis. Our data suggest that nitrite stress is highly damaging to PSII and disrupts PSII activity by a stepwise mechanism in which the acceptor side is the initial target. IMPORTANCE In our previous studies, an alga-based technology was proposed to fix the large amounts of nitrite that are released from NOX-rich flue gases and proved to be a promising industrial strategy for flue gas NOX bioremediation (W. Chen et al., Environ Sci Technol 50:1620-1627, 2016, https://doi.org/10.1021/acs.est.5b04696; X. Zhang et al., Environ Sci Technol 48:10497-10504, 2014, https://doi.org/10.1021/es5013824). However, the toxic effects of high concentrations of nitrite on algal cells remain obscure. The analysis of growth rates, photochemistry, and protein profiles in our study provides important evidence that the inhibition by nitrite occurs

  10. Highly water-soluble platinum(II) complexes as GLUT substrates for targeted therapy: improved anticancer efficacy and transporter-mediated cytotoxic properties.

    Science.gov (United States)

    Liu, Pengxing; Lu, Yanhui; Gao, Xiangqian; Liu, Ran; Zhang-Negrerie, Daisy; Shi, Ying; Wang, Yiqiang; Wang, Songqing; Gao, Qingzhi

    2013-03-25

    Glucose-conjugated malonato-platinum(II) complexes are designed and synthesized to target tumor-specific active transporters, namely, glucose transporters (GLUTs); the complexes exhibit much higher aqueous solubility by 150 times, improved potency in cytotoxicities by 10 times, and increased therapeutic index by over 30 fold compared to the newest generation of clinical drugs oxaliplatin.

  11. Resveratrol inhibits Hexokinases II mediated glycolysis in non-small cell lung cancer via targeting Akt signaling pathway.

    Science.gov (United States)

    Li, Wei; Ma, Xiaoqian; Li, Na; Liu, Huasheng; Dong, Qiong; Zhang, Juan; Yang, Cejun; Liu, Yin; Liang, Qi; Zhang, Shengwang; Xu, Chang; Song, Wei; Tan, Shiming; Rong, Pengfei; Wang, Wei

    2016-12-10

    Deregulation of glycolysis was often observed in human cancer cells. In the present study, we reported resveratrol, a small polyphenol, which has been intensively studied in various tumor models, has a profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via regulation of glycolysis. Resveratrol impaired hexokinase II (HK2)-mediated glycolysis, and markedly inhibited anchorage-dependent and -independent growth of NSCLC cells. Exposure to resveratrol decreased EGFR and downstream kinases Akt and ERK1/2 activation. Moreover, we revealed that resveratrol impaired glucose metabolism by mainly inhibiting expression of HK2 mediated by the Akt signaling pathway, and exogenous overexpression of constitutively activated Akt1 in NSCLC cells substantially rescued resveratrol-induced glycolysis suppression. The in vivo data indicated that resveratrol obviously suppressed tumor growth in a xenograft mouse model. Our results suggest targeting HK2 or metabolic enzymes appears to be a new approach for clinical NSCLC prevention or treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  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 proinflammatory markers than amlodipine alone.

  13. Icariside II Effectively Reduces Spatial Learning and Memory Impairments in Alzheimer’s Disease Model Mice Targeting Beta-Amyloid Production

    Science.gov (United States)

    Yan, Lingli; Deng, Yuanyuan; Gao, Jianmei; Liu, Yuangui; Li, Fei; Shi, Jingshan; Gong, Qihai

    2017-01-01

    Icariside II (ICS II) is a broad-spectrum anti-cancer natural compound extracted from Herba Epimedii Maxim. Recently, the role of ICS II has been investigated in central nervous system, especially have a neuroprotective effect in Alzheimer’s disease (AD). In this study, we attempted to investigate the effects of ICS II, on cognitive deficits and beta-amyloid (Aβ) production in APPswe/PS1dE9 (APP/PS1) double transgenic mice. It was found that chronic ICS II administrated not only effectively ameliorated cognitive function deficits, but also inhibited neuronal degeneration and reduced the formation of plaque burden. ICS II significantly suppressed Aβ production via promoting non-amyloidogenic APP cleavage process by up-regulating a disintegrin and metalloproteinase domain 10 (ADAM10) expression, inhibited amyloidogenic APP processing pathway by down-regulating amyloid precursor protein (APP) and β-site amyloid precursor protein cleavage enzyme 1 (BACE1) expression in APP/PS1 transgenic mice. Meanwhile, ICS II attenuated peroxisome proliferator-activated receptor-γ (PPARγ) degradation as well as inhibition of eukaryotic initiation factor α phosphorylation (p-eIF2α) and PKR endoplasmic reticulum regulating kinase phosphorylation (p-PERK). Moreover, phosphodiesterase type 5 inhibitors (PDE5-Is) have recently emerged as a possible therapeutic target for cognitive enhancement via inhibiting Aβ levels, and we also found that ICS II markedly decreased phosphodiesterase-5A (PDE5A) expression. In conclusion, the present study demonstrates that ICS II could attenuate spatial learning and memory impairments in APP/PS1 transgenic mice. This protection appears to be due to the increased ADAM10 expression and decreased expression of both APP and BACE1, resulting in inhibition of Aβ production in the hippocampus and cortex. Inhibition of PPARγ degradation and PERK/eIF2α phosphorylation are involved in the course, therefore suggesting that ICS II might be a promising

  14. Cellular misfolded proteins rescued from degradation by MHC class II molecules are possible targets for autoimmune diseases.

    Science.gov (United States)

    Arase, Noriko; Arase, Hisashi

    2015-11-01

    The major function of major histocompatibility complex (MHC) class II molecules is the presentation of peptide antigens to helper T cells. However, when misfolded proteins are associated with MHC class II molecules in the endoplasmic reticulum, they are transported to the cell surface by MHC class II molecules without processing to peptides. Of note, misfolded proteins complexed with MHC class II molecules are specifically recognized by autoantibodies produced in patients with autoimmune diseases such as rheumatoid arthritis and antiphospholipid syndrome. Furthermore, autoantibody binding to misfolded proteins complexed with MHC class II molecules is associated with the susceptibility to autoimmune diseases conferred by each MHC class II allele. Therefore, misfolded proteins rescued from degradation by MHC class II molecules may be recognized as 'neo-self' antigens by the immune system and be involved in the pathogenicity of autoimmune diseases.

  15. PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II.

    Science.gov (United States)

    Voz, M L; Agten, N S; Van de Ven, W J; Kas, K

    2000-01-01

    PLAG1, a novel developmentally regulated C2H2 zinc finger gene, is consistently rearranged and overexpressed in pleomorphic adenomas of the salivary glands with 8q12 translocations. In this report, we show that PLAG1 is a nuclear protein that binds DNA in a specific manner. The consensus PLAG1 binding site is a bipartite element containing a core sequence, GRGGC, and a G-cluster, RGGK, separated by seven random nucleotides. DNA binding is mediated mainly via three of the seven zinc fingers, with fingers 6 and 7 interacting with the core and finger 3 with the G-cluster. In transient transactivation assays, PLAG1 specifically activates transcription from its consensus DNA binding site, indicating that PLAG1 is a genuine transcription factor. Potential PLAG1 binding sites were found in the promoter 3 of the human insulin-like growth factor II (IGF-II) gene. We show that PLAG1 binds IGF-II promoter 3 and stimulates its activity. Moreover, IGF-II transcripts derived from the P3 promoter are highly expressed in salivary gland adenomas overexpressing PLAG1. In contrast, they are not detectable in adenomas without abnormal PLAG1 expression nor in normal salivary gland tissue. This indicates a perfect correlation between PLAG1 and IGF-II expression. All of these results strongly suggest that IGF-II is one of the PLAG1 target genes, providing us with the first clue for understanding the role of PLAG1 in salivary gland tumor development.

  16. 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.

  17. Telmisartan inhibited angiotensin II-induced collagen metabolic imbalance without directly targeting TGF-β 1/Smad signaling pathway in cardiac fibroblasts.

    Science.gov (United States)

    Zhang, Y; Zhao, N A; Wang, J K; Zhu, S M; Zhu, H L; Liu, B; Cui, Q W; Guan, G C; Tian, G

    2015-12-01

    Cardiac fibrosis is an important pathological process of cardiac remodeling. A large number of studies have shown that telmisartan can attenuate cardiac fibrosis through acting on angiotensin II 1 receptor (AT1R), and TGF-β 1/Smad signaling molecule is an important pathway to achieve this effect. The aim of the study was to clarify whether, with excessive activation of RAAS system, telmisartan could also directly target TGF-β 1/Smad signaling pathway to have the function of anti-cardiac fibrosis. In this study, neonatal rat cardiac fibroblasts were cultured and AngII or TGF-β 1 was administered for treatment or pre-incubation, and then telmisartan was used for 24 hours' incubation. Western blot and enzyme-linked immunosorbent assay (ELISA) tests were performed to detect protein expressions. The results showed that telmisartan could inhibit collagen synthesis and collagen metabolic imbalance under the effect of Ang II, but telmisartan could not have such function in TGF-β 1-induced cardiac fibroblasts. It was further confirmed by western blot method that telmisartan could inhibit TGF-β 1/Smad signaling molecule expression under the effect of Ang II, but telmisartan had no effect on TGF-β 1-induced Smad signaling molecule expression. According to the present study telmisartan played a role of anticardiac fibrosis without directly targeting TGF-β 1/Smad signaling pathway molecule.

  18. 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)

    Julovi, Sohel M; Xue, Aiqun; 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

    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. 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. 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. Our data suggest that ApoA-II enhance targeting potential of lipid in pancreatic cancer which may have imaging and drug delivery potentialities.

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

    Directory of Open Access Journals (Sweden)

    Sohel M Julovi

    Full Text Available 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.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.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.Our data suggest that ApoA-II enhance targeting potential of lipid in pancreatic cancer which may have imaging and drug delivery potentialities.

  20. Immobilization of ALA-Zn(II) Coordination Polymer Pro-photosensitizers on Magnetite Colloidal Supraparticles for Target Photodynamic Therapy of Bladder Cancer.

    Science.gov (United States)

    Tan, Jing; Sun, Chuanyu; Xu, Ke; Wang, Changchun; Guo, Jia

    2015-12-16

    5-Aminolevulinic acid (ALA) is a widely used photodynamic therapy (PDT) prodrug in the clinic. It can be metalized to the photosensitizer PpIX, which produces toxic singlet oxygen to kill cancer cells upon visible light irradiation. Herein, a core/shell-structured vehicle is designed to comprise magnetite colloidal supraparticles (MCSPs) as cores and ALA-Zn(II) coordination polymers as shells (Fe3O4@ALA-Zn(II) ) for target pro-photosensitizer delivery. The coordination polymers with 2D layered structures are locally deposited on the MCSPs by the complexation of the ALA and Zn(II) ions, and are readily controlled by varying the feed precursors and reaction temperatures. The maximum conjugated ALA amount is up to 17%. The Fe3O4@ALA-Zn(II) microspheres exhibit pH-sensitive release of ALA in acidic environment and rapid magnetic responsiveness. Cytotoxicity results demonstrate that Fe3O4@ALA-Zn(II) shows a significant inhibitory effect to T24 cells and is nontoxic to 293T normal cells as exposed to the 630 nm visible light for a very short time, which may due to the selective accumulation of ALA-induced PpIX in T24 cancer cells. Compared to the ALA used alone, the coordination polymer form is more efficient because of the bioactivity of incorporated Zn ions despite underlying the same apoptosis mechanism as ALA agent.

  1. Flavonoid inhibitors as novel antimycobacterial agents targeting Rv0636, a putative dehydratase enzyme involved in Mycobacterium tuberculosis fatty acid synthase II.

    Science.gov (United States)

    Brown, Alistair K; Papaemmanouil, Athina; Bhowruth, Veemal; Bhatt, Apoorva; Dover, Lynn G; Besra, Gurdyal S

    2007-10-01

    Flavonoids comprise a large group of bioactive polyphenolic plant secondary metabolites. Several of these possess potent in vivo activity against Escherichia coli and Plasmodium falciparum, targeting enzymes involved in fatty acid biosynthesis, such as enoyl-ACP-reductase, beta-ketoacyl-ACP reductase and beta-hydroxyacyl-ACP dehydratase. Herein, we report that butein, isoliquirtigenin, 2,2',4'-trihydroxychalcone and fisetin inhibit the growth of Mycobacterium bovis BCG. Furthermore, in vitro inhibition of the mycolic-acid-producing fatty acid synthase II (FAS-II) of Mycobacterium smegmatis suggests a mode of action related to those observed in E. coli and P. falciparum. Through a bioinformatic approach, we have established the product of Rv0636 as a candidate for the unknown mycobacterial dehydratase, and its overexpression in M. bovis BCG conferred resistance to growth inhibition by butein and isoliquirtigenin, and relieved inhibition of fatty acid and mycolic acid biosynthesis in vivo. Furthermore, after overexpression of Rv0636 in M. smegmatis, FAS-II was less sensitive to these inhibitors in vitro. Overall, the data suggest that these flavonoids are inhibitors of mycobacterial FAS-II and in particular Rv0636, which represents a strong candidate for the beta-hydroxyacyl-ACP dehydratase enzyme of M. tuberculosis FAS-II.

  2. Target and beam-target spin asymmetries in exclusive pion electroproduction for $Q^2>1$ GeV$^2$. II. $e p \\rightarrow e \\pi^0 p$

    CERN Document Server

    Bosted, P E; Adhikari, K P; Adikaram, D; Akbar, Z; Amaryan, M J; Pereira, S Anefalos; 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; Alaoui, A El; Fassi, L El; 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; Camacho, C Munoz; 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

    2016-01-01

    Beam-target double-spin asymmetries and target single-spin asymmetries were measured for the exclusive $\\pi^0$ electroproduction reaction $\\gamma^* p \\to p \\pi^0$, expanding an analysis of the $\\gamma^* p \\to n \\pi^+$ 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 Lab. The kinematic range covered is $1.1target asymmetries were found to generally be greater than zero, with relatively modest \\phicmsp dependence. The target asymmetries exhibit very strong \\phicmsp dependence, with a change in sign occurring between results at low $W$ and high $W$, in contrast to $\\pi^+$ electroproduction. Reasonable agreement is found with phenomenological fits to previous data for $W<1.6$ GeV, but significant differences are se...

  3. Sol-gel encapsulation of binary Zn(II) compounds in silica nanoparticles. Structure-activity correlations in hybrid materials targeting Zn(II) antibacterial use.

    Science.gov (United States)

    Halevas, E; Nday, C M; Kaprara, E; Psycharis, V; Raptopoulou, C P; Jackson, G E; Litsardakis, G; Salifoglou, A

    2015-10-01

    In the emerging issue of enhanced multi-resistant properties in infectious pathogens, new nanomaterials with optimally efficient antibacterial activity and lower toxicity than other species attract considerable research interest. In an effort to develop such efficient antibacterials, we a) synthesized acid-catalyzed silica-gel matrices, b) evaluated the suitability of these matrices as potential carrier materials for controlled release of ZnSO4 and a new Zn(II) binary complex with a suitably designed well-defined Schiff base, and c) investigated structural and textural properties of the nanomaterials. Physicochemical characterization of the (empty-loaded) silica-nanoparticles led to an optimized material configuration linked to the delivery of the encapsulated antibacterial zinc load. Entrapment and drug release studies showed the competence of hybrid nanoparticles with respect to the a) zinc loading capacity, b) congruence with zinc physicochemical attributes, and c) release profile of their zinc load. The material antimicrobial properties were demonstrated against Gram-positive (Staphylococcus aureus, Bacillus subtilis, Bacillus cereus) and negative (Escherichia coli, Pseudomonas aeruginosa, Xanthomonas campestris) bacteria using modified agar diffusion methods. ZnSO4 showed less extensive antimicrobial behavior compared to Zn(II)-Schiff, implying that the Zn(II)-bound ligand enhances zinc antimicrobial properties. All zinc-loaded nanoparticles were less antimicrobially active than zinc compounds alone, as encapsulation controls their release, thereby attenuating their antimicrobial activity. To this end, as the amount of loaded zinc increases, the antimicrobial behavior of the nano-agent improves. Collectively, for the first time, sol-gel zinc-loaded silica-nanoparticles were shown to exhibit well-defined antimicrobial activity, justifying due attention to further development of antibacterial nanotechnology.

  4. Comparing the suitability of autodock, gold and glide for the docking and predicting the possible targets of Ru(II)-based complexes as anticancer agents.

    Science.gov (United States)

    Adeniyi, Adebayo A; Ajibade, Peter A

    2013-03-25

    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-cymene)L2(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.

  5. 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.

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

    Science.gov (United States)

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

    2016-05-19

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

  7. 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.

  8. In vitro DNA binding, pBR322 plasmid cleavage and molecular modeling study of chiral benzothiazole Schiff-base-valine Cu(II) and Zn(II) complexes to evaluate their enantiomeric biological disposition for molecular target DNA.

    Science.gov (United States)

    Alizadeh, Rahman; Afzal, Mohd; Arjmand, Farukh

    2014-10-15

    Bicyclic heterocyclic compounds viz. benzothiazoles are key components of deoxyribonucleic acid (DNA) molecules and participate directly in the encoding of genetic information. Benzothiazoles, therefore, represent a potent and selective class of antitumor compounds. The design and synthesis of chiral antitumor chemotherapeutic agents of Cu(II) and Zn(II), L- and -D benzothiazole Schiff base-valine complexes 1a &b and 2a &b, respectively were carried out and thoroughly characterized by spectroscopic and analytical techniques. Interaction of 1a and b and 2a and b with CT DNA by employing UV-vis, florescence, circular dichroic methods and cleavage studies of 1a with pBR322 plasmid, molecular docking were done in order to demonstrate their enantiomeric disposition toward the molecular drug target DNA. Interestingly, these studies unambiguously demonstrated the greater potency of L-enantiomer in comparison to D-enantiomer.

  9. In vitro DNA binding, pBR322 plasmid cleavage and molecular modeling study of chiral benzothiazole Schiff-base-valine Cu(II) and Zn(II) complexes to evaluate their enantiomeric biological disposition for molecular target DNA

    Science.gov (United States)

    Alizadeh, Rahman; Afzal, Mohd; Arjmand, Farukh

    2014-10-01

    Bicyclic heterocyclic compounds viz. benzothiazoles are key components of deoxyribonucleic acid (DNA) molecules and participate directly in the encoding of genetic information. Benzothiazoles, therefore, represent a potent and selective class of antitumor compounds. The design and synthesis of chiral antitumor chemotherapeutic agents of Cu(II) and Zn(II), L- and -D benzothiazole Schiff base-valine complexes 1a &b and 2a &b, respectively were carried out and thoroughly characterized by spectroscopic and analytical techniques. Interaction of 1a and b and 2a and b with CT DNA by employing UV-vis, florescence, circular dichroic methods and cleavage studies of 1a with pBR322 plasmid, molecular docking were done in order to demonstrate their enantiomeric disposition toward the molecular drug target DNA. Interestingly, these studies unambiguously demonstrated the greater potency of L-enantiomer in comparison to D-enantiomer.

  10. 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

  11. Statistical analysis of particle flux flowing into the end-target in between attached and detached states in the linear divertor plasma simulator NAGDIS-II

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, H. [National Institute for Fusion Science, Toki (Japan); Department of Fusion Science, SOKENDAI, Toki (Japan); Ohno, N.; Onda, T.; Takeyama, K.; Tsuji, Y. [Graduate School of Engineering, Nagoya University, Nagoya (Japan); Kajita, S.; Kuwabara, T. [Institute of Materials and Systems for Sustainability, Nagoya University (Japan)

    2016-08-15

    We have investigated the particle flux flowing into the axisymmetric end-target in the transient state from attached to detached divertor conditions in the linear plasma device NAGDIS-II. In the transient state, a dramatic decrease of the mean particle flux and a large-amplitude fluctuation with negative and positive spikes were observed. We have analyzed the fluctuation with a newly suggested analysis technique: pre-multiplied cubic spectrum with the wavelet transform. Analysis result indicates that these spikes consist of a few kilohertz components. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  12. Rational drug design and synthesis of molecules targeting the angiotensin II type 1 and type 2 receptors.

    Science.gov (United States)

    Kellici, Tahsin F; Tzakos, Andreas G; Mavromoustakos, Thomas

    2015-03-02

    The angiotensin II (Ang II) type 1 and type 2 receptors (AT1R and AT2R) orchestrate an array of biological processes that regulate human health. Aberrant function of these receptors triggers pathophysiological responses that can ultimately lead to death. Therefore, it is important to design and synthesize compounds that affect beneficially these two receptors. Cardiovascular disease, which is attributed to the overactivation of the vasoactive peptide hormone Αng II, can now be treated with commercial AT1R antagonists. Herein, recent achievements in rational drug design and synthesis of molecules acting on the two AT receptors are reviewed. Quantitative structure activity relationships (QSAR) and molecular modeling on the two receptors aim to assist the search for new active compounds. As AT1R and AT2R are GPCRs and drug action is localized in the transmembrane region the role of membrane bilayers is exploited. The future perspectives in this field are outlined. Tremendous progress in the field is expected if the two receptors are crystallized, as this will assist the structure based screening of the chemical space and lead to new potent therapeutic agents in cardiovascular and other diseases.

  13. Radiological considerations on multi-MW targets Part II After-heat and temperature distribution in packed tantalum spheres

    CERN Document Server

    Magistris, M

    2005-01-01

    CERN is designing a Superconducting Proton Linac (SPL) to provide a 2.2GeV, 4MW proton beam to feed facilities like, for example, a future Neutrino Factory or a Neutrino SuperBeam. One of the most promising target candidates is a stationary consisting of a Ti container filled with small Ta pellets. The power deposited as heat by the radioactive nuclides (the so-called after-heat) can considerably increase the target temperature after ceasing operation, if no active cooling is provided. An estimate of the induced radioactivity and after-heat was performed with the FLUKA Monte Carlo code. To estimate the highest temperature reached inside the target, the effective thermal conductivity of packed spheres was evaluated using the basic cell method. A method for estimating the contribution to heat transmission from radiation is also discussed1).

  14. 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.

  15. Functionalization of Ruthenium(II) terpyridine complexes with cyclic RGD pep-tides to target integrin receptors in cancer cells

    NARCIS (Netherlands)

    Hahn, Eva M.; Estrada Ortiz, Natalia; Han, Jiaying; Ferreira, Vera F. C.; Kapp, Tobias G.; Correia, Joao D. G.; Casini, Angela; Kuehn, Fritz E.

    2016-01-01

    The lack of selectivity for cancer cells and the resulting negative impact on healthy tissue is a severe drawback of actual cancer chemotherapy. Tethering of cytotoxic drugs to targeting vectors such as peptides, which recognize receptors overexpressed on the surface of tumor cells, is one possible

  16. Tumor-targeted intracellular delivery of anticancer drugs through the mannose-6-phosphate/insulin-like growth factor II receptor

    NARCIS (Netherlands)

    Prakash, Jai; Beljaars, Leonie; Harapanahalli, Akshay K.; Zeinstra-Smith, Mieke; de Jager-Krikken, Alie; Hessing, Martin; Steen, Herman; Poelstra, Klaas

    2010-01-01

    Tumor-targeting of anticancer drugs is an interesting approach for the treatment of cancer since chemotherapies possess several adverse effects. In the present study, we propose a novel strategy to deliver anticancer drugs to the tumor cells through the mannose-6-phosphate/insulin-like growth factor

  17. The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs.

    Science.gov (United States)

    Johnstone, Timothy C; Suntharalingam, Kogularamanan; Lippard, Stephen J

    2016-03-09

    The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing nonclassical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown, and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this Review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore nonclassical platinum(II) complexes with trans geometry or with a monofunctional coordination mode, polynuclear platinum(II) compounds, platinum(IV) prodrugs, dual-threat agents, and photoactivatable platinum(IV) complexes. Nanoparticles designed to deliver platinum(IV) complexes will also be discussed, including carbon nanotubes, carbon nanoparticles, gold nanoparticles, quantum dots, upconversion nanoparticles, and polymeric micelles. Additional nanoformulations, including supramolecular self-assembled structures, proteins, peptides, metal-organic frameworks, and coordination polymers, will then be described. Finally, the significant clinical progress made by nanoparticle formulations of platinum(II) agents will be reviewed. We anticipate that such a synthesis of disparate research efforts will not only help to generate new drug development ideas and strategies, but also will reflect our optimism that the next generation of approved platinum cancer drugs is about to arrive.

  18. 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.

  19. 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

    Major histocompatibility complex (MHC) molecules are a key element of the cellular immune response. Encoded by the MHC they are a family of highly polymorphic peptide receptors presenting peptide antigens for the surveillance by T cells. We have shown that certain organic compounds can amplify...... immune responses by catalyzing the peptide loading of human class II MHC molecules HLA-DR. Here we show now that they achieve this by interacting with a defined binding site of the HLA-DR peptide receptor. Screening of a compound library revealed a set of adamantane derivatives that strongly accelerated......, 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...

  20. Targeted gene knockdown in zebrafish reveals distinct intraembryonic functions for insulin-like growth factor II signaling.

    Science.gov (United States)

    White, Yvonne A R; Kyle, Joshua T; Wood, Antony W

    2009-09-01

    IGF-II is the predominant IGF ligand regulating prenatal growth in all vertebrates, including humans, but its central role in placental development has confounded efforts to fully elucidate its functions within the embryo. Here we use a nonplacental model vertebrate (zebrafish) to interrogate the intraembryonic functions of IGF-II signaling. The zebrafish genome contains two coorthologs of mammalian IGF2 (igf2a, igf2b), which exhibit distinct patterns of expression during embryogenesis. Expression of igf2a mRNA is restricted to the notochord, primarily during segmentation/neurulation. By contrast, igf2b mRNA is expressed in midline tissues adjacent to the notochord, with additional sites of expression in the ventral forebrain, and the pronephros. To identify their intraembryonic functions, we suppressed the expression of each gene with morpholino oligonucleotides. Knockdown of igf2a led to defects in dorsal midline development, characterized by delayed segmentation, notochord undulations, and ventral curvature. Similarly, suppression of igf2b led to defects in dorsal midline development but also induced ectopic fusion of the nephron primordia, and defects in ventral forebrain development. Subsequent onset of severe body edema in igf2b, but not igf2a morphants, further suggested a distinct role for igf2b in development of the embryonic kidney. Simultaneous knockdown of both genes increased the severity of dorsal midline defects, confirming a conserved role for both genes in dorsal midline development. Collectively, these data provide evidence that the zebrafish orthologs of IGF2 function in dorsal midline development during segmentation/neurulation, whereas one paralog, igf2b, has evolved additional, distinct functions during subsequent organogenesis.

  1. 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 .

  2. DNA-based aptamer fails as a simultaneous cancer targeting agent and drug delivery vehicle for a phenanthroline-based platinum(II) complex.

    Science.gov (United States)

    McGinely, Nicola L; Plumb, Jane A; Wheate, Nial J

    2013-11-01

    The sgc8c aptamer is a 41-base DNA oligonucleotide that binds to leukaemia cells with high affinity and specificity. In this work we examined the utility of this aptamer as both a delivery vehicle and an active targeting agent for an inert platinum complex [(1,10-phenathroline)(ethylenediamine)platinum(II)](2+). The aptamer forms a stem-and-loop confirmation as determined by circular dichroism. This conformation is adopted in both water and phosphate buffered saline solutions. The metal complex binds through intercalation into the aptamer's double helical stem with a binding constant of approximately 4.3 × 10(4) M(-1). Binding of the metal complex to the aptamer had a significant effect on the aptamer's global conformation, and increased its melting temperature by 28°C possibly through lengthening and stiffening of the aptamer stem. The effect of the aptamer on the metal complex's cytotoxicity and cellular uptake was determined using in vitro assays with the target leukaemia cell line CCRF-CEM and the off-target ovarian cancer cell lines A2780 and A2780cp70. The aptamer has little inherent cytotoxicity and when used to deliver the metal complex results in a significant decrease in the metal complex's cytotoxicity and uptake. The reason(s) for the poor uptake and activity may be due to the change in aptamer conformation which affects its ability to recognise leukaemia cells.

  3. Unravelling the transcriptomic landscape of the major phase II UDP-glucuronosyltransferase drug metabolizing pathway using targeted RNA sequencing.

    Science.gov (United States)

    Tourancheau, A; Margaillan, G; Rouleau, M; Gilbert, I; Villeneuve, L; Lévesque, E; Droit, A; Guillemette, C

    2016-02-01

    A comprehensive view of the human UDP-glucuronosyltransferase (UGT) transcriptome is a prerequisite to the establishment of an individual's UGT metabolic glucuronidation signature. Here, we uncover the transcriptome landscape of the 10 human UGT gene loci in normal and tumoral metabolic tissues by targeted RNA next-generation sequencing. Alignment on the human hg19 reference genome identifies 234 novel exon-exon junctions. We recover all previously known UGT1 and UGT2 enzyme-coding transcripts and identify over 130 structurally and functionally diverse novel UGT variants. We further expose a revised genomic structure of UGT loci and provide a comprehensive repertoire of transcripts for each UGT gene. Data also uncover a remodelling of the UGT transcriptome occurring in a tissue- and tumor-specific manner. The complex alternative splicing program regulating UGT expression and protein functions is likely critical in determining detoxification capacity of an organ and stress-related responses, with significant impact on drug responses and diseases.

  4. 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.

  5. 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.

  6. Mechanisms of Nrf2/Keap1-Dependent Phase II Cytoprotective and Detoxifying Gene Expression and Potential Cellular Targets of Chemopreventive Isothiocyanates

    Directory of Open Access Journals (Sweden)

    Biswa Nath Das

    2013-01-01

    Full Text Available Isothiocyanates (ITCs are abundantly found in cruciferous vegetables. Epidemiological studies suggest that chronic consumption of cruciferous vegetables can lower the overall risk of cancer. Natural ITCs are key chemopreventive ingredients of cruciferous vegetables, and one of the prime chemopreventive mechanisms of natural isothiocyanates is the induction of Nrf2/ARE-dependent gene expression that plays a critical role in cellular defense against electrophiles and reactive oxygen species. In the present review, we first discuss the underlying mechanisms how natural ITCs affect the intracellular signaling kinase cascades to regulate the Keap1/Nrf2 activities, thereby inducing phase II cytoprotective and detoxifying enzymes. We also discuss the potential cellular protein targets to which natural ITCs are directly conjugated and how these events aid in the chemopreventive effects of natural ITCs. Finally, we discuss the posttranslational modifications of Keap1 and nucleocytoplasmic trafficking of Nrf2 in response to electrophiles and oxidants.

  7. Overview on the current status on virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part II.

    Science.gov (United States)

    Geromichalos, George D; Alifieris, Constantinos E; Geromichalou, Elena G; Trafalis, Dimitrios T

    2016-01-01

    Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Nowadays, new generation of anticancer drugs, able to inhibit more than one pathway, is believed to play a major role in contemporary anticancer drug research. In this way, polypharmacology, focusing on multi-target drugs, has emerged as a new paradigm in drug discovery. A number of recent successful drugs have in part or in whole emerged from a structure-based research approach. Many advances including crystallography and informatics are behind these successes. In this part II we will review the role and methodology of ligand-, structure- and fragment-based computer-aided drug design computer aided drug desing (CADD), virtual high throughput screening (vHTS), de novo drug design, fragment-based design and structure-based molecular docking, homology modeling, combinatorial chemistry and library design, pharmacophore model chemistry and informatics in modern drug discovery.

  8. 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.

  9. Inhibition of the mammalian target of rapamycin (mTOR in advanced pancreatic cancer: results of two phase II studies

    Directory of Open Access Journals (Sweden)

    Zhang Yujian

    2010-07-01

    Full Text Available Abstract Background The phosphoinositide 3-kinase (PI3K/Akt pathway is constitutively activated in pancreatic cancer and the mammalian target of rapamycin (mTOR kinase is an important mediator for its signaling. Our recent in vitro studies suggest that prolonged exposure of pancreatic cancer cells to mTOR inhibitors can promote insulin receptor substrate-PI3K interactions and paradoxically increase Akt phosphorylation and cyclin D1 expression in pancreatic cancer cells (negative feedback loop. The addition of erlotinib to rapamycin can down-regulate rapamycin-stimulated Akt and results in synergistic antitumor activity with erlotinib in preclinical tumor models. Methods Two studies prospectively enrolled adult patients with advanced pancreatic cancer, Eastern Cooperative Oncology Group performance status 0-1, adequate hematologic, hepatic and renal parameters and measurable disease. In Study A, temsirolimus was administered intravenously at 25 mg weekly. In Study B, everolimus was administered orally at 30 mg weekly and erlotinib was administered at 150 mg daily. The primary endpoint in both studies was overall survival at 6 months. Secondary endpoints included time to progression, progression-free survival, overall survival, response rate, safety and toxicity. Pretreatment tumor biopsies were analyzed by immunofluorescence and laser scanning cytometry for the expression of pmTOR/mTOR, pAkt/Akt, pErk/Erk, pS6, p4EBP-1 and PTEN. Results Five patients enrolled in Study A; Two patients died within a month (rapid disease progression and hemorrhagic stroke, respectively. One patient developed dehydration and another developed asthenia. Sixteen patients enrolled in Study B.: 12 males, all ECOG PS = 1. Median cycles = 1 (range 1-2. Grade 4 toxicity: hyponatremia (n = 1, Grade 3: diarrhea (n = 1, cholangitis (n = 3, hyperglycemia (n = 1, fatigue (n = 1. Grade 2: pneumonia (n = 2, dehydration (n = 2, nausea (n = 2, neutropenia (n = 1, mucositis (n = 2

  10. Photometric Variability in Kepler Target Stars. II. An Overview of Amplitude, Periodicity, and Rotation in First Quarter Data

    CERN Document Server

    Basri, Gibor; Batalha, Natalie; Gilliland, Ronald L; Jenkins, Jon; Borucki, William J; Koch, David; Caldwell, Doug; Dupree, Andrea K; Latham, David W; Marcy, Geoffrey W; Meibom, Soeren; Howell, Steve; Brown, Tim

    2010-01-01

    We provide an overview of stellar variability in the first quarter of data from the Kepler mission. The intent of this paper is to examine the entire sample of over 150,000 target stars for periodic behavior in their lightcurves, and relate this to stellar characteristics. These data constitute an unprecedented study of stellar variability given its great precision and complete time coverage (with a half hour cadence). Because the full Kepler pipeline is not currently suitable for a study of stellar variability of this sort, we describe our procedures for treating the "raw" pipeline data. About half of the total sample exhibits convincing periodic variability up to two weeks, with amplitudes ranging from differential intensity changes less than 10^{-4} up to more than 10 percent. K and M dwarfs have a greater fraction of period behavior than G dwarfs. The giants in the sample have distinctive quasi-periodic behavior, but are not periodic in the way we define it. Not all periodicities are due to rotation, and ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-03-01

    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: {minus}11{+-}19 MPa ({minus}4{+-}6%) for yield strength (YS), {minus}3{+-}15 MPa ({minus}1{+-}3%) for ultimate tensile strength (UTS), {minus}5{+-}2% strain for uniform elongation (UE), and {minus}4{+-}2% strain for total elongation (TE). Of these changes, the decrease in {minus}1{+-}6 MPa (0{+-}1%) for UTS, {minus}5{+-}2% for UE, and {minus}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.

  12. Tanshinone II-A sodium sulfonate (DS-201) enhances human BKCa channel activity by selectively targeting the pore-forming α subunit.

    Science.gov (United States)

    Tan, Xiao-qiu; Cheng, Xiu-li; Yang, Yan; Yan, Li; Gu, Jing-li; Li, Hui; Zeng, Xiao-rong; Cao, Ji-min

    2014-11-01

    Tanshinone II-A sodium sulfonate (DS-201), a water-soluble derivative of Tanshinone II-A, has been found to induce vascular relaxation and activate BKCa channels. The aim of this study was to explore the mechanisms underlying the action of DS-201 on BKCa channels. Human BKCa channels containing α subunit alone or α plus β1 subunits were expressed in HEK293 cells. BKCa currents were recorded from the cells using patch-clamp technique. The expression and trafficking of BKCa subunits in HEK293 cells or vascular smooth muscle cells (VSMCs) were detected by Western blotting, flow cytometry and confocal microscopy. DS-201 (40-160 μmol/L) concentration-dependently increased the total open probability of BKCa channels in HEK293 cells, associated with enhancements of Ca(2+) and voltage dependence as well as a delay in deactivation. Coexpression of β1 subunit did not affect the action of DS-201: the values of EC50 for BKCa channels containing α subunit alone and α plus β1 subunit were 66.6±1.5 and 62.0±1.1 μmol/L, respectively. In both HEK293 cells and VSMCs, DS-201 (80 μmol/L) markedly increased the expression of α subunit without affecting β1 subunit. In HEK293 cells, DS-201 enriched the membranous level of α subunit, likely by accelerating the trafficking and suppressing the internalization of α subunit. In both HEK293 cells and VSMCs, DS-201 (≥320 μmol/L) induced significant cytotoxicity. DS-201 selectively targets the pore-forming α subunit of human BKCa channels, thus enhancing the channel activities and increasing the subunit expression and trafficking, whereas the β1 subunit does not contribute to the action of DS-201.

  13. A [Mn18Dy] SMM resulting from the targeted replacement of the central MnII in the S = 83/2 [Mn19]-aggregate with DyIII.

    Science.gov (United States)

    Ako, Ayuk M; Mereacre, Valeriu; Clérac, Rodolphe; Wernsdorfer, Wolfgang; Hewitt, Ian J; Anson, Christopher E; Powell, Annie K

    2009-02-07

    Anisotropy can be introduced into the [Mn(19)]-aggregate, which currently has the highest known spin ground state of S = 83/2, by the targeted replacement of the central Mn(II) cation with Dy(III) leading to a [Mn(18)Dy] complex with the same core topology showing slow relaxation of the magnetisation.

  14. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02)

    Science.gov (United States)

    Iwamoto, Fabio M.; Lamborn, Kathleen R.; Robins, H. Ian; Mehta, Minesh P.; Chang, Susan M.; Butowski, Nicholas A.; DeAngelis, Lisa M.; Abrey, Lauren E.; Zhang, Wei-Ting; Prados, Michael D.; Fine, Howard A.

    2010-01-01

    The objective of this phase II single-arm study was to evaluate the efficacy and safety of pazopanib, a multi-targeted tyrosine kinase inhibitor, against vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, platelet-derived growth factor receptor-α and -β, and c-Kit, in recurrent glioblastoma. Patients with ≤2 relapses and no prior anti-VEGF/VEGFR therapy were treated with pazopanib 800 mg daily on 4-week cycles without planned interruptions. Brain magnetic resonance imaging and clinical reassessment were made every 8 weeks. The primary endpoint was efficacy as measured by 6-month progression-free survival (PFS6). Thirty-five GBM patients with a median age of 53 years and median Karnofsky performance scale of 90 were accrued. Grade 3/4 toxicities included leukopenia (n = 1), lymphopenia (n = 2), thrombocytopenia (n = 1), ALT elevation (n = 3), AST elevation (n = 1), CNS hemorrhage (n = 1), fatigue (n = 1), and thrombotic/embolic events (n = 3); 8 patients required dose reduction. Two patients had a partial radiographic response by standard bidimensional measurements, whereas 9 patients (6 at the 8-week point and 3 only within the first month of treatment) had decreased contrast enhancement, vasogenic edema, and mass effect but <50% reduction in tumor. The median PFS was 12 weeks (95% confidence interval [CI]: 8–14 weeks) and only 1 patient had a PFS time ≥6 months (PFS6 = 3%). Thirty patients (86%) had died and median survival was 35 weeks (95% CI: 24–47 weeks). Pazopanib was reasonably well tolerated with a spectrum of toxicities similar to other anti-VEGF/VEGFR agents. Single-agent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses. ClinicalTrials.gov identifier: NCT00459381. PMID:20200024

  15. Age-dependent targeting of protein phosphatase 1 to Ca2+/calmodulin-dependent protein kinase II by spinophilin in mouse striatum.

    Directory of Open Access Journals (Sweden)

    Anthony J Baucum

    Full Text Available Mechanisms underlying age-dependent changes of dendritic spines on striatal medium spiny neurons are poorly understood. Spinophilin is an F-actin- and protein phosphatase 1 (PP1-binding protein that targets PP1 to multiple downstream effectors to modulate dendritic spine morphology and function. We found that calcium/calmodulin-dependent protein kinase II (CaMKII directly and indirectly associates with N- and C-terminal domains of spinophilin, but F-actin can displace CaMKII from the N-terminal domain. Spinophilin co-localizes PP1 with CaMKII on the F-actin cytoskeleton in heterologous cells, and spinophilin co-localizes with synaptic CaMKII in neuronal cultures. Thr286 autophosphorylation enhances the binding of CaMKII to spinophilin in vitro and in vivo. Although there is no change in total levels of Thr286 autophosphorylation, maturation from postnatal day 21 into adulthood robustly enhances the levels of CaMKII that co-immunoprecipitate with spinophilin from mouse striatal extracts. Moreover, N- and C-terminal domain fragments of spinophilin bind more CaMKII from adult vs. postnatal day 21 striatal lysates. Total levels of other proteins that interact with C-terminal domains of spinophilin decrease during maturation, perhaps reducing competition for CaMKII binding to the C-terminal domain. In contrast, total levels of α-internexin and binding of α-internexin to the spinophilin N-terminal domain increases with maturation, perhaps bridging an indirect interaction with CaMKII. Moreover, there is an increase in the levels of myosin Va, α-internexin, spinophilin, and PP1 in striatal CaMKII immune complexes isolated from adult and aged mice compared to those from postnatal day 21. These changes in spinophilin/CaMKII interactomes may contribute to changes in striatal dendritic spine density, morphology, and function during normal postnatal maturation and aging.

  16. Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog–Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032

    Science.gov (United States)

    Robinson, Giles W.; Orr, Brent A.; Wu, Gang; Gururangan, Sridharan; Lin, Tong; Qaddoumi, Ibrahim; Packer, Roger J.; Goldman, Stewart; Prados, Michael D.; Desjardins, Annick; Chintagumpala, Murali; Takebe, Naoko; Kaste, Sue C.; Rusch, Michael; Allen, Sariah J.; Onar-Thomas, Arzu; Stewart, Clinton F.; Fouladi, Maryam; Boyett, James M.; Gilbertson, Richard J.; Curran, Tom; Ellison, David W.; Gajjar, Amar

    2015-01-01

    Purpose Two phase II studies assessed the efficacy of vismodegib, a sonic hedgehog (SHH) pathway inhibitor that binds smoothened (SMO), in pediatric and adult recurrent medulloblastoma (MB). Patients and Methods Adult patients enrolled onto PBTC-025B and pediatric patients enrolled onto PBTC-032 were treated with vismodegib (150 to 300 mg/d). Protocol-defined response, which had to be sustained for 8 weeks, was confirmed by central neuroimaging review. Molecular tests to identify patterns of response and insensitivity were performed when tissue was available. Results A total of 31 patients were enrolled onto PBTC-025B, and 12 were enrolled onto PBTC-032. Three patients in PBTC-025B and one in PBTC-032, all with SHH-subgroup MB (SHH-MB), exhibited protocol-defined responses. Progression-free survival (PFS) was longer in those with SHH-MB than in those with non-SHH–MB, and prolonged disease stabilization occurred in 41% of patient cases of SHH-MB. Among those with SHH-MB, loss of heterozygosity of PTCH1 was associated with prolonged PFS, and diffuse staining of P53 was associated with reduced PFS. Whole-exome sequencing identified mutations in SHH genes downstream from SMO in four of four tissue samples from nonresponders and upstream of SMO in two of four patients with favorable responses. Conclusion Vismodegib exhibits activity against adult recurrent SHH-MB but not against recurrent non-SHH–MB. Inadequate accrual of pediatric patients precluded conclusions in this population. Molecular analyses support the hypothesis that SMO inhibitor activity depends on the genomic aberrations within the tumor. Such inhibitors should be advanced in SHH-MB studies; however, molecular and genomic work remains imperative to identify target populations that will truly benefit. PMID:26169613

  17. 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.

  18. A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

    Science.gov (United States)

    Tosco, A; De Gregorio, F; Esposito, S; De Stefano, D; Sana, I; Ferrari, E; Sepe, A; Salvadori, L; Buonpensiero, P; Di Pasqua, A; Grassia, R; Leone, C A; Guido, S; De Rosa, G; Lusa, S; Bona, G; Stoll, G; Maiuri, M C; Mehta, A; Kroemer, G; Maiuri, L; Raia, V

    2016-08-01

    We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (PCftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment.

  19. Galactose conjugated platinum(II) complex targeting the Warburg effect for treatment of non-small cell lung cancer and colon cancer.

    Science.gov (United States)

    Wu, Meng; Li, Hong; Liu, Ran; Gao, Xiangqian; Zhang, Menghua; Liu, Pengxing; Fu, Zheng; Yang, Jinna; Zhang-Negrerie, Daisy; Gao, Qingzhi

    2016-03-03

    Malignant neoplasms exhibit a higher rate of glycolysis than normal cells; this is known as the Warburg effect. To target it, a galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-chloromalonato-platinum(II) complex (Gal-Pt) was designed, synthesized, and evaluated in five human cancer cell lines and against two different xenograft tumour models. Gal-Pt exhibits much higher aqueous solubility (over 25 times) and improved cytotoxicity than oxaliplatin, especially in human colon (HT29) and lung (H460) cancer cell lines. The safety profile of Gal-Pt was investigated in vivo by exploring the maximum tolerated dose (MTD) and animal mortality rate. The ratios of the animal lethal dosage values to the cytotoxicity in HT29 (LD50/IC50) showed that Gal-Pt was associated with an increased therapeutic index by over 30-fold compared to cisplatin and oxaliplatin. We evaluated in vivo antitumor activity by single agent intravenous treatment comparison studies of Gal-Pt (50 mg/kg as 65% MTD) and cisplatin (3 mg/kg, as 80% MTD) in a H460 lung cancer xenograft model, and with oxaliplatin (7 mg/kg, as 90% MTD) in a HT29 colon cancer xenograft model. The results show that Gal-Pt was more efficacious against H460 than cisplatin, and had superior potency in HT29 cells compared to oxaliplatin under nontoxic dosage conditions. The dependency between cytotoxicity of Gal-Pt and glucose transporters (GLUTs) was investigated by using quercetin as an inhibitor of GLUTs in HT29 cells. The cytotoxic potency of Gal-Pt was highly reduced by the inhibitor, suggesting that the uptake of Gal-Pt was regulated by glucose transporters. The GLUT mediated transportability and cellular uptake of Gal-Pt was also demonstrated using a fluorescent glucose bioprobe in HT29 competition assay.

  20. cobalt (ii), nickel (ii)

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The manganese (II), cobalt (II), nickel (II) and copper (II) complexes of N, N' – ... temperature and coordinated water were determined ... indicating fairly stable complex compounds (Table 1). The complex compounds are insoluble [Table 2] in water and common organic solvents, but are readily soluble in ...

  1. 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

    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...... 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...

  2. Threonine-4 of mammalian RNA polymerase II CTD is targeted by Polo-like kinase 3 and required for transcriptional elongation.

    Science.gov (United States)

    Hintermair, Corinna; Heidemann, Martin; Koch, Frederic; Descostes, Nicolas; Gut, Marta; Gut, Ivo; Fenouil, Romain; Ferrier, Pierre; Flatley, Andrew; Kremmer, Elisabeth; Chapman, Rob D; Andrau, Jean-Christophe; Eick, Dirk

    2012-06-13

    Eukaryotic RNA polymerase II (Pol II) has evolved an array of heptad repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 at the carboxy-terminal domain (CTD) of the large subunit (Rpb1). Differential phosphorylation of Ser2, Ser5, and Ser7 in the 5' and 3' regions of genes coordinates the binding of transcription and RNA processing factors to the initiating and elongating polymerase complexes. Here, we report phosphorylation of Thr4 by Polo-like kinase 3 in mammalian cells. ChIPseq analyses indicate an increase of Thr4-P levels in the 3' region of genes occurring subsequently to an increase of Ser2-P levels. A Thr4/Ala mutant of Pol II displays a lethal phenotype. This mutant reveals a global defect in RNA elongation, while initiation is largely unaffected. Since Thr4 replacement mutants are viable in yeast we conclude that this amino acid has evolved an essential function(s) in the CTD of Pol II for gene transcription in mammalian cells.

  3. Mannose-6-phosphate/insulin-like growth Factor-II receptors may represent a target for the selective delivery of mycophenolic acid to fibrogenic cells

    NARCIS (Netherlands)

    Greupink, Albert; Bakker, Hester; van Goor, H.; de Borst, M.H.; Beljaars, L.; Poelstra, Klaas

    2006-01-01

    Purpose. The insulin-like growth factor axis plays an important role in fibrogenesis. However, little is known about mannose-6-phosphate/Insulin-like growth factor-II receptor (M6P/IGF-IIR) expression during fibrosis. When expressed preferentially on fibrogenic cells, this receptor may be used to se

  4. Sialyltransferase ST8Sia-II assembles a subset of polysialic acid that directs hippocampal axonal targeting and promotes fear behavior.

    Science.gov (United States)

    Angata, Kiyohiko; Long, Jeffrey M; Bukalo, Olena; Lee, Wenjau; Dityatev, Alexander; Wynshaw-Boris, Anthony; Schachner, Melitta; Fukuda, Minoru; Marth, Jamey D

    2004-07-30

    Polysialic acid (PSA) is a post-translational protein modification that is widely expressed among neural cell types during development. Found predominantly on the neural cell adhesion molecule (NCAM), PSA becomes restricted to regions of neurogenesis and neuroplasticity in the adult. In the mammalian genome, two polysialyltransferases termed ST8Sia-II and ST8Sia-IV have been hypothesized to be responsible for the production of PSA in vivo. Approaches to discover PSA function have involved the application of endoneuraminidase-N to remove PSA and genetic manipulations in the mouse to deplete either NCAM or ST8Sia-IV. Here we report the production and characterization of mice deficient in the ST8Sia-II polysialyltransferase. We observed alterations in brain PSA expression unlike those observed in mice lacking ST8Sia-IV. This included a PSA deficit in regions of neurogenesis but without changes in the frequency of mitotic neural progenitor cells. In further contrast with ST8Sia-IV deficiency, loss of ST8Sia-II did not impair hippocampal synaptic plasticity but instead resulted in the misguidance of infrapyramidal mossy fibers and the formation of ectopic synapses in the hippocampus. Consistent with studies of animal models bearing these morphological changes, ST8Sia-II-deficient mice exhibited higher exploratory drive and reduced behavioral responses to Pavlovian fear conditioning. PSA produced by the ST8Sia-II polysialyltransferase modifies memory and behavior processes that are distinct from the neural roles reported for ST8Sia-IV. This genetic partitioning of PSA formation engenders discrete neurological processes and reveals that this post-translational modification forms the predominant basis for the multiple functions attributed to the NCAM glycoprotein.

  5. Probing the biological evaluations of a new designed Pt(II) complex using spectroscopic and theoretical approaches: human hemoglobin as a target.

    Science.gov (United States)

    Abazari, Omid; Shafaei, Zahra; Divsalar, Adeleh; Eslami-Moghadam, Mahbubeh; Ghalandari, Behafarid; Saboury, Ali Akbar

    2016-05-01

    In recent years, using heavy metal compounds such as platinum as anticancer agent is one of the common ways in chemical therapy. In this study, a new anticancer compound of glycine derivatives of Pt(II) complex (amyl-glycine1, 10-phenanthroline Platinum nitrate) was designed, and the biological effects of this novel compound on the alterations in the function and structure of human hemoglobin (Hb) at different temperatures of 25 and 37°C were assessed by applying various spectroscopic (fluorescence and circular dichroism (CD)) and theoretical methods. Fluorescence data indicated the strong ability of Pt(II) complex to quench the intrinsic fluorescence of Hb. The binding constant, number of binding sites, and thermodynamic parameters at two temperatures were calculated, and the results indicated the major possibility of occurring van der Waals force or hydrogen bond interactions in the Pt(II) complex-Hb interaction. For evaluating the alteration of secondary structure of Hb upon interaction with various concentrations of complex, far-UV CD spectra were used and it was observed that in high dose of complex, significant changes were occurred which is indicative of some side effects in overdosing of this complex. On the other hand, the molecular docking results illustrate that are well in agreement in obtaining data with spectroscopy. Above results suggested that using Pt(II) complex as an anticancer agent, model drug in high-dose usage might cause some disordering in structure and function of Hb as well as improve understanding of the side effects of newly designed metal anticancer drugs undergoing.

  6. 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.

  7. 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 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.

  8. Cinnamomum verum component 2-methoxycinnamaldehyde: a novel antiproliferative drug inducing cell death through targeting both topoisomerase I and II in human colorectal adenocarcinoma COLO 205 cells

    Directory of Open Access Journals (Sweden)

    Kuen-daw Tsai

    2016-06-01

    Full Text Available Background: Cinnamomum verum is used to manufacture the spice cinnamon. In addition, the plant has been used as a Chinese herbal medication. Methods: We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA, a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human colorectal adenocarcinoma COLO 205 cells. Specifically, cell viability was evaluated by colorimetric assay; apoptosis was determined by flow cytometry and morphological analysis with bright field, acridine orange, and neutral red stainings, as well as comet assay; topoisomerase I activity was determined by assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VACs were determined by neutral red staining. Results: The results demonstrate that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (ΔΨm loss, activation of both caspase-3 and -9, increase of annexin V+PI+ cells, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated VAC, cytotoxicity, and inhibitions of topoisomerase I as well as II activities. Additional study demonstrated the antiproliferative effect of 2-MCA found in a nude mice model. Conclusions: Our data implicate that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of pro-apoptotic molecules, associated with increased lysosomal vacuolation. In vivo 2-MCA reduced the tumor burden that could have significant clinical impact. Indeed, similar effects were found in other tested cell lines, including human hepatocellular carcinoma SK-Hep-1 and Hep 3B, lung adenocarcinoma A549 and squamous cell carcinoma NCI-H520, and T-lymphoblastic MOLT-3 (results not shown. Our data implicate

  9. Targeting Angiotensin II Type-1 Receptor (AT1R) Inhibits the Harmful Phenotype of Plasmodium-Specific CD8(+) T Cells during Blood-Stage Malaria.

    Science.gov (United States)

    Silva-Filho, João L; Caruso-Neves, Celso; Pinheiro, Ana A S

    2017-01-01

    CD8(+) T-cell response is critical in the pathogenesis of cerebral malaria during blood-stage. Our group and other have been shown that angiotensin II (Ang II) and its receptor AT1 (AT1R), a key effector axis of renin-angiotensin system (RAS), have immune regulatory effects on T cells. Previously, we showed that inhibition of AT1R signaling protects mice against the lethal disease induced by Plasmodium berghei ANKA infection However, most of the Ang II/AT1R actions were characterized by using only pharmacological approaches, the effects of which may not always be due to a specific receptor blockade. In addition, the mechanisms of action of the AT1R in inducing the pathogenic activity of Plasmodium-specific CD8(+) T cells during blood-stage were not determined. Here, we examined how angiotensin II/AT1R axis promotes the harmful response of Plasmodium-specific CD8(+) T-cell during blood-stage by using genetic and pharmacological approaches. We evaluated the response of wild-type (WT) and AT1R(-/-)Plasmodium-specific CD8(+) T cells in mice infected with a transgenic PbA lineage expressing ovalbumin; and in parallel infected mice receiving WT Plasmodium-specific CD8(+) T cells were treated with losartan (AT1R antagonist) or captopril (ACE inhibitor). Both, AT1R(-/-) OT-I cells and WT OT-I cells from losartan- or captopril-treated mice showed lower expansion, reduced IL-2 production and IL-2Rα expression, lower activation (lower expression of CD69, CD44 and CD160) and lower exhaustion profiles. AT1R(-/-) OT-I cells also exhibit lower expression of the integrin LFA-1 and the chemokine receptors CCR5 and CXCR3, known to play a key role in the development of cerebral malaria. Moreover, AT1R(-/-) OT-I cells produce lower amounts of IFN-γ and TNF-α and show lower degranulation upon restimulation. In conclusion, our results show the pivotal mechanisms of AT1R-induced harmful phenotype of Plasmodium-specific CD8(+) T cells during blood-stage malaria.

  10. Targeting Angiotensin II Type-1 Receptor (AT1R) Inhibits the Harmful Phenotype of Plasmodium-Specific CD8+ T Cells during Blood-Stage Malaria

    Science.gov (United States)

    Silva-Filho, João L.; Caruso-Neves, Celso; Pinheiro, Ana A. S.

    2017-01-01

    CD8+ T-cell response is critical in the pathogenesis of cerebral malaria during blood-stage. Our group and other have been shown that angiotensin II (Ang II) and its receptor AT1 (AT1R), a key effector axis of renin-angiotensin system (RAS), have immune regulatory effects on T cells. Previously, we showed that inhibition of AT1R signaling protects mice against the lethal disease induced by Plasmodium berghei ANKA infection However, most of the Ang II/AT1R actions were characterized by using only pharmacological approaches, the effects of which may not always be due to a specific receptor blockade. In addition, the mechanisms of action of the AT1R in inducing the pathogenic activity of Plasmodium-specific CD8+ T cells during blood-stage were not determined. Here, we examined how angiotensin II/AT1R axis promotes the harmful response of Plasmodium-specific CD8+ T-cell during blood-stage by using genetic and pharmacological approaches. We evaluated the response of wild-type (WT) and AT1R−/− Plasmodium-specific CD8+ T cells in mice infected with a transgenic PbA lineage expressing ovalbumin; and in parallel infected mice receiving WT Plasmodium-specific CD8+ T cells were treated with losartan (AT1R antagonist) or captopril (ACE inhibitor). Both, AT1R−/− OT-I cells and WT OT-I cells from losartan- or captopril-treated mice showed lower expansion, reduced IL-2 production and IL-2Rα expression, lower activation (lower expression of CD69, CD44 and CD160) and lower exhaustion profiles. AT1R−/− OT-I cells also exhibit lower expression of the integrin LFA-1 and the chemokine receptors CCR5 and CXCR3, known to play a key role in the development of cerebral malaria. Moreover, AT1R−/− OT-I cells produce lower amounts of IFN-γ and TNF-α and show lower degranulation upon restimulation. In conclusion, our results show the pivotal mechanisms of AT1R-induced harmful phenotype of Plasmodium-specific CD8+ T cells during blood-stage malaria. PMID:28261571

  11. 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.

  12. Repairing the Sickle Cell mutation. II. Effect of psoralen linker length on specificity of formation and yield of third strand-directed photoproducts with the mutant target sequence.

    Science.gov (United States)

    Amosova, Olga; Broitman, Steven L; Fresco, Jacques R

    2003-08-15

    Three identical deoxyoligonucleotide third strands with a 3'-terminal psoralen moiety attached by linkers that differ in length (N = 16, 6 and 4 atoms) and structure were examined for their ability to form triplex-directed psoralen photoproducts with both the mutant T residue of the Sickle Cell beta-globin gene and the comparable wild-type sequence in linear duplex targets. Specificity and yield of UVA (365 nm) and visible (419 nm) light-induced photoadducts were studied. The total photoproduct yield varies with the linker and includes both monoadducts and crosslinks at various available pyrimidine sites. The specificity of photoadduct formation at the desired mutant T residue site was greatly improved by shortening the psoralen linker. In particular, using the N-4 linker, psoralen interaction with the residues of the non-coding duplex strand was essentially eliminated, while modification of the Sickle Cell mutant T residue was maximized. At the same time, the proportion of crosslink formation at the mutant T residue upon UV irradiation was much greater for the N-4 linker. The photoproducts formed with the wild-type target were fully consistent with its single base pair difference. The third strand with the N-4 linker was also shown to bind to a supercoiled plasmid containing the Sickle Cell mutation site, giving photoproduct yields comparable with those observed in the linear mutant target.

  13. Leveraging NMR and X-ray Data of the Free Ligands to Build Better Drugs Targeting Angiotensin II Type 1 G-Protein Coupled Receptor.

    Science.gov (United States)

    Kellici, Tahsin F; Ntountaniotis, Dimitrios; Kritsi, Eftichia; Zervou, Maria; Zoumpoulakis, Panagiotis; Potamitis, Constantinos; Durdagi, Serdar; Salmas, Ramin Ekhteiari; Ergun, Gizem; Gokdemir, Ebru; Halabalaki, Maria; Gerothanassis, Ioannis P; Liapakis, George; Tzakos, Andreas; Mavromoustakos, Thomas

    2016-01-01

    The angiotensin II type 1 receptor (AT1R) has been recently crystallized. A new era has emerged for the structure-based rational drug design and the synthesis of novel AT1R antagonists. In this critical review, the X-ray crystallographic data of commercially available AT1R antagonists in free form are analyzed and compared with the conformational analysis results obtained using a combination of NMR spectroscopy and Molecular Modeling. The same AT1R antagonists are docked and compared in terms of their interactions in their binding site using homology models and the crystallized AT1R receptor. Various aspects derived from these comparisons regarding rational drug design are outlined.

  14. Towards the simplification of MHC typing protocols: targeting classical MHC class II genes in a passerine, the pied flycatcher Ficedula hypoleuca

    Directory of Open Access Journals (Sweden)

    Canal David

    2010-09-01

    Full Text Available Abstract Background Major Histocompatibility Complex (MHC has drawn the attention of evolutionary biologists due to its importance in crucial biological processes, such as sexual selection and immune response in jawed vertebrates. However, the characterization of classical MHC genes subjected to the effects of natural selection still remains elusive in many vertebrate groups. Here, we have tested the suitability of flanking intron sequences to guide the selective exploration of classical MHC genes driving the co-evolutionary dynamics between pathogens and their passerine (Aves, Order Passeriformes hosts. Findings Intronic sequences flanking the usually polymorphic exon 2 were isolated from different species using primers sitting on conserved coding regions of MHC class II genes (β chain. Taking the pied flycatcher Ficedula hypoleuca as an example, we demonstrate that careful primer design can evade non-classical MHC gene and pseudogene amplification. At least four polymorphic and expressed loci were co-replicated using a single pair of primers in five non-related individuals (N = 28 alleles. The cross-amplification and preliminary inspection of similar MHC fragments in eight unrelated songbird taxa suggests that similar approaches can also be applied to other species. Conclusions Intron sequences flanking the usually polymorphic exon 2 may assist the specific investigation of classical MHC class II B genes in species characterized by extensive gene duplication and pseudogenization. Importantly, the evasion of non-classical MHC genes with a more specific function and non-functional pseudogenes may accelerate data collection and diminish lab costs. Comprehensive knowledge of gene structure, polymorphism and expression profiles may be useful not only for the selective examination of evolutionarily relevant genes but also to restrict chimera formation by minimizing the number of co-amplifying loci.

  15. miR-135b Promotes Cancer Progression by Targeting Transforming Growth Factor Beta Receptor II (TGFBR2 in Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Jialu Li

    Full Text Available The transforming growth factor beta (TGF-β signaling pathway is a tumor-suppressor pathway that is commonly inactivated in colorectal cancer (CRC. The inactivation of TGFBR2 is the most common genetic event affecting the TGF-β signaling pathway. However, the mechanism by which cancer cells downregulate TGFBR2 is unclear. In this study, we found that the TGFBR2 protein levels were consistently upregulated in CRC tissues, whereas its mRNA levels varied in these tissues, suggesting that a post-transcriptional mechanism is involved in the regulation of TGFBR2. Because microRNAs (miRNAs are powerful post-transcriptional regulators of gene expression, we performed bioinformatic analyses to search for miRNAs that potentially target TGFBR2. We identified the specific targeting site of miR-135b in the 3'-untranslated region (3'-UTR of TGFBR2. We further identified an inverse correlation between the levels of miR-135b and TGFBR2 protein, but not mRNA, in CRC tissue samples. By overexpressing or silencing miR-135b in CRC cells, we experimentally validated that miR-135b directly binds to the 3'-UTR of the TGFBR2 transcript and regulates TGFBR2 expression. Furthermore, the biological consequences of the targeting of TGFBR2 by miR-135b were examined using in vitro cell proliferation and apoptosis assays. We demonstrated that miR-135b exerted a tumor-promoting effect by inducing the proliferation and inhibiting the apoptosis of CRC cells via the negative regulation of TGFBR2 expression. Taken together, our findings provide the first evidence supporting the role of miR-135b as an oncogene in CRC via the inhibition of TGFBR2 translation.

  16. Identification, design and biological evaluation of bisaryl quinolones targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2).

    Science.gov (United States)

    Pidathala, Chandrakala; Amewu, Richard; Pacorel, Bénédicte; Nixon, Gemma L; Gibbons, Peter; Hong, W David; Leung, Suet C; Berry, Neil G; Sharma, Raman; Stocks, Paul A; Srivastava, Abhishek; Shone, Alison E; Charoensutthivarakul, Sitthivut; Taylor, Lee; Berger, Olivier; Mbekeani, Alison; Hill, Alasdair; Fisher, Nicholas E; Warman, Ashley J; Biagini, Giancarlo A; Ward, Stephen A; O'Neill, Paul M

    2012-03-08

    A program was undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a dehydrogenase of the mitochondrial electron transport chain of the malaria parasite Plasmodium falciparum. PfNDH2 has only one known inhibitor, hydroxy-2-dodecyl-4-(1H)-quinolone (HDQ), and this was used along with a range of chemoinformatics methods in the rational selection of 17 000 compounds for high-throughput screening. Twelve distinct chemotypes were identified and briefly examined leading to the selection of the quinolone core as the key target for structure-activity relationship (SAR) development. Extensive structural exploration led to the selection of 2-bisaryl 3-methyl quinolones as a series for further biological evaluation. The lead compound within this series 7-chloro-3-methyl-2-(4-(4-(trifluoromethoxy)benzyl)phenyl)quinolin-4(1H)-one (CK-2-68) has antimalarial activity against the 3D7 strain of P. falciparum of 36 nM, is selective for PfNDH2 over other respiratory enzymes (inhibitory IC(50) against PfNDH2 of 16 nM), and demonstrates low cytotoxicity and high metabolic stability in the presence of human liver microsomes. This lead compound and its phosphate pro-drug have potent in vivo antimalarial activity after oral administration, consistent with the target product profile of a drug for the treatment of uncomplicated malaria. Other quinolones presented (e.g., 6d, 6f, 14e) have the capacity to inhibit both PfNDH2 and P. falciparum cytochrome bc(1), and studies to determine the potential advantage of this dual-targeting effect are in progress.

  17. 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.

  18. Small Diameter Bomb Increment II (SDB II)

    Science.gov (United States)

    2015-12-01

    Equipment and the Joint Mission Planning System. The SDB II Program will develop and field a single-weapon USAF storage container and a dual DoN weapon...weapon directly impacted the target but did not detonate. Due to a lack of telemetry data, because live fire test assets are not equipped with telemetry

  19. Identification, design and biological evaluation of heterocyclic quinolones targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2).

    Science.gov (United States)

    Leung, Suet C; Gibbons, Peter; Amewu, Richard; Nixon, Gemma L; Pidathala, Chandrakala; Hong, W David; Pacorel, Bénédicte; Berry, Neil G; Sharma, Raman; Stocks, Paul A; Srivastava, Abhishek; Shone, Alison E; Charoensutthivarakul, Sitthivut; Taylor, Lee; Berger, Olivier; Mbekeani, Alison; Hill, Alasdair; Fisher, Nicholas E; Warman, Ashley J; Biagini, Giancarlo A; Ward, Stephen A; O'Neill, Paul M

    2012-03-08

    Following a program undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68, a molecule suitable for further development. In order to reduce ClogP and improve solubility of CK-2-68 incorporation of a variety of heterocycles, within the side chain of the quinolone core, was carried out, and this approach led to a lead compound SL-2-25 (8b). 8b has IC(50)s in the nanomolar range versus both the enzyme and whole cell P. falciparum (IC(50) = 15 nM PfNDH2; IC(50) = 54 nM (3D7 strain of P. falciparum) with notable oral activity of ED(50)/ED(90) of 1.87/4.72 mg/kg versus Plasmodium berghei (NS Strain) in a murine model of malaria when formulated as a phosphate salt. Analogues in this series also demonstrate nanomolar activity against the bc(1) complex of P. falciparum providing the potential added benefit of a dual mechanism of action. The potent oral activity of 2-pyridyl quinolones underlines the potential of this template for further lead optimization studies.

  20. Discovery and development of kibdelomycin, a new class of broad-spectrum antibiotics targeting the clinically proven bacterial type II topoisomerase.

    Science.gov (United States)

    Singh, Sheo B

    2016-12-15

    Kibdelomycin is a complex novel antibiotic, discovered by applying a highly sophisticated chemical-genetic Staphylococcus aureus Fitness Test (SaFT) approach, that inhibits the clinically established bacterial targets, gyrase and topoisomerase IV. It exhibits broad-spectrum antibacterial activity against aerobic bacteria including MRSA and Acinetobacter baumannii. It is slowly bactericidal and has a low frequency of resistance. In an anaerobic environment, it exhibits narrow-spectrum activity and inhibits the growth of gut bacteria Clostridium difficile (MIC 0.125μg/mL) without affecting the growth of commensal Gram-negative organisms particularly, Bacteroides sp. It is highly efficacious in the hamster model of C. difficile infection providing 100% protection at >6mg/kg and 80% protection at 1.56mg/kg by oral dosing without systemic exposure. X-ray co-crystal structures of kibdelomycin bound to GyrB and ParE showed a unique dual arm 'U shaped' multisite binding never encountered with any other gyrase inhibitors. Kibdelomycin is poised for preclinical development for C. difficile treatment, and most importantly, the co-crystal structures of kibdelomycin provide unique insight for structure-guided structure modification, which could lead to better broader-spectrum systemic antibiotic potentially covering many ESKAPE pathogens. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. An integrated platform for directly widely-targeted quantitative analysis of feces part II: An application for steroids, eicosanoids, and porphyrins profiling.

    Science.gov (United States)

    Song, Yuelin; Song, Qingqing; Li, Jun; Zheng, Jiao; Li, Chun; Zhang, Yuan; Zhang, Lingling; Jiang, Yong; Tu, Pengfei

    2016-08-19

    Steroids, especially bile acids, along with eicosanoids and porphyrins in feces play pivotal roles for the clinical diagnosis of various diseases. However, their reliable measurement is extensively obstructed by poor stability, structural diversity, broad content ranges, and tedious sample preparation protocols that account for a majority of the measurement errors. In current study, in-depth component screening was initially carried out by flexibly integrating diverse modes, such as predefined multiple reaction monitoring, stepped multiple ion monitoring, neutral loss scan, and precursor ion scan on a hybrid triple quadrupole-linear ion trap mass spectrometer, which also provided MS(2) spectra via enhanced product ion experiments. Meanwhile, a hybrid ion trap-time of flight mass spectrometer served as a complementary tool by providing accurate mass spectral information. Afterwards, because authentic compounds were unavailable for most analytes, an online optimization strategy was then proposed to optimize parameters, including precursor-to-product ion transitions and spectrometric parameters, notably collision energy. Finally, direct analysis of all detected components in feces was carried out by employing a platform integrating online pressurized liquid extraction, turbulent flow chromatography, and LC-MS/MS, and applying those optimized parameters. Seventy-one compounds, including 52 steroids and 13 eicosanoids, together with 6 porphyrins, were found and annotated in a fecal pool, and then relatively quantified in various fecal matrices. The quantitative dataset was subjected for multivariate statistical analysis and significant differences were observed among the quantitative chemome profiles of the fecal matrices from different groups. The findings obtained in the two parts demonstrated that the analytical platform in combination with the work-flow is qualified for not only directly simultaneous measurement of diverse endogenous substances, but widely targeted

  2. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.

    Science.gov (United States)

    Izzo, Nicholas J; Xu, Jinbin; Zeng, Chenbo; Kirk, Molly J; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Cruchaga, Carlos; Goate, Alison; Cahill, Michael A; Arancio, Ottavio; Mach, Robert H; Craven, Rolf; Head, Elizabeth; LeVine, Harry; Spires-Jones, Tara L; Catalano, Susan M

    2014-01-01

    Abeta oligomers in AD and is a tractable target for small molecule disease-modifying therapeutics.

  3. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.

    Directory of Open Access Journals (Sweden)

    Nicholas J Izzo

    effects of Abeta oligomers in AD and is a tractable target for small molecule disease-modifying therapeutics.

  4. Sequential (gemcitabine/vinorelbine and concurrent (gemcitabine radiochemotherapy with FDG-PET-based target volume definition in locally advanced non-small cell lung cancer: first results of a phase I/II study

    Directory of Open Access Journals (Sweden)

    Stanzel Sven

    2007-06-01

    Full Text Available Abstract Background The aim of the study was to determine the maximal tolerated dose (MTD of gemcitabine every two weeks concurrent to radiotherapy, administered during an aggressive program of sequential and simultaneous radiochemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC and to evaluate the efficacy of this regime in a phase II study. Methods 33 patients with histologically confirmed NSCLC were enrolled in a combined radiochemotherapy protocol. 29 patients were assessable for evaluation of toxicity and tumor response. Treatment included two cycles of induction chemotherapy with gemcitabine (1200 mg/m2 and vinorelbine (30 mg/m2 at day 1, 8 and 22, 29 followed by concurrent radiotherapy (2.0 Gy/d; total dose 66.0 Gy and chemotherapy with gemcitabine every two weeks at day 43, 57 and 71. Radiotherapy planning included [18F] fluorodeoxyglucose positron emission tomography (FDG PET based target volume definition. 10 patients were included in the phase I study with an initial gemcitabine dose of 300 mg/m2. The dose of gemcitabine was increased in steps of 100 mg/m2 until the MTD was realized. Results MTD was defined for the patient group receiving gemcitabine 500 mg/m2 due to grade 2 (next to grade 3 esophagitis in all patients resulting in a mean body weight loss of 5 kg (SD = 1.4 kg, representing 8% of the initial weight. These patients showed persisting dysphagia 3 to 4 weeks after completing radiotherapy. In accordance with expected complications as esophagitis, dysphagia and odynophagia, we defined the MTD at this dose level, although no dose limiting toxicity (DLT grade 3 was reached. In the phase I/II median follow-up was 15.7 months (4.1 to 42.6 months. The overall response rate after completion of therapy was 64%. The median overall survival was 19.9 (95% CI: [10.1; 29.7] months for all eligible patients. The median disease-free survival for all patients was 8.7 (95% CI: [2.7; 14.6] months. Conclusion

  5. 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

  6. 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.

  7. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  8. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  9. Status of DOE/JAERI collaborative program phase II and phase III capsules

    Energy Technology Data Exchange (ETDEWEB)

    Pawel, J.E.; Lenox, K.E. [Oak Ridge National Lab., TN (United States); Ioka, I.

    1996-04-01

    During this reporting period, the HFIR-MFE-RB-200J-1 spectrally tailored capsules were disassembled and the individual specimens recovered, sorted, and identified. Tensile testing and irradiation creep measurements will be performed during the next reporting period.

  10. Mammalian Target of Rapamycin (mTOR) Tagging Promotes Dendritic Branch Variability through the Capture of Ca2+/Calmodulin-dependent Protein Kinase II α (CaMKIIα) mRNAs by the RNA-binding Protein HuD.

    Science.gov (United States)

    Sosanya, Natasha M; Cacheaux, Luisa P; Workman, Emily R; Niere, Farr; Perrone-Bizzozero, Nora I; Raab-Graham, Kimberly F

    2015-06-26

    The fate of a memory, whether stored or forgotten, is determined by the ability of an active or tagged synapse to undergo changes in synaptic efficacy requiring protein synthesis of plasticity-related proteins. A synapse can be tagged, but without the "capture" of plasticity-related proteins, it will not undergo long lasting forms of plasticity (synaptic tagging and capture hypothesis). What the "tag" is and how plasticity-related proteins are captured at tagged synapses are unknown. Ca(2+)/calmodulin-dependent protein kinase II α (CaMKIIα) is critical in learning and memory and is synthesized locally in neuronal dendrites. The mechanistic (mammalian) target of rapamycin (mTOR) is a protein kinase that increases CaMKIIα protein expression; however, the mechanism and site of dendritic expression are unknown. Herein, we show that mTOR activity mediates the branch-specific expression of CaMKIIα, favoring one secondary, daughter branch over the other in a single neuron. mTOR inhibition decreased the dendritic levels of CaMKIIα protein and mRNA by shortening its poly(A) tail. Overexpression of the RNA-stabilizing protein HuD increased CaMKIIα protein levels and preserved its selective expression in one daughter branch over the other when mTOR was inhibited. Unexpectedly, deleting the third RNA recognition motif of HuD, the domain that binds the poly(A) tail, eliminated the branch-specific expression of CaMKIIα when mTOR was active. These results provide a model for one molecular mechanism that may underlie the synaptic tagging and capture hypothesis where mTOR is the tag, preventing deadenylation of CaMKIIα mRNA, whereas HuD captures and promotes its expression in a branch-specific manner.

  11. Mammalian Target of Rapamycin (mTOR) Tagging Promotes Dendritic Branch Variability through the Capture of Ca2+/Calmodulin-dependent Protein Kinase II α (CaMKIIα) mRNAs by the RNA-binding Protein HuD*

    Science.gov (United States)

    Sosanya, Natasha M.; Cacheaux, Luisa P.; Workman, Emily R.; Niere, Farr; Perrone-Bizzozero, Nora I.; Raab-Graham, Kimberly F.

    2015-01-01

    The fate of a memory, whether stored or forgotten, is determined by the ability of an active or tagged synapse to undergo changes in synaptic efficacy requiring protein synthesis of plasticity-related proteins. A synapse can be tagged, but without the “capture” of plasticity-related proteins, it will not undergo long lasting forms of plasticity (synaptic tagging and capture hypothesis). What the “tag” is and how plasticity-related proteins are captured at tagged synapses are unknown. Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα) is critical in learning and memory and is synthesized locally in neuronal dendrites. The mechanistic (mammalian) target of rapamycin (mTOR) is a protein kinase that increases CaMKIIα protein expression; however, the mechanism and site of dendritic expression are unknown. Herein, we show that mTOR activity mediates the branch-specific expression of CaMKIIα, favoring one secondary, daughter branch over the other in a single neuron. mTOR inhibition decreased the dendritic levels of CaMKIIα protein and mRNA by shortening its poly(A) tail. Overexpression of the RNA-stabilizing protein HuD increased CaMKIIα protein levels and preserved its selective expression in one daughter branch over the other when mTOR was inhibited. Unexpectedly, deleting the third RNA recognition motif of HuD, the domain that binds the poly(A) tail, eliminated the branch-specific expression of CaMKIIα when mTOR was active. These results provide a model for one molecular mechanism that may underlie the synaptic tagging and capture hypothesis where mTOR is the tag, preventing deadenylation of CaMKIIα mRNA, whereas HuD captures and promotes its expression in a branch-specific manner. PMID:25944900

  12. DARHT II Scaled Accelerator Tests on the ETA II Accelerator*

    Energy Technology Data Exchange (ETDEWEB)

    Weir, J T; Anaya Jr, E M; Caporaso, G J; Chambers, F W; Chen, Y; Falabella, S; Lee, B S; Paul, A C; Raymond, B A; Richardson, R A; Watson, J A; Chan, D; Davis, H A; Day, L A; Scarpetti, R D; Schultze, M E; Hughes, T P

    2005-05-26

    The DARHT II accelerator at LANL is preparing a series of preliminary tests at the reduced voltage of 7.8 MeV. The transport hardware between the end of the accelerator and the final target magnet was shipped to LLNL and installed on ETA II. Using the ETA II beam at 5.2 MeV we completed a set of experiments designed reduce start up time on the DARHT II experiments and run the equipment in a configuration adapted to the reduced energy. Results of the beam transport using a reduced energy beam, including the kicker and kicker pulser system will be presented.

  13. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Green, Mark A.

    2000-03-22

    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.

  14. Targeting peroxiredoxins against leukemia.

    Science.gov (United States)

    Liu, Chuan-Xu; Zhou, Hu-Chen; Yin, Qian-Qian; Wu, Ying-Li; Chen, Guo-Qiang

    2013-01-15

    Peroxiredoxins (Prx), a family of small non-seleno peroxidases, are important regulators for cellular reactive oxygen species (ROS), which contribute to many signaling pathways and pathogenesis of diseases. Targeting redox homeostasis is being developed as a promising therapeutic strategy for many diseases such as cancers. This mini-review attempts to focus on our recent discoveries on adenanthin as the first natural molecule to specifically target the resolving cysteines of Prx I and Prx II and thus inhibit their peroxidase activities, and its role in differentiation induction in vitro and in vivo of acute myeloid leukemic cells.

  15. Pb II

    African Journals Online (AJOL)

    Windows User

    ISSN 1684–5315 ©2012 Academic Journals ... Exposure to Pb above permissible limit (50 ppb in water) .... taken and analyzed for residual metal concentration determination. ..... loss in Pb(II) sorption capacity up to five cycles of reuse of.

  16. Container II

    OpenAIRE

    Baraklianou, Stella

    2016-01-01

    Container II, self-published artists book.\\ud The book was made on the occasion of the artists residency at the Banff Arts Centre, in Alberta Canada. \\ud \\ud Container II is a performative piece, it worked in conjunction with the photographic installation "Stage Set: Cool Tone" . (photographic floor installation, Reclaimed wood, frames, 130x145cm, 2016) \\ud The photographic installation was also part of the artists residency titled "New Materiality" at the Banff Arts Centre. \\ud \\ud Limited E...

  17. 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...

  18. 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...

  19. 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 bu

  20. 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 bu

  1. 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.

  2. Class II Microcins

    Science.gov (United States)

    Vassiliadis, Gaëlle; Destoumieux-Garzón, Delphine; Peduzzi, Jean

    Class II microcins are 4.9- to 8.9-kDa polypeptides produced by and active against enterobacteria. They are classified into two subfamilies according to their structure and their gene cluster arrangement. While class IIa microcins undergo no posttranslational modification, class IIb microcins show a conserved C-terminal sequence that carries a salmochelin-like siderophore motif as a posttranslational modification. Aside from this C-terminal end, which is the signature of class IIb microcins, some sequence similarities can be observed within and between class II subclasses, suggesting the existence of common ancestors. Their mechanisms of action are still under investigation, but several class II microcins use inner membrane proteins as cellular targets, and some of them are membrane-active. Like group B colicins, many, if not all, class II microcins are TonB- and energy-dependent and use catecholate siderophore receptors for recognition/­translocation across the outer membrane. In that context, class IIb microcins are considered to have developed molecular mimicry to increase their affinity for their outer membrane receptors through their salmochelin-like posttranslational modification.

  3. Targeted phototherapy

    Directory of Open Access Journals (Sweden)

    Zonun Sanga

    2015-03-01

    Full Text Available Conventional phototherapy uses a whole body cabinet or body part machines for the hand, foot or scalp. It has many disadvantages, due to which new phototherapy techniques have been developed. These new techniques are called targeted phototherapy. They include excimer laser, the intense pulse light (IPL system, photodynamic therapy, and an ultraviolet (UV light source with a sophisticated delivery system which is easy to operate by hand. The mechanisms of action of targeted phototherapy systems are similar to those in conventional UVB/UVA therapy. They have many advantages including lower risk of side effects, avoidance of exposure of unnecessary sites, faster response, and shorter duration of treatment. But they also have disadvantages such as high costs and inability to use them for extensive areas. This review article discusses targeted phototherapy, its mechanisms of action, and advantages and disadvantages in comparison to conventional phototherapy.

  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. Sequential (gemcitabine/vinorelbine) and concurrent (gemcitabine) radiochemotherapy with FDG-PET-based target volume definition in locally advanced non-small cell lung cancer: first results of a phase I/II study

    OpenAIRE

    Stanzel Sven; Kaiser Hans J; Krohn Thomas; Reinartz Patrick; Pinkawa Michael; Piroth Marc; Gagel Bernd; Breuer Christian; Asadpour Branka; Schmachtenberg Axel; Eble Michael J

    2007-01-01

    Abstract Background The aim of the study was to determine the maximal tolerated dose (MTD) of gemcitabine every two weeks concurrent to radiotherapy, administered during an aggressive program of sequential and simultaneous radiochemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC) and to evaluate the efficacy of this regime in a phase II study. Methods 33 patients with histologically confirmed NSCLC were enrolled in a combined radiochemotherapy protocol. 29 patien...

  6. 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...

  7. Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy : Post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial

    NARCIS (Netherlands)

    Eijkelkamp, Wouter B. A.; Zhang, Zhongxin; Remuzzi, Giuseppe; Parving, Hans-Henrik; Cooper, Mark E.; Keane, William F.; Shahinfar, Shahnaz; Gleim, Gilbert W.; Weir, Matthew R.; Brenner, Barry M.; de Zeeuw, Dick

    2007-01-01

    Albuminuria reduction could be renoprotective in hypertensive patients with diabetic nephropathy. However, the current use of renin-angiotensin-system intervention is targeted to BP only. Therefore, this study investigated the adequacy of this approach in 1428 patients with hypertension and diabetic

  8. Target Space $\

    CERN Document Server

    Huggett, Nick

    2015-01-01

    This paper investigates the significance of T-duality in string theory: the indistinguishability with respect to all observables, of models attributing radically different radii to space -- larger than the observable universe, or far smaller than the Planck length, say. Two interpretational branch points are identified and discussed. First, whether duals are physically equivalent or not: by considering a duality of the familiar simple harmonic oscillator, I argue that they are. Unlike the oscillator, there are no measurements 'outside' string theory that could distinguish the duals. Second, whether duals agree or disagree on the radius of 'target space', the space in which strings evolve according to string theory. I argue for the latter position, because the alternative leaves it unknown what the radius is. Since duals are physically equivalent yet disagree on the radius of target space, it follows that the radius is indeterminate between them. Using an analysis of Brandenberger and Vafa (1989), I explain wh...

  9. Felipe II

    Directory of Open Access Journals (Sweden)

    Carlos Restrepo Canal

    1962-04-01

    Full Text Available Como parte de la monumental Historia de España que bajo la prestante y acertadísima dirección de don Ramón Menéndez Pidal se comenzó a dar a la prensa desde 1954 por la Editorial Espasa Calpe S. A., aparecieron en 1958 dos tomos dedicados al reinado de Felipe II; aquella época en que el imperio español alcanzó su unidad peninsular juntamente con el dilatado poderío que le constituyó en la primera potencia de Europa.

  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. DARHT2 X-ray converter target system comparison

    Energy Technology Data Exchange (ETDEWEB)

    Bergstrom, P M; Caporaso, G J; Chen, Y J; Ho, D D; McCarrick, J F; Pincosy, P A; Rambo, P W

    1999-03-24

    Four short current pulses with various pulse widths and spacing will be delivered to the x-ray converter target on the second-axis of the Dual-Axis Radiographic Hydrodynamic Test (DARHT-II) facility. To ensure that the DARHT-II multi-pulse target will provide enough target material for x-ray production for all four pulses, the target needs either to survive the strike of four electron pulses or to accommodate target replenishment. A distributed target may survive hitting of four electron pulses. For target replenishment, two types of target configurations are being considered: stationary target systems with beam repositioning and dynamic moving target systems. They compare these three target systems and their radiographic performance.

  12. Gene targeting in malaria parasites.

    Science.gov (United States)

    Ménard, R; Janse, C

    1997-10-01

    Gene targeting, which permits alteration of a chosen gene in a predetermined way by homologous recombination, is an emerging technology in malaria research. Soon after the development of techniques for stable transformation of red blood cell stages of Plasmodium falciparum and Plasmodium berghei, genes of interest were disrupted in the two species. The main limitations of gene targeting in malaria parasites result from the intracellular growth and slow replication of these parasites. On the other hand, the technology is facilitated by the very high rate of homologous recombination following transformation with targeting constructs (approximately 100%). Here, we describe (i) the vector design and the type of mutation that may be generated in a target locus, (ii) the selection and screening strategies that can be used to identify clones with the desired modification, and (iii) the protocol that was used for disrupting the circumsporozoite protein (CS) and thrombospondin-related anonymous protein (TRAP) genes of P. berghei.

  13. An antisense oligodeoxynucleotide targeted against the type II sub. beta. regulatory subunit mRNA of protein kinase inhibits cAMP-induced differentiation in HL-60 leukemia cells without affecting phorbol ester effects

    Energy Technology Data Exchange (ETDEWEB)

    Tortora, G.; Clair, T.; Cho-Chung, Y.S. (National Institutes of Health, Bethesda, MD (USA))

    1990-01-01

    The type II{sub {beta}} regulatory subunit of cAMP-dependent protein kinase (RII{sub {beta}}) has been hypothesized to play an important role in the growth inhibition and differentiation induced by site-selective cAMP analogs in human cancer cells, but direct proof of this function has been lacking. To address this tissue, HL-60 human promyelocytic leukemia cells were exposed to RII{sub {beta}} antisense synthetic oligodeoxynucleotide, and the effects on cAMP-induced growth regulation were examined. Exposure of these cells to RII{sub {beta}} antisense oligodeoxynucleotide resulted in a decrease in cAMP analog-induced growth inhibition and differentiation without apparent effect on differentiation induced by phorbol esters. This loss in cAMP growth regulatory function correlated with a decrease in basal and induced levels of RII{sub {beta}} protein. Exposure to RII{sub {beta}} sense, RI{sub {alpha}} and RII{sub {alpha}} antisense, or irrelevant oligodeoxynucleotides had no such effect. These results show that the RII{sub {beta}} regulatory subunit of protein kinase plays a critical role in the cAMP-induced growth regulation of HL-60 leukemia cells.

  14. Phase II study of targeted therapy with temozolomide in acute myeloid leukaemia and high-risk myelodysplastic syndrome patients pre-screened for low O(6) -methylguanine DNA methyltransferase expression.

    Science.gov (United States)

    Brandwein, Joseph M; Kassis, Jeannine; Leber, Brian; Hogge, Donna; Howson-Jan, Kang; Minden, Mark D; Galarneau, André; Pouliot, Jean-François

    2014-12-01

    Resistance to temozolomide is largely mediated by the DNA repair enzyme O(6) -methylguanine DNA methyltransferase (MGMT). We conducted a prospective multicentre study of patients with previously untreated acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) who were not candidates for intensive therapy. Patient selection was based on MGMT expression by Western blot. Patients with MGMT:ACTB (β-actin) ratio temozolomide 200 mg/m(2) /d ×7 d. Patients achieving a complete response (CR) could receive up to 12 monthly cycles of temozolomide ×5/28 d. Of 166 patients screened, 81 (49%) demonstrated low MGMT expression; 45 of these were treated with temozolomide. The overall response rate was 53%; 36% achieved complete clearance of blasts, with 27% achieving a CR/CR with incomplete platelet recovery (CRp). Factors associated with a trend toward a higher response rate included MDS, methylated MGMT promoter and standard cytogenetic risk group. Induction and post-remission cycles were well-tolerated and most patients were treated on an outpatient basis. Patient who achieved CR/CRp had a superior overall survival compared to partial or non-responders. In conclusion, targeted therapy based on pre-selection for low MGMT expression was associated with a higher response rate to temozolomide compared to previous reports of unselected patients.

  15. Abundance analysis of prime B-type targets for asteroseismology II. B6--B9.5 stars in the field of view of the CoRoT

    CERN Document Server

    Niemczura, E; Aerts, C

    2009-01-01

    The CoRoT satellite is collecting precise time-resolved photometry for tens of asteroseismology targets. To ensure a correct interpretation of the CoRoT data, the atmospheric parameters, chemical compositions, and rotational velocities of the stars must be determined. The main goal of the ground-based seismology support program for the CoRoT mission was to obtain photometric and spectroscopic data for stars in the fields monitored by the satellite. These ground-based observations were collected in the GAUDI archive. High-resolution spectra of more than 200 B-type stars are available in this database, and about 45% of them is analysed here. To derive the effective temperature of the stars, we used photometric indices. Surface gravities were obtained by comparing observed and theoretical Balmer line profiles. To determine the chemical abundances and rotational velocities, we used a spectrum synthesis method, which consisted of comparing the observed spectrum with theoretical ones based on the assumption of LTE....

  16. Insulin-like growth factor II (IGF-II).

    Science.gov (United States)

    O'Dell, S D; Day, I N

    1998-07-01

    Insulin-like growth factor II (IGF-II) plays a key role in mammalian growth, influencing foetal cell division and differentiation and possibly metabolic regulation. The mature 67 amino acid peptide shares sequence homology with both insulin and IGF-I. The liver is the main endocrine source of IGFs, but autocrine/paracrine activity is found in most tissues. The type 1 receptor mediates most of the biological effects of IGF-I and IGF-II; the type 2 receptor is involved with IGF-II degradation. Binding proteins may both localise IGFs to the receptors and regulate their activities. The IGF2 gene is maternally imprinted in mouse and human. Relaxation of IGF2 imprinting occurs in the Beckwith-Wiedemann syndrome of somatic overgrowth, sporadic Wilms' tumour and a number of other cancers. In the general adult population, the IGF2-INS gene cluster may also influence body weight, in which case IGF-II function could become a target for therapeutic intervention in obesity.

  17. 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

  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. Target reservoirs for CO/sub 2/ miscible flooding. Task two: summary of available reservoir and geological data. Vol. II: Rocky Mountain states geological and reservoir data. Part 4: Paradox, Uinta, eastern Utah overthrust, Big Horn, Wind River, Powder River, Red Desert, and Great Divide basins; CACHE-Ismay through WERTZ-Madison fields. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Cobb, L.B.; Marlow, R.

    1981-10-01

    This report describes work performed by Gruy Federal, Inc., as the second of six tasks under contract with the US Department of Energy. The stated objective of this study is to build a solid engineering foundation to serve as the basis for field mini- and pilot tests in both high and low oil saturation carbonate reservoirs for the purpose of extending the technology base in carbon dioxide miscible flooding. The six tasks in this study are: (1) summary of available CO/sub 2/ field test data; (2) summary of existing reservoir and geological data; (3) selection of target reservoirs; (4) selection of specific reservoirs for CO/sub 2/ injection tests; (5) selection of specific sites for test wells in carbonate reservoirs; and (6) drilling and coring activities. The report for Task Two consists of a summary of existing reservoir and geological data on carbonate reservoirs located in west Texas, southeast New Mexico, and the Rocky Mountain states. It is contained in two volumes, each with several parts. The present volume, in four parts, is a summary of reservoir data for fields in the Rocky Mountain states. Volume One contains data for Permian basin fields in west Texas and southeast New Mexico. While a serious effort was made to obtain all publicly available data for the fields considered, sufficiently reliable data on important reservoir parameters were not always available for every field. The data in Volume II show 143 carbonate reservoirs in the study area may be suitable for CO/sub 2/ miscible flooding. Using a general estimate of enhanced oils recovery by CO/sub 2/ flooding of 10% of original oil in place, some 619 million barrels of oil could be recovered by widespread application of CO/sub 2/ flooding in the study area. Mississippian and Ordovician reservoirs appear to be the most promising targets for the process.

  1. Mannose receptor-targeted vaccines.

    Science.gov (United States)

    Keler, Tibor; Ramakrishna, Venky; Fanger, Michael W

    2004-12-01

    Targeting antigens to endocytic receptors on professional antigen-presenting cells (APCs) represents an attractive strategy to enhance the efficacy of vaccines. Such APC-targeted vaccines have an exceptional ability to guide exogenous protein antigens into vesicles that efficiently process the antigen for major histocompatibility complex class I and class II presentation. Efficient targeting not only requires high specificity for the receptor that is abundantly expressed on the surface of APCs, but also the ability to be rapidly internalised and loaded into compartments that contain elements of the antigen-processing machinery. The mannose receptor (MR) and related C-type lectin receptors are particularly designed to sample antigens (self and non-self), much like pattern recognition receptors, to integrate the innate with adaptive immune responses. In fact, a variety of approaches involving delivery of antigens to the MR have demonstrated effective induction of potent cellular and humoral immune responses. Yet, although several lines of evidence in diverse experimental systems attest to the efficacy of targeted vaccine strategies, it is becoming increasingly clear that additional signals, such as those afforded by adjuvants, may be critical to elicit sustained immunity. Therefore, MR-targeted vaccines are likely to be most efficacious in vivo when combined with agents that elicit complementary activation signals. Certainly, a better understanding of the mechanism associated with the induction of immune responses as a result of targeting antigens to the MR, will be important in exploiting MR-targeted vaccines not only for mounting immune defenses against cancer and infectious disease, but also for specific induction of tolerance in the treatment of autoimmune disease.

  2. Small Diameter Bomb Increment II (SDB II)

    Science.gov (United States)

    2013-12-01

    been further delays to the F-35 System Development and Demonstration ( SDD ) program. As a result, the SDB II integration will be accomplished as a...follow-on integration to the F-35 SDD . SDB II OT&E on the F-35 will not be completed by the FRP threshold of October 2019, thus delaying the FRP decision

  3. Gene targeting in embryonic stem cells, II: conditional technologies

    Science.gov (United States)

    Genome modification via transgenesis has allowed researchers to link genotype and phenotype as an alternative approach to the characterization of random mutations through evolution. The synergy of technologies from the fields of embryonic stem (ES) cells, gene knockouts, and protein-mediated recombi...

  4. Factor II deficiency

    Science.gov (United States)

    ... if one or more of these factors are missing or are not functioning like they should. Factor II is one such coagulation factor. Factor II deficiency runs in families (inherited) and is very rare. Both parents must ...

  5. The RNA polymerase II elongation complex.

    Science.gov (United States)

    Aso, T; Conaway, J W; Conaway, R C

    1995-11-01

    The initiation stage of transcription by RNA polymerase II has long been regarded as the primary site for regulation of eukaryotic gene expression. Nevertheless, a growing body of evidence reveals that the RNA polymerase II elongation complex is also a major target for regulation. Biochemical studies are implicating an increasing number of transcription factors in the regulation of elongation, and these transcription factors are being found to function by a diverse collection of mechanisms. Moreover, unexpected features of the structure and catalytic mechanism of RNA polymerase II are forcing a reconsideration of long-held views on the mechanics of some of the most basic aspects of polymerase function. In this review, we will describe recent insights into the structures and functions of RNA polymerase II and the transcription factors that control its activity during the elongation stage of eukaryotic messenger RNA synthesis.

  6. 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...

  7. Downregulated Hsa-let-7f contributes to the loss of type II collagen by targeting interleukin-10/STAT3 signaling pathway in degenerative lumbar scoliosis%退变性腰椎侧凸发病中Hsa-let-7f调控白细胞介素10/STAT3信号通路的作用

    Institute of Scientific and Technical Information of China (English)

    王磊; 李天旺; 刘建强; 刘晓宗; 王照国; 田艳; 张永兴; 王伟

    2016-01-01

    物治疗靶点。%BACKGROUND:MicroRNAs (miRNAs) play an important role in a variety of diseases. Investigation of miRNA expression profile in degenerative lumbar scoliosis is beneficial for understanding its pathogenesis, providing a novel therapeutic target. Therefore, we tested the hypothesis that miRNAs promote intervertebral disc degeneration through the interleukin-10/STAT3 signaling pathway, a potential regulator of intervertebral disc degeneration. OBJECTIVE:To compare the differentialy expressed miRNAs in the intervertebral disc tissues from patients with degenerative lumbar scoliosis and normal controls and to identify specific miRNAs in degenerative lumbar scoliosis folowed by functional validation. METHODS: An initial screening of miRNA expression in nucleus pulposus tissues by miRNA Solexa Sequencing was performed in samples from 10 patients with degenerative lumbar scoliosis and 10 controls, respectively. Subsequently, differentialy expressed miRNAs were validated using qRT-PCR. The level of differentialy expressed miRNAs in degenerative nucleus pulposus tissues was investigated. Then, functional analysis of the miRNAs in regulating type II colagen expression was carried out. Western blot and luciferase reporter assay were used to further confirm the target gene. RESULTS AND CONCLUSION: We identified 30 miRNAs that were differentialy expressed (16 upregulated and 14 downregulated) in patients with degenerative lumbar scoliosis compared with controls. Folowing qRT-PCR confirmation, Has-let-7f was significantly down-regulated in degenerative nucleus pulposus tissues as compared with controls. Moreover, its level was correlated with the severity of disc degeneration. Overexpression of Has-let-7f promoted type II colagen expression in nucleus pulposus cels. Knockout of interleukin-10 induced effects on nucleus pulposus cels similar to Has-let-7f. Bioinformatics target prediction identified interleukin-10 as a putative target of Has-let-7f. Furthermore, luciferase reporter assays demonstrated that

  8. In Vivo Probe of Lipid II-Interacting Proteins.

    Science.gov (United States)

    Sarkar, Sourav; Libby, Elizabeth A; Pidgeon, Sean E; Dworkin, Jonathan; Pires, Marcos M

    2016-07-11

    β-Lactams represent one of the most important classes of antibiotics discovered to date. These agents block Lipid II processing and cell wall biosynthesis through inactivation of penicillin-binding proteins (PBPs). PBPs enzymatically load cell wall building blocks from Lipid II carrier molecules onto the growing cell wall scaffold during growth and division. Lipid II, a bottleneck in cell wall biosynthesis, is the target of some of the most potent antibiotics in clinical use. Despite the immense therapeutic value of this biosynthetic pathway, the PBP-Lipid II association has not been established in live cells. To determine this key interaction, we designed an unnatural d-amino acid dipeptide that is metabolically incorporated into Lipid II molecules. By hijacking the peptidoglycan biosynthetic machinery, photoaffinity probes were installed in combination with click partners within Lipid II, thereby allowing, for the first time, demonstration of PBP interactions in vivo with Lipid II.

  9. 42 CFR 457.310 - Targeted low-income child.

    Science.gov (United States)

    2010-10-01

    ...) Definition. A targeted low-income child is a child who meets the standards set forth below and the... family income at or below 200 percent of the Federal poverty line for a family of the size involved; (ii... definition of targeted low-income children: (1) Children eligible for certain State health benefits coverage...

  10. 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

  11. 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 essent

  12. Electrically charged targets

    Science.gov (United States)

    Goodman, Ronald K.; Hunt, Angus L.

    1984-01-01

    Electrically chargeable laser targets and method for forming such charged targets in order to improve their guidance along a predetermined desired trajectory. This is accomplished by the incorporation of a small amount of an additive to the target material which will increase the electrical conductivity thereof, and thereby enhance the charge placed upon the target material for guidance thereof by electrostatic or magnetic steering mechanisms, without adversely affecting the target when illuminated by laser energy.

  13. Targeted multi-pinhole SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Branderhorst, Woutjan; Blezer, Erwin L.A. [University Medical Centre Utrecht, Image Sciences Institute and Rudolf Magnus Institute of Neuroscience, Utrecht (Netherlands); Vastenhouw, Brendan; Have, Frans van der; Beekman, Freek J. [University Medical Centre Utrecht, Image Sciences Institute and Rudolf Magnus Institute of Neuroscience, Utrecht (Netherlands); Molecular Imaging Laboratories BV, Utrecht (Netherlands); Delft University of Technology, Section of Radiation Detection and Medical Imaging, Applied Sciences, Delft (Netherlands); Bleeker, Wim K. [Genmab BV, Utrecht (Netherlands)

    2011-03-15

    Small-animal single photon emission computed tomography (SPECT) with focused multi-pinhole collimation geometries allows scanning modes in which large amounts of photons can be collected from specific volumes of interest. Here we present new tools that improve targeted imaging of specific organs and tumours, and validate the effects of improved targeting of the pinhole focus. A SPECT system with 75 pinholes and stationary detectors was used (U-SPECT-II). An XYZ stage automatically translates the animal bed with a specific sequence in order to scan a selected volume of interest. Prior to stepping the animal through the collimator, integrated webcams acquire images of the animal. Using sliders, the user designates the desired volume to be scanned (e.g. a xenograft or specific organ) on these optical images. Optionally projections of an atlas are overlaid semiautomatically to locate specific organs. In order to assess the effects of more targeted imaging, scans of a resolution phantom and a mouse myocardial phantom, as well as in vivo mouse cardiac and tumour scans, were acquired with increased levels of targeting. Differences were evaluated in terms of count yield, hot rod visibility and contrast-to-noise ratio. By restricting focused SPECT scans to a 1.13-ml resolution phantom, count yield was increased by a factor 3.6, and visibility of small structures was significantly enhanced. At equal noise levels, the small-lesion contrast measured in the myocardial phantom was increased by 42%. Noise in in vivo images of a tumour and the mouse heart was significantly reduced. Targeted pinhole SPECT improves images and can be used to shorten scan times. Scan planning with optical cameras provides an effective tool to exploit this principle without the necessity for additional X-ray CT imaging. (orig.)

  14. Fixed Target Collisions at STAR

    Science.gov (United States)

    Meehan, Kathryn C.

    2016-12-01

    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.

  15. The SNS/HFIR Web Portal System for SANS

    Science.gov (United States)

    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.

    2010-10-01

    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.

  16. The SNS/HFIR Web Portal System for SANS

    Energy Technology Data Exchange (ETDEWEB)

    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 [Oak Ridge National Laboratory (United States); Green, Mark L, E-mail: campbellsi@ornl.go [Tech-X Corporation, Boulder, CO (United States)

    2010-10-01

    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.

  17. 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.

  18. Hydrosol II Project; El Proyecto Hydrosol II

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Martinez, A.

    2008-07-01

    At present energy production is based on the combustion of fossil fuels and is the main cause of greenhouse gas emissions, which is to say it is the main cause of the climate change that is affecting the planet. On a worldwide scale, the use of solar concentration systems with systems capable of dissociating water is considered, from both an energy and an economic standpoint, as the most important long-term goal in the production of solar fuels to reduce the costs of hydrogen and to ensure practically zero carbon dioxide emissions. The Hydrosol II project has the largest pilot plant of its kind, and the Hydrosol II reactors will be capable of breaking up the water molecule on the basis of thermochemical cycles at moderate temperatures. The Hydrosol II project pilot plant is now a reality, located in the SSPS heliostats field of the Almeria Solar Platform. (Author)

  19. 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...

  20. Targeting targeted agents: open issues for clinical trial design

    Directory of Open Access Journals (Sweden)

    Giannarelli Diana

    2009-05-01

    Full Text Available Abstract Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present. Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources.

  1. Ternary biosorption studies of Cd(II), Cr(III) and Ni(II) on shelled Moringa oleifera seeds.

    Science.gov (United States)

    Sharma, Parul; Kumari, Pushpa; Srivastava, M M; Srivastava, Shalini

    2007-01-01

    Competitive biosorption of Cd(II), Cr(III) and Ni(II) on unmodified shelled Moringa oleifera seeds (SMOS) present in ternary mixture were compared with the single metal solution. The extent of adsorption capacity of the ternary metal ions tested on unmodified SMOS was low (10-20%) as compared to single metal ions. SMOS removed the target metal ions in the selectivity order of Cd(II) > Cr(III) > Ni(II). Sorption equilibria, calculated from adsorption data, explained favorable performance of biosorption system. Regeneration of exhausted biomass was also attempted for several cycles with a view to restore the sorbent to its original state.

  2. Targeted therapies for cancer

    Science.gov (United States)

    ... nih.gov/pubmed/23589545 . Kummar S, Murgo AJ, Tomaszewski JE, Doroshow JH. Therapeutic targeting of cancer cells: Era of molecularly targeted agents. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, ...

  3. Targeted Cancer Therapies

    Science.gov (United States)

    ... changes, hair depigmentation) Problems with blood clotting and wound healing High blood pressure Gastrointestinal perforation (a rare side effect of some targeted therapies) Certain side effects of some targeted therapies have ...

  4. High Power Cryogenic Targets

    Energy Technology Data Exchange (ETDEWEB)

    Gregory Smith

    2011-08-01

    The development of high power cryogenic targets for use in parity violating electron scattering has been a crucial ingredient in the success of those experiments. As we chase the precision frontier, the demands and requirements for these targets have grown accordingly. We discuss the state of the art, and describe recent developments and strategies in the design of the next generation of these targets.

  5. Rom II-forordningen

    DEFF Research Database (Denmark)

    Pii, Tine; Nielsen, Peter Arnt

    2008-01-01

    Artiklen redegør for de vigtigste regler i Europaparlamentets og Rådets forordning om lovvalgsregler for forpligtelser uden for kontraktforhold (Rom II) og sammenligner dem med dansk ret.......Artiklen redegør for de vigtigste regler i Europaparlamentets og Rådets forordning om lovvalgsregler for forpligtelser uden for kontraktforhold (Rom II) og sammenligner dem med dansk ret....

  6. Ovarian Cancer Stage II

    Science.gov (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage II Add to My Pictures View /Download : ... 1650x675 View Download Large: 3300x1350 View Download Title: Ovarian Cancer Stage II Description: Three-panel drawing of stage ...

  7. Upgrade of the area II spectrograph

    Energy Technology Data Exchange (ETDEWEB)

    Rehm, K.E.; Bolduc, C.

    1995-08-01

    Because of the low beam energies required for experiments of astrophysical interest, the first test experiments with radioactive {sup 18}F beams can be performed in Area II. Because of the shorter distances between ion source and detector this also results in higher transmission efficiencies. The Enge split-pole spectrograph, which was not used during the last 8 years, was equipped with a new cryopump system, upgrades to the magnet power supply and the NMR system were performed. A rotating target system was built which should alleviate target deterioration effects that were observed in first test experiments.

  8. Alternate operating scenarios for NDCX-II

    Energy Technology Data Exchange (ETDEWEB)

    Sharp, W.M., E-mail: wmsharp@lbl.gov [Lawrence Livermore National Laboratory, Livermore, CA, United States of America (United States); Friedman, A.; Grote, D.P.; Cohen, R.H.; Lund, S.M. [Lawrence Livermore National Laboratory, Livermore, CA, United States of America (United States); Vay, J.-L.; Waldron, W.L. [Lawrence Berkeley National Laboratory, Berkeley, CA, United States of America (United States)

    2014-01-01

    NDCX-II is a newly completed accelerator facility at LBNL, built to study ion-heated warm dense matter, as well as aspects of ion-driven targets and intense-beam dynamics for inertial-fusion energy. The baseline design calls for using 12 induction cells to accelerate 30–50 nC of Li{sup +} ions to 1.2 MeV. During commissioning, though, we plan to extend the source lifetime by extracting less total charge. Over time, we expect that NDCX-II will be upgraded to substantially higher energies, necessitating the use of heavier ions to keep a suitable deposition range in targets. For operational flexibility, the option of using a helium plasma source is also being investigated. Each of these options requires development of an alternate acceleration schedule. The schedules here are worked out with a fast-running 1-D particle-in-cell code ASP.

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

    Science.gov (United States)

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

    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.

  10. Angiotensin II during Experimentally Simulated Central Hypovolemia

    DEFF Research Database (Denmark)

    Jensen, Theo Walther; Olsen, Niels Vidiendal

    2016-01-01

    Central hypovolemia, defined as diminished blood volume in the heart and pulmonary vascular bed, is still an unresolved problem from a therapeutic point of view. The development of pharmaceutical agents targeted at specific angiotensin II receptors, such as the non-peptidergic AT2-receptor agonist...... of these agents in a hypovolemic setting. We argue that the latest debates on the effect of angiotensin II during hypovolemia might guide for future studies, investigating the effect of such agents during experimentally simulated central hypovolemia. The purpose of this review is to examine the role...... of angiotensin II during episodes of central hypovolemia. To examine this, we reviewed results from studies with three experimental models of simulated hypovolemia: head up tilt table test, lower body negative pressure, and hemorrhage of animals. A systemic literature search was made with the use of Pub...

  11. Targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Neal Rosen; Carlos Arteaga

    2011-01-01

    With unprecedented understanding of molecular events underlying human cancer in this genomic era, a large number of drugs specifically targeting hypothesized oncogenic drivers to which tumors are potentially addicted to have been developed and continue to be developed. These targeted cancer therapies are being actively tested in clinical trials with mixed successes. This editorial provides an overview on successful targeted cancer drugs on the market and those drugs that are in late clinical development stages. Importantly, the article lays out main challenges in developing molecular targeted therapies and potential path forward to overcome these challenges, as well as opportunities for China in this new era of targeted agents. The editorial serves as an introduction to the Targeted Cancer Therapies serias that will review in depth of major pathways and drugs targeting these pathways to be published in the coming issues of the Chinese Journal of Cancer.

  12. 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

  13. 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.

  14. Co-targeting cancer drug escape pathways confers clinical advantage for multi-target anticancer drugs.

    Science.gov (United States)

    Tao, Lin; Zhu, Feng; Xu, Feng; Chen, Zhe; Jiang, Yu Yang; Chen, Yu Zong

    2015-12-01

    Recent investigations have suggested that anticancer therapeutics may be enhanced by co-targeting the primary anticancer target and the corresponding drug escape pathways. Whether this strategy confers statistically significant clinical advantage has not been systematically investigated. This question was probed by the evaluation of the clinical status and the multiple targets of 23 approved and 136 clinical trial multi-target anticancer drugs with particular focus on those co-targeting EGFR, HER2, Abl, VEGFR2, mTOR, PI3K, Alk, MEK, KIT, and DNA topoisomerase, and some of the 14, 7, 13, 20, 6, 5, 7, 2, 4 and 10 cancer drug escape pathways respectively. Most of the approved (73.9%) and phase III (75.0%), the majority of the Phase II (62.8%) and I (53.6%), and the minority of the discontinued (35.3%) multi-target drugs were found to co-target cancer drug escape pathways. This suggests that co-targeting anticancer targets and drug escape pathways confer significant clinical advantage and such strategy can be more extensively explored. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. (II) and Pb (II) ions from aqueous media using Sta

    African Journals Online (AJOL)

    Joshua Konne

    Removal of Ni (II), Co (II) and Pb (II) ions from aqueous media using Starch. Stabilized Magnetic ... initial metal concentration and contact time on the removal processes was investigated. The results .... India) supplied NaOH and the Fe salts.

  16. Type II fatty acid synthesis is essential only for malaria parasite late liver stage development

    OpenAIRE

    Vaughan, Ashley M.; O'Neill, Matthew T.; Tarun, Alice S.; Camargo, Nelly; Phuong, Thuan M; Aly, Ahmed S I; Cowman, Alan F.; Kappe, Stefan H. I.

    2008-01-01

    Intracellular malaria parasites require lipids for growth and replication. They possess a prokaryotic type II fatty acid synthesis (FAS II) pathway that localizes to the apicoplast plastid organelle and is assumed to be necessary for pathogenic blood stage replication. However, the importance of FAS II throughout the complex parasite life cycle remains unknown. We show in a rodent malaria model that FAS II enzymes localize to the sporozoite and liver stage apicoplast. Targeted deletion of Fab...

  17. Influence of Arsenic (III, Cadmium (II, Chromium (VI, Mercury (II, and Lead (II Ions on Human Triple Negative Breast Cancer (HCC1806 Cell Cytotoxicity and Cell Viability

    Directory of Open Access Journals (Sweden)

    Tsdale F. Mehari

    2017-01-01

    Full Text Available The hazardous consequences of heavy metal ions (HMIs on human health necessitate the immediate need to probe fundamentally the interactions and cytotoxic effects of HMIs on humans. This study investigated the influence of five toxic HMIs (arsenic (As (III, cadmium (Cd (II, chromium (Cr (VI, mercury (Hg (II, and lead (Pb (II on human TNBC (HCC 1806 cell viability using optical microscopy, trypan blue dye-exclusion assays, and flow cytometry. The TNBC cells were exposed to varying concentrations of HMIs for 24 and 48 hours. We evaluated the influence of the concentrations and duration of HMIs exposure on TNBC cell viability. Light microscopy, cell viability assays, revealed that after 48-hour treatment of TNBC cells with 1 x 10-5 M of As (III, Cd (II, Hg (II, Cr (IV, and Pb (II resulted in cell viabilities of 23%, 34%, 35%, 56%, 91% respectively, suggesting that As (III has the greatest cytotoxicity (77% cell death while Pb (II showed the least (9% cell death. Furthermore, flow cytometry revealed that while Pb (II, As (III and Cr (IV had significant increases in cell death, Hg (II caused a G1 arrest. Together, this study revealed that HMIs cause a differential cytotoxic effect on TNBC cells and suggest that they may have very different genotoxic targets and implications in their mutagenic potential.

  18. Targeted Molecular Therapies for SBMA.

    Science.gov (United States)

    Rinaldi, Carlo; Malik, Bilal; Greensmith, Linda

    2016-03-01

    Spinal and bulbar muscular atrophy (SBMA) is a late-onset neuromuscular disease caused by a polyglutamine expansion in the androgen receptor gene which results in progressive spinal and bulbar motor neuron degeneration, and muscle atrophy. Although the causative genetic defect is known, until recently, the molecular pathogenesis of the disease was unclear, resulting in few, if any, targets for therapy development. However, over the past decade, our understanding of the pathomechanisms that play a role in SBMA has increased dramatically, and several of these pathways and mechanisms have now been investigated as possible therapeutic targets. In this review, we discuss some of the key pathomechanisms implicated in SBMA and describe some of the therapeutic strategies that have been tested in SBMA to date, which fall into four main categories: (i) gene silencing; (ii) protein quality control and/or increased protein degradation; (iii) androgen deprivation; and (iv) modulation of AR function. Finally, it is also now clear that in addition to a greater understanding of the molecular mechanisms that underlie disease, the development of an effective disease modifying therapy for SBMA will require the coordinated, collaborative effort of research teams with diverse areas of expertise, clinicians, pharmaceutical companies as well as patient groups.

  19. Targeted tumor radiotherapy

    Directory of Open Access Journals (Sweden)

    Unak Perihan

    2002-01-01

    Full Text Available Targeted tumor radiotherapy is selectively delivery of curative doses of radiation to malignant sites. The aim of the targeted tumor radiotherapy is to use the radionuclides which have high LET particle emissions conjugated to appropriate carrier molecules. The radionuclides are selectively collected by tumor cells, depositing lethal doses to tumor cells while no admission occur to normal cells. In theory, targeted radiotherapy has several advantages over conventional radiotherapy since it allows a high radiation dose to be administered without causing normal tissue toxicity, although there are some limitations in the availability of appropriate targeting agents and in the calculations of administered doses. Therefore, for routine clinical applications more progress is still needed. In this article, the potential use of targeted tumor radiotherapy is briefly reviewed. More general aspects and considerations, such as potential radionuclides, mechanisms of tumor targeting was also outlined.

  20. Targeting Notch to target cancer stem cells.

    Science.gov (United States)

    Pannuti, Antonio; Foreman, Kimberly; Rizzo, Paola; Osipo, Clodia; Golde, Todd; Osborne, Barbara; Miele, Lucio

    2010-06-15

    The cellular heterogeneity of neoplasms has been at the center of considerable interest since the "cancer stem cell hypothesis", originally formulated for hematologic malignancies, was extended to solid tumors. The origins of cancer "stem" cells (CSC) or tumor-initiating cells (TIC; henceforth referred to as CSCs) and the methods to identify them are hotly debated topics. Nevertheless, the existence of subpopulations of tumor cells with stem-like characteristics has significant therapeutic implications. The stem-like phenotype includes indefinite self-replication, pluripotency, and, importantly, resistance to chemotherapeutics. Thus, it is plausible that CSCs, regardless of their origin, may escape standard therapies and cause disease recurrences and/or metastasis after apparently complete remissions. Consequently, the idea of selectively targeting CSCs with novel therapeutics is gaining considerable interest. The Notch pathway is one of the most intensively studied putative therapeutic targets in CSC, and several investigational Notch inhibitors are being developed. However, successful targeting of Notch signaling in CSC will require a thorough understanding of Notch regulation and the context-dependent interactions between Notch and other therapeutically relevant pathways. Understanding these interactions will increase our ability to design rational combination regimens that are more likely to prove safe and effective. Additionally, to determine which patients are most likely to benefit from treatment with Notch-targeting therapeutics, reliable biomarkers to measure pathway activity in CSC from specific tumors will have to be identified and validated. This article summarizes the most recent developments in the field of Notch-targeted cancer therapeutics, with emphasis on CSC.

  1. Targeting Sphingosine Kinase-1 To Inhibit Melanoma

    Science.gov (United States)

    Madhunapantula, SubbaRao V.; Hengst, Jeremy; Gowda, Raghavendra; Fox, Todd E.; Yun, Jong K; Robertson, Gavin P.

    2012-01-01

    SUMMARY Resistance to therapies develops rapidly for melanoma leading to more aggressive disease. Therefore, agents are needed that specifically inhibit proteins or pathways controlling the development of this disease, which can be combined, dependent on genes deregulated in a particular patient’s tumors. This study shows that elevated sphingosine-1-phosphate (S-1-P) levels resulting from increased activity of sphingosine kinase-1 (SPHK1) occur in advanced melanomas. Targeting SPHK1 using siRNA decreased anchorage dependent and independent growth as well as sensitized melanoma cells to apoptosis inducing agents. Pharmacological SPHK1 inhibitors SKI-I but not SKI-II decreased S-1-P content, elevated ceramide levels, caused a G2-M block and induced apoptotic cell death in melanomas. Targeting SPHK1 using siRNA or the pharmacological agent called SKI-I, decreased the levels of pAKT. Furthermore, SKI-I inhibited the expression of CYCLIN D1 protein and increased the activity of caspase-3/7, which in turn led to the degradation of PARP. In animals, SKI-I but not SKI-II retarded melanoma growth by 25-40%. Thus, targeting SPHK1 using siRNAs or SKI-I has therapeutic potential for melanoma treatment either alone or in combination with other targeted agents. PMID:22236408

  2. 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.

  3. Target Window Reliability

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-11

    The target window design implemented and tested in experiments at ANL have performed without failure for the available beam of 6 mm FWHM on a 12 mm diameter target. However, scaling that design to a 25 mm diameter target size for a 12 mm FWHM beam has proven problematic. Combined thermal and mechanical (pressure induced) stresses and strains are too high to maintain the small coolant gaps and provide adequate fatigue lifetime.

  4. Moving Target Defense

    CERN Document Server

    Jajodia, Sushil; Swarup, Vipin; Wang, Cliff; Wang, X Sean

    2011-01-01

    Moving Target Defense: Creating Asymmetric Uncertainty for Cyber Threats was developed by a group of leading researchers. It describes the fundamental challenges facing the research community and identifies new promising solution paths. Moving Target Defense which is motivated by the asymmetric costs borne by cyber defenders takes an advantage afforded to attackers and reverses it to advantage defenders. Moving Target Defense is enabled by technical trends in recent years, including virtualization and workload migration on commodity systems, widespread and redundant network connectivity, instr

  5. 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.

  6. 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.

  7. 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...

  8. 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....

  9. PIP-II Status and Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, Stephen [Fermilab; Derwent, Paul [Fermilab; Lebedev, Valeri [Fermilab; Mishra, Shekhar [Fermilab; Mitchell, Donald [Fermilab; Yakovlev, Vyacheslav P. [Fermilab

    2015-06-01

    Proton Improvement Plan-II (PIP-II) is the centerpiece of Fermilab's plan for upgrading the accelerator complex to establish the leading facility in the world for particle physics research based on intense proton beams. PIP-II has been developed to provide 1.2 MW of proton beam power at the start of operations of the Long Baseline Neutrino Facility (LBNF), while simultaneously providing a platform for eventual extension of LBNE beam power to >2MW and enabling future initiatives in rare processes research based on high duty factor/higher beam power operations. PIP-II is based on the construction of a new 800 MeV superconducting linac, augmented by improvements to the existing Booster, Recycler, and Main Injector complex. PIP-II is currently in the development stage with an R&D program underway targeting the front end and superconducting RF acceleration technologies. This paper will describe the status of the PIPII conceptual development, the associated technology R&D programs, and the strategy for project implementation.

  10. 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...

  11. 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...

  12. Strongly luminescing ruthenium(II)/ruthenium(II) and ruthenium(II)/platinum(II) binuclear complexes

    Energy Technology Data Exchange (ETDEWEB)

    Sahai, R.; Baucom, D.A.; Rillema, D.P.

    1986-10-08

    Two strongly luminescing complexes, ruthenium(II)/ruthenium(II) homobinuclear complex and ruthenium(II)/platinum(II) heterobinuclear complex, have been prepared and characterized. The organic part of the complex is 4,4'-dimethyl-2,2' bipyridine dimer. The luminescence behavior of the homobinuclear and heterobinculear complexes was found to be comparable to that of Ru(bpy)/sub 3//sup 2 +/, although the luminescence maxima were shifted from 615 to 620 nm. These complexes exhibit good stability due to the bidentate chelating capability of the bridging ligand. These new complexes can provide the opportunity for detailed photophysical studies related to donor-acceptor interactions and to the possibility of two simultaneous single-electron transfer events. 17 references, 2 figures.

  13. 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...

  14. SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo.

    Science.gov (United States)

    Yang, Li; Weng, Wei; Sun, Zhi-Xin; Fu, Xian-Jie; Ma, Jun; Zhuang, Wen-Fang

    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.

  15. Simulated E-Bomb Effects on Electronically Equipped Targets

    Science.gov (United States)

    2009-09-01

    65 Figure 23. GBU-10 Paveway II (From: Bombas Guidas, 2009) ........................... 66 Figure 24. Representative Laser Guided Bomb...from the target. A picture of the GBU- 10 bomb is in Figure 23. Figure 23. GBU-10 Paveway II (From: Bombas Guidas, 2009) According to the Air...Retrieved June 16, 2009, from http://www.globalsecurity.org/military/systems/munitions/blu-82.htm Bombas Guidas. Retrieved June 23 2009, from

  16. Mod II engine development

    Science.gov (United States)

    Karl, David W.

    1987-01-01

    The Mod II engine, a four-cylinder, automotive Stirling engine utilizing the Siemens-Rinia double-acting concept, was assembled and became operational in January 1986. This paper describes the Mod II engine, its first assembly, and the subsequent development work done on engine components up to the point that engine performance characterization testing took place. Performance data for the engine are included.

  17. DUMAND II status report

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, T. (ICRR, University of Tokyo, Japan (JP)); Becker-Szendy, R.; Bosetti, P.; Boynton, P.E.; Bradner, H.; Camerini, U.; Clem, J.; Commichau, V.; Dau, D.; Dye, S.; Grieder, P.K.F.; Hayashino, T.; Hazen, E.; Jaworski, M.; Kitamura, T.; Kobayakawa, K.; Koske, P.; Learned, J.G.; Ley, C.; Lord, J.J.; March, R.; Matsuno, S.; Minkowski, P.; Mitsui, K.; O' Connor, D.; Ohashi, Y.; Okada, A.; Peterson, V.Z.; Rathlev, J.; Roberts, A.; Roos, C.E.; Sakuda, M.; Samm, D.; Stenger, V.J.; Tanaka, S.; Uehara, S.; Webster, M.; Wilkins, G.; Wilkes, R.J.; Yamaguchi, A.; Yamamoto, I.; Young, K.K. (University of Bern, Switzerland (CH) Boston University, (USA) University of Hawaii, (USA) University of Kiel, Germany (DE) Kobe University, Japan (JP) Kinki University, Japan (JP) Okayama Science University, Japan (JP) Scripps Institute of Oceanography, (USA) Tohoku University, Japan (JP) ICRR, University of tokyo, Japan (JP) NLHEP Tsukuba, Japan (JP) Vanderbilt University, (USA) University of Washington, (US

    1991-04-05

    The scientific goals, design, capabilities, and status of the DUMAND II detector system are described. In June, 1989, the High Energy Physics Advisory Panel recommended support for construction of DUMAND II to the U.S. Department of Energy. Funding began in 1990, and prototype development for various detector subsystems is under way. Current plans include deployment of the shore cable, junction box and three strings of optical detector modules in 1992, and expansion to the full 9-string configuration in 1993.

  18. DUMAND II status report

    Science.gov (United States)

    Aoki, T.; Becker-Szendy, R.; Bosetti, P.; Boynton, P. E.; Bradner, H.; Camerini, U.; Clem, J.; Commichau, V.; Dau, D.; Dye, S.; Grieder, P. K. F.; Hayashino, T.; Hazen, E.; Jaworski, M.; Kitamura, T.; Kobayakawa, K.; Koske, P.; Learned, J. G.; Ley, C.; Lord, J. J.; March, R.; Matsuno, S.; Minkowski, P.; Mitsui, K.; O'Connor, D.; Ohashi, Y.; Okada, A.; Peterson, V. Z.; Rathlev, J.; Roberts, A.; Roos, C. E.; Sakuda, M.; Samm, D.; Stenger, V. J.; Tanaka, S.; Uehara, S.; Webster, M.; Wilkins, G.; Wilkes, R. J.; Yamaguchi, A.; Yamamoto, I.; Young, K. K.

    1991-04-01

    The scientific goals, design, capabilities, and status of the DUMAND II detector system are described. In June, 1989, the High Energy Physics Advisory Panel recommended support for construction of DUMAND II to the U.S. Department of Energy. Funding began in 1990, and prototype development for various detector subsystems is under way. Current plans include deployment of the shore cable, junction box and three strings of optical detector modules in 1992, and expansion to the full 9-string configuration in 1993.

  19. Ecuaciones Diferenciales II

    OpenAIRE

    Mañas Baena, Manuel; Martínez Alonso, Luis

    2015-01-01

    En este manual se revisan diferentes aspectos sobre las ecuaciones diferenciales en derivadas parciales de utilidad para los físicos. Se elaboraron como notas de clase de la asignatura Ecuaciones II, del plan 1993 de la Licenciatura de Física de la UCM. Actualmente cubre un 75% de la asignatura Métodos Matemáticos II del Grado de Física de la UCM.

  20. ASTRID II satellit projekt

    DEFF Research Database (Denmark)

    Jørgensen, John Leif; Primdahl, Fritz

    1997-01-01

    The report describes the instruments developed for the Swedish micro satellite "ASTRID II". Specifications of the two instruments realized under this contract, a Stellar Compass and a CSC magnetometer are given follwed by a description of the project status and plan.......The report describes the instruments developed for the Swedish micro satellite "ASTRID II". Specifications of the two instruments realized under this contract, a Stellar Compass and a CSC magnetometer are given follwed by a description of the project status and plan....

  1. A Targeting Microbubble for Ultrasound Molecular Imaging.

    Directory of Open Access Journals (Sweden)

    James Shue-Min Yeh

    Full Text Available Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (streptavidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(streptavidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii effective for real-time imaging; and (iii effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld.To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging.Microbubbles with a previously unreported generic (non-targeting components composition were grafted with anti-E-selectin F(ab'2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster. The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8, demonstrating a high degree of non-invasive molecular quantification.Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i-(iii desired for

  2. 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...

  3. Inhibition of Zn(II binding type IA topoisomerases by organomercury compounds and Hg(II.

    Directory of Open Access Journals (Sweden)

    Bokun Cheng

    Full Text Available Type IA topoisomerase activities are essential for resolving DNA topological barriers via an enzyme-mediated transient single strand DNA break. Accumulation of topoisomerase DNA cleavage product can lead to cell death or genomic rearrangement. Many antibacterial and anticancer drugs act as topoisomerase poison inhibitors that form stabilized ternary complexes with the topoisomerase covalent intermediate, so it is desirable to identify such inhibitors for type IA topoisomerases. Here we report that organomercury compounds were identified during a fluorescence based screening of the NIH diversity set of small molecules for topoisomerase inhibitors that can increase the DNA cleavage product of Yersinia pestis topoisomerase I. Inhibition of relaxation activity and accumulation of DNA cleavage product were confirmed for these organomercury compounds in gel based assays of Escherichia coli topoisomerase I. Hg(II, but not As(III, could also target the cysteines that form the multiple Zn(II binding tetra-cysteine motifs found in the C-terminal domains of these bacterial topoisomerase I for relaxation activity inhibition. Mycobacterium tuberculosis topoisomerase I activity is not sensitive to Hg(II or the organomercury compounds due to the absence of the Zn(II binding cysteines. It is significant that the type IA topoisomerases with Zn(II binding domains can still cleave DNA when interfered by Hg(II or organomercury compounds. The Zn(II binding domains found in human Top3α and Top3β may be potential targets of toxic metals and organometallic complexes, with potential consequence on genomic stability and development.

  4. Biotherapies in systemic lupus erythematosus: New targets.

    Science.gov (United States)

    Lazaro, Estibaliz; Scherlinger, Marc; Truchetet, Marie-Elise; Chiche, Laurent; Schaeverbeke, Thierry; Blanco, Patrick; Richez, Christophe

    2016-09-20

    Systemic lupus erythematosus (SLE) is an autoimmune disease with a polymorphic presentation. The variability in the clinical expression and severity of SLE makes new treatments both essential and challenging to develop. Several biotherapies targeting different pathophysiological pathways have been developed over the past 15 years. The results of Phase II trials were encouraging but rarely borne out by Phase III trials. Recent data, which are discussed in detail in this review, allowed belimumab - a monoclonal antibody against BLyS (B-lymphocyte stimulator) - to become the first biotherapy approved for use in SLE. Other molecules targeting B cells include the two anti-BLyS antibodies tabalumab and blisibimod; atacicept, which targets both BLyS and APRIL (a proliferation-inducing ligand); and the monoclonal antibody to CD22 epratuzumab. The rekindling of interest in the B-cell pathway has also driven new clinical research into rituximab, a monoclonal antibody targeting CD20 with evaluations of new strategies. A new and promising approach is the use of inhibitors of the type 1 interferon (IFN) pathway, of which the most promising is anifrolumab, a monoclonal antibody targeting the type 1 IFN receptor. In this review, we discuss study findings and their clinical relevance, present the most promising targets, and analyze possible explanations to negative results, such as inappropriate patient selection and treatment response criteria or the erratic use of high-dose glucocorticoid therapy.

  5. The functional performance of the Argus II retinal prosthesis

    OpenAIRE

    2013-01-01

    Visual prostheses are devices to treat profound vision loss by stimulating secondary nerve cells anywhere along the visual pathway, typically with electrical pulses. The Argus® II implant, developed by Second Sight Medical Products (SSMP, Sylmar, CA, USA), targets the retina and features 60 electrodes that electrically stimulate the surviving retinal neurons. Of the approximately 20 research groups that are actively developing visual prostheses, SSMP has the longest track record. The Argus II...

  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. 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 rand

  8. Modelling Recycling Targets

    DEFF Research Database (Denmark)

    Hill, Amanda Louise; Leinikka Dall, Ole; Andersen, Frits M.

    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...

  9. Vibrotactile target saliency

    NARCIS (Netherlands)

    Toet, A.; Groen, E.l.; Oosterbeek, M.T.J.; Hooge, I.T.C.

    2008-01-01

    We tested the saliency of a single vibrotractile target (T) among 2 to 7 nontargets (N), presented by 8 tactors that were equally distributed over a horizontal band around the torso. Targets and nontargets had different pulse duration, but the same activation period and no onset asynchrony. T-N simi

  10. Segmented Target Design

    Science.gov (United States)

    Merhi, Abdul Rahman; Frank, Nathan; Gueye, Paul; Thoennessen, Michael; MoNA Collaboration

    2013-10-01

    A proposed segmented target would improve decay energy measurements of neutron-unbound nuclei. Experiments like this have been performed at the National Superconducting Cyclotron Laboratory (NSCL) located at Michigan State University. Many different nuclei are produced in such experiments, some of which immediately decay into a charged particle and neutron. The charged particles are bent by a large magnet and measured by a suite of charged particle detectors. The neutrons are measured by the Modular Neutron Array (MoNA) and Large Multi-Institutional Scintillation Array (LISA). With the current target setup, a nucleus in a neutron-unbound state is produced with a radioactive beam impinged upon a beryllium target. The resolution of these measurements is very dependent on the target thickness since the nuclear interaction point is unknown. In a segmented target using alternating layers of silicon detectors and Be-targets, the Be-target in which the nuclear reaction takes place would be determined. Thus the experimental resolution would improve. This poster will describe the improvement over the current target along with the status of the design. Work supported by Augustana College and the National Science Foundation grant #0969173.

  11. 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 rand

  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. Vibrotactile target saliency

    NARCIS (Netherlands)

    Toet, A.; Groen, E.l.; Oosterbeek, M.T.J.; Hooge, I.T.C.

    2008-01-01

    We tested the saliency of a single vibrotractile target (T) among 2 to 7 nontargets (N), presented by 8 tactors that were equally distributed over a horizontal band around the torso. Targets and nontargets had different pulse duration, but the same activation period and no onset asynchrony. T-N simi

  14. Nonlinear acoustic landmine detection: comparison of off-target soil background and on-target soil-mine nonlinear effects

    Science.gov (United States)

    Korman, Murray S.; Sabatier, James M.; Pauls, Kathleen E.; Genis, Sean A.

    2006-05-01

    When airborne sound at two primary tones, f I, f II (closely spaced near a resonance) excites the soil surface over a buried landmine, soil wave motion interacts with the landmine generating a scattered surface profile which can be measured over the "target." Profiles at the primaries f I, f II, and nonlinearly generated combination frequencies f I-(f II-f I) and f II+(f II-f I) , 2f I-(f II-f I), f I+f II and 2f II+(f II-f I) (among others) have been measured for a VS 2.2 plastic, inert, anti-tank landmine, buried at 3.6 cm in sifted loess soil and in a gravel road bed. [M.S. Korman and J.M. Sabatier, J. Acoust. Soc. Am. 116, 3354-3369 (2004)]. It is observed that the "on target" to "off target" contrast ratio for the sum frequency component can be ~20 dB higher than for either primary. The vibration interaction between the top-plate interface of a buried plastic landmine and the soil above it appears to exhibit many characteristics of the mesoscopic/nanoscale nonlinear effects that are observed in geomaterials like sandstone. Near resonance, the bending (softening) of a family of increasing amplitude tuning curves, involving the vibration over the landmine, exhibits a linear relationship between the peak particle velocity and corresponding frequency. Tuning curve experiments are performed both on and off the mine in an effort to understand the nonlinearities in each case.

  15. Nuclear target development

    Energy Technology Data Exchange (ETDEWEB)

    Greene, J.P.; Thomas, G.E.

    1995-08-01

    The Physics Division operates a target development laboratory that produces thin foil targets needed for experiments performed at the ATLAS and Dynamitron accelerators. Targets are not only produced for the Physics Division but also for other divisions and occasionally for other laboratories and universities. In the past year, numerous targets were fabricated by vacuum evaporation either as self-supporting foils or on various substrates. Targets produced included Ag, Au, {sup 10,11}B, {sup 138}Ba, Be, {sup 12}C, {sup 40}Ca, {sup 116}Cd, {sup 155,160}Gd, {sup 76}Ge, In, LID, {sup 6}LiH, Melamine, Mg, {sup 142,150}Nd, {sup 58}Ni, {sup 206,208}Pb, {sup 194}Pt, {sup 28}Si, {sup 144,148}Sm, {sup 120,122,124}Sn, Ta, {sup 130}Te, ThF{sub 4}, {sup 46,50}Ti, TiH, U, UF{sub 4}, {sup 182}W and {sup 170}Yb. Polypropylene and aluminized polypropylene, along with metallized Mylar were produced for experiments at ATLAS. A number of targets of {sup 11}B of various thickness were made for the DEP 2-MeV Van de Graff accelerator. An increased output of foils fabricated using our small rolling mill included targets of Au, C, {sup 50}Cr, Cu, {sup 155,160}Gd, Mg, {sup 58}Ni, {sup 208}Pb, {sup 105,110}Pd. Sc, Ti, and {sup 64,66}Zn.

  16. 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.

  17. Sensitive electrochemical sensor using a graphene–polyaniline nanocomposite for simultaneous detection of Zn(II), Cd(II), and Pb(II)

    Energy Technology Data Exchange (ETDEWEB)

    Ruecha, Nipapan [Program in Macromolecular Science, Faculty of Science, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok 10330 (Thailand); Rodthongkum, Nadnudda [Metallurgy and Materials Science Research Institute, Chulalongkorn University, Soi Chula 12, Phayathai Road, Patumwan, Bangkok 10330 (Thailand); Cate, David M. [Department of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523 (United States); Volckens, John [Department of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523 (United States); Department of Mechanical Engineering, Colorado State University, Fort Collins, Colorado 80523 (United States); Chailapakul, Orawon, E-mail: orawon@chula.ac.th [Electrochemistry and Optical Spectroscopy Research Unit (EOSRU), Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok 10330 (Thailand); National Center of Excellence for Petroleum, Petrochemicals, Advanced Materials, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok 10330 (Thailand); Henry, Charles S., E-mail: chuck.henry@colostate.edu [Department of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523 (United States); Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523 (United States)

    2015-05-18

    Highlights: • Detection limits for Zn, Pb, and Cd using ASV were 1, 0.1, and 0.1 μg L{sup −1}, respectively. • G/PANI-modification led to a 3× improvement in signal vs. unmodified electrodes. • ASV on a plastic substrate exhibited better sensitivity than on a paper substrate. • Zn, Pb, and Cd were measured in human serum using method of standard addition. - Abstract: This work describes the development of an electrochemical sensor for simultaneous detection of Zn(II), Cd(II), and Pb(II) using a graphene–polyaniline (G/PANI) nanocomposite electrode prepared by reverse-phase polymerization in the presence of polyvinylpyrrolidone (PVP). Two substrate materials (plastic film and filter paper) and two nanocomposite deposition methods (drop-casting and electrospraying) were investigated. Square-wave anodic stripping voltammetry currents were higher for plastic vs. paper substrates. Performance of the G/PANI nanocomposites was characterized by scanning electron microscopy (SEM) and cyclic voltammetry. The G/PANI-modified electrode exhibited high electrochemical conductivity, producing a three-fold increase in anodic peak current (vs. the unmodified electrode). The G/PANI-modified electrode also showed evidence of increased surface area under SEM. Square-wave anodic stripping voltammetry was used to measure Zn(II), Cd(II), and Pb(II) in the presence of Bi(III). A linear working range of 1–300 μg L{sup −1} was established between anodic current and metal ion concentration with detection limits (S/N = 3) of 1.0 μg L{sup −1} for Zn(II), and 0.1 μg L{sup −1} for both Cd(II) and Pb(II). The G/PANI-modified electrode allowed selective determination of the target metals in the presence of common metal interferences including Mn(II), Cu(II), Fe(III), Fe(II), Co(III), and Ni(II). Repeat assays on the same device demonstrated good reproducibility (%RSD < 11) over 10 serial runs. Finally, this system was utilized for determining Zn(II), Cd(II), and Pb(II) in

  18. Internal polarized targets

    Energy Technology Data Exchange (ETDEWEB)

    Kinney, E.R.; Coulter, K.; Gilman, R.; Holt, R.J.; Kowalczyk, R.S.; Napolitano, J.; Potterveld, D.H.; Young, L. (Argonne National Lab., IL (USA)); Mishnev, S.I.; Nikolenko, D.M.; Popov, S.G.; Rachek, I.A.; Temnykh, A.B.; Toporkov, D.K.; Tsentalovich, E.P.; Wojtsekhowski, B.B. (AN SSSR, Novosibirsk (USSR). Inst. Yadernoj Fiziki)

    1989-01-01

    Internal polarized targets offer a number of advantages over external targets. After a brief review of the basic motivation and principles behind internal polarized targets, the technical aspects of the atomic storage cell will be discussed in particular. Sources of depolarization and the means by which their effects can be ameliorated will be described, especially depolarization by the intense magnetic fields arising from the circulating particle beam. The experience of the Argonne Novosibirsk collaboration with the use of a storage cell in a 2 GeV electron storage ring will be the focus of this technical discussion. 17 refs., 11 figs.

  19. AA antiproton production target

    CERN Multimedia

    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.

  20. STIS target acquisition

    Science.gov (United States)

    Kraemer, Steve; Downes, Ron; Katsanis, Rocio; Crenshaw, Mike; McGrath, Melissa; Robinson, Rich

    1997-01-01

    We describe the STIS autonomous target acquisition capabilities. We also present the results of dedicated tests executed as part of Cycle 7 calibration, following post-launch improvements to the Space Telescope Imaging Spectrograph (STIS) flight software. The residual pointing error from the acquisitions are < 0.5 CCD pixels, which is better than preflight estimates. Execution of peakups show clear improvement of target centering for slits of width 0.1 sec or smaller. These results may be used by Guest Observers in planning target acquisitions for their STIS programs.

  1. Mod II engine performance

    Science.gov (United States)

    Richey, Albert E.; Huang, Shyan-Cherng

    1987-01-01

    The testing of a prototype of an automotive Stirling engine, the Mod II, is discussed. The Mod II is a one-piece cast block with a V-4 single-crankshaft configuration and an annular regenerator/cooler design. The initial testing of Mod II concentrated on the basic engine, with auxiliaries driven by power sources external to the engine. The performance of the engine was tested at 720 C set temperature and 820 C tube temperature. At 720 C, it is observed that the power deficiency is speed dependent and linear, with a weak pressure dependency, and at 820 C, the power deficiency is speed and pressure dependent. The effects of buoyancy and nozzle spray pattern on the heater temperature spread are investigated. The characterization of the oil pump and the operating cycle and temperature spread tests are proposed for further evaluation of the engine.

  2. About APPLE II Operation

    Science.gov (United States)

    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° 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.

  3. SYNTHESIS AND CHARACTERIZATION OF SALICYLALDAZINE AND ITS METAL (II) COMPLEXES DERIVED FROM METAL (II) CHLORIDES

    OpenAIRE

    Jamila wazir

    2016-01-01

    The salicylaldazine (ligand) and its metal (II) complexes like copper (II), nickel (II), zinc (II), cobalt (II) and manganese (II) complexes has been synthesized and characterized by different techniques using FTIR, UV-VIS spectroscopy. The ligand (salicylaldazine) is synthesized by the condensation reaction of salicylaldehyde and hydrazine sulfate. The salicylaldazine metal (II) complexes like Cu (II) , Ni(II), Zn (II), Co(II), Mn(II) were prepared by using metal (II) chloride in dioxane. Th...

  4. Targeting thapsigargin towards tumors

    DEFF Research Database (Denmark)

    Doan, Nhu Thi Quynh; Paulsen, Eleonora Sandholdt; Sehgal, Pankaj

    2015-01-01

    substrates for either prostate specific antigen (PSA) or prostate specific membrane antigen (PSMA) prodrugs were created, which selectively affect prostate cancer cells or neovascular tissue in tumors. One of the prodrug is currently tested in clinical phase II. The prodrug under clinical trial has been...

  5. 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

  6. 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

  7. Type-II Leptogenesis

    CERN Document Server

    Kim, Jihn E

    2016-01-01

    I will talk on our new theory on baryogenesis through type-II leptogenesis which is different from the well-known type-I leptogenesis. I will comment on the Jarlskog phases, $\\delta_{\\rm CKM}$ and $\\delta_{\\rm PMNS}$, in the CKM and PMNS matrices. In the type-II leptogenesis, the PMNS phase is used for Sakharov's condition on the global quantum number generation in the Universe. For this to be effective, the SU(2)$\\times$U(1) gauge symmetry must be broken during the leptogenesis epoch.

  8. 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.

  9. Targeting bacterial toxins.

    Science.gov (United States)

    Ivarsson, Mattias E; Leroux, Jean-Christophe; Castagner, Bastien

    2012-04-23

    Protein toxins constitute the main virulence factors of several species of bacteria and have proven to be attractive targets for drug development. Lead candidates that target bacterial toxins range from small molecules to polymeric binders, and act at each of the multiple steps in the process of toxin-mediated pathogenicity. Despite recent and significant advances in the field, a rationally designed drug that targets toxins has yet to reach the market. This Review presents the state of the art in bacterial toxin targeted drug development with a critical consideration of achieved breakthroughs and withstanding challenges. The discussion focuses on A-B-type protein toxins secreted by four species of bacteria, namely Clostridium difficile (toxins A and B), Vibrio cholerae (cholera toxin), enterohemorrhagic Escherichia coli (Shiga toxin), and Bacillus anthracis (anthrax toxin), which are the causative agents of diseases for which treatments need to be improved. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. MHC class II tetramers made from isolated recombinant α and β chains refolded with affinity-tagged peptides

    DEFF Research Database (Denmark)

    Braendstrup, Peter; Justesen, Sune Frederik Lamdahl; Osterbye, Thomas

    2013-01-01

    Targeting CD4+ T cells through their unique antigen-specific, MHC class II-restricted T cell receptor makes MHC class II tetramers an attractive strategy to identify, validate and manipulate these cells at the single cell level. Currently, generating class II tetramers is a specialized undertaking...

  11. MOLECULAR ANALYSIS OF THE TOPOISOMERASE-II ALPHA-GENE AND ITS EXPRESSION IN HUMAN OVARIAN-CANCER

    NARCIS (Netherlands)

    VANDERZEE, AGJ; DEVRIES, EGE; HOLLEMA, H; KAYE, SB; BROWN, R; KEITH, WN

    Background: DNA topoisomerase II enzymes are key targets for the group of anti-tumour agents known as topoisomerase inhibitors. In general, cell lines which express high levels of topoisomerase II are sensitive to the cytotoxic effects of the topoisomerase poisons. The levels of topoisomerase II

  12. Issues in Target Tracking

    Science.gov (United States)

    2010-05-01

    the CUSUM (Page) test yields the quickest detection of a change of distribution for the case of i.i.d. observations [3]. In fact, in a (highly...11. Autocorrelation of the CUSUM increments, sn, under H1 (target present). Issues in Target Tracking RTO-EN-SET-157(2010...restrictive condition that the increments of the cumulative sum, sn, be i.i.d. [3], [22]. Fig. 11 plots the autocorrelation of the CUSUM increments as a

  13. VSOP Science Targets

    OpenAIRE

    Hirabayashi, H.; Inoue, M.; 平林, 久; 井上, 允

    1991-01-01

    The VLBI Space Observatory Programme (VSOP) started in 1989,and the observations will start in 1995. VSOP Science targets are reviewed in relation to Japanese VLBI activities. Regions surrounding accreting disks and jets of Active Galactic Nuclei (AGN) will be the most important targets. The physics and distances to water vapor masing regions in and outside the Galaxy can be studied in more detail. VSOP can cover various objects like young supernova and gravitational lensing objects.

  14. Decrease in blood pressure and regression of cardiovascular complications by angiotensin II vaccine in mice.

    Directory of Open Access Journals (Sweden)

    Futoshi Nakagami

    Full Text Available Vaccines have been recently developed to treat various diseases such as cancer, rheumatoid arthritis and Alzheimer's disease in addition to infectious diseases. However, before use in the clinical setting, vaccines targeting self-antigens must be demonstrated to be effective and safe, evoking an adequate humoral immune response from B cells while avoiding T cell activation in response to self. Although the vaccine targeting angiotensin II (Ang II is efficient in rodents and humans, little is known regarding the immunological activation and safety of the vaccine. In this study, we evaluated the efficiency and safety of an Ang II peptide vaccine in mice. Immunization with Ang II conjugated to keyhole limpet hemocyanin (KLH successfully induced the production of anti-Ang II antibody, which blocked Ang II signaling in human aortic smooth muscle cells. However, Ang II itself did not activate T cells, as assessed by the proliferation and lymphokine production of T cells in immunized mice, whereas KLH activated T cells. In an Ang II-infused model, the non-immunized mice showed high blood pressure (BP, whereas the immunized mice (Ang II-KLH showed a significant decrease in systolic BP, accompanied by significant reductions in cardiac hypertrophy and fibrosis. Importantly, anti-Ang II antibody titer was not elevated even after the administration of large amounts of Ang II, indicating that Ang II itself boosted antibody production, most likely due to less activation of T cells. In addition, no accumulation of inflammatory cells was observed in immunized mice, because endogenous Ang II would not activate T cells after immunization with Ang II-KLH. Taken together, these data indicate that vaccines targeting Ang II might be effective to decrease high BP and prevent cardiovascular complications without severe side effects.

  15. 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.

  16. Mechanisms used for genomic proliferation by thermophilic group II introns.

    Directory of Open Access Journals (Sweden)

    Georg Mohr

    Full Text Available Mobile group II introns, which are found in bacterial and organellar genomes, are site-specific retroelements hypothesized to be evolutionary ancestors of spliceosomal introns and retrotransposons in higher organisms. Most bacteria, however, contain no more than one or a few group II introns, making it unclear how introns could have proliferated to higher copy numbers in eukaryotic genomes. An exception is the thermophilic cyanobacterium Thermosynechococcus elongatus, which contains 28 closely related copies of a group II intron, constituting approximately 1.3% of the genome. Here, by using a combination of bioinformatics and mobility assays at different temperatures, we identified mechanisms that contribute to the proliferation of T. elongatus group II introns. These mechanisms include divergence of DNA target specificity to avoid target site saturation; adaptation of some intron-encoded reverse transcriptases to splice and mobilize multiple degenerate introns that do not encode reverse transcriptases, leading to a common splicing apparatus; and preferential insertion within other mobile introns or insertion elements, which provide new unoccupied sites in expanding non-essential DNA regions. Additionally, unlike mesophilic group II introns, the thermophilic T. elongatus introns rely on elevated temperatures to help promote DNA strand separation, enabling access to a larger number of DNA target sites by base pairing of the intron RNA, with minimal constraint from the reverse transcriptase. Our results provide insight into group II intron proliferation mechanisms and show that higher temperatures, which are thought to have prevailed on Earth during the emergence of eukaryotes, favor intron proliferation by increasing the accessibility of DNA target sites. We also identify actively mobile thermophilic introns, which may be useful for structural studies, gene targeting in thermophiles, and as a source of thermostable reverse transcriptases.

  17. Dark Blue II

    OpenAIRE

    2013-01-01

    Dark Blue II, high fired porcelain, decorated with cobalt chloride, woodfired with salt. 10,5 x 10,5 x 19 cm. Ferdigstilt: 2012. Innkjøpt til Collection of The American Museum of Ceramic Art, Pomona, California, USA.

  18. AND Zn(II)

    African Journals Online (AJOL)

    recovered by suction filtration, washed with distilled water and recrystallized .... dried in vacuum to afford the Ni(II)-L complex (0.23 g, 68%) as a deep brown solid. ..... were observed indicating that the polymer film is electrochemically active.

  19. MARC II and COBOL

    Directory of Open Access Journals (Sweden)

    Henriette D. Avram

    1968-12-01

    Full Text Available A description of the machine processing of MARC II records using COBOL for an application on the Library of Congress System 360/30. Emphasis is on the manipulation by COBOL of highly complex variable length MARC records containing variable length fields.

  20. 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

  1. 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…

  2. Dianilinedichloridozinc(II

    Directory of Open Access Journals (Sweden)

    Islam Ullah Khan

    2010-05-01

    Full Text Available In the title compound, [ZnCl2(C6H7N2], the ZnII ion (site symmetry 2 adopts a near-regular tetrahedral ZnN2Cl2 coordination geometry. In the crystal, molecules are linked by N—H...Cl hydrogen bonds, generating (100 sheets containing R22(8 loops.

  3. Targeted Radiolabeled Compounds in Glioma Therapy.

    Science.gov (United States)

    Cordier, Dominik; Krolicki, Leszek; Morgenstern, Alfred; Merlo, Adrian

    2016-05-01

    Malignant gliomas of World Health Organization (WHO) grades II-IV represent the largest entity within the group of intrinsic brain tumors and are graded according to their pathophysiological features with survival times between more than 10 years (WHO II) and only several months (WHO IV). Gliomas arise from astrocytic or oligodendrocytic precursor cells and exhibit an infiltrative growth pattern lacking a clearly identifiable tumor border. The development of effective treatment strategies of the invasive tumor cell front represents the main challenge in glioma therapy. The therapeutic standard consists of surgical resection and, depending on the extent of resection and WHO grade, adjuvant external beam radiotherapy or systemic chemotherapy. Within the last decades, there has been no major improvement of the prognosis of patients with glioma. The consistent overexpression of neurokinin type 1 receptors in gliomas WHO grades II-IV has been used to develop a therapeutic substance P-based targeting system. A substance P-analogue conjugated to the DOTA or DOTAGA chelator has been labeled with different alpha-particle or beta-particle emitting radionuclides for targeted glioma therapy. The radiopharmaceutical has been locally injected into the tumors or the resection cavity. In several clinical studies, the methodology has been examined in adjuvant and neoadjuvant clinical settings. Although no large controlled series have so far been generated, the results of radiolabeled substance P-based targeted glioma therapy compare favorably with standard therapy. Recently, labeling with the alpha particle emitting Bi-213 has been found to be promising due to the high linear energy transfer and the very short tissue range of 0.08 mm. Further development needs to focus on the improvement of the stability of the compound and the application by dedicated catheter systems to improve the intratumoral distribution of the radiopharmaceutical within the prognostically critical

  4. 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.

  5. Inhibitory role of peroxiredoxin II (Prx II) on cellular senescence.

    Science.gov (United States)

    Han, Ying-Hao; Kim, Hyun-Sun; Kim, Jin-Man; Kim, Sang-Keun; Yu, Dae-Yeul; Moon, Eun-Yi

    2005-08-29

    Reactive oxygen species (ROS) were generated in all oxygen-utilizing organisms. Peroxiredoxin II (Prx II) as one of antioxidant enzymes may play a protective role against the oxidative damage caused by ROS. In order to define the role of Prx II in organismal aging, we evaluated cellular senescence in Prx II(-/-) mouse embryonic fibroblast (MEF). As compared to wild type MEF, cellular senescence was accelerated in Prx II(-/-) MEF. Senescence-associated (SA)-beta-galactosidase (Gal)-positive cell formation was about 30% higher in Prx II(-/-) MEF. N-Acetyl-l-cysteine (NAC) treatment attenuated SA-beta-Gal-positive cell formation. Prx II(-/-) MEF exhibited the higher G2/M (41%) and lower S (1.6%) phase cells as compared to 24% and 7.3% [corrected] in wild type MEF, respectively. A high increase in the p16 and a slight increase in the p21 and p53 levels were detected in PrxII(-/-) MEF cells. The cellular senescence of Prx II(-/-) MEF was correlated with the organismal aging of Prx II(-/-) mouse skin. While extracellular signal-regulated kinase (ERK) and p38 activation was detected in Prx II(-/-) MEF, ERK and c-Jun N-terminal kinase (JNK) activation was detected in Prx II(-/-) skin. These results suggest that Prx II may function as an enzymatic antioxidant to prevent cellular senescence and skin aging.

  6. 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.

  7. Epoxyeicosatrienoic acid analog attenuates angiotensin II hypertension and kidney injury.

    Science.gov (United States)

    Khan, Abdul Hye; Falck, John R; Manthati, Vijaya L; Campbell, William B; Imig, John D

    2014-01-01

    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 (10 mg/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.

  8. The Sinuous Target

    Energy Technology Data Exchange (ETDEWEB)

    Zwaska, R. [Fermilab

    2015-06-01

    We report on the concept for a target material comprised of a multitude of interlaced wires of small dimension. This target material concept is primarily directed at high-power neutrino targets where the thermal shock is large due to small beam sizes and short durations; it also has applications to other high-power targets, particularly where the energy deposition is great or a high surface area is preferred. This approach ameliorates the problem of thermal shock by engineering a material with high strength on the micro-scale, but a very low modulus of elasticity on the meso-scale. The low modulus of elasticity is achieved by constructing the material of spring-like wire segments much smaller than the beam dimension. The intrinsic bends of the wires will allow them to absorb the strain of thermal shock with minimal stress. Furthermore, the interlaced nature of the wires provides containment of any segment that might become loose. We will discuss the progress on studies of analogue materials and fabrication techniques for sinuous target materials.

  9. Production Target Design Report

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dale, Gregory E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Olivas, Eric Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-28

    The Northstar 99Mo production target, a cylindrical length of 100Mo rod, has evolved considerably since its first conception.  The cylinder was very early sliced into disks to increase the heat transfer area, first to 1 mm thick disks then to the current 0.5 mm thick.  The coolant was changed early in the target development from water to helium to eliminate corrosion and dissolution.  The diameter has increased from initially 6 mm to 12 mm, the current diameter of the test target now at ANL, to nominally 28 mm (26-30.6 mm, depending upon optimal beam spot size and shape).  The length has also changed to improve the production to cost ratio, so now the target is nominally 41 mm long (excluding coolant gaps between disks), and irradiated on both ends.  This report summarizes the current status of the plant target design.

  10. Targeted assets risk analysis.

    Science.gov (United States)

    Bouwsema, Barry

    2013-01-01

    Risk assessments utilising the consolidated risk assessment process as described by Public Safety Canada and the Centre for Security Science utilise the five threat categories of natural, human accidental, technological, human intentional and chemical, biological, radiological, nuclear or explosive (CBRNE). The categories of human intentional and CBRNE indicate intended actions against specific targets. It is therefore necessary to be able to identify which pieces of critical infrastructure represent the likely targets of individuals with malicious intent. Using the consolidated risk assessment process and the target capabilities list, coupled with the CARVER methodology and a security vulnerability analysis, it is possible to identify these targeted assets and their weaknesses. This process can help emergency managers to identify where resources should be allocated and funding spent. Targeted Assets Risk Analysis (TARA) presents a new opportunity to improve how risk is measured, monitored, managed and minimised through the four phases of emergency management, namely, prevention, preparation, response and recovery. To reduce risk throughout Canada, Defence Research and Development Canada is interested in researching the potential benefits of a comprehensive approach to risk assessment and management. The TARA provides a framework against which potential human intentional threats can be measured and quantified, thereby improving safety for all Canadians.

  11. The Green Bank Telescope Galactic H II Region Discovery Survey

    CERN Document Server

    Bania, T M; Balser, Dana S; Rood, R T

    2010-01-01

    We discovered a large population of previously unknown Galactic H II regions by using the Green Bank Telescope to detect their hydrogen radio recombination line emission. Since recombination lines are optically thin at 3 cm wavelength, we can detect H II regions across the entire Galactic disk. Our targets were selected based on spatially coincident 24 micron and 21 cm continuum emission. For the Galactic zone -16 deg < L_gal < 67 deg and abs(B_gal) < 1 deg, we detected 602 discrete recombination line components from 448 lines of sight, 95% of the sample targets, which more than doubles the number of known H II regions in this part of the Milky Way. We found 25 new first quadrant nebulae with negative LSR velocities, placing them beyond the Solar orbit. Because we can detect all nebulae inside the Solar orbit that are ionized by O-stars, the Discovery Survey targets, when combined with existing H II region catalogs, give a more accurate census of Galactic H II regions and their properties. The distri...

  12. pyridine Zn(II) and Cu(II) Complexes

    African Journals Online (AJOL)

    NICO

    2014-09-03

    Sep 3, 2014 ... The kinetics, mechanism and polymer microstructure studies of ring-opening polymerization (ROP) of lactides (LA) by Zn(II) and Cu(II) ... transparency, ease of processing and ease of microbial decompo- sition or degradation.

  13. Rheumatoid Rescue of Misfolded Cellular Proteins by MHC Class II Molecules: A New Hypothesis for Autoimmune Diseases.

    Science.gov (United States)

    Arase, Hisashi

    2016-01-01

    Misfolded proteins localized in the endoplasmic reticulum are degraded promptly and thus are not transported outside cells. However, misfolded proteins in the endoplasmic reticulum are rescued from protein degradation upon association with major histocompatibility complex (MHC) class II molecules and are transported to the cell surface by MHC class II molecules without being processed to peptides. Studies on the misfolded proteins rescued by MHC class II molecules have revealed that misfolded proteins associated with MHC class II molecules are specific targets for autoantibodies produced in autoimmune diseases. Furthermore, a strong correlation has been observed between autoantibody binding to misfolded proteins associated with MHC class II molecules and the autoimmune disease susceptibility conferred by each MHC class II allele. These new insights into MHC class II molecules suggest that misfolded proteins rescued from protein degradation by MHC class II molecules are recognized as "neo-self" antigens by immune system and are involved in autoimmune diseases as autoantibody targets.

  14. 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

  15. ASDIR-II. Volume II. Program Description

    Science.gov (United States)

    1975-01-01

    34- - , *f,7J ,, .I .I).’ t•I r ojo o o I D - ý flo 1 1nt o - IV0C Kൈ.,4M %n -tI.,n aV 16ncc~’’ 4 1’ 1 ,m In %nOIN~CIN, t~tt & In, .)mrif4 ftj’.3N4).iiM...In 4.4 teat W 4.V . mI N )41 CD W4.4 ’( mal . I". CV ’. - C- .4 kq *W k, W i . C~ C L &j C11 t.4 t-JC IV . th- LZ %Pe W il IN . I’M VI. i l ~l I ) S P...4 -9 3 1a -4 - w-eq 4 - 4 - a. in 1`, mal 4.) 7, ;-riMrim- tfn ~n(l4 Sc~mn r I Al A’ X -’ t ;V N X XDl ;0I -M ’.C xci)At.x;7 ; u ,A )XU ,X;uxvA i a

  16. Price-level Targeting versus Inflation Targeting: A Free Lunch?

    OpenAIRE

    Svensson, Lars E O

    1996-01-01

    Price-level targeting (without base drift) and inflation targeting (with base drift) are compared under commitment and discretion, with persistence in unemployment. Price-level targeting is often said to imply more short-run inflation variability and thereby more employment variability than inflation targeting. Counter to this conventional wisdom, under discretion a price-level target results in lower inflation variability than an inflation target (if unemployment is at least moderately persi...

  17. 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.

  18. Perspectives on Magnetized Target Fusion Power Plants

    Science.gov (United States)

    Miller, R. L.

    2007-06-01

    One approach to Magnetized Target Fusion (MTF) builds upon the ongoing experimental effort (FRX-L) to generate a Field Reversed Configuration (FRC) target plasma suitable for translation and cylindrical-liner (i.e., converging flux conserver) implosion. Numerical modeling is underway to elucidate key performance drivers for possible future power-plant extrapolations. The fusion gain, Q (ratio of DT fusion yield to the sum of initial liner kinetic energy plus plasma formation energy), sets the power-plant duty cycle for a nominal design electric power [ e.g. 1,000 MWe(net)]. A pulsed MTF power plant of this type derives from the historic Fast Liner Reactor (FLR) concept and shares attributes with the recent Inertial Fusion Energy (IFE) Z-pinch and laser-driven pellet HYLIFE-II conceptual designs.

  19. Cooled particle accelerator target

    Science.gov (United States)

    Degtiarenko, Pavel V.

    2005-06-14

    A novel particle beam target comprising: a rotating target disc mounted on a retainer and thermally coupled to a first array of spaced-apart parallel plate fins that extend radially inwardly from the retainer and mesh without physical contact with a second array of spaced-apart parallel plate fins that extend radially outwardly from and are thermally coupled to a cooling mechanism capable of removing heat from said second array of spaced-apart fins and located within the first array of spaced-apart parallel fins. Radiant thermal exchange between the two arrays of parallel plate fins provides removal of heat from the rotating disc. A method of cooling the rotating target is also described.

  20. Modelling Recycling Targets

    DEFF Research Database (Denmark)

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

    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...

  1. 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.

  2. Setting reference targets

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. 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.

  4. Removal of Pb(II) and Cd(II) ions from aqueous solution by thiosemicarbazide modified chitosan.

    Science.gov (United States)

    Li, Manlin; Zhang, Zengqiang; Li, Ronghua; Wang, Jim J; Ali, Amjad

    2016-05-01

    The removal of Pb(II) and Cd(II) ions from aqueous solution by thiosemicarbazide modified chitosan (TCS) was studied in this article. The synthesized TCS was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), element analysis, N2 adsorption-desorption, scanning electron microscopy (SEM) and X-ray photoelectron spectrophotometer (XPS). Moreover, the influence of solution pH, contact time, initial heavy metal concentration, and solution temperature on the adsorption process was examined, and the adsorbent reusability and adsorption mechanisms were also studied. The results showed that TCS adsorbed greater amount of Pb(II) and Cd(II) ions than the raw chitosan. The adsorption amounts of Pb(II) and Cd(II) ions were affected by increasing solution pH and temperature. The maximum adsorption capacities of the TCS for Pb(II) and Cd(II) ions were found to be 325.2 and 257.2 mg/g, respectively. The endothermic adsorption fitted the pseudo-second-order kinetics equation and the adsorption isotherms could be well described by Langmuir model. The metal ions adsorption mechanism was concluded to be mainly dominated by complexation reaction process. The desorption study indicated that the target adsorbent was easy to be regenerated.

  5. AA antiproton production target

    CERN Multimedia

    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.

  6. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available , Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study Methodology Results Optimal Exploration Target Zones Pravesh Debba1, Emmanual M.J. Carranza2, Alfred Stein2, Freek D. van der Meer2 1CSIR, Logistics... and Quantitative Methods, CSIR Built Environment 2International Institute for Geo-Information Science and Earth Observation (ITC), Hengelosestraat 99, P.O. Box 6, 7500AA Enschede, The Netherlands Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer...

  7. RADTRAN II user guide

    Energy Technology Data Exchange (ETDEWEB)

    Madsen, M M; Wilmot, E L; Taylor, J M

    1983-02-01

    RADTRAN II is a flexible analytical tool for calculating both the incident-free and accident impacts of transporting radioactive materials. The consequences from incident-free shipments are apportioned among eight population subgroups and can be calculated for several transport modes. The radiological accident risk (probability times consequence summed over all postulated accidents) is calculated in terms of early fatalities, early morbidities, latent cancer fatalities, genetic effects, and economic impacts. Groundshine, inhalation, direct exposure, resuspension, and cloudshine dose pathways are modeled to calculate the radiological health risks from accidents. Economic impacts are evaluated based on costs for emergency response, cleanup, evacuation, income loss, and land use. RADTRAN II can be applied to specific scenario evaluations (individual transport modes or specified combinations), to compare alternative modes or to evaluate generic radioactive material shipments. Unit-risk factors can easily be evaluated to aid in performing generic analyses when several options must be compared with the amount of travel as the only variable.

  8. Multiple endocrine neoplasia (MEN) II

    Science.gov (United States)

    Sipple syndrome; MEN II; Pheochromocytoma - MEN II; Thyroid cancer - pheochromocytoma; Parathyroid cancer - pheochromocytoma ... is most often with a tumor called a pheochromocytoma . Involvement of the thyroid gland is most often ...

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Angiotensin II during experimentally simulated central hypovolemia

    Directory of Open Access Journals (Sweden)

    Theo Walther Jensen

    2016-03-01

    Full Text Available Abstract:Central hypovolemia, defined as diminished blood volume in the heart and pulmonary vascular bed, is still an unresolved problem from a therapeutic point of view. The development of pharmaceutical agents targeted at specific angiotensin II receptors, like the non-peptidergic AT2-receptor agonist compound 21, is yielding many opportunities to uncover more knowledge about angiotensin II receptor profiles and possible therapeutic use. Cardiovascular, anti-inflammatory and neuroprotective therapeutic use of compound 21 have been suggested. However, there has not yet been a focus on the use of these agents in a hypovolemic setting. We argue that the latest debates on the effect of angiotensin II during hypovolemia might guide for future studies investigating the effect of such agents during experimentally simulated central hypovolemia. The purpose of this review is to examine the role of angiotensin II during episodes of central hypovolemia.To examine this, we reviewed results from studies with three experimental models of simulated hypovolemia: head up tilt table test, lower body negative pressure, and hemorrhage of animals. A systemic literature search was made with the use of PubMed/MEDLINE for studies that measured variables of the renin-angiotensin system or its effect during simulated hypovolemia. 12 articles, using one of the three models, were included and showed a possible organ protective effect and an effect on the sympathetic system of angiotensin II during hypovolemia. The results support the possible organ protective vasodilatory role for the AT2-receptor during hypovolemia on both the kidney and the splanchnic tissue.

  14. 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.

  15. 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.

  16. Cervantes y Felipe II

    Directory of Open Access Journals (Sweden)

    Ludovik Osterc

    1999-12-01

    Full Text Available Como es sabido, el 13 de septiembre de 1598, a las cinco de la mañana, falleció en el Escorial el Rey Felipe II. Sevilla que según sus historiadores siempre se distinguió entre todas las ciudades de España por el fausto y suntuosidad de los sucesos solemnes, ya sea cuando los monarcas se dignaban visitarla, ya sea cuando se trataba de honrar su memoria con ocasión de su muerte, se habia excedido a si misma en el reinado de Felipe II. La pública y señorial entrada de su padre, el emperador Carlos V cuando en 1526 vino a esta ciudad para realizar sus bodas con la Infanta Isabel de Portugal, que por su magnificencia consignan sus anales, como superior a cuantas hubo antes en análogas circunstancias, no puede compararse con el recibimiento dispensado a Felipe II, el año de 1570, que por encargo de su Cabildo describió la docta pluma de Mal Lara.

  17. 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...

  18. Active Target Simulation

    Science.gov (United States)

    Smith, Nathan; Draznik, Peter; Frank, Nathan

    2012-10-01

    We have simulated an existing experimental design to determine the resolution improvement upon energy measurements of neutron unbound nuclei. A number of experiments of this type have been performed at the National Superconducting Cyclotron Laboratory (NSCL), located at Michigan State University. An excited nucleus is typically produced with a radioactive beam interacting with a passive Beryllium target. Many different nuclei are produced in experiment, each of which immediately decays into a charged particle and neutron. The charged particles are detected and the neutrons interact in scintillation detectors such as the Modular Neutron Array (MoNA) and Large Multi-Institutional Scintillation Array (LISA). In our simulation, we have constructed an active target that provides additional information such that the point of nuclear interaction within the target may be determined. This information improves the resolution in decay energy measurements of neutron unbound isotopes. This presentation will cover some aspects of the simulation process, as well as showing some of the results that demonstrate the simulated improvement over a passive target.

  19. Target chambers for gammashpere

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, M.P.; Falout, J.W.; Nardi, B.G. [and others

    1995-08-01

    One of our responsibilities for Gammasphere, was designing and constructing two target chambers and associated beamlines to be used with the spectrometer. The first chamber was used with the early implementation phase of Gammasphere, and consisted of two spun-Al hemispheres welded together giving a wall thickness of 0.063 inches and a diameter of 12 inches.

  20. Microenvironmental targets in sarcoma

    Directory of Open Access Journals (Sweden)

    Monika eEhnman

    2015-11-01

    Full Text Available Sarcomas are rare malignant tumors affecting all age groups. They are typically classified according to their resemblance to corresponding normal tissue. Their heterogeneous features, for example in terms of disease-driving genetic aberrations and body location, complicate both disease classification and development of novel treatment regimens. Many years of failure of improved patient outcome in clinical trials has lead to the conclusion that novel targeted therapies are likely needed in combination with current multimodality regimens. Sarcomas have not, in contrast to the common carcinomas, been the subject for larger systematic studies on how tumor behavior relates to characteristics of the tumor microenvironment. There is consequently an urgent need for identifying suitable molecular targets, not only in tumor cells, but also in the tumor microenvironment. This review discusses preclinical and clinical data about potential molecular targets in sarcomas. Studies on targeted therapies involving the tumor microenvironment are prioritized. A greater understanding of the biological context is expected to facilitate more successful design of future clinical trials in sarcoma.

  1. Major Targets for 2010

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ This year, the main targets we have set for economic and social development are: increasing GDP by approximately 8 percent, creating jobs for more than 9 million people, keeping the urban registered unemployment rate no higher than 4.6 percent, holding the rise in consumer prices to around 3 percent, and improving the balance of payments.

  2. Cancer immunotherapy targeting neoantigens.

    Science.gov (United States)

    Lu, Yong-Chen; Robbins, Paul F

    2016-02-01

    Neoantigens are antigens encoded by tumor-specific mutated genes. Studies in the past few years have suggested a key role for neoantigens in cancer immunotherapy. Here we review the discoveries of neoantigens in the past two decades and the current advances in neoantigen identification. We also discuss the potential benefits and obstacles to the development of effective cancer immunotherapies targeting neoantigens.

  3. 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.

  4. The functional performance of the Argus II retinal prosthesis.

    Science.gov (United States)

    Stronks, H Christiaan; Dagnelie, Gislin

    2014-01-01

    Visual prostheses are devices to treat profound vision loss by stimulating nerve cells anywhere along the visual pathway, typically with electrical pulses. The Argus II implant, developed by Second Sight Medical Products (SSMP, Sylmar, CA, USA), targets the retina and features 60 electrodes that electrically stimulate the surviving retinal neurons. Of the approximately 20 research groups that are actively developing visual prostheses, SSMP has the longest track record. The Argus II was the first visual prosthesis to become commercially available: it received the European conformity mark in 2011 and FDA approval was granted in early 2013 for humanitarian use in the USA. Meanwhile, the Argus II safety/benefit study has been extended for research purposes, and is still ongoing. In this review, we will discuss the performance of the Argus II in restoring sight to the blind, and we will shed light on its expected developments in the coming years.

  5. Group II intron-anchored gene deletion in Clostridium.

    Directory of Open Access Journals (Sweden)

    Kaizhi Jia

    Full Text Available Clostridium plays an important role in commercial and medical use, for which targeted gene deletion is difficult. We proposed an intron-anchored gene deletion approach for Clostridium, which combines the advantage of the group II intron "ClosTron" system and homologous recombination. In this approach, an intron carrying a fragment homologous to upstream or downstream of the target site was first inserted into the genome by retrotransposition, followed by homologous recombination, resulting in gene deletion. A functional unknown operon CAC1493-1494 located in the chromosome, and an operon ctfAB located in the megaplasmid of C. acetobutylicum DSM1731 were successfully deleted by using this approach, without leaving antibiotic marker in the genome. We therefore propose this approach can be used for targeted gene deletion in Clostridium. This approach might also be applicable for gene deletion in other bacterial species if group II intron retrotransposition system is established.

  6. 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

  7. A comparative study on Pb(II), Cd(II), Cu(II)

    African Journals Online (AJOL)

    user

    Co(II) while it decreased in the presence of Cu(II) in the studied range of concentration variation. Maximum Pb(II) .... size variation in the range of 2 to 10 nm. ...... Zinc-bromine Battery, Lead-acid and Lithium Batteries, Arsenic Remediation from.

  8. STABILITY OF BINARY COMPLEXES OF Pb(II), Cd(II) AND Hg(II ...

    African Journals Online (AJOL)

    Preferred Customer

    ABSTRACT. Binary complexes of maleic acid with toxic metal ions such as Pb(II), Cd(II) and Hg(II) have been ... By binding the metal ions electrostatically to the negatively charged ..... results in highly stable seven membered rings (Figure 3).

  9. Ets-1 upregulation mediates angiotensin II-related cardiac fibrosis.

    Science.gov (United States)

    Hao, Guanghua; Han, Zhenhua; Meng, Zhe; Wei, Jin; Gao, Dengfeng; Zhang, Hong; Wang, Nanping

    2015-01-01

    Ets-1, the prototypical member of the family of Ets transcription factors, has been shown to participate in tissue fibrotic remodeling. However, its role in cardiac fibrosis has not been established. The aim of this study was to investigate the role of Ets-1 in profibrotic actions of angiotensin II (Ang II) in cardiac fibroblasts (CFs) and in the in vivo heart. In growth-arrested CFs, Ang II induced Ets-1 expression in a time- and concentration-dependent manner. Pretreatment with Ang II type 1 receptor blocker losartan, protein kinase C inhibitor bisindolylmaleimide I, extracellular signal-regulated kinase (ERK) inhibitor PD98059, or c-Jun NH(2)-terminal kinase (JNK) inhibitor SP600125 partly inhibited this induction accompanied with impaired cell proliferation and production of plasminogen activator inhibitor-1 (PAI-1) and connective tissue growth factor (CTGF) protein, the two downstream targets of Ets-1. Knockdown of Ets-1 by siRNA significantly inhibited the inductive effects of Ang II on cell proliferation and expression of CTGF and PAI-1. Moreover, the levels of Ets-1, PAI-1 and CTGF protein were simultaneously upregulated in left ventricle of Ang II-infused rats in parallel with an increase in the activation of ERK and JNK. Our data suggest that Ets-1 may mediate Ang II-induced cardiac fibrotic effects.

  10. HTLV-1 p30II: selective repressor of gene expression

    Directory of Open Access Journals (Sweden)

    Green Patrick L

    2004-11-01

    Full Text Available Abstract Human T-lymphotropic virus type-1 (HTLV-1 is a complex retrovirus that causes adult T-cell leukemia/lymphoma (ATL and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 pX ORF II encodes two proteins, p13II and p30II whose roles are beginning to be defined in the virus life cycle. Previous studies indicate the importance of these viral proteins in the ability of the virus to maintain viral loads and persist in an animal model of HTLV-1 infection. Intriguing new studies indicate that p30II is a multifunctional regulator that differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein (CBP/p300 and specifically binds and represses tax/rex mRNA nuclear export. A new study characterized the role of p30II in regulation of cellular gene expression using comprehensive human gene arrays. Interestingly, p30II is an overall repressor of cellular gene expression, while selectively favoring the expression of regulatory gene pathways important to T lymphocytes. These new findings suggest that HTLV-1, which is associated with lymphoproliferative diseases, uses p30II to selectively repress cellular and viral gene expression to favor the survival of cellular targets ultimately resulting in leukemogenesis.

  11. Polarization discrimination between repeater false-target and radar target

    Institute of Scientific and Technical Information of China (English)

    SHI LongFei; WANG XueSong; XIAO ShunPing

    2009-01-01

    High fidelity repeater false-target badly affects a radar system's detecting, tracking, and data processing. It is an available approach of confronting false-target for radar that discriminates firstly and then eliminates. Whereas for the technique progress about the repeater false-target jam, it is more and more difficult to discriminate this jam in the time-domain, frequency-domain, or space-domain. The technique using polarization information to discriminate the target and false-target is discussed in this paper. With the difference that false-target signal vector's polarization ratio is fixed and target echo signal vector's polarization ratio is variational along with radar transmission signal's polarization, we transform the discrimination problem to beeline distinguish problem in the 2-dim complex space. The distributing characteristic expression of the false-target discrimination statistic is constructed, with which the discrimination ratio of false-target is analyzed. For the target case, the decomposed model of target scattering matrix and the concept of distinguish quantity are proposed. Then, the discrimination ratio of target can be forecasted according to target distinguish quantity. Thus, the performance of discrimination method has been analyzed integrally. The simulation results demonstrate the method in this paper is effective on the discrimination of target and false-target.

  12. Gene Targeting in Neuroendocrinology.

    Science.gov (United States)

    Candlish, Michael; De Angelis, Roberto; Götz, Viktoria; Boehm, Ulrich

    2015-09-20

    Research in neuroendocrinology faces particular challenges due to the complex interactions between cells in the hypothalamus, in the pituitary gland and in peripheral tissues. Within the hypothalamus alone, attempting to target a specific neuronal cell type can be problematic due to the heterogeneous nature and level of cellular diversity of hypothalamic nuclei. Because of the inherent complexity of the reproductive axis, the use of animal models and in vivo experiments are often a prerequisite in reproductive neuroendocrinology. The advent of targeted genetic modifications, particularly in mice, has opened new avenues of neuroendocrine research. Within this review, we evaluate various mouse models used in reproductive neuroendocrinology and discuss the different approaches to generate genetically modified mice, along with their inherent advantages and disadvantages. We also discuss a variety of versatile genetic tools with a focus on their potential use in reproductive neuroendocrinology.

  13. Foucault on targets.

    Science.gov (United States)

    Lynch, John

    2004-01-01

    This paper seeks to gain an insight into the behavior of a large NHS trust, in its attempt to meet a 90 percent patient access target, in a week long national audit in March 2003. Why did individuals act in dramatically different ways to their norm over this period. The work of Michel Foucault is used to explore these issues. The discourses of power, knowledge, discipline and governmentality are identified as key foucaudian themes that offer an alternative interpretation of how individuals behave in their place of work. The importance of the historical context of discourse within the NHS cannot be underestimated in shaping the behavior of individuals and groups today. Power and knowledge permeate NHS organizations through disciplinary practices and dressage. Governmentality seeks to maintain the status quo through disciplinary processes such as national healthcare targets. The natural response of NHS organizations is therefore, to seek order and conformity rather than disorder and conflict.

  14. Recognizing occluded MSTAR targets

    Science.gov (United States)

    Bhanu, Bir; Jones, Grinnell, III

    2000-08-01

    This paper presents an approach for recognizing occluded vehicle targets in Synthetic Aperture Radar (SAR) images. Using quasi-invariant local features, SAR scattering center locations and magnitudes, a recognition algorithm is presented that successfully recognizes highly occluded versions of actual vehicles from the MSTAR public data. Extensive experimental results are presented to show the effect of occlusion on recognition performance in terms of Probability of Correct Identification, Receiver Operating Characteristic (ROC) curves and confusion matrices. The effect of occlusion on performance of this recognition algorithm is accurately predicted. Combined effects such as occlusion and measured positional noise, as well as occlusion and other observed extended operating conditions (e.g., articulation) are also addressed. Although excellent forced recognition results can be achieved at very high (70%) occlusion, practical limitations are found due to the similarity of unoccluded confuser vehicles to highly occluded targets.

  15. Targeting biodefense markets.

    Science.gov (United States)

    Olinger, Gene Garrard

    2009-10-01

    The "World Vaccine Congress 2009" held in Washington D.C. (April 20-23, 2009) sponsored several sessions focused on the vaccine market targeting biodefense. On day one of the congress, a panel discussion outlined the federal progress in medical countermeasure preparedness that included emerging infections, influenza, and biodefense focuses. The second day, a session focused on the biodefense vaccine market with both government and industry members discussing the opportunities and challenges associated with the budding market.

  16. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available Debba, Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study Methodology Results Optimal Exploration Target Zones Pravesh Debba1, Emmanual M.J. Carranza2, Alfred Stein2, Freek D. van der Meer2 1... Debba, Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study Methodology Results Outline 1 Introduction to Remote Sensing 2 Background and Objective of the study 3 Methodology 4 Results Optimal...

  17. Targeting the bone marrow: applications in stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Orchard, K. [Southampton University Hospital Trust, Southampton (United Kingdom). Department of Haematology; Cooper, M. [St. Bartholomew' s Hospital, London (United Kingdom). Pharmacy Department

    2004-12-01

    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.

  18. 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

  19. 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

  20. 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!

  1. 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

  2. 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.

  3. Dibromidotris(dimethylaminemagnesium(II

    Directory of Open Access Journals (Sweden)

    Michael Bolte

    2009-08-01

    Full Text Available The Mg centre in the title compound, [MgBr2(C2H7N3], is pentacoordinated in a trigonal-bipyramidal mode with the two Br atoms in axial positions and the N atoms of the dimethylamine ligands in equatorial positions. The MgII centre is located on a crystallographic twofold rotation axis. The crystal structure is stabilized by N—H...Br hydrogen bonds. The N atom and H atoms of one dimethylamine ligand are disordered over two equally occupied positions.

  4. 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

  5. PIVKA-II

    Institute of Scientific and Technical Information of China (English)

    建石良介

    2005-01-01

    @@ PIVKA-II是通过维生素K缺乏或拮抗剂II诱导的蛋白质 (protein induced by vitamine K absence or antagonist-II),又称为右旋-γ-羧基-凝血酶原(des-γ-carboxy prothrombin),它是肝脏合成的无凝血活性的异常凝血酶原.自从Liebman等(1984年)报道以来,PIVKA-II作为肝细胞癌的特异性肿瘤标志物,是临床上不可缺少的检查.

  6. Complex variables II essentials

    CERN Document Server

    Solomon, Alan D

    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. Complex Variables II includes elementary mappings and Mobius transformation, mappings by general functions, conformal mappings and harmonic functions, applying complex functions to a

  7. Skin and bones. II.

    Science.gov (United States)

    Orlow, S J; Watsky, K L; Bolognia, J L

    1991-09-01

    Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. The first part of this review, published in the August 1991 issue of this JOURNAL, dealt with the first two categories; part II discusses categories 3 through 8.

  8. Amorphous iron (II) carbonate

    DEFF Research Database (Denmark)

    Sel, Ozlem; Radha, A.V.; Dideriksen, Knud;

    2012-01-01

    exothermic than that of amorphous calcium carbonate (ACC). This suggests that enthalpy of crystallization in carbonate systems is ionic-size controlled, which may have significant implications in a wide variety of conditions, including geological sequestration of anthropogenic carbon dioxide.......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...

  9. Diaquabis(benzyloxyacetatocopper(II

    Directory of Open Access Journals (Sweden)

    Xiao-Min Hao

    2008-05-01

    Full Text Available In the title mononuclear complex, [Cu(C9H9O32(H2O2], the CuII ion, located on an inversion center, is hexacoordinated by four O atoms from two benzyloxyacetate ligands [Cu—O = 1.9420 (14 and 2.2922 (14 Å] and two water molecules [Cu—O = 2.0157 (15 Å] in a distorted octahedral geometry. In the crystal structure, intermolecular O—H...O hydrogen bonds link the molecules into layers parallel to the bc plane.

  10. 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

  11. 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

  12. 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

  13. 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

  14. Follicular penetration and targeting.

    Science.gov (United States)

    Lademann, Jürgen; Otberg, Nina; Jacobi, Ute; Hoffman, Robert M; Blume-Peytavi, Ulrike

    2005-12-01

    In the past, intercellular penetration was assumed to be the most important penetration pathway of topically applied substances. First hints that follicular penetration needs to be taken into consideration were confirmed by recent investigations, presented during the workshop "Follicular Penetration and Targeting" at the 4th Intercontinental Meeting of Hair Research Societies", in Berlin 2004. Hair follicles represent an efficient reservoir for the penetration of topically applied substances with subsequent targeting of distinct cell populations, e.g., nestin-expressing follicular bulge cells. The volume of this reservoir can be determined by differential stripping technology. The follicular penetration processes are significantly influenced by the state of the follicular infundibulum; recent experimental investigations could demonstrate that it is essential to distinguish between open and closed hair follicles. Topically applied substances can only penetrate into open hair follicle. Knowledge of follicular penetration is of high clinical relevance for functional targeting of distinct follicular regions. Human hair follicles show a hair-cycle-dependent variation of the dense neuronal and vascular network. Moreover, during hair follicle cycling with initiation of anagen, newly formed vessels occur. Thus, the potential of nestin-expressing hair follicle stem cells to form neurons and blood vessels was investigated.

  15. 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.

  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. The Belle II Detector

    Science.gov (United States)

    Piilonen, Leo; Belle Collaboration, II

    2017-01-01

    The Belle II detector is now under construction at the KEK laboratory in Japan. This project represents a substantial upgrade of the Belle detector (and the KEKB accelerator). The Belle II experiment will record 50 ab-1 of data, a factor of 50 more than that recorded by Belle. This large data set, combined with the low backgrounds and high trigger efficiencies characteristic of an e+e- experiment, should provide unprecedented sensitivity to new physics signatures in B and D meson decays, and in τ lepton decays. The detector comprises many forefront subsystems. The vertex detector consists of two inner layers of silicon DEPFET pixels and four outer layers of double-sided silicon strips. These layers surround a beryllium beam pipe having a radius of only 10 mm. Outside of the vertex detector is a large-radius, small-cell drift chamber, an ``imaging time-of-propagation'' detector based on Cerenkov radiation for particle identification, and scintillating fibers and resistive plate chambers used to identify muons. The detector will begin commissioning in 2017.

  18. Volume II: Compendium Abstracts

    Science.gov (United States)

    2008-08-01

    canards, and by measuring the reflected laser light’s location, one can use trigonometry to find the angle that the canard is at and calibrate it... obstacles to process integration are discussed. The author wishes to acknowledge the mentorship of Eugene Zakar. 32 A Projectile/Target Interaction...survivability, and sustainability. Using laser detection and ranging (LADAR) for robot navigation and obstacle avoidance is an active area of

  19. Evaluation of the computerized procedures Manual II (COPMA II)

    Energy Technology Data Exchange (ETDEWEB)

    Converse, S.A. [North Carolina State Univ., Raleigh, NC (United States)

    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.

  20. 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

  1. Spatiotopic buildup of saccade target representation depends on target size.

    Science.gov (United States)

    Zimmermann, Eckart

    2016-12-01

    How we maintain spatial stability across saccade eye movements is an open question in visual neuroscience. A phenomenon that has received much attention in the field is our seemingly poor ability to discriminate the direction of transsaccadic target displacements. We have recently shown that discrimination performance increases the longer the saccade target has been previewed before saccade execution (Zimmermann, Morrone, & Burr, 2013). We have argued that the spatial representation of briefly presented stimuli is weak but that a strong representation is needed for transsaccadic, i.e., spatiotopic localization. Another factor that modulates the representation of saccade targets is stimulus size. The representation of spatially extended targets is more noisy than that of point-like targets. Here, I show that the increase in transsaccadic displacement discrimination as a function of saccade target preview duration depends on target size. This effect was found for spatially extended targets-thus replicating the results of Zimmermann et al. (2013)-but not for point-like targets. An analysis of saccade parameters revealed that the constant error for reaching the saccade target was bigger for spatially extended than for point-like targets, consistent with weaker representation of bigger targets. These results show that transsaccadic displacement discrimination becomes accurate when saccade targets are spatially extended and presented longer, thus resembling closer stimuli in real-world environments.

  2. Particle Simulations of DARHT-II Transport System

    Energy Technology Data Exchange (ETDEWEB)

    Poole, B; Chen, Y J

    2001-06-11

    The DARHT-II beam line utilizes a fast stripline kicker to temporally chop a high current electron beam from a single induction LINAC and deliver multiple temporal electron beam pulses to an x-ray converter target. High beam quality needs to be maintained throughout the transport line from the end of the accelerator through the final focus lens to the x-ray converter target to produce a high quality radiographic image. Issues that will affect beam quality such as spot size and emittance at the converter target include dynamic effects associated with the stripline kicker as well as emittance growth due to the nonlinear forces associated with the kicker and various focusing elements in the transport line. In addition, dynamic effects associated with transverse resistive wall instability as well as gas focusing will affect the beam transport. A particle-in-cell code is utilized to evaluate beam transport in the downstream transport line in DARHT-II. External focusing forces are included utilizing either analytic expressions or field maps. Models for wakefields from the beam kicker, transverse resistive wall instability, and gas focusing are included in the simulation to provide a more complete picture of beam transport in DARHT-II. From these simulations, for various initial beam loads based on expected accelerator performance the temporally integrated target spot size and emittance can be estimated.

  3. Particle Simulations of DARHT-II Transport System

    Energy Technology Data Exchange (ETDEWEB)

    Poole, B; Chen, Y J

    2001-06-11

    The DARHT-II beam line utilizes a fast stripline kicker to temporally chop a high current electron beam from a single induction LINAC and deliver multiple temporal electron beam pulses to an x-ray converter target. High beam quality needs to be maintained throughout the transport line from the end of the accelerator through the final focus lens to the x-ray converter target to produce a high quality radiographic image. Issues that will affect beam quality such as spot size and emittance at the converter target include dynamic effects associated with the stripline kicker as well as emittance growth due to the nonlinear forces associated with the kicker and various focusing elements in the transport line. In addition, dynamic effects associated with transverse resistive wall instability as well as gas focusing will affect the beam transport. A particle-in-cell code is utilized to evaluate beam transport in the downstream transport line in DARHT-II. External focusing forces are included utilizing either analytic expressions or field maps. Models for wakefields from the beam kicker, transverse resistive wall instability, and gas focusing are included in the simulation to provide a more complete picture of beam transport in DARHT-II. From these simulations, for various initial beam loads based on expected accelerator performance the temporally integrated target spot size and emittance can be estimated.

  4. A comparison of three different target-controlled remifentanil infusion rates during target-controlled propofol infusion for oocyte retrieval

    Directory of Open Access Journals (Sweden)

    Demet Coskun

    2011-01-01

    Full Text Available OBJECTIVE: To evaluate the effects of three different target-controlled remifentanil infusion rates during target-controlled propofol infusion on hemodynamic parameters, pain, sedation, and recovery score during oocyte retrieval. METHODS: Sixty-nine women were scheduled for oocyte retrieval. Target-controlled propofol infusion at an effectsite concentration of 1.5 μg/mL was instituted. The patients were randomly allocated to receive remifentanil at an effect-site concentration of either 1.5 (group I, n = 23, 2 (group II, n = 23 or 2.5 ng/mL (group III, n = 23. Hemodynamic variables, sedation, pain, the Aldrete recovery score, and side effects were recorded. RESULTS: Hemodynamic variables, sedation and pain scores and the number of patients with the maximum Aldrete recovery score 10 min after the procedure were comparable among the groups. The number of patients in group III with the maximum Aldrete recovery score 5 min after the procedure was significantly lower than that in groups I and II. One patient in group II and one patient in group III suffered from nausea. CONCLUSION: Similar pain-free conscious sedation conditions without significant changes in hemodynamic parameters were provided by all three protocols. However, target controlled infusion of remifentanil at 1.5 or 2 ng/mL proved superior at providing early recovery compared to 2.5 ng/mL.

  5. A comparison of three different target-controlled remifentanil infusion rates during target-controlled propofol infusion for oocyte retrieval.

    Science.gov (United States)

    Coskun, Demet; Gunaydin, Berrin; Tas, Ayca; Inan, Gozde; Celebi, Hulya; Kaya, Kadir

    2011-01-01

    To evaluate the effects of three different target-controlled remifentanil infusion rates during target-controlled propofol infusion on hemodynamic parameters, pain, sedation, and recovery score during oocyte retrieval. Sixty-nine women were scheduled for oocyte retrieval. Target-controlled propofol infusion at an effect-site concentration of 1.5 μg/mL was instituted. The patients were randomly allocated to receive remifentanil at an effect-site concentration of either 1.5 (group I, n = 23), 2 (group II, n = 23) or 2.5 ng/mL (group III, n = 23). Hemodynamic variables, sedation, pain, the Aldrete recovery score, and side effects were recorded. Hemodynamic variables, sedation and pain scores and the number of patients with the maximum Aldrete recovery score 10 min after the procedure were comparable among the groups. The number of patients in group III with the maximum Aldrete recovery score 5 min after the procedure was significantly lower than that in groups I and II. One patient in group II and one patient in group III suffered from nausea. Similar pain-free conscious sedation conditions without significant changes in hemodynamic parameters were provided by all three protocols. However, target controlled infusion of remifentanil at 1.5 or 2 ng/mL proved superior at providing early recovery compared to 2.5 ng/mL.

  6. Cartilage turnover reflected by metabolic processing of type II collagen

    DEFF Research Database (Denmark)

    Gudmann, Karoline Natasja Stæhr; Wang, Jianxia; Hoielt, Sabine

    2014-01-01

    ). This is expected to originate primarily from remodeling of hyaline cartilage. A mouse monoclonal antibody (Mab) was raised in mouse, targeting specifically PIIBNP (QDVRQPG) and used in development of the assay. The specificity, sensitivity, 4-parameter fit and stability of the assay were tested. Levels of PIIBNP......The aim of this study was to enable measurement of cartilage formation by a novel biomarker of type II collagen formation. The competitive enzyme-linked immunosorbent assay (ELISA) Pro-C2 was developed and characterized for assessment of the beta splice variant of type II procollagen (PIIBNP...

  7. Experimental analysis of the mechanism of chromatin remodeling by RNA polymerase II

    Science.gov (United States)

    Gaykalova, Daria A.; Kulaeva, Olga I.; Pestov, Nikolai A.; Hsieh, Fu-Kai; Studitsky, Vasily M.

    2014-01-01

    The vital process of transcription by RNA polymerase II (Pol II) occurs in chromatin environment in eukaryotic cells; in fact, moderately transcribed genes retain nucleosomal structure. Recent studies suggest that chromatin structure presents a strong barrier for transcribing Pol II in vitro, and that DNA-histone interactions are only partially and transiently disrupted during transcript elongation on moderately active genes. Furthermore, elongating Pol II complex is one of the major targets during gene regulation. Below we describe a highly purified, defined experimental system that recapitulates many important properties of transcribed chromatin in vitro and allows detailed analysis of the underlying mechanisms. PMID:22910212

  8. Open Targets: a platform for therapeutic target identification and validation

    Science.gov (United States)

    Koscielny, Gautier; An, Peter; Carvalho-Silva, Denise; Cham, Jennifer A.; Fumis, Luca; Gasparyan, Rippa; Hasan, Samiul; Karamanis, Nikiforos; Maguire, Michael; Papa, Eliseo; Pierleoni, Andrea; Pignatelli, Miguel; Platt, Theo; Rowland, Francis; Wankar, Priyanka; Bento, A. Patrícia; Burdett, Tony; Fabregat, Antonio; Forbes, Simon; Gaulton, Anna; Gonzalez, Cristina Yenyxe; Hermjakob, Henning; Hersey, Anne; Jupe, Steven; Kafkas, Şenay; Keays, Maria; Leroy, Catherine; Lopez, Francisco-Javier; Magarinos, Maria Paula; Malone, James; McEntyre, Johanna; Munoz-Pomer Fuentes, Alfonso; O'Donovan, Claire; Papatheodorou, Irene; Parkinson, Helen; Palka, Barbara; Paschall, Justin; Petryszak, Robert; Pratanwanich, Naruemon; Sarntivijal, Sirarat; Saunders, Gary; Sidiropoulos, Konstantinos; Smith, Thomas; Sondka, Zbyslaw; Stegle, Oliver; Tang, Y. Amy; Turner, Edward; Vaughan, Brendan; Vrousgou, Olga; Watkins, Xavier; Martin, Maria-Jesus; Sanseau, Philippe; Vamathevan, Jessica; Birney, Ewan; Barrett, Jeffrey; Dunham, Ian

    2017-01-01

    We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org. PMID:27899665

  9. Mod II Stirling engine overviews

    Science.gov (United States)

    Farrell, Roger A.

    1988-01-01

    The Mod II engine is a second-generation automotive Stirling engine (ASE) optimized for part-power operation. It has been designed specifically to meet the fuel economy and exhaust emissions objectives of the ASE development program. The design, test experience, performance, and comparison of data to analytical performance estimates of the Mod II engine to date are reviewed. Estimates of Mod II performance in its final configuration are also given.

  10. 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.

  11. Low intensity beam target unit

    CERN Multimedia

    1976-01-01

    This is a wheel fitted with many targets around its periphery (each with three longitudinally arranged thin rods) of which one is placed into the beam via a rotation of the wheel. Upstream of each target is placed a luminescent screen, aligbed on each target axis and viewed with a TV camera, to make sure that one is hitting the target. This target unit was probably used to study target's behaviour (like beam heating). Gualtiero Del Torre stands on the left, Pierre Gerdil on the right.

  12. Targeted therapy in melanoma.

    Science.gov (United States)

    Kudchadkar, Ragini R; Smalley, Keiran S M; Glass, L Frank; Trimble, James S; Sondak, Vernon K

    2013-01-01

    Since the discovery of activating mutations in the BRAF oncogene in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. We review the latest developments in our understanding of the role of BRAF/MEK/ERK pathway signaling in melanoma, and the development of inhibitors of this pathway. We also explore alternative mutations seen in melanoma, such as NRAS, KIT, GNAQ, and GNA11, and the drug development that is ongoing based on this biology. Strategies for the management of the vexing clinical problem of BRAF inhibitor resistance, primarily via combination therapy, are outlined. With the recent approval of the BRAF inhibitor vemurafenib for stage IV metastatic melanoma, use of this agent is expanding in the United States. Thus, management of the skin toxicities of this agent, such as squamous cell carcinomas, "acneiform" eruptions, hand-foot syndrome, and panniculitis, will be a growing problem facing dermatologists today. We discuss the toxicities of targeted agents in use for melanoma, in particular the dermatologic effects and the management of these skin toxicities.

  13. Target Housing Material Options

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-11

    With gas cooling, heat transfer coefficients are low compared to water. The benefit of gas from a heat transfer point of view is that there is really no upper temperature limit for the coolant, as compared to water, which is limited ultimately by the critical point, and in practice the critical heat flux. In our case with parallel flow channels, water is limited to even lower operating limits by nucleate boiling. So gas can get as hot as the containment material will allow, but to get the density and heat transfer up to something reasonable, we must also increase pressure, thus increasing stress on the containment, namely the front and back faces. We are designing to ASME BPVC, which, for most materials allows a maximum stress of UTS/3. So we want the highest possible UTS. For reference, the front face stress in the 12 mm target at 300 psi was about 90 MPa. The inconel 718 allowable stress at 900°C is 1/3 of 517 or 172 MPa. So we are in a very safe place, but the uTS is dropping rapidly with temperature above 900°C. As we increase target diameter, the challenge will be to keep the stress down. We are probably looking at keeping the allowable at or above the present value, and at as high a temperature as possible.

  14. Targeting adipose tissue

    Directory of Open Access Journals (Sweden)

    Haas Bodo

    2012-10-01

    Full Text Available Abstract Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT is generally known and stores excess energy in the form of triacylglycerol (TG, insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP. The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET, however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs, activators of peroxisome proliferator-activated receptor γ (PPARγ a ‘master’ regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity.

  15. 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.

  16. 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.

  17. 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.

  18. Topoisomerase II poisoning by indazole and imidazole complexes of ruthenium

    Indian Academy of Sciences (India)

    Y N Vashisht Gopal; Anand K Kondapi

    2001-06-01

    Trans-imidazolium (bis imidazole) tetrachloro ruthenate (RuIm) and trans-indazolium (bis indazole) tetrachloro ruthenate (RuInd) are ruthenium coordination complexes, which were first synthesized and exploited for their anticancer activity. These molecules constitute two of the few most effective anticancer ruthenium compounds. The clinical use of these compounds however was hindered due to toxic side effects on the human body. Our present study on topoisomerase II poisoning by these compounds shows that they effectively poison the activity of topoisomerase II by forming a ternary cleavage complex of DNA, drug and topoisomerase II. The thymidine incorporation assays show that the inhibition of cancer cell proliferation correlates with topoisomerase II poisoning. The present study on topoisomerase II poisoning by these two compounds opens a new avenue for renewing further research on these compounds. This is because they could be effective lead candidates for the development of more potent and less toxic ruthenium containing topoisomerase II poisons. Specificity of action on this molecular target may reduce the toxic effects of these ruthenium-containing molecules and thus improve their therapeutic index.

  19. 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...

  20. A Note on Inflation Targeting.

    Science.gov (United States)

    Lai, Ching-chong; Chang, Juin-jen

    2001-01-01

    Presents a pedagogical graphical exposition to illustrate the stabilizing effect of price target zones. Finds that authorities' commitment to defend a price target zone affects the public's inflation expectations and, in turn, reduces actual inflation. (RLH)

  1. Scaling of exploding pusher targets

    Energy Technology Data Exchange (ETDEWEB)

    Nuckolls, J.H.

    1977-08-22

    A theory of exploding pusher laser pusher targets is compared to results of LASNEX calculations and to Livermore experiments. A scaling relationship is described which predicts the optimum target/pulse combinations as a function of the laser power.

  2. 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.

  3. [Targeted therapies for melanoma].

    Science.gov (United States)

    Leiter, U; Meier, F; Garbe, C

    2014-07-01

    Since the discovery of activating mutations in the BRAF oncogene and also stimulation of immune mediated antitumor response in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. This article addresses the latest developments of BRAF/MEK/ERK pathway signaling. In addition, the development of drugs to attack alternative mutations in melanoma, such as NRAS and KIT is described. Strategies for the management of BRAF inhibitor resistance, such as with combination therapy, are outlined. Antitumor immune therapies with monoclonal antibodies such as ipilimumab which acts by promoting T-cell activation or antibody blockade of programmed death-1 (PD-1) led to a long term response in metastatic melanoma. Results of latest clinical studies including the toxicity profile are described. Due to selective kinase inhibitors and immune checkpoint blockade, the therapy of unresectable metastatic melanoma has greatly improved and long-term survival of patients with metastatic melanoma seems a real possibility.

  4. ORION laser target diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    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. [Plasma Physics Department, Atomic Weapons Establishment, Aldermaston, Reading, Berkshire RG7 4PR (United Kingdom); and others

    2012-10-15

    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.

  5. New Insight into the Molecular Drug Target of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Vivian Soetikno

    2014-01-01

    Full Text Available Diabetic nephropathy (DN lowered quality of life and shortened life expectancy amongst those affected. Evidence indicates interaction between advanced glycation end products (AGEs, activated protein kinase C (PKC and angiotensin II exacerbate the progression of DN. Inhibitors of angiotensin-converting enzyme (ACEIs, renin angiotensin aldosterone system (RAAS, AGEs, and PKC have been tested for slowing down the progression of DN. The exact molecular drug targets that lead to the amelioration of renal injury in DN are not well understood. This review summarizes the potential therapeutic targets, based on putative mechanism in the progression of the disease.

  6. From Toxins Targeting Ligand Gated Ion Channels to Therapeutic Molecules

    Directory of Open Access Journals (Sweden)

    Antoine Taly

    2011-03-01

    Full Text Available Ligand-gated ion channels (LGIC play a central role in inter-cellular communication. This key function has two consequences: (i these receptor channels are major targets for drug discovery because of their potential involvement in numerous human brain diseases; (ii they are often found to be the target of plant and animal toxins. Together this makes toxin/receptor interactions important to drug discovery projects. Therefore, toxins acting on LGIC are presented and their current/potential therapeutic uses highlighted.

  7. The Healthy Worker Survivor Effect: Target Parameters and Target Populations.

    Science.gov (United States)

    Brown, Daniel M; Picciotto, Sally; Costello, Sadie; Neophytou, Andreas M; Izano, Monika A; Ferguson, Jacqueline M; Eisen, Ellen A

    2017-07-15

    We offer an in-depth discussion of the time-varying confounding and selection bias mechanisms that give rise to the healthy worker survivor effect (HWSE). In this update of an earlier review, we distinguish between the mechanisms collectively known as the HWSE and the statistical bias that can result. This discussion highlights the importance of identifying both the target parameter and the target population for any research question in occupational epidemiology. Target parameters can correspond to hypothetical workplace interventions; we explore whether these target parameters' true values reflect the etiologic effect of an exposure on an outcome or the potential impact of enforcing an exposure limit in a more realistic setting. If a cohort includes workers hired before the start of follow-up, HWSE mechanisms can limit the transportability of the estimates to other target populations. We summarize recent publications that applied g-methods to control for the HWSE, focusing on their target parameters, target populations, and hypothetical interventions.

  8. Targeting of Antibodies using Aptamers

    OpenAIRE

    2003-01-01

    The chapter presents a methodology for the rapid selection of aptamers against antibody targets. It is a detailed account of the various methodological steps that describe the selection of aptamers, including PCR steps, buffers to be used, target immobilisation, partitioning and amplification of aptamers, clonning and sequencing, to results in high affinity and specificity ligands for the chosen target antibody.

  9. New molecular targets against cervical cancer

    Directory of Open Access Journals (Sweden)

    Duenas-Gonzalez A

    2014-12-01

    Full Text Available Alfonso Duenas-Gonzalez,1,2 Alberto Serrano-Olvera,3 Lucely Cetina,4 Jaime Coronel4 1Unit of Biomedical Research in Cancer, Instituto de Investigaciones Biomedicas UNAM/Instituto Nacional de Cancerologia, Mexico City, 2ISSEMyM Cancer Center, Toluca, 3Medical Oncology Service, ABC Medical Center, Mexico City, 4Division of Clinical Research, Instituto Nacional de Cancerologia, Mexico City, Mexico On behalf of the Tumor Study Group Abstract: Cervical cancer is the third most commonly diagnosed cancer worldwide and the fourth leading cause of cancer death in women. Major advances but still insufficient achievements in the treatment of locally advanced and high-risk early stage patients have occurred in the last decade with the incorporation of concurrent cisplatin with radiation and, lately, gemcitabine added to cisplatin chemoradiation. Despite a number of clinical studies incorporating molecular-targeted therapy as radiosensitizers being in progress, so far, only antiangiogenic therapy with bevacizumab added to cisplatin chemoradiation has demonstrated safety and shown encouraging results in a Phase II study. In advanced disease, cisplatin doublets do not have a great impact on the natural history of the disease with median survival rates not exceeding 13 months. The first Phase III study of bevacizumab, added to cisplatin or a non-cisplatin-containing doublet, showed significant increase in both overall survival and progression-free survival. Further studies are needed before bevacizumab plus chemotherapy can be considered the standard of care for advanced disease. Characterization of the mutational landscape of cervical cancer has already been initiated, indicating that, for now, few of these targetable alterations match with available agents. Progress in both the mutational landscape knowledge and developments of novel targeted therapies may result in more effective and individualized treatments for cervical cancer. The potential efficacy of

  10. Structure-based receptor MIMICS targeted against bacterial superantigen toxins

    Science.gov (United States)

    Gupta, Goutam; Hong-Geller, Elizabeth; Shiflett, Patrick R.; Lehnert, Nancy M.

    2009-08-18

    The invention provides therapeutic compositions useful in the treatment of bacterial superantigen mediated conditions, such as Toxic Shock Syndrome. The compositions comprise genetically engineered bifunctional polypeptides containing a specific T-cell receptor binding domain and a specific MHC class II receptor binding domain, each targeting non-overlapping epitopes on a superantigen molecule against which they are designed. The anti-superantigen "receptor mimetics" or "chimeras" are rationally designed to recreate the modality of superantigen binding directly to both the TCR and the MHC-II receptor, and are capable of acting as decoys for superantigen binding, effectively out-competing the host T-cell and MHC-II receptors, the natural host receptors.

  11. Novel roles for metallothionein-I + II (MT-I + II) in defense responses, neurogenesis, and tissue restoration after traumatic brain injury: insights from global gene expression profiling in wild-type and MT-I + II knockout mice

    DEFF Research Database (Denmark)

    Penkowa, Milena; Cáceres, Mario; Borup, Rehannah

    2006-01-01

    . A genomic approach, such as the use of microarrays, provides much insight in this regard, especially if combined with the use of gene-targeted animals. We report here the results of one of these studies comparing wild-type and metallothionein-I + II knockout mice subjected to a cryolesion...... times consistent with the processes involved in the initial tissue injury and later regeneration of the parenchyma, as well as a prominent effect of MT-I + II deficiency. The results thoroughly confirmed the importance of the antioxidant proteins MT-I + II in the response of the brain to injury...

  12. Recent results from AMANDA II

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, K.; Ahrens, J.; Bai, X.; Barwick, S.W.; Becka, T.; Becker, K.-H.; Bernardini, E.; Bertrand, D.; Binon, F.; Biron, A.; Boeser, S.; Botner, O.; Bouhali, O.; Burgess, T.; Carius, S.; Castermans, T.; Chen, A.; Chirkin, D.; Conrad, J.; Cooley, J.; Cowen, D.F.; Davour, A.; De Clercq, C.; De Young, T.; Desiati, P.; Dewulf, J.-P.; Doksus, P.; Ekstroem, P.; Feser, T.; Gaisser, T.K.; Gaug, M.; Gerhardt, L.; Goldschmidt, A.; Hallgren, A.; Halzen, F.; Hardtke, R.; Hauschildt, T.; Hellwig, M.; Herque, P.; Hill, G.C.; Hulth, P.O.; Hundertmark, S.; Jacobsen, J.; Karle, A.; Koci, B.; Koepke, L.; Kuehn, K.; Kowalski, M.; Lamoureux, J.I.; Leich, H.; Leuthold, M.; Lindahl, P.; Liubarsky, I.; Madsen, J.; Marciniewski, P.; Matis, H.S.; McParland, C.P.; Minaeva, Y.; Miocinovic, P.; Morse, R.; Nahnhauer, R.; Neunhoeffer, T.; Niessen, P.; Nygren, D.R.; Ogelman, H.; Olbrechts, Ph.; Perez de los Heros, C.; Pohl, A.C.; Price, P.B.; Przybylski, G.T.; Rawlins, K.; Resconi, E.; Rhode, W.; Ribordy, M.; Richter, S.; Rodriguez Martino, J.; Ross, D.; Sander, H.-G.; Schmidt, T.; Schneider, D.; Schwarz, R.; Silvestri, A.; Solarz, M.; Spiczak, G.M.; Spiering, C.; Steele, D.; Steffen, P.; Stokstad, R.G.; Sudhoff, P.; Sulanke, K.-H.; Taboada, I.; Thollander, L.; Tilav, S.; Walck, C.; Weinheimer, C.; Wiebusch, C.H.; Wiedemann, C.; Wischnewski, R.; Wissing, H.; Woschnagg, K.; Yodh, G.; Young, S

    2003-04-01

    We present new data taken with the AMANDA-II neutrino telescope array. The AMANDA-II upgrade was completed at the beginning of 2000. It significantly extends the sensitivity of the 10-string AMANDA-B10 detector to high- and ultrahigh-energy neutrino fluxes into regions of interest for probing current astrophysical models which remain unexplored by other experiments.

  13. Annex II technical documentation assessed.

    Science.gov (United States)

    van Drongelen, A W; Roszek, B; van Tienhoven, E A E; Geertsma, R E; Boumans, R T; Kraus, J J A M

    2005-12-01

    Annex II of the Medical Device Directive (MDD) is used frequently by manufacturers to obtain CE-marking. This procedure relies on a full quality assurance system and does not require an assessment of the individual medical device by a Notified Body. An investigation into the availability and the quality of technical documentation for Annex II devices revealed severe shortcomings, which are reported here.

  14. Molecular targeted therapy for pancreatic adenocarcinoma: A review of completed and ongoing late phase clinical trials.

    Science.gov (United States)

    Mosquera, Catalina; Maglic, Dino; Zervos, Emmanuel E

    2016-12-01

    Molecular targeted therapy is widely utilized and effective in a number of solid tumors. In pancreatic adenocarcinoma, targeted therapy has been extensively evaluated; however, survival improvement of this aggressive disease using a targeted strategy has been minimal. The purpose of this study is to review therapeutic molecular targets in completed and ongoing later phase (II and III) clinical trials to have a better understanding of the rationale and progress towards targeted molecular therapies for pancreatic cancer. The PubMed database and the NCDI clinical trial website (www.clinicaltrials.gov) were queried to identify phase II and III completed and published (PubMed) and ongoing (clinicaltrials.gov) trials using the keywords: pancreatic cancer and molecular targeted therapy. The search engines were further limited by adding Phase II or III, active enrollment and North American. A total of 14 completed and published phase II/III clinical trials and 17 ongoing trials were identified. Evaluated strategies included inhibition of growth factor receptors (EGFR, PDGFR, VGFR, IGF-1R), tyrosine kinase inhibitors, MEK1/2, mTOR blockade and PI3K and HER2-neu pathway inhibitors. Only one trial conducted by the National Cancer Institute of Canada and the PANTAR trial have demonstrated a survival improvement from EGFR inhibition using erlotinib. These trials ultimately led to FDA approval of erlotinib/Tarceva in advanced stage disease. It remains unclear whether new combinations of cytotoxic chemotherapy or immunotherapy plus molecular targeted therapy will be beneficial in management of pancreatic adenocarcinoma. Despite a number of phase II and III trials, to date, only erlotinib has emerged as an approved targeted therapy in pancreatic adenocarcinoma. There are several ongoing late phase trials evaluating a number of targets, the results of which will become available over the next 1 to 2 years. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. RTNS-II operations guidebook

    Energy Technology Data Exchange (ETDEWEB)

    Heikkinen, D.W.

    1985-04-01

    This guidebook is intended to provide training criteria, procedures and guidelines for operation of the RTNS-II neutron sources and ancilliary equipment. Use of this document requires full knowledge of the RTNS-II Facility Safety Procedure (FSP) and any Operational Safety Procedures (OSP) in effect. The RTNS-II FSP defines the hazards which may be encountered at RTNS-II and defines the procedures which must be followed in performing any task including operations. The purpose of this document is to provide a central source of detailed information concerning systems and equipment used in operating the RTNS-II neutron sources on a day-to-day basis. All members of the Operations Group are expected to be familiar with its contents. It is also intended to be used in training new members of the Operations Group.

  16. Organizing MHC Class II Presentation

    Directory of Open Access Journals (Sweden)

    David R Fooksman

    2014-04-01

    Full Text Available Major histocompatibility complex (MHC class II molecules are ligands for CD4+ T cells and are critical for initiating the adaptive immune response. This review is focused on what is currently known about MHC class II organization at the plasma membrane of antigen presenting cells and how this affects antigen presentation to T cells. The organization and diffusion of class II molecules have been measured by a variety of biochemical and microscopic techniques. Membrane lipids and other proteins have been implicated in MHC class II organization and function. However, when compared with the organization of MHC class I or TCR complexes, much less is known about MHC class II. Since clustering of T cell receptors occurs during activation, the organization of MHC molecules prior to recognition and during synapse formation may be critical for antigen presentation.

  17. Neurofibromatosis Type II

    Directory of Open Access Journals (Sweden)

    Akram Kasiri Ghahi

    2003-08-01

    Full Text Available Neurofibromatosis type 2 (NF2 is an inherited disease which is mainly characterized by the development of multiple schwannomas and meningiomas.  Incidence of the disease is about 1 in 60,000. Affected individuals inevitably develop schwannomas, typically affecting both auditory-vestibular nerve which lead in hearing loss and deafness. The majority of patients present with hearing loss, which is usually unilateral at onset and may be accompanied or preceded by tinnitus. Vestibular schwannomas may also cause dizziness or imbalance as a first symptom. Nausea, vomiting or true vertigo are rare symptoms, except in late-stage disease. NF II is caused by a defect in the gene that normally gives rise to a product called Merlin or Schwannomin, located on chromosome 22. Diagnosis is based on clinical and neuroimaging studies. Presymptomatic genetic testing is an integral part of the management of NF2 families. Prenatal diagnosis and pre-implantation genetic diagnosis is possible.

  18. The Cu II Spectrum

    Directory of Open Access Journals (Sweden)

    Alexander Kramida

    2017-02-01

    Full Text Available New wavelength measurements in the vacuum ultraviolet (VUV, ultraviolet and visible spectral regions have been combined with available literature data to refine and extend the description of the spectrum of singly ionized copper (Cu II. In the VUV region, we measured 401 lines using a concave grating spectrograph and photographic plates. In the UV and visible regions, we measured 276 lines using a Fourier-transform spectrometer. These new measurements were combined with previously unpublished data from the thesis of Ross, with accurate VUV grating measurements of Kaufman and Ward, and with less accurate older measurements of Shenstone to construct a comprehensive list of ≈2440 observed lines, from which we derived a revised set of 379 optimized energy levels, complemented with 89 additional levels obtained using series formulas. Among the 379 experimental levels, 29 are new. Intensities of all lines observed in different experiments have been reduced to the same uniform scale by using newly calculated transition probabilities (A-values. We combined our calculations with published measured and calculated A-values to provide a set of 555 critically evaluated transition probabilities with estimated uncertainties, 162 of which are less than 20%.

  19. Lithium ion beam driven hohlraums for PBFA II

    Energy Technology Data Exchange (ETDEWEB)

    Dukart, R.J.

    1994-05-06

    In our light ion inertial confinement fusion (ICF) program, fusion capsules are driven with an intense x-ray radiation field produced when an intense beam of ions penetrates a radiation case and deposits energy in a foam x-ray conversion region. A first step in the program is to generate and measure these intense fields on the Particle Beam Fusion Accelerator II (PBFA II). Our goal is to generate a 100-eV radiation temperature in lithium ion beam driven hohlraums, the radiation environment which will provide the initial drive temperature for ion beam driven implosion systems designed to achieve high gain. In this paper, we describe the design of such hohlraum targets and their predicted performance on PBFA II as we provide increasing ion beam intensities.

  20. Target irradiation experiments. [Hydra accelerator

    Energy Technology Data Exchange (ETDEWEB)

    1976-01-01

    Target irradiation experiments have been carried out on the Hydra accelerator, operating at powers between 0.15 and 0.3 TW. As listed in Table I, four types of spherical shell targets have been studied: 3 mm diameter, 200 ..mu..m and 50 ..mu..m wall thickness Au targets; 3 mm diameter, 300 ..mu..m wall thickness plastic targets; and 0.85 mm diameter, 10 ..mu..m wall thickness Ni targets. When compared to a practical range for 700 keV electrons, the ratio of shell thickness to electron range varied between 0.03 for the Ni targets to 1.5 for the thick walled Au targets. Multiple exposure optical holography was utilized to determine ablator velocity, and a one-dimensional hydrodynamical materials code CHARTD was utilized to model target response and infer beam deposition. Energy deposition varied from 1 TW/gm for thick Au targets up to 8 TW/gm for thin Ni targets, and pusher velocities ranged between 0.5 and 3.5 cm/..mu..sec. Neutron production from D/sub 2/ and DT filled Ni exploding pusher targets was measured using Ag and Li activation counters and gated scintillator photomultiplier time of flight detectors.

  1. β2-Glycoprotein I/HLA class II complexes are novel autoantigens in antiphospholipid syndrome.

    Science.gov (United States)

    Tanimura, Kenji; Jin, Hui; Suenaga, Tadahiro; Morikami, Satoko; Arase, Noriko; Kishida, Kazuki; Hirayasu, Kouyuki; Kohyama, Masako; Ebina, Yasuhiko; Yasuda, Shinsuke; Horita, Tetsuya; Takasugi, Kiyoshi; Ohmura, Koichiro; Yamamoto, Ken; Katayama, Ichiro; Sasazuki, Takehiko; Lanier, Lewis L; Atsumi, Tatsuya; Yamada, Hideto; Arase, Hisashi

    2015-04-30

    Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy complications. β2-glycoprotein I (β2GPI) complexed with phospholipid is recognized as a major target for autoantibodies in APS; however, less than half the patients with clinical manifestations of APS possess autoantibodies against the complexes. Therefore, the range of autoantigens involved in APS remains unclear. Recently, we found that human leukocyte antigen (HLA) class II molecules transport misfolded cellular proteins to the cell surface via association with their peptide-binding grooves. Furthermore, immunoglobulin G heavy chain/HLA class II complexes were specific targets for autoantibodies in rheumatoid arthritis. Here, we demonstrate that intact β2GPI, not peptide, forms a complex with HLA class II molecules. Strikingly, 100 (83.3%) of the 120 APS patients analyzed, including those whose antiphospholipid antibody titers were within normal range, possessed autoantibodies that recognize β2GPI/HLA class II complexes in the absence of phospholipids. In situ association between β2GPI and HLA class II was observed in placental tissues of APS patients but not in healthy controls. Furthermore, autoantibodies against β2GPI/HLA class II complexes mediated complement-dependent cytotoxicity against cells expressing the complexes. These data suggest that β2GPI/HLA class II complexes are a target in APS that might be involved in the pathogenesis.

  2. Selective separation of Cu (II), Zn (II), and Cd (II) by solvent extraction

    Institute of Scientific and Technical Information of China (English)

    XIE Keng; WEN Jiankang; HUA Yixin; RUAN Renman

    2008-01-01

    An experimental investigation was presented on the separation of Cu (II), Zn (II), and Cd (II) from a rich sulfate leachate of zinc slag by solvent extraction. The results of orthogonal experiments indicate that LIX 984N is highly selective and very efficient in the extraction of Cu (II), and the analysis of variance indicates that the sequence of parameters according to their influence on the separation efficiency is phase ratio>LIX 984N concentration>pH value>extraction time. The optimal condition for copper extraction is obtained as 25% of LIX 984N concentration, 7 min of extraction time, 3:2 of phase ratio O/A, and pH=1.7. The separation of Zn (II) and Cd (II) was performed after the copper extraction from the raffinate. Comparative analysis of the separation with di-2-ethylhexyl phosphoric acid (D2EHPA), D2EHPA-tributyl-phosophate (TBP) synergistic extracting system, and 2-ethylhexyl phosphonic acid mono 2-ethylhexyl ester (HEHEHP) was made at pH=2.0. It is demonstrated that the extraction efficiency with D2EHPA is improved after being saponified by sodium hydroxide, and D2EHPA-TBP synergistic extracting, as well as HEHEHP, has a superior selectivity to Zn (II) over Cd (II).

  3. EURISOL High Power Targets

    CERN Document Server

    Kadi, Y; Lindroos, M; Ridikas, D; Stora, T; Tecchio, L; CERN. Geneva. BE Department

    2009-01-01

    Modern Nuclear Physics requires access to higher yields of rare isotopes, that relies on further development of the In-flight and Isotope Separation On-Line (ISOL) production methods. The limits of the In-Flight method will be applied via the next generation facilities FAIR in Germany, RIKEN in Japan and RIBF in the USA. The ISOL method will be explored at facilities including ISAC-TRIUMF in Canada, SPIRAL-2 in France, SPES in Italy, ISOLDE at CERN and eventually at the very ambitious multi-MW EURISOL facility. ISOL and in-flight facilities are complementary entities. While in-flight facilities excel in the production of very short lived radioisotopes independently of their chemical nature, ISOL facilities provide high Radioisotope Beam (RIB) intensities and excellent beam quality for 70 elements. Both production schemes are opening vast and rich fields of nuclear physics research. In this article we will introduce the targets planned for the EURISOL facility and highlight some of the technical and safety cha...

  4. Magnetic targeted drug delivery

    Directory of Open Access Journals (Sweden)

    Timothy Wiedmann

    2009-10-01

    Full Text Available Lung cancer is the most common cause of death from cancer in both men and women. Treatment by intravenous or oral administration of chemotherapy agents results in serious and often treatment-limiting side effects. Delivery of drugs directly to the lung by inhalation of an aerosol holds the promise of achieving a higher concentration in the lung with lower blood levels. To further enhance the selective lung deposition, it may be possible to target deposition by using external magnetic fields to direct the delivery of drug coupled to magnetic particles. Moreover, alternating magnetic fields can be used to induce particle heating, which in turn controls the drug release rate with the appropriate thermal sensitive material.With this goal, superparamagetic nanoparticles (SPNP were prepared and characterized, and enhanced magnetic deposition was demonstrated in vitro and in vivo. SPNPs were also incorporated into a lipid-based/SPNP aerosol formulation, and drug release was shown to be controlled by thermal activation. Because of the inherent imaging potential of SPNPs, this use of nanotechnology offers the possibility of coupling the diagnosis of lung cancer to drug release, which perhaps will ultimately provide the “magic bullet” that Paul Ehrlich originally sought.

  5. Emerging targets in migraine.

    Science.gov (United States)

    Hoffmann, Jan; Goadsby, Peter J

    2014-01-01

    Migraine is a common and highly disabling neurological disorder. Despite the complexity of its pathophysiology, substantial advances have been achieved over the past 20 years in its understanding, as well as the development of pharmacological treatment options. The development of serotonin 5-HT(1B/1D) receptor agonists ("triptans") substantially improved the acute treatment of migraine attacks. However, many migraineurs do not respond satisfactorily to triptans and cardiovascular co-morbidities limit their use in a significant number of patients. As migraine is increasingly considered to be a disorder of the brain, and preclinical and clinical data indicate that the observed vasodilation is merely an epiphenomenon, research has recently focused on the development of neurally acting compounds that lack vasoconstrictor properties. This review highlights the most important pharmacological targets for which compounds have been developed that are highly likely to enter or have already advanced into clinical trials for the acute and preventive treatment of migraine. In this context, preclinical and clinical data on compounds acting on calcitonin gene-related peptide or its receptor, the 5-HT(1F) receptor, nitric oxide synthase, and acid-sensing ion channel blockers are discussed.

  6. Can Co(II) or Cd(II) substitute for Zn(II) in zinc fingers?

    Indian Academy of Sciences (India)

    P Rabindra Reddy; M Radhika

    2001-02-01

    Zinc finger domains consist of sequences of amino acids containing cysteine and histidine residues tetrahedrally coordinated to a zinc ion. The role of zinc in a DNA binding finger was considered purely structural due to the absence of redox chemistry in zinc. However, whether other metals e.g. Co(II) or Cd(II) can substitute Zn(II) is not settled. For an answer the detailed interaction of Co(II) and Cd(II) with cysteine methylester and histidine methylester has been investigated as a model for the zinc core in zinc fingers. The study was extended to different temperatures to evaluate the thermodynamic parameters associated with these interactions. The results suggest that zinc has a unique role.

  7. Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans

    Science.gov (United States)

    Li, Yan-Hui; Zhang, Gai-Gai

    2016-01-01

    DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation. PMID:27027346

  8. The target effect: visual memory for unnamed search targets.

    Science.gov (United States)

    Thomas, Mark D; Williams, Carrick C

    2014-01-01

    Search targets are typically remembered much better than other objects even when they are viewed for less time. However, targets have two advantages that other objects in search displays do not have: They are identified categorically before the search, and finding them represents the goal of the search task. The current research investigated the contributions of both of these types of information to the long-term visual memory representations of search targets. Participants completed either a predefined search or a unique-object search in which targets were not defined with specific categorical labels before searching. Subsequent memory results indicated that search target memory was better than distractor memory even following ambiguously defined searches and when the distractors were viewed significantly longer. Superior target memory appears to result from a qualitatively different representation from those of distractor objects, indicating that decision processes influence visual memory.

  9. NEWLY IDENTIFIED EXTENDED GREEN OBJECTS (EGOs) FROM THE SPITZER GLIMPSE II SURVEY. II. MOLECULAR CLOUD ENVIRONMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xi; Gan Conggui; Shen Zhiqiang [Key Laboratory for Research in Galaxies and Cosmology, Shanghai Astronomical Observatory, Chinese Academy of Sciences, Shanghai 200030 (China); Ellingsen, Simon P.; Titmarsh, Anita [School of Mathematics and Physics, University of Tasmania, Hobart, Tasmania (Australia); He Jinhua, E-mail: chenxi@shao.ac.cn [Key Laboratory for the Structure and Evolution of Celestial Objects, Yunnan Astronomical Observatory/National Astronomical Observatory, Chinese Academy of Sciences, P.O. Box 110, Kunming 650011, Yunnan Province (China)

    2013-06-01

    We have undertaken a survey of molecular lines in the 3 mm band toward 57 young stellar objects using the Australia Telescope National Facility Mopra 22 m radio telescope. The target sources were young stellar objects with active outflows (extended green objects (EGOs)) newly identified from the GLIMPSE II survey. We observe a high detection rate (50%) of broad line wing emission in the HNC and CS thermal lines, which combined with the high detection rate of class I methanol masers toward these sources (reported in Paper I) further demonstrates that the GLIMPSE II EGOs are associated with outflows. The physical and kinematic characteristics derived from the 3 mm molecular lines for these newly identified EGOs are consistent with these sources being massive young stellar objects with ongoing outflow activity and rapid accretion. These findings support our previous investigations of the mid-infrared properties of these sources and their association with other star formation tracers (e.g., infrared dark clouds, methanol masers and millimeter dust sources) presented in Paper I. The high detection rate (64%) of the hot core tracer CH{sub 3}CN reveals that the majority of these new EGOs have evolved to the hot molecular core stage. Comparison of the observed molecular column densities with predictions from hot core chemistry models reveals that the newly identified EGOs from the GLIMPSE II survey are members of the youngest hot core population, with an evolutionary time scale of the order of 10{sup 3} yr.

  10. Options Study - Phase II

    Energy Technology Data Exchange (ETDEWEB)

    R. Wigeland; T. Taiwo; M. Todosow; W. Halsey; J. Gehin

    2010-09-01

    The Options Study has been conducted for the purpose of evaluating the potential of alternative integrated nuclear fuel cycle options to favorably address the issues associated with a continuing or expanding use of nuclear power in the United States. The study produced information that can be used to inform decisions identifying potential directions for research and development on such fuel cycle options. An integrated nuclear fuel cycle option is defined in this study as including all aspects of the entire nuclear fuel cycle, from obtaining natural resources for fuel to the ultimate disposal of used nuclear fuel (UNF) or radioactive wastes. Issues such as nuclear waste management, especially the increasing inventory of used nuclear fuel, the current uncertainty about used fuel disposal, and the risk of nuclear weapons proliferation have contributed to the reluctance to expand the use of nuclear power, even though it is recognized that nuclear power is a safe and reliable method of producing electricity. In this Options Study, current, evolutionary, and revolutionary nuclear energy options were all considered, including the use of uranium and thorium, and both once-through and recycle approaches. Available information has been collected and reviewed in order to evaluate the ability of an option to clearly address the challenges associated with the current implementation and potential expansion of commercial nuclear power in the United States. This Options Study is a comprehensive consideration and review of fuel cycle and technology options, including those for disposal, and is not constrained by any limitations that may be imposed by economics, technical maturity, past policy, or speculated future conditions. This Phase II report is intended to be used in conjunction with the Phase I report, and much information in that report is not repeated here, although some information has been updated to reflect recent developments. The focus in this Options Study was to

  11. Stiffnites. Part II

    Directory of Open Access Journals (Sweden)

    Maria Teresa Pareschi

    2011-06-01

    Full Text Available

    The dynamics of a stiffnite are here inferred. A stiffnite is a sheet-shaped, gravity-driven submarine sediment flow, with a fabric made up of marine ooze. To infer stiffnite dynamics, order of magnitude estimations are used. Field deposits and experiments on materials taken from the literature are also used. Stiffnites can be tens or hundreds of kilometers wide, and a few centimeters/ meters thick. They move on the sea slopes over hundreds of kilometers, reaching submarine velocities as high as 100 m/s. Hard grain friction favors grain fragmentation and formation of triboelectrically electrified particles and triboplasma (i.e., ions + electrons. Marine lipids favor isolation of electrical charges. At first, two basic assumptions are introduced, and checked a posteriori: (a in a flowing stiffnite, magnetic dipole moments develop, with the magnetization proportional to the shear rate. I have named those dipoles as Ambigua. (b Ambigua are ‘vertically frozen’ along stiffnite streamlines. From (a and (b, it follows that: (i Ambigua create a magnetic field (at peak, >1 T. (ii Lorentz forces sort stiffnite particles into two superimposed sheets. The lower sheet, L+, has a sandy granulometry and a net positive electrical charge density. The upper sheet, L–, has a silty muddy granulometry and a net negative electrical charge density; the grains of sheet L– become finer upwards. (iii Faraday forces push ferromagnetic grains towards the base of a stiffnite, so that a peak of magnetic susceptibility characterizes a stiffnite deposit. (iv Stiffnites harden considerably during their motion, due to magnetic confinement. Stiffnite deposits and inferred stiffnite characteristics are compatible with a stable flow behavior against bending, pinch, or other macro instabilities. In the present report, a consistent hypothesis about the nature of Ambigua is provided.

  12. National Energy Plan II

    Energy Technology Data Exchange (ETDEWEB)

    None

    1979-01-01

    This volume contains the Administration's second National Energy Plan, as required by section 801 of the Department of Energy Organization Act (Public Law 95-91). A second volume will contain an assessment of the environmental trends associated with the energy futures reported here. Detailed appendices to the Plan will be published separately. The eight chapters and their subtitles are: Crisis and Uncertainty in the World Energy Future (The Immediate Crisis and the Continuing Problem, The Emergence of the Energy Problem, The Uncertainties of the World Energy Future, World Oil Prices, Consequences for the U.S.); The U.S. Energy Future: The Implications for Policy (The Near-, Mid-, and Long-Term, The Strategy in Perspective); Conservation (Historical Changes in Energy Use, Post-Embargo Changes - In Detail, Conservation Policies and Programs, The Role of Conservation); Oil and Gas (Oil, Natural Gas); Coal and Nuclear (Coal, Nuclear, Policy for Coal and Nuclear Power); Solar and Other Inexhaustible Energy Sources (Solar Energy, Geothermal, Fusion, A Strategy for Inexhaustible Resources); Making Decisions Promptly and Fairly (Managing Future Energy Crises: Emergency Planning, Managing the Current Shortfall: The Iranian Response Plan, Managing the Long-Term Energy Problem: The Institutional Framework, Fairness in Energy Policy, Public Participation in the Development of Energy Policy); and NEP-II and the Future (The Second National Energy Plan and the Nation's Energy Future, The Second National Energy Plan and the Economy, Employment and Energy Policy, The Second National Energy Plan and Individuals, The Second National Energy Plan and Capital Markets, and The Second National Energy Plan and the Environment). (ERA citation 04:041097)

  13. First commissioning experiments at DARHT-II

    Energy Technology Data Exchange (ETDEWEB)

    Ekdahl, C. A. (Carl A.); Abeyta, E. O. (Epifanio Orlando); Caudill, L. D. (Larry D.); Dalmas, D. A. (Dale Allen); Eversole, S. A. (Steven A.); Gallegos, R. A. (Robert A.); Harrison, J. F. (James F.); Holzscheiter, M. H. (Michael H.); Johnson, J. B. (Jeffrey B.); Jacquez, E. B. (Edward B.); McCuistian, B. T. (Brian T.); Montoya, N. A. (Nicholas A.); Nath, S. (Subrata); Neilsen, K. E. (Kurt E.); Oro, D. M. (David M.); Rodriguez, L. R. (Leroy R.); Rodriguez, P. (Patrick); Sanchez, M. (Manolito); Scarpetti, R. (Raymond); Schauer, M. M. (Michael M.); Simmons, D. F. (David F.); Smith, H. V. (H. Vernon); Studebaker, J. K. (Jan K.); Sullivan, G. W. (Gary W.); Swinney, C. A. (Charles A.); Temple, R. D. (Rodney Dean); Chen, Y. J. (Yu-Jiuan); Houck, T. L. (Timothy L.); Henestroza, E. (Enrique); Eylon, S. (Shmuel); Fawley, W. M. (William Marshall); Yu, S.; Bender, H. A. (Howard A.); Broste, W. B. (William B.); Carlson, C. A. (Carl A.); Durtschi, G. M. (Grant M.); Frayer, D. K. (Daniel K.); Johnson, D. E. (Douglas E.); Jones, K. C. (Kenneth C.); Meidinger, A. (Alfred); Moy, K. J.; Sturgess, R. E. (Ronald E.); Tom, C. Y.

    2004-01-01

    The second axis of the Dual Axis Radiographic Hydro-Test (DARHT) facility will provide up to four short (< 150 ns) radiation pulses for flash radiography of high-explosive driven implosion experiments. To accomplish this the DARBT-II linear induction accelerator (LIA) will produce a 2-kA electron beam with 18-MeV kinetic energy, constant to within {+-}0.5% for 2-{mu}s. A fast kicker will cleave four short pulses out of the 2-{mu}s flattop, with the bulk of the beam diverted into a dump. The short pulses will then be transported to the final-focus magnet, and focused onto a tantalum target for conversion to bremsstrahlung pulses for radiography. DARHT-II is a collaborative effort between the Los Alamos, Lawrence Livermore, and Lawrence Berkeley National Laboratories of the University of California. The first tests of the second axis accelerator were designed to demonstrate the technology, and to meet the modest performance requirements for closing out. The DARHT-II construction project. These experiments demonstrated that we could indeed produce a 1.2 kA beam with pulse length 0.5-1.2 {mu}s and accelerate it to 12.5 MeV. These de-rated parameters were chosen to minimize risk of damage in these first experiments with this novel accelerator. The beam showed no evidence of the BBU instability for these parameters. In fact, we had to reduce the magnetic guide field by a factor of 5 before BBU was observed.

  14. Chemical speciation of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II binary complexes of l-methionine in 1,2-propanediol-water mixtures

    Directory of Open Access Journals (Sweden)

    M. Padma Latha

    2007-04-01

    Full Text Available Chemical speciation of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II complexes of L-methionine in 0.0-60 % v/v 1,2-propanediol-water mixtures maintaining an ionic strength of 0.16 M at 303 K has been studied pH metrically. The active forms of ligand are LH2+, LH and L-. The predominant species detected are ML, MLH, ML2, ML2H, ML2H2 and MLOH. Models containing different numbers of species were refined by using the computer program MINIQUAD 75. The best-fit chemical models were arrived at based on statistical parameters. The trend in variation of complex stability constants with change in the dielectric constant of the medium is explained on the basis of electrostatic and non-electrostatic forces.

  15. Quininium tetra-chloridozinc(II).

    Science.gov (United States)

    Chen, Li-Zhuang

    2009-09-05

    The asymmetric unit of the title compound {systematic name: 2-[hydr-oxy(6-meth-oxy-quinolin-1-ium-4-yl)meth-yl]-8-vinyl-quinuclidin-1-ium tetra-chlorido-zinc(II)}, (C(20)H(26)N(2)O(2))[ZnCl(4)], consists of a double proton-ated quininium cation and a tetra-chloridozinc(II) anion. The Zn(II) ion is in a slightly distorted tetra-hedral coordination environment. The crystal structure is stabilized by inter-molecular N-H⋯Cl and O-H⋯Cl hydrogen bonds.

  16. Delta II commercial space transportation

    Science.gov (United States)

    Meyers, J. F.

    1988-07-01

    Delta II is an upgraded variant of the Delta family of launch vehicles that has been in use by NASA since 1960. Among the design improvements incorporated by Delta II is a cryogenic-propellant second stage, a 2.89-m diameter satellite-protecting nose fairing, graphite/epoxy solid rocket motor cases, and 12:1 main engine expansion nozzle. The manufacturer/operator offers Delta II customers a dedicated, single satellite launch capability fully tailored to the given spacecraft's unique mission requirements.

  17. KRAS and MAPK1 Gene Amplification in Type II Ovarian Carcinomas

    Directory of Open Access Journals (Sweden)

    Noriyuki Ishikawa

    2013-07-01

    Full Text Available In this study, we examined the clinical significance of KRAS and MAPK1 amplification and assessed whether these amplified genes were potential therapeutic targets in type II ovarian carcinoma. Using fluorescence in situ hybridization, immunohistochemistry, and retrospectively collected clinical data, KRAS and MAPK1 amplifications were identified in 9 (13.2% and 5 (7.4% of 68 type II ovarian carcinoma tissue samples, respectively. Interestingly, co-amplification of KRAS and MAPK1 seemed to be absent in the type II ovarian carcinomas tested, except one case. Active phospho-ERK1/2 was identified in 26 (38.2% out of 68 type II ovarian carcinomas and did not correlate with KRAS or MAPK1 amplification. There was no significant relationship between KRAS amplification and overall or progression-free survival in patients with type II ovarian carcinoma. However, patients with MAPK1 amplification had significantly poorer progression-free survival than patients without MAPK1 amplification. Moreover, type II ovarian carcinoma cells with concomitant KRAS amplification and mutation exhibited dramatic growth reduction following treatment with the MEK inhibitor PD0325901. These findings indicate that KRAS/MAPK1 amplification is critical for the growth of a subset of type II ovarian carcinomas. Additionally, RAS/RAF/MEK/ERK pathway-targeted therapy may benefit selected patients with type II ovarian carcinoma harboring KRAS/MAPK1 amplifications.

  18. The OLYMPUS internal hydrogen target

    Energy Technology Data Exchange (ETDEWEB)

    Bernauer, J.C., E-mail: bernauer@mit.edu [Massachusetts Institute of Technology, Laboratory for Nuclear Science, Cambridge, MA 02139 (United States); Carassiti, V.; Ciullo, G. [Istituto Nazionale di Fisica Nucleare and Università, 44100 Ferrara (Italy); Henderson, B.S. [Massachusetts Institute of Technology, Laboratory for Nuclear Science, Cambridge, MA 02139 (United States); Ihloff, E.; Kelsey, J. [Massachusetts Institute of Technology, Laboratory for Nuclear Science, Cambridge, MA 02139 (United States); MIT-Bates Linear Accelerator Center, Middleton, MA 01949 (United States); Lenisa, P. [Istituto Nazionale di Fisica Nucleare and Università, 44100 Ferrara (Italy); Milner, R. [Massachusetts Institute of Technology, Laboratory for Nuclear Science, Cambridge, MA 02139 (United States); MIT-Bates Linear Accelerator Center, Middleton, MA 01949 (United States); Schmidt, A. [Massachusetts Institute of Technology, Laboratory for Nuclear Science, Cambridge, MA 02139 (United States); Statera, M. [Istituto Nazionale di Fisica Nucleare and Università, 44100 Ferrara (Italy)

    2014-08-01

    An internal hydrogen target system was developed for the OLYMPUS experiment at DESY, in Hamburg, Germany. The target consisted of a long, thin-walled, tubular cell within an aluminum scattering chamber. Hydrogen entered at the center of the cell and exited through the ends, where it was removed from the beamline by a multistage pumping system. A cryogenic coldhead cooled the target cell to counteract heating from the beam and increase the density of hydrogen in the target. A fixed collimator protected the cell from synchrotron radiation and the beam halo. A series of wakefield suppressors reduced heating from beam wakefields. The target system was installed within the DORIS storage ring and was successfully operated during the course of the OLYMPUS experiment in 2012. Information on the design, fabrication, and performance of the target system is reported.

  19. Facility target insert shielding assessment

    Energy Technology Data Exchange (ETDEWEB)

    Mocko, Michal [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-06

    Main objective of this report is to assess the basic shielding requirements for the vertical target insert and retrieval port. We used the baseline design for the vertical target insert in our calculations. The insert sits in the 12”-diameter cylindrical shaft extending from the service alley in the top floor of the facility all the way down to the target location. The target retrieval mechanism is a long rod with the target assembly attached and running the entire length of the vertical shaft. The insert also houses the helium cooling supply and return lines each with 2” diameter. In the present study we focused on calculating the neutron and photon dose rate fields on top of the target insert/retrieval mechanism in the service alley. Additionally, we studied a few prototypical configurations of the shielding layers in the vertical insert as well as on the top.

  20. Oxide Fiber Targets at ISOLDE

    CERN Document Server

    Köster, U; Carminati, D; Catherall, R; Cederkäll, J; Correia, J G; Crepieux, B; Dietrich, M; Elder, K; Fedosseev, V; Fraile-Prieto, L M; Franchoo, S; Fynbo, H O U; Georg, U; Giles, T; Joinet, A; Jonsson, O C; Kirchner, R; Lau, C; Lettry, Jacques; Maier, H J; Mishin, V I; Oinonen, M; Peräjärvi, K; Ravn, H L; Rinaldi, T; Santana-Leitner, M; Wahl, U; Weissman, L

    2003-01-01

    Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxyde fiber targets are less critical since they may maintain their open structure even when starting to fuse together at some contact points. The experience with various oxyde fiber targets (titania, zirconia, ceria and thoria) used in the last years at ISOLDE is reviewed. For short-lived isotopes of Cu, Ga and Xe the zirconia and ceria targets respectively provided significantly higher yields than any other target (metal foils, oxide powders, etc.) tested before. Titania fibers, which were not commercially available, were produced in a relic process by impregnation of a rayon felt in a titanium chloride solution and subsequent calcination by heating the dried felt in air. Thoria fibers were obtained either by the same process or by burning commercial gas lantern mantle cloth. In the future a beryllia fiber target could be used to produce...