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Sample records for unirradiated cintichem-type targets

  1. Safety analysis for operating the Annular Core Research Reactor with Cintichem-type targets installed in the central region of the core

    Energy Technology Data Exchange (ETDEWEB)

    PARMA JR.,EDWARD J.

    2000-01-01

    Production of the molybdenum-99 isotope at the Annular Core Research Reactor requires highly enriched, uranium oxide loaded targets to be irradiated for several days in the high neutron-flux region of the core. This report presents the safety analysis for the irradiation of up to seven Cintichem-type targets in the central region of the core and compares the results to the Annular Core Research Reactor Safety Analysis Report. A 19 target grid configuration is presented that allows one to seven targets to be irradiated, with the remainder of the grid locations filled with aluminum ''void'' targets. Analyses of reactor, neutronic, thermal hydraulics, and heat transfer calculations are presented. Steady-state operation and accident scenarios are analyzed with the conclusion that the reactor can be operated safely with seven targets in the grid, and no additional risk to the public.

  2. Loss tangent measurements on unirradiated alumina

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J.; Goulding, R.H. [Oak Ridge National Lab., TN (United States)

    1996-04-01

    Unirradiated room temperature loss tangent for sapphire and several commercial grades of polycrystalline alumina are complied for frequencies between 10{sup 5} and 4x10{sup 11} Hz. Sapphire exhibits significantly lower values for the loss tangent at frequencies up to 10{sup 11} Hz. The loss tangents of 3 different grades of Wesgo alumina (AL300, AL995, AL998) and 2 different grades of Coors alumina (AD94, AD995) have typical values near {approx}10{sup -4} at a frequency of 10{sup 8} Hz. On the other hand, the loss tangent of Vitox alumina exhibits a large loss peak tan d{approx} 5x10{sup -3} at this frequency.

  3. Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

    Science.gov (United States)

    Lam, R. K. K.; Fung, Y. K.; Han, W.; Yu, K. N.

    2015-01-01

    The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed. PMID:25625514

  4. Fatigue behavior of unirradiated V-5Cr-5Ti

    Energy Technology Data Exchange (ETDEWEB)

    Gieseke, B.G.; Stevens, C.O.; Grossbeck, M.L. [Oak Ridge National Lab., TN (United States)

    1995-04-01

    The objective of this research is to determine the low cycle fatigue behavior of V-5Cr-5Ti alloys for a range of temperatures and the extent of environmental effects at ambient temperatures. The results of in-vacuum low cycle fatigue tests are presented for unirradiated V-5Cr-5Ti tested at room temperature, 240, and 400{degree}C. A comparison of the fatigue data generated in rough and high vacuums shows that a pronounced environmental degradation of the fatiuge properties exists in this alloy at room temperature. Fatigue life was reduced by as much as 84%. Cyclic stress range data and SEM observations suggest that this reduction is due to a combination of increases in rates of crack initiation and subsequent growth. The relative contribution of each difference is dependent upon the strain range.

  5. Optimization of Hydride Rim Formation in Unirradiated Zr 4 Cladding

    Energy Technology Data Exchange (ETDEWEB)

    Shimskey, Rick W.; Hanson, Brady D.; MacFarlan, Paul J.

    2013-09-30

    The purpose of this work is to build on the results reported in the M2 milestone M2FT 13PN0805051, document number FCRD-USED-2013-000151 (Hanson, 2013). In that work, it was demonstrated that unirradiated samples of zircaloy-4 cladding could be pre-hydrided at temperatures below 400°C in pure hydrogen gas and that the growth of hydrides on the surface could be controlled by changing the surface condition of the samples and form a desired hydride rim on the outside diameter of the cladding. The work performed at Pacific Northwest National Laboratory since the issuing of the M2 milestone has focused its efforts to optimize the formation of a hydride rim on available zircaloy-4 cladding samples by controlling temperature variation and gas flow control during pre-hydriding treatments. Surface conditioning of the outside surface was also examined as a variable. The results of test indicate that much of the variability in the hydride thickness is due to temperature variation occurring in the furnaces as well as how hydrogen gas flows across the sample surface. Efforts to examine other alloys, gas concentrations, and different surface conditioning plan to be pursed in the next FY as more cladding samples become available

  6. a Study of Stress Relaxation Rate in Un-Irradiated and Neutron-Irradiated Stainless Steel

    Science.gov (United States)

    Ghauri, I. M.; Afzal, Naveed; Zyrek, N. A.

    Stress relaxation rate in un-irradiated and neutron-irradiated 303 stainless steel was investigated at room temperature. The specimens were exposed to 100 mC, Ra-Be neutron source of continuous energy 2-12 MeV for a period ranging from 4 to 16 days. The tensile deformation of the specimens was carried out using a Universal Testing Machine at 300 K. During the deformation, straining was frequently interrupted by arresting the cross head to observe stress relaxation at fixed load. Stress relaxation rate, s, was found to be stress dependent i.e. it increased with increasing stress levels σ0 both in un-irradiated and irradiated specimens, however the rate was lower in irradiated specimens than those of un-irradiated ones. A further decrease in s was observed with increase in exposure time. The experiential decrease in the relaxation rate in irradiated specimens is ascribed to strong interaction of glide dislocations with radiation induced defects. The activation energy for the movement of dislocations was found to be higher in irradiated specimens as compared with the un-irradiated ones.

  7. High Temperature Tensile Properties of Unirradiated and Neutron Irradiated 20 Cr-35 Ni Austenitic Steel

    Energy Technology Data Exchange (ETDEWEB)

    Roy, R.B.; Solly, B.

    1966-12-15

    The tensile properties of an unirradiated and neutron irradiated (at 40 deg C) 20 % Cr, 35 % Ni austenitic steel have been studied at 650 deg C, 750 deg C and 820 deg C. The tensile elongation and mode of fracture (transgranular) of unirradiated specimens tested at room temperature and 650 deg C are almost identical. At 750 deg C and 820 deg C the elongation decreases considerably and a large part of the total elongation is non-uniform. Furthermore, the mode of fracture at these temperatures is intergranular and microscopic evidence suggests that fracture is caused by formation and linkup of grain boundary cavities. YS and UTS decrease monotonically with temperature. Irradiated specimens show a further decrease in ductility and an increase in the tendency to grain boundary cracking. Irradiation has no significant effect on the YS, but the UTS are reduced. The embrittlement of the irradiated specimens is attributed to the presence of He and Li atoms produced during irradiation and the possible mechanisms are discussed. Prolonged annealing of irradiated and unirradiated specimens at 650 deg C appears to have no significant effect on tensile properties.

  8. Kinetic analysis for non-isothermal decomposition of unirradiated and γ-irradiated indium acetyl acetonate

    Directory of Open Access Journals (Sweden)

    Refaat Mohammed Mahfouz

    2011-03-01

    Full Text Available Kinetic studies for the non-isothermal decomposition of un-irradiated and γ-irradiated indium acetyl acetonate In(acac3 with 10² kGy total γ-ray dose were carried out in static air. The results showed that the decomposition proceeds in one major step in the temperature range of 150-250 °C with the formation of In2O3 as solid residue. The non-isothermal data for un-irradiated and γ-irradiated In(acac3 were analysed using linear Flynn-Wall-Ozawa (FWO and nonlinear Vyazovkin (VYZ iso-conversional methods. The results of application of these free models on the investigated data showed a systematic dependence of Ea on α indicating a simple decomposition process. No significant changes were observed in both decomposition behaviour and (Eα-α dependency between unirradiated and γ-irradiated In(acac3. Calcination of In(acac3 at 400 °C for 5 hours led to the formation of In2O3 monodispersed nanoparticles. X-ray diffraction, FTIR and SEM techniques were employed for characterization of the synthesised nanoparticles. This is the first attempt to prepare In2O3 nanoparticles by solid state thermal decomposition of In(acac3.

  9. Safety Analysis Report for Packaging: The unirradiated fuel shipping container USA/9853/AF

    Energy Technology Data Exchange (ETDEWEB)

    1991-10-18

    The HFBR Unirradiated Fuel Shipping Container was designed and fabricated at the Oak Ridge National Laboratory in 1978 for the transport of fuel for the High Flux Beam Reactor (HFBR) for Brookhaven National Laboratory. The package has been evaluated analytically, as well as the comparison to tests on similar packages, to demonstrate compliance with the applicable regulations governing packages in which radioactive and fissile materials are transported. The contents of this Safety Analysis Report for Packaging (SARP) are based on Regulatory Guide 7.9 (proposed Revision 2 - May 1986), 10 CFR Part 71, DOE Order 1540.2, DOE Order 5480.3, and 49 CFR Part 173.

  10. Safety Analysis Report for Packaging: The unirradiated fuel shipping container USA/9853/AF

    Energy Technology Data Exchange (ETDEWEB)

    1991-10-18

    The HFBR Unirradiated Fuel Shipping Container was designed and fabricated at the Oak Ridge National Laboratory in 1978 for the transport of fuel for the High Flux Beam Reactor (HFBR) for Brookhaven National Laboratory. The package has been evaluated analytically, as well as the comparison to tests on similar packages, to demonstrate compliance with the applicable regulations governing packages in which radioactive and fissile materials are transported. The contents of this Safety Analysis Report for Packaging (SARP) are based on Regulatory Guide 7.9 (proposed Revision 2 - May 1986), 10 CFR Part 71, DOE Order 1540.2, DOE Order 5480.3, and 49 CFR Part 173.

  11. Rescue effects in radiobiology: Unirradiated bystander cells assist irradiated cells through intercellular signal feedback

    Energy Technology Data Exchange (ETDEWEB)

    Chen, S. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Zhao, Y. [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Han, W. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Chiu, S.K. [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Zhu, L. [Office of Admission and Careers Advisory Service, Shenzhen University, Shenzhen 518060 (China); Wu, L. [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)

    2011-01-10

    Mammalian cells respond to ionization radiation by sending out extracellular signals to affect non-irradiated neighboring cells, which is referred to as radiation induced bystander effect. In the present paper, we described a phenomenon entitled the 'rescue effects', where the bystander cells rescued the irradiated cells through intercellular signal feedback. The effect was observed in both human primary fibroblast (NHLF) and cancer cells (HeLa) using two-cell co-culture systems. After co-culturing irradiated cells with unirradiated bystander cells for 24 h, the numbers of 53BP1 foci, corresponding to the number of DNA double-strand breaks in the irradiated cells were less than those in the irradiated cells that were not co-cultured with the bystander cells (0.78 {+-} 0.04 foci/cell vs. 0.90 {+-} 0.04 foci/cell) at a statistically significant level. Similarly, both micronucleus formation and extent of apoptosis in the irradiated cells were different at statistically significant levels if they were co-cultured with the bystander cells. Furthermore, it was found that unirradiated normal cells would also reduce the micronucleus formation in irradiated cancer cells. These results suggested that the rescue effects could participate in repairing the radiation-induced DNA damages through a media-mediated signaling feedback, thereby mitigating the cytotoxicity and genotoxicity of ionizing radiation.

  12. Overview and Critical Assessment of the Tensile Properties of unirradiated and irradiated EUROFER97

    Energy Technology Data Exchange (ETDEWEB)

    Lucon, E.; Vandermeulen, W.

    2007-10-15

    Material research represents a crucial issue for the assessment of fusion as a future viable source of energy. Structural materials, in particular, need to show a superior mechanical and chemical behaviour to guarantee the safe operation of the reactor during its whole lifetime, while retaining low activation characteristics to minimise the environmental impact of the produced waste. In this context, specific efforts have been focused for the last twenty years in Europe, Japan and the US, on developing suitable Reduced Activation Ferritic Martensitic (RAFM) steels as candidate structural materials. EUROFER97 has recently emerged in Europe as the reference material for the DEMO design. In the framework of the Long-Term Programme of EFDA (European Fusion Development Agreement), a coordinated effort has been launched aimed at providing a critical assessment of the mechanical and microstructural properties of EUROFER97 in the unirradiated and irradiated conditions, based on the results accumulated since the late 90ies within numerous EFDA tasks.

  13. Reactor Materials Program electrochemical potential measurements by ORNL with unirradiated and irradiated stainless steel specimens

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, E.W.; Caskey, G.R. Jr.

    1993-07-01

    Effect of irradiation of stainless steel on electrochemical potential (ECP) was investigated by measurements in dilute HNO{sub 3} and H{sub 2}O{sub 2} solutions, conditions simulating reactor moderator. The electrodes were made from unirradiated/irradiated, unsensitized/sensitized specimens from R-reactor piping. Results were inconclusive because of budgetary restrictions. The dose rate may have been too small to produce a significant radiolytic effect. Neither the earlier CERT corrosion susceptibility tests nor the present ECP measurements showed a pronounced effect of irradiation on susceptibility of the stainless steel to IGSCC; this is confirmed by the absence in the stainless steel of the SRS reactor tanks (except for the C Reactor tank knuckle area).

  14. Sperm quantity and size variation in un-irradiated and irradiated males of the malaria mosquito Anopheles arabiensis Patton

    NARCIS (Netherlands)

    Helinski, M.; Knols, B.G.J.

    2009-01-01

    Anopheles mosquitoes are important candidates for genetic control strategies. However, little is known about sperm quality and quantity as determinants of male reproductive success. In this study, sperm quantity and length variation were assessed in testes of un-irradiated and irradiated Anopheles

  15. Sperm quantity and size variation in un-irradiated and irradiated males of the malaria mosquito Anopheles arabiensis Patton

    NARCIS (Netherlands)

    Helinski, M.; Knols, B.G.J.

    2009-01-01

    Anopheles mosquitoes are important candidates for genetic control strategies. However, little is known about sperm quality and quantity as determinants of male reproductive success. In this study, sperm quantity and length variation were assessed in testes of un-irradiated and irradiated Anopheles a

  16. Obtention of fracture properties of unirradiated fuel cladding from ring compression tests

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Rengel, M.A. [Departamento de Ciencia de Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos Profesor Aranguren s/n, E-28040 Madrid (Spain); Consejo de Seguridad Nuclear (CSN), Justo Dorado 11, E-28040 Madrid (Spain); Gomez, F.J.; Ruiz-Hervias, J.; Caballero, L.; Valiente, A. [Departamento de Ciencia de Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos Profesor Aranguren s/n, E-28040 Madrid (Spain)

    2009-06-15

    Zirconium alloy cladding is used as the first structural barrier to contain the nuclear fuel and the fission products. In addition to its neutron transparency, this material has a good corrosion resistance and remarkable mechanical properties at operational temperatures. Consequently, it is or paramount importance to precisely characterize the mechanical behaviour and fracture properties of irradiated cladding to ensure a safe operation. It is known that the mechanical behaviour of unirradiated zirconium alloy cladding is anisotropic. The elastoplastic response depends on the direction, namely radial, hoop or longitudinal. For this reason, different fracture properties should be expected in each direction. From the various tests employed to characterize the mechanical behaviour along the hoop direction in nuclear fuel cladding, the ring compression test is particularly useful to study material fracture. With this test it is possible to determine the moment when a real crack is formed, due to a sudden decrease in the applied load at a given displacement value. The aim of this research is to determine as precisely as possible the value of the fracture energy from the ring compression test load vs. displacement curves. To this end, a finite element calculation incorporating the cohesive zone model was performed. In this case, the cohesive zone theory is applied in its simplest form. It is considered that the cohesive crack transfers a constant stress until the displacement of this cohesive crack reaches a critical value. At this precise moment a real crack is generated. The properties of the softening curve of the cohesive zone model can be obtained by directly comparing the experimental load vs. displacement records with the finite element calculations. The area under the softening curve is the fracture energy, which is directly related with the material fracture toughness. The experimental data used in this work have been obtained on unirradiated Zirlo cladding

  17. High resolution X-ray diffraction studies on unirradiated and irradiated strontium hexaferrite crystals

    Indian Academy of Sciences (India)

    Balwinder Kaur; Monita Bhat; F Licci; Ravi Kumar; K K Bamzai; P N Kotru

    2012-04-01

    High-resolution X-ray diffraction technique, employing a three-crystal monochromator–collimator combination is used to study the irradiation induced defects in flux grown Sr-hexaferrite crystals irradiated with 50 MeV Li3+ ion beams at room temperature with a fluence value of 1 × 1014 ions/cm2. The diffraction curves of the irradiated crystals suggest the possibility of creation of low angle grain boundaries and other point/clusters of defects causing amorphization in the irradiated crystals. The perfection of the irradiated and unirradiated (0001) cleaved surfaces of the crystals is studied using the bulk method of X-ray topography. The topographs supplement the findings suggestive of modifications in the crystalline quality of SrFe12O19 on irradiation with SHI of Li3+. Etching of the (0001) cleaved surfaces in H3PO4 at 120°C suggests that the dissolution characteristics of the surfaces get affected on irradiation with SHI of Li3+, besides supporting the findings of HRXRD and X-ray topography regarding modifications in the perfection of SrFe12O19 on irradiation.

  18. Properties of unirradiated and irradiated Ti-6Al-4V alloy for ITER flexible connectors

    Energy Technology Data Exchange (ETDEWEB)

    Rodchenkov, B.S., E-mail: rodchen@nikiet.ru [Research and Development Institute of Power Engineering (RDIPE), P.O. Box 788, Moscow 101000 (Russian Federation); Evseev, M.V. [Institute of Reactor Materials, Zarechnyi, Sverdlovsk Region 624051 (Russian Federation); Strebkov, Yu.S. [Research and Development Institute of Power Engineering (RDIPE), P.O. Box 788, Moscow 101000 (Russian Federation); Sinelnikov, L.P.; Shushlebin, V.V. [Institute of Reactor Materials, Zarechnyi, Sverdlovsk Region 624051 (Russian Federation)

    2011-10-01

    The high strength ({alpha} + {beta}) Ti-6Al-4V alloy was selected as the material for flexible attachments of the shield blanket modules in the ITER reactor. The different technologies used for manufacturing this alloy are: forging, stamping or pressing. The microstructures resulting from these processing methods can vary significantly and as a consequence the properties, including irradiation behavior, also vary. There are limited data available on the irradiation behavior of these materials. Specimens cut in the longitudinal and transversal directions of forged and stamped material were studied, with some of the specimens hydrogen charged to {approx}400 ppm H{sub 2}. In the unirradiated condition the forged alloy had slightly more ductility than the stamped alloy. The strength properties of both were practically the same. Neutron irradiation of these materials in the IVV-2M reactor reached doses of {approx}0.2 and 0.3 dpa at temperatures 240-260 deg. C. Irradiation resulted in substantial hardening and significant decrease of the fracture toughness of specimens from both materials.

  19. Subtask 12D6: Fatigue behavior of unirradiated V-5Cr-5Ti

    Energy Technology Data Exchange (ETDEWEB)

    Gieseke, B.G.; Stevens, C.O.; Grossbeck, M.L. [Oak Ridge National Lab., TN (United States)

    1995-03-01

    The objective of this research is to determine the low cycle fatigue behavior of V-5Cr-5Ti alloys for a range of temperatures and the extent of environmental effects at ambient temperatures. The results of in-vacuum low cycle fatigue tests are presented for unirradiated V-5Cr-5Ti tested at room temperature (25, 250, and 400{degrees}C). A comparison of the fatigue data generated in rough and high vacuums shows that a pronounced environmental degradation of the fatigue properties exists in the alloy at room temperature. Fatigue life was reduced by as much as 84%. Cyclic stress range data and SEM observations suggest that this reduction is due to a combination of increases in rates of crack initiation and subsequent growth. The relative contribution of each difference is dependent upon the strain range. In high vacuum, the fatigue results also show a trend of increasing cyclic life with increasing temperature between 25 and 400{degrees}C. From the limited data available, life at 25{degrees}C averages 1.7 times that at 25{degrees}C, and at 400{degrees}C, life averages 3.2 times that at room temperature. Like the environmental effects at 25{degrees}C, the effect of temperature seems to be a function of strain range at each temperature. The total strain range and cycles to failure were correlated using a power law relationship and compared to 20% cold-worked 316 stainless steel and several vanadium-base alloys. The results suggest that V-SCr-5Ti has better resistance to fatigue than 316-SS in the temperature range of 25 to 400{degrees}C. At 400{degrees}C, the data also show that V-5Cr-5Ti out performs Vanstar alloys 7 and 8 over the entire range of strains investigated. Furthermore, the fatigue properties of the V-5Cr-5Ti alloy compare favorably to V-15Cr-57i (at 25{degrees}C) and Vanstar 9 (at 400{degrees}C) at strains greater than 1%. At lower strains, the lower fatigue resistance of V-5Cr-5Ti is attributed to the higher strengths of the V-15Cr-5Ti and Vanstar 9 alloys.

  20. Comparison of ring compression testing to three point bend testing for unirradiated ZIRLO cladding

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2015-04-01

    Safe shipment and storage of nuclear reactor discharged fuel requires an understanding of how the fuel may perform under the various conditions that can be encountered. One specific focus of concern is performance during a shipment drop accident. Tests at Savannah River National Laboratory (SRNL) are being performed to characterize the properties of fuel clad relative to a mechanical accident condition such as a container drop. Unirradiated ZIRLO tubing samples have been charged with a range of hydride levels to simulate actual fuel rod levels. Samples of the hydrogen charged tubes were exposed to a radial hydride growth treatment (RHGT) consisting of heating to 400°C, applying initial hoop stresses of 90 to 170 MPa with controlled cooling and producing hydride precipitates. Initial samples have been tested using both a) ring compression test (RCT) which is shown to be sensitive to radial hydride and b) three-point bend tests which are less sensitive to radial hydride effects. Hydrides are generated in Zirconium based fuel cladding as a result of coolant (water) oxidation of the clad, hydrogen release, and a portion of the released (nascent) hydrogen absorbed into the clad and eventually exceeding the hydrogen solubility limit. The orientation of the hydrides relative to the subsequent normal and accident strains has a significant impact on the failure susceptability. In this study the impacts of stress, temperature and hydrogen levels are evaluated in reference to the propensity for hydride reorientation from the circumferential to the radial orientation. In addition the effects of radial hydrides on the Quasi Ductile Brittle Transition Temperature (DBTT) were measured. The results suggest that a) the severity of the radial hydride impact is related to the hydrogen level-peak temperature combination (for example at a peak drying temperature of 400°C; 800 PPM hydrogen has less of an impact/ less radial hydride fraction than 200 PPM hydrogen for the same thermal

  1. Mechanical properties of type 316L stainless steel welded joint for ITER vacuum vessel (1). Experiment of unirradiated welded joint

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Shigeru; Fukaya, Kiyoshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Ishiyama, Shintaro [Japan Atomic Energy Research Inst., Oarai, Ibaraki (Japan). Oarai Research Establishment; Takahashi, Hiroyuki; Koizumi, Kouichi [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment

    2001-01-01

    In design activity of ITER, the vacuum vessel (VV) is ranked as one of the most important components in core reactor from the view point of first barrier to tritium release from the reactor. The VV of ITER is designed as double walled structure so that some parts of them are not qualified in the conventional design standards. So it is necessary to prepare the new design standards to be applied them. JAERI has executed the preparation activity of the new design standards and the technical data to support them. In this study, the results of metallographic observation and mechanical properties of unirradiated type 316L stainless steel welded joint were reported. (author)

  2. Properties of unirradiated fuel element graphites H-451 and SO818. [Bulk density, tensile properties, thermal expansion, thermal conductivity

    Energy Technology Data Exchange (ETDEWEB)

    Engle, G.B.; Johnson, W.R.

    1976-10-08

    Nuclear graphites H-451, lot 440 (Great Lakes Carbon Corporation (GLCC)), and SO818 (Airco Speer Division, Air Reduction Corporation (AS)) are described, and physical, mechanical, and chemical property data are presented for the graphites in the unirradiated state. A summary of the mean values of the property data and of data on TS-1240 and H-451, lot 426, is tabulated. A direct comparison of H-451, lot 426, chosen for Fort St. Vrain (FSV) fuel reload production, TS-1240, and SO818 may be made from the table. (auth)

  3. Dissolution of unirradiated UO{sub 2} fuel in synthetic groundwater. Final report (1996-1998)

    Energy Technology Data Exchange (ETDEWEB)

    Ollila, K. [VTT Chemical Technology, Espoo (Finland)

    1999-05-01

    This study was a part of the EU R and D programme 1994-1998: Nuclear Fission Safety, entitled `Source term for performance assessment of spent fuel as a waste form`. The research carried out at VTT Chemical Technology was focused on the effects of granitic groundwater composition and redox conditions on UO{sub 2} solubility and dissolution mechanisms. The synthetic groundwater compositions simulated deep granitic fresh and saline groundwaters, and the effects of the near-field material, bentonite, on very saline groundwater. Additionally, the Spanish granite/bentonite water was used. The redox conditions (Eh), which are obviously the most important factors that influence on UO{sub 2} solubility under the disposal conditions of spent fuel, varied from strongly oxidising (air-saturated), anaerobic (N{sub 2}, O{sub 2} < l ppm) to reducing (N{sub 2}, low Eh). The objective of the air-saturated dissolution experiments was to yield the maximum solution concentrations of U, and information on the formation of secondary phases that control the concentrations, with different groundwater compositions. The static batch solubility experiments of long duration (up to 1-2 years) were performed using unirradiated UO{sub 2} pellets and powder. Under anaerobic and reducing conditions, the solubilities were also approached from oversaturation. The results of the oxic, air-saturated dissolution experiments with UO{sub 2} powder showed that the increase in the salinity (< 1.7 M) had a minor effect on the measured steady-state concentrations of U. The concentrations, (1.2 ...2.5) x 10{sup -5} M, were at the level of the theoretical solubility of schoepite or another uranyl oxide hydrate, e.g. becquerelite (possibly Na-polyuranate). The higher alkalinity of the fresh (Allard) composition increased the aqueous U concentration. Only some kind of oxidised U-phase (U{sub 3}O{sub 8}-UO{sub 3}) was identified with XRD when studying possible secondary phases after the contact time of one year

  4. New method to calculate the mechanical properties of unirradiated fuel cladding from ring tensile tests

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Rengel, M.A. [Departamento de Ciencia de Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos, Profesor Aranguren s/n, E-28040 Madrid (Spain); Consejo de Seguridad Nuclear (CSN), Justo Dorado 11, E-28040 Madrid (Spain); Gomez, F.J.; Ruiz-Hervias, J.; Caballero, L.; Valiente, A. [Departamento de Ciencia de Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos, Profesor Aranguren s/n, E-28040 Madrid (Spain)

    2009-06-15

    displacement of the loading piece and another one between the equivalent stress in the same point and the nominal applied stress. In the first iteration a calculation is performed with an approximate plastic stress-strain law, and the two above-mentioned relationships are used to determine a new law from the experimental results. In the second iteration the calculation takes into account the new plastic stress-strain law and determines two new relationships. After a few iterations an excellent fit is obtained. This method is an improvement of the original method by Arsene and Bai [3] and allows obtaining the plastic stress-strain curve in the hoop direction in a consistent way. The experimental data used in this work to check the validity of the procedure have been obtained on unirradiated Zirlo cladding, with the standard alloy composition and geometry (outer diameter of the cladding 9.5 mm and a wall thickness of 0.56 mm). References: [1]. Arsene, S.; Bai, J.B. A new approach to measuring transverse properties of structural tubing by a ring test, Journal of Testing and Evaluation, 24: 386-391 (1996) [2]. Arsene, S.; Bai, J. 'A new approach to measuring transverse properties of structural tubing by a ring test-experimental investigation', Journal of Testing and Evaluation, 26: 26-30 (1998) [3]. Arsene, S.; Bai, J.B.; 'Hydride embrittlement and irradiation effects on the hoop mechanical properties of pressurized water reactor (PWR) and boiling-water reactor (BWR) zircaloy cladding tubes: Part I. Hydride embrittlement in stress-relieved, annealed, and recrystallized zircaloys at 20 deg. C and 300 deg. C', Metallurgical and materials and transactions A, 34A: 553-566 (2003) [4]. Chang-Sun Seok, Bong-Kook, K.Linga, 'The properties of the ring and burst creep of zirlo claddings', Engineering Failure Analysis, 13: 389-397 (2006). (authors)

  5. Special Analysis for the Disposal of the INL Waste Associated with the Unirradiated Light Water Breeder Reactor (LWBR) Waste Stream at the Area 5 Radioactive Waste Management Site

    Energy Technology Data Exchange (ETDEWEB)

    Shott, Gregory [National Security Technologies, LLC, Las Vegas, NV (United States)

    2017-03-21

    This special analysis (SA) evaluates whether the Idaho National Laboratory (INL) Waste Associated with the Unirradiated Light Water Breeder Reactor (LWBR) waste stream (INEL167203QR1, Revision 0) is suitable for shallow land burial (SLB) at the Area 5 Radioactive Waste Management Site (RWMS) on the Nevada National Security Site (NNSS). Disposal of the INL Waste Associated with the Unirradiated LWBR waste meets all U.S. Department of Energy (DOE) Manual DOE M 435.1-1, “Radioactive Waste Management Manual,” Chapter IV, Section P performance objectives (DOE 1999). The INL Waste Associated with the Unirradiated LWBR waste stream is recommended for acceptance with the condition that the total uranium-233 (233U) inventory be limited to 2.7E13 Bq (7.2E2 Ci).

  6. Lift-based up-ender and methods using same to manipulate a shipping container containing unirradiated nuclear fuel

    Energy Technology Data Exchange (ETDEWEB)

    Nilles, Michael J.

    2017-08-01

    A shipping container containing an unirradiated nuclear fuel assembly is lifted off the ground by operating a crane to raise a lifting tool comprising a winch. The lifting tool is connected with the shipping container by a rigging line connecting with the shipping container at a lifting point located on the shipping container between the top and bottom of the shipping container, and by winch cabling connecting with the shipping container at the top of the shipping container. The shipping container is reoriented by operating the winch to adjust the length of the winch cabling so as to rotate the shipping container about the lifting point. Shortening the winch cabling rotates the shipping container about the lifting point from a horizontal orientation to a vertical orientation, while lengthening the winch cabling rotates the shipping container about the lifting point from the vertical orientation to the horizontal orientation.

  7. Radiation quality-dependence of bystander effect in unirradiated fibroblasts is associated with TGF-β1-Smad2 pathway and miR-21 in irradiated keratinocytes

    Science.gov (United States)

    Yin, Xiaoming; Tian, Wenqian; Wang, Longxiao; Wang, Jingdong; Zhang, Shuyu; Cao, Jianping; Yang, Hongying

    2015-01-01

    Traditional radiation biology states that radiation causes damage only in cells traversed by ionizing radiation. But radiation-induced bystander effect (RIBE), which refers to the biological responses in unirradiated cells when the neighboring cells are exposed to radiation, challenged this old dogma and has become a new paradigm of this field. By nature, RIBEs are the consequences of intercellular communication between irradiated and unirradiated cells. However, there are still some important questions remain unanswered such as whether RIBE is dependent on radiation quality, what are the determining factors if so, etc. Using a transwell co-culture system, we found that HaCaT keratinocytes irradiated with α-particles but not X-rays could induce bystander micronucleus formation in unirradiated WS1 fibroblasts after co-culture. More importantly, the activation of TGF-β1-Smad2 pathway and the consistent decrease of miR-21 level in α-irradiated HaCaT cells were essential to the micronucleus induction in bystander WS1 cells. On the other hand, X-irradiation did not induce bystander effect in unirradiated WS1 cells, accompanied by lack of Smad2 activation and consistent decrease of miR-21 in X-irradiated HaCaT cells. Taken together, these results suggest that the radiation quality-dependence of bystander effect may be associated with the TGF-β1-Smad2 pathway and miR-21 in irradiated cells. PMID:26080011

  8. Radiation quality-dependence of bystander effect in unirradiated fibroblasts is associated with TGF-β1-Smad2 pathway and miR-21 in irradiated keratinocytes.

    Science.gov (United States)

    Yin, Xiaoming; Tian, Wenqian; Wang, Longxiao; Wang, Jingdong; Zhang, Shuyu; Cao, Jianping; Yang, Hongying

    2015-06-16

    Traditional radiation biology states that radiation causes damage only in cells traversed by ionizing radiation. But radiation-induced bystander effect (RIBE), which refers to the biological responses in unirradiated cells when the neighboring cells are exposed to radiation, challenged this old dogma and has become a new paradigm of this field. By nature, RIBEs are the consequences of intercellular communication between irradiated and unirradiated cells. However, there are still some important questions remain unanswered such as whether RIBE is dependent on radiation quality, what are the determining factors if so, etc. Using a transwell co-culture system, we found that HaCaT keratinocytes irradiated with α-particles but not X-rays could induce bystander micronucleus formation in unirradiated WS1 fibroblasts after co-culture. More importantly, the activation of TGF-β1-Smad2 pathway and the consistent decrease of miR-21 level in α-irradiated HaCaT cells were essential to the micronucleus induction in bystander WS1 cells. On the other hand, X-irradiation did not induce bystander effect in unirradiated WS1 cells, accompanied by lack of Smad2 activation and consistent decrease of miR-21 in X-irradiated HaCaT cells. Taken together, these results suggest that the radiation quality-dependence of bystander effect may be associated with the TGF-β1-Smad2 pathway and miR-21 in irradiated cells.

  9. Tensile and electrical properties of unirradiated and irradiated Hycon 3HP{trademark} CuNiBe

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-10-01

    The unirradiated tensile properties of two different heats of Hycon 3HP{trademark} CuNiBe (HT Temper) have been measured over the temperature range of 20-500{degrees}C for longitudinal and long transverse orientations. The room temperature electrical conductivity has also been measured for both heats. Both heats exhibited a very good combination of strength and conductivity at room temperature. The strength remained relatively high at all test temperatures, with a yield strength of 420-520 MPa at 500{degrees}C. However, low levels of ductility (<5% uniform elongation) were observed at test temperatures above 200-250{degrees}C, due to flow localization adjacent to grain boundaries. Fission neutron irradiation to a dose of {approximately}0.7 dpa at temperatures between 100 and 240{degrees}C produced a slight increase in strength and a significant decrease in ductility. The measured tensile elongation increased with increasing irradiation temperature, with a uniform elongation of {approximately}3.3% observed at 240{degrees}C. The electrical conductivity decreased slightly following irradiation, due to the presence of defect clusters and Ni, Zn, Co transmutation products. The data indicate that CuNiBe alloys have irradiated tensile and electrical properties comparable or superior to CuCrZr and oxide dispersion strengthened copper at temperatures <250{degrees}C, and may be suitable for certain fusion energy structural applications.

  10. The Analysis of the General Performance and Mechanical Behavior of Unirradiated FeCrAl Alloys Before and After Welding

    Energy Technology Data Exchange (ETDEWEB)

    Gussev, Maxim N. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-06-03

    The present report summarizes and discusses the preliminary results for the in-depth characterization of the modern, nuclear-grade FeCrAl alloys currently under development. The alloys were designed for enhanced radiation tolerance and weldability, and the research is currently being pursued by the Department of Energy (DOE) Nuclear Energy Enabling Technologies (NEET) program. Last year, seven candidate FeCrAl alloys with well-controlled chemistry and microstructures were designed and produced; welding was performed under well-controlled conditions. The structure and general performance of unirradiated alloys were assessed using standardized and advanced microstructural characterization techniques and mechanical testing. The primary objective is to identify the best candidate alloy, or at a minimum to identify the contributing factors that increase the weldability and radiation tolerance of FeCrAl alloys, therefore enabling future generations of FeCrAl alloys to deliver better performance parameters. This report is structured so as to describe these critical assessments of the weldability; radiation tolerance will be reported on in later reports from this program.

  11. Disposition of Unirradiated Sodium Bonded EBR-II Driver Fuel Elements and HEU Scrap: Work Performed for FY 2007

    Energy Technology Data Exchange (ETDEWEB)

    Karen A Moore

    2007-04-01

    Specific surplus high enriched uranium (HEU) materials at the Idaho National Laboratory (INL) Materials and Fuels Complex (MFC) will be transferred to a designated off-site receiving facility. The DOE High Enriched Uranium Disposition Program Office (HDPO) will determine which materials, if any, will be prepared and transferred to an off-site facility for processing and eventual fabrication of fuel for nuclear reactors. These surplus HEU materials include approximately 7200 kg unirradiated sodium-bonded EBR-II driver fuel elements, and nearly 800 kg of HEU casting scrap from the process which formed various sodium-bonded fuels (including the EBR-II driver elements). Before the driver fuel can be packaged for shipment, the fuel elements will require removal of the sodium bond. The HEU scrap will also require repackaging in preparation for off-site transport. Preliminary work on this task was authorized by BWXT Y-12 on Nov 6, 2006 and performed in three areas: • Facility Modifications • Safety Documentation • Project Management

  12. The influence of late-stage pupal irradiation and increased irradiated: un-irradiated male ratio on mating competitiveness of the malaria mosquito Anopheles arabiensis Patton.

    Science.gov (United States)

    Helinski, M E H; Knols, B G J

    2009-06-01

    Competitiveness of released males in genetic control programmes is of critical importance. In this paper, we explored two scenarios to compensate for the loss of mating competitiveness after pupal stage irradiation in males of the malaria mosquito Anopheles arabiensis. First, competition experiments with a higher ratio of irradiated versus un-irradiated males were performed. Second, pupae were irradiated just prior to emergence and male mating competitiveness was determined. Males were irradiated in the pupal stage with a partially or fully-sterilizing dose of 70 or 120 Gy, respectively. Pupae were irradiated aged 20-26 h (young) as routinely performed, or the pupal stage was artificially prolonged by cooling and pupae were irradiated aged 42-48 h (old). Irradiated males competed at a ratio of 3:1:1 to un-irradiated males for mates in a large cage design. At the 3:1 ratio, the number of females inseminated by males irradiated with 70 Gy as young pupae was similar to the number inseminated by un-irradiated males for the majority of the replicates. At 120 Gy, significantly fewer females were inseminated by irradiated than by un-irradiated males. The irradiation of older pupae did not result in a significantly improved male mating competitiveness compared to the irradiation of young pupae. Our findings indicate that the loss of competitiveness after pupal stage irradiation can be compensated for by a threefold increase of irradiated males, but only for the partially-sterilizing dose. In addition, cooling might be a useful tool to facilitate handling processes of large numbers of mosquitoes in genetic control programmes.

  13. Cell cycle tracking for irradiated and unirradiated bystander cells in a single colony with exposure to a soft X-ray microbeam.

    Science.gov (United States)

    Kaminaga, Kiichi; Noguchi, Miho; Narita, Ayumi; Hattori, Yuya; Usami, Noriko; Yokoya, Akinari

    2016-11-01

    To establish a new experimental technique to explore the photoelectric and subsequent Auger effects on the cell cycles of soft X-ray microbeam-irradiated cells and unirradiated bystander cells in a single colony. Several cells located in the center of a microcolony of HeLa-Fucci cells consisting of 20-80 cells were irradiated with soft X-ray (5.35 keV) microbeam using synchrotron radiation as a light source. All cells in the colony were tracked for 72 h by time-lapse microscopy imaging. Cell cycle progression, division, and death of each cell in the movies obtained were analyzed by pedigree assay. The number of cell divisions in the microcolony was also determined. The fates of these cells were clarified by tracking both irradiated and unirradiated bystander cells. Irradiated cells showed significant cell cycle retardation, explosive cell death, or cell fusion after a few divisions. These serious effects were also observed in 15 and 26% of the bystander cells for 10 and 20 Gy irradiation, respectively, and frequently appeared in at least two daughter or granddaughter cells from a single-parent cell. We successfully tracked the fates of microbeam-irradiated cells and unirradiated bystander cells with live cell recordings, which have revealed the dynamics of soft X-ray irradiated and unirradiated bystander cells for the first time. Notably, cell deaths or cell cycle arrests frequently arose in closely related cells. These details would not have been revealed by a conventional immunostaining imaging method. Our approach promises to reveal the dynamic cellular effects of soft X-ray microbeam irradiation and subsequent Auger processes from various endpoints in future studies.

  14. 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.

  15. Oxidative dissolution of unirradiated Mimas MOX fuel (U/Pu oxides) in carbonated water under oxic and anoxic conditions

    Science.gov (United States)

    Odorowski, Mélina; Jégou, Christophe; De Windt, Laurent; Broudic, Véronique; Peuget, Sylvain; Magnin, Magali; Tribet, Magaly; Martin, Christelle

    2016-01-01

    Few studies exist concerning the alteration of Mimas Mixed-OXide (MOX) fuel, a mixed plutonium and uranium oxide, and data is needed to better understand its behavior under leaching, especially for radioactive waste disposal. In this study, two leaching experiments were conducted on unirradiated MOX fuel with a strong alpha activity (1.3 × 109 Bq.gMOX-1 reproducing the alpha activity of spent MOX fuel with a burnup of 47 GWd·tHM-1 after 60 years of decay), one under air (oxic conditions) for 5 months and the other under argon (anoxic conditions with [O2] MOX pellets under both oxic and anoxic conditions were similar, demonstrating the predominant effect of alpha radiolysis on the oxidative dissolution of the pellets. The uranium released was found to be mostly in solution as carbonate species according to modeling, whereas the Am and Pu released were significantly sorbed or precipitated onto the TiO2 reactor. An intermediate fraction of Am (12%) was also present as colloids. SEM and EPMA results indicated a preferential dissolution of the UO2 matrix compared to the Pu-enriched agglomerates, and Raman spectroscopy showed the Pu-enriched agglomerates were slightly oxidized during leaching. Unlike Pu-enriched zones, the UO2 grains were much more sensitive to oxidative dissolution, but the presence of carbonates did not enable observation of an oxidized layer by Raman spectroscopy with the exception of a few areas revealing the presence of U4O9. This data shows the heterogeneous nature of the alteration and the need to combine information from different techniques to determine the origin of releases.

  16. 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...

  17. Special Analysis for the Disposal of the Idaho National Laboratory Unirradiated Light Water Breeder Reactor Rods and Pellets Waste Stream at the Area 5 Radioactive Waste Management Site, Nevada National Security Site, Nye County, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    Shott, Gregory [NSTec

    2014-08-31

    The purpose of this special analysis (SA) is to determine if the Idaho National Laboratory (INL) Unirradiated Light Water Breeder Reactor (LWBR) Rods and Pellets waste stream (INEL103597TR2, Revision 2) is suitable for disposal by shallow land burial (SLB) at the Area 5 Radioactive Waste Management Site (RWMS). The INL Unirradiated LWBR Rods and Pellets waste stream consists of 24 containers with unirradiated fabricated rods and pellets composed of uranium oxide (UO2) and thorium oxide (ThO2) fuel in zirconium cladding. The INL Unirradiated LWBR Rods and Pellets waste stream requires an SA because the 229Th, 230Th, 232U, 233U, and 234U activity concentrations exceed the Nevada National Security Site (NNSS) Waste Acceptance Criteria (WAC) Action Levels.

  18. About the mechanisms governing the hydrogen effect on visco plasticity of unirradiated fully annealed zircaloy-4 sheet

    Energy Technology Data Exchange (ETDEWEB)

    Rupa, N [Electricite de France (EDF), Nuclear Power Div., Lab. Group, 93 - Saint-Denis (France); Clavel, M. [Universite de Technologie de Compiegne, Centre de Recherches de Royalliu, 60 (France); Bouffioux, P.; Domain, C. [Electricite de France, Research engineer, RD Div., Material Study Branch, 77 - Moret sur Loing (France); Legris, A. [Lille-1 Univ., UMR 8517, 59 - Villeneuve-d' Ascq (France)

    2002-07-01

    It has been observed that hydrogen either in solid solution or precipitated under the form of hydrides has an impact on the visco-plasticity of CWSR Zircaloy-4 cladding tubes, increasing significantly the creep resistance. The use of TEM on the structurally complex CWSR material being unlikely to identify the deformation mechanisms, it has been decided to complete this R and D program on recrystallized material. A study has been carried out on fully annealed unirradiated Zircaloy-4 sheet used for the manufacturing of the fuel subassembly grids. Mechanical tests were performed for large ranges of temperatures (300 to 400 deg C), stresses (120 to 250 MPa), and strain rates (2 x 10{sup -7} to 2 x 10{sup -3} s{sup -1}) on as-received and hydrided specimen. The results emphasize: - Hydrogen in solid solution induces a softening of the material. The TEM observations have revealed identical structure of dislocations for both as-received and hydrided specimens. The softening has been particularly observed when dynamic strain aging is activated. It is assumed that atomic hydrogen decreases the dislocation pinning caused by interstitial and/or enhances the intrinsic mobility of the dislocations. With respect to ab initio calculation, atomic hydrogen might be trapped easily by the core of the dislocation, this phenomenon contributing to decrease the lattice friction and to enhance planar glide. - Precipitated hydrides induce a hardening of the material as observed for CWSR Zircaloy 4. The magnitude of the phenomenon depends upon temperature and stress. An analysis of the unload sequences for tension tests and of the secondary strain rates for creep tests leads to the conclusion that hydrides change the kinematics hardening by increasing the internal stress with respect to the as-received material. TEM observation combined with this visco-plasticity approach has revealed that: first, as long as the internal stress is increasing versus plastic strain, hydride are obstacles to

  19. Irradiation programme MANITU: Results of pre-examinations and Charpy tests with unirradiated materials; Bestrahlungsprogramm MANITU. Ergebnisse der Voruntersuchungen und der Kerbschlagbiegeversuche mit den unbestrahlten Werkstoffen

    Energy Technology Data Exchange (ETDEWEB)

    Rieth, M.; Dafferner, B.; Ries, H.; Romer, O.

    1995-04-01

    The irradiation project MANITU was planned in the frame of the European Long-term Fusion Materials Development Programme. The results of MANITU will have a lasting influence on the future actions within the materials development programme. The problem of the irradiation induced embrittlement of possible martensitic alloy candidates is still unsolved. But after the evaluation of sub-size Charpy tests with the unirradiated refrence specimens of MANITU a first tendency is recognizable. The Charpy properties of the newly developed low activation 7-10% Cr-WVTa alloys are clearly better compared with the modified commerical 10-11% Cr-NiMoVNb steels. In the present report the pre-examinations are documented and the Charpy test results with unirradiated reference specimens are analysed and assessed. (orig.) [Deutsch] Das Bestrahlungsprojekt MANITU wurde im Rahmen des europaeischen Langzeitprogramms fuer Materialentwicklung fuer die Kernfusion geplant. Die daraus gewonnenen Ergebnisse werden das weitere Vorgehen bei der Materialentwicklung entscheidend beeinflussen. Das Problem der bestrahlungsinduzierten Versproedung bei den in Frage kommenden martensitischen Werkstoffen ist nach wie vor ungeloest. Eine erste Tendenz zeichnet sich nach der Auswertung der Kerbschlagbiegeversuche an den unbestrahlten miniaturisierten Referenzproben des MANITU-Programms ab. Die neu entwickelten niedrig aktivierbaren 7-10% Cr-WVTa-Legierungen weisen gegenueber den modifizierten kommerziellen 10-11% Cr-NiMoVNb-Staehlen deutlich bessere Kerbschlageigenschaften auf. Im vorliegenden Bericht werden die Voruntersuchungen dokumentiert und die Ergebnisse aus den Kerbschlagbiegeversuchen der unbestrahlten Referenzproben analysiert und bewertet. (orig.)

  20. Model Free Approach for Non-Isothermal Decomposition of Un-Irradiated and g-Irradiated Silver Acetate: New Route for Synthesis of Ag2O Nanoparticles

    Directory of Open Access Journals (Sweden)

    Naser M. Abd El-Salam

    2010-09-01

    Full Text Available Kinetic studies for the non-isothermal decomposition of unirradiated and γ‑irradiated silver acetate with 103 kGy total γ-ray doses were carried out in air. The results showed that the decomposition proceeds in one major step in the temperature range of (180–270 °C with the formation of Ag2O as solid residue. The non-isothermal data for un‑irradiated and γ-irradiated silver acetate were analyzed using Flynn-Wall-Ozawa (FWO and nonlinear Vyazovkin (VYZ iso-conversional methods. These free models on the investigated data showed a systematic dependence of Ea on a indicating a simple decomposition process. No significant changes in the thermal decomposition behavior of silver acetate were recorded as a result of γ-irradiation. Calcinations of γ-irradiated silver acetate (CH3COOAg at 200 °C for 2 hours only led to the formation of pure Ag2O mono-dispersed nanoparticles. X-ray diffraction, FTIR and SEM techniques were employed for characterization of the synthesized nanoparticles.

  1. Radiation induced synthesis of In{sub 2}O{sub 3} nanoparticles - Part II: Synthesis of In{sub 2}O{sub 3} nanoparticles by thermal decomposition of un-irradiated and γ-irradiated indium acetylacetonate

    Energy Technology Data Exchange (ETDEWEB)

    Al-Resheedi, Ajayb Saud; Alhokbany, Norah Saad [Department of Chemistry, College of Science, King Saud University, KSU, (Saudi Arabia); Mahfouz, Refaat Mohammed, E-mail: rmhfouz@science.au.edu.eg [Chemistry Department, Faculty of Science, Assiut University, AUN, (Egypt)

    2015-09-15

    Pure cubic phase, In{sub 2}O{sub 3} nanoparticles with porous structure were synthesized by solid state thermal oxidation of un-irradiated and γ-irradiated indium acetyl acetonate in presence and absence of sodium dodecyl sulphate as surfactant. The as- synthesized In{sub 2}O{sub 3} nanoparticles were characterized by X-ray diffraction (XRD), fourier transformation infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transition electron microscopy (TEM) and thermogravimetry (TG). The shapes and morphologies of as- synthesized In{sub 2}O{sub 3} nanoparticles were highly affected by γ-irradiation of indium acetyl acetonate precursor and by addition of sodium dodecyl sulphate as surfactant. Calcination of un-irradiated indium acetyl acetonate precursor to 4 hours of 600 °C leads to the formation of spherical- shaped accumulative and merged In{sub 2}O{sub 3} nanoparticles with porous structure, whereas irregular porous architectures composed of pure In{sub 2}O{sub 3} nanoparticles were obtained by using γ-irradiated indium acetylacetonate precursor. The as- prepared In{sub 2}O{sub 3} nano products exhibit photoluminescence emission (PL) property and display thermal stability in a wide range of temperature (25-800 °C) which suggest possible applications in nanoscale optoelectronic devices. (author)

  2. The non-targeted effects of radiation are perpetuated by exosomes.

    Science.gov (United States)

    Al-Mayah, Ammar; Bright, Scott; Chapman, Kim; Irons, Sarah; Luo, Ping; Carter, David; Goodwin, Edwin; Kadhim, Munira

    2015-02-01

    Exosomes contain cargo material from endosomes, cytosol, plasma membrane and microRNA molecules, they are released by a number of non-cancer and cancer cells into both the extracellular microenvironment and body fluids such as blood plasma. Recently we demonstrated radiation-induced non-targeted effects [NTE: genomic instability (GI) and bystander effects (BE)] are partially mediated by exosomes, particularly the RNA content. However the mechanistic role of exosomes in NTE is yet to be fully understood. The present study used MCF7 cells to characterise the longevity of exosome-induced activity in the progeny of irradiated and unirradiated bystander cells. Exosomes extracted from conditioned media of irradiated and bystander progeny were added to unirradiated cells. Analysis was carried out at 1 and 20/24 population doublings following medium/exosome transfer for DNA/chromosomal damage. Results confirmed exosomes play a significant role in mediating NTE of ionising radiation (IR). This effect was remarkably persistent, observed >20 doublings post-irradiation in the progeny of bystander cells. Additionally, cell progeny undergoing a BE were themselves capable of inducing BE in other cells via exosomes they released. Furthermore we investigated the role of exosome cargo. Culture media from cells exposed to 2 Gy X-rays was subjected to ultracentrifugation and four inoculants prepared, (a) supernatants with exosomes removed, and pellets with (b) exosome proteins denatured, (c) RNA degraded, and (d) a combination of protein-RNA inactivation. These were added to separate populations of unirradiated cells. The BE was partially inhibited when either exosome protein or exosome RNA were inactivated separately, whilst combined RNA-protein inhibition significantly reduced or eliminated the BE. These results demonstrate that exosomes are associated with long-lived signalling of the NTE of IR. Both RNA and protein molecules of exosomes work in a synergistic manner to initiate NTE

  3. 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,...

  4. 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,...

  5. The non-targeted effects of radiation are perpetuated by exosomes

    Energy Technology Data Exchange (ETDEWEB)

    Al-Mayah, Ammar; Bright, Scott; Chapman, Kim [Genomic Instability Group, Oxford Brookes University, Gipsy Lane Campus, Headington, Oxford OX3 0BP (United Kingdom); Irons, Sarah [Insect Virus Research Group, Oxford Brookes University, Gipsy Lane Campus, Headington, Oxford OX3 0BP (United Kingdom); Luo, Ping [Izon Science Ltd., The Oxford Science Park, Magdalen Centre, Robert Robinson Avenue, Oxford OX4 4GA (United Kingdom); Carter, David [Chromatin and non-coding RNA, Oxford Brookes University, Gipsy Lane Campus, Headington, Oxford OX3 0BP (United Kingdom); Goodwin, Edwin [The New Mexico Consortium, Los Alamos, NM 87544 (United States); Kadhim, Munira, E-mail: mkadhim@brookes.ac.uk [Genomic Instability Group, Oxford Brookes University, Gipsy Lane Campus, Headington, Oxford OX3 0BP (United Kingdom)

    2015-02-15

    Highlights: • Radiation induces a DNA damaging process in bystander cells through cell–cell signalling. • Exosome RNA and protein molecules play crucial roles in bystander effects. • Cell progeny inherit the ability to secret bystander effect-inducing exosomes. • This mechanism is most likely accountable for the propagation of GI. - Abstract: Exosomes contain cargo material from endosomes, cytosol, plasma membrane and microRNA molecules, they are released by a number of non-cancer and cancer cells into both the extracellular microenvironment and body fluids such as blood plasma. Recently we demonstrated radiation-induced non-targeted effects [NTE: genomic instability (GI) and bystander effects (BE)] are partially mediated by exosomes, particularly the RNA content. However the mechanistic role of exosomes in NTE is yet to be fully understood. The present study used MCF7 cells to characterise the longevity of exosome-induced activity in the progeny of irradiated and unirradiated bystander cells. Exosomes extracted from conditioned media of irradiated and bystander progeny were added to unirradiated cells. Analysis was carried out at 1 and 20/24 population doublings following medium/exosome transfer for DNA/chromosomal damage. Results confirmed exosomes play a significant role in mediating NTE of ionising radiation (IR). This effect was remarkably persistent, observed >20 doublings post-irradiation in the progeny of bystander cells. Additionally, cell progeny undergoing a BE were themselves capable of inducing BE in other cells via exosomes they released. Furthermore we investigated the role of exosome cargo. Culture media from cells exposed to 2 Gy X-rays was subjected to ultracentrifugation and four inoculants prepared, (a) supernatants with exosomes removed, and pellets with (b) exosome proteins denatured, (c) RNA degraded, and (d) a combination of protein–RNA inactivation. These were added to separate populations of unirradiated cells. The BE was

  6. 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...

  7. P-selectin is a nanotherapeutic delivery target in the tumor microenvironment.

    Science.gov (United States)

    Shamay, Yosi; Elkabets, Moshe; Li, Hongyan; Shah, Janki; Brook, Samuel; Wang, Feng; Adler, Keren; Baut, Emily; Scaltriti, Maurizio; Jena, Prakrit V; Gardner, Eric E; Poirier, John T; Rudin, Charles M; Baselga, José; Haimovitz-Friedman, Adriana; Heller, Daniel A

    2016-06-29

    Disseminated tumors are poorly accessible to nanoscale drug delivery systems because of the vascular barrier, which attenuates extravasation at the tumor site. We investigated P-selectin, a molecule expressed on activated vasculature that facilitates metastasis by arresting tumor cells at the endothelium, for its potential to target metastases by arresting nanomedicines at the tumor endothelium. We found that P-selectin is expressed on cancer cells in many human tumors. To develop a targeted drug delivery platform, we used a fucosylated polysaccharide with nanomolar affinity to P-selectin. The nanoparticles targeted the tumor microenvironment to localize chemotherapeutics and a targeted MEK (mitogen-activated protein kinase kinase) inhibitor at tumor sites in both primary and metastatic models, resulting in superior antitumor efficacy. In tumors devoid of P-selectin, we found that ionizing radiation guided the nanoparticles to the disease site by inducing P-selectin expression. Radiation concomitantly produced an abscopal-like phenomenon wherein P-selectin appeared in unirradiated tumor vasculature, suggesting a potential strategy to target disparate drug classes to almost any tumor.

  8. 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.

  9. 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

  10. Mitochondrial-targeted human catalase affords neuroprotection from proton irradiation.

    Science.gov (United States)

    Liao, Alicia C; Craver, Brianna M; Tseng, Bertrand P; Tran, Katherine K; Parihar, Vipan K; Acharya, Munjal M; Limoli, Charles L

    2013-07-01

    Significant past work has linked radiation exposure of the CNS to elevated levels of oxidative stress and inflammation. These secondary reactive processes are both dynamic and persistent and are believed to compromise the functionality of the CNS, in part, by disrupting endogenous neurogenesis in the hippocampus. While evidence has shown neurogenesis to be sensitive to irradiation and redox state, the mechanistic basis underlying these effects is incompletely understood. To clarify the role of reactive oxygen species (ROS) in mediating radiation-induced changes in neurogenesis we have analyzed transgenic mice that overexpress human catalase localized to the mitochondria. With this model, we investigated the consequences of low dose and clinically relevant proton irradiation on neurogenesis, and how that process is modified in response to genetic disruption of mitochondrial ROS levels. In unirradiated animals, basal neurogenesis was improved significantly by reductions in mitochondrial ROS. In animals subjected to proton exposure, hippocampal progenitor cell proliferation was attenuated significantly by overexpression of human catalase in the mitochondria. Furthermore, expression of the MCAT transgene significantly improved neurogenesis in WT animals after low-dose proton exposure (0.5 Gy), with similar trends observed at higher dose (2 Gy). Our report documents for the first time the impact of proton irradiation on hippocampal neurogenesis, and the neuroprotective properties of reducing mitochondrial ROS through the targeted overexpression of catalase. © 2013 by Radiation Research Society

  11. 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...

  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 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, ...

  14. 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 ...

  15. 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.

  16. Transduced monocyte/macrophages targeted to murine skin by UV light.

    Science.gov (United States)

    Zhang, Alexandra Y; Wu, Caiyun; Zhou, Lixin; Ismail, Sahar A; Tao, Jianming; McCormick, Laura L; Cooper, Kevin D; Gilliam, Anita C

    2006-01-01

    We have selectively targeted monocyte/macrophages overexpressing an immunomodulatory molecule, latency-associated peptide (LAP), a naturally occurring antagonist for transforming growth factor-beta1, to murine skin utilizing UV light to produce a cutaneous influx of transduced monocyte/macrophages. Bone marrow (BM) cells from BALB/c mice were transduced in vitro with a retroviral construct containing green fluorescent protein (GFP) for detection and human LAP (hLAP) as a test molecule. The transduced BM cells were then cultured in vitro with granulocyte-macrophage colony-stimulating factor (GM-CSF) to produce differentiation to monocyte/macrophages. More than 80% of transduced BM cells were CD11b-positive and MOMA-positive by fluorescence-activated cell-sorter analysis and secreted LAP by ELISA after 10 days of culture in granulocyte-macrophage colony-stimulating factor (GM-CSF). Transduced monocyte/macrophages containing either GFP or hLAP-GFP were then injected intravenously into BALB/c mice. One-half of recipients in each group were exposed to UVB (72 mJ) to induce monocyte/macrophage infiltration into skin. Recipients were sacrificed 60 h after UV irradiation. We found transduced cutaneous macrophages expressing GFP by examining with fluorescence microscopy frozen skin sections of recipient mice immunostained with antibodies to GFP and to macrophage marker F4/80. We identified hLAP sequences by polymerase chain reaction (PCR) of total DNA in recipient blood and UV-irradiated skin but not in unirradiated skin. LAP sequences were also detected at much lower levels in other organs (lung, spleen, and liver) by PCR. Therefore, we have shown that genetically altered monocytic cells can be injected intravenously and targeted to mouse skin by UV exposure. This macrophage-based gene-transfer method may be a potentially useful immunotherapeutic approach for delivering monocyte/macrophage-derived products to skin.

  17. 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.

  18. 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

  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. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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...

  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. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. An ISOLDE target unit

    CERN Multimedia

    Maximilien Brice

    2002-01-01

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

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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...

  14. ISOLDE back on target

    CERN Multimedia

    Anaïs Schaeffer

    2014-01-01

    Today, Friday 1 August, the ISOLDE installation, supplied by the beams of the PS Booster, restarted its physics programme. After a shutdown of almost a year and a half, there was a real buzz in the air as the first beam of protons hit the target of the first post-LS1 ISOLDE experiment.   One of the new target-handling robots installed by ISOLDE during LS1. Many improvements have been made to the ISOLDE installation during LS1. One of the main projects was the installation of new robots for handling the targets (see photo 1). “Our targets are bombarded by protons from the PS Booster’s beams and become very radioactive,” explains Maria Jose Garcia Borge, spokesperson for the ISOLDE collaboration. “They therefore need to be handled carefully, which is where the robots come in. The robots we had until now were already over 20 years old and were starting to suffer from the effects of radiation. So LS1 was a perfect opportunity to replace them with more moder...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

    2016-12-05

    The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. 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.

  8. Implementing Target Value Design.

    Science.gov (United States)

    Alves, Thais da C L; Lichtig, Will; Rybkowski, Zofia K

    2017-04-01

    An alternative to the traditional way of designing projects is the process of target value design (TVD), which takes different departure points to start the design process. The TVD process starts with the client defining an allowable cost that needs to be met by the design and construction teams. An expected cost in the TVD process is defined through multiple interactions between multiple stakeholders who define wishes and others who define ways of achieving these wishes. Finally, a target cost is defined based on the expected profit the design and construction teams are expecting to make. TVD follows a series of continuous improvement efforts aimed at reaching the desired goals for the project and its associated target value cost. The process takes advantage of rapid cycles of suggestions, analyses, and implementation that starts with the definition of value for the client. In the traditional design process, the goal is to identify user preferences and find solutions that meet the needs of the client's expressed preferences. In the lean design process, the goal is to educate users about their values and advocate for a better facility over the long run; this way owners can help contractors and designers to identify better solutions. This article aims to inform the healthcare community about tools and techniques commonly used during the TVD process and how they can be used to educate and support project participants in developing better solutions to meet their needs now as well as in the future.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Thermal compatibility studies of unirradiated UMo alloys dispersed in aluminum

    Science.gov (United States)

    Lee, Don Bae; Kim, Ki Hwan; Kim, Chang Kyu

    1997-11-01

    The thermal compatibility of centrifugally atomized UMo alloys with aluminium has been studied. The results of the investigations show that the U-2 wt% Mo/aluminum dispersions increase in volume by 26% at 400°C after 2000 h. This large volume change is mainly due to the formation of voids and cracks resulting from nearly complete interdiffusion of UMo and aluminum. No significant dimensional changes occur in the U-10 wt% Mo/aluminum dispersions. Interdiffusion between U-10 wt% Mo and aluminum is found to be minimal. The different diffusion behavior is primarily due to the fact that U-10 wt% Mo particles are much more supersaturated with substitutional molybdenum than U-2 wt% Mo particles. The aluminum diffuses into the U-2 wt% Mo particles relatively rapidly along grain boundary with nearly pure uranium, forming UAl 3 almost fully throughout the 2000 h anneal, whereas the molybdenum supersaturated in the U-10 wt% Mo particles inhibits the diffusion of aluminum atoms. U-10 wt% Mo displays superior thermal compatibility with aluminum compared to U-2 wt% Mo.

  17. Plastic flow properties and fracture toughness characterization of unirradiated and irradiated tempered martensitic steels

    Science.gov (United States)

    Spätig, P.; Bonadé, R.; Odette, G. R.; Rensman, J. W.; Campitelli, E. N.; Mueller, P.

    2007-08-01

    We investigate the plastic flow properties at low and high temperature of the tempered martensitic steel Eurofer97. We show that below room temperature, where the Peierls friction on the screw dislocation is active, it is necessary to modify the usual Taylor's equation between the flow stress and the square root of the dislocation density and to include explicitly the Peierls friction stress in the equation. Then, we compare the fracture properties of the Eurofer97 with those of the F82H steel. A clear difference of the fracture toughness-temperature behavior was found in the low transition region. The results indicate a sharper transition for Eurofer97 than for the F82H. Finally, the shift of the median toughness-temperature curve of the F82H steel was determined after two neutron irradiations performed in the High Flux Reactor in Petten.

  18. Distribution of properties in nuclear reactor vessel shells in the unirradiated state

    Science.gov (United States)

    Skundin, M. A.; Chernobaeva, A. A.; Zhurko, D. A.; Krasikov, E. A.; Medvedev, K. I.

    2013-04-01

    The distributions of the chemical composition, the strength characteristics, and critical ductile-brittle transition temperature T cr are studied in the axial, radial, and tangential directions of the material of a test ring cut from a standard forging used for a VVER-1000 reactor vessel shell. The values of T cr of specimens cut from the test ring are shown to be well below those of the internal volume of the shell, which can explain the substantial scatter of the results obtained on reference specimens cut from the base metal.

  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. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. Learning About Intervention Target Zones

    OpenAIRE

    Klein, Michael W; Karen K. Lewis

    1991-01-01

    This paper provides a framework for evaluating how market participants' beliefs about foreign exchange target zones change as they learn about central bank intervention policy. In order to examine this behavior, we first generalize the standard target zone model to allow for intra-marginal intervention. Intra-marginal intervention implies that the position of market participants' beliefs about the target zone can be determined from their beliefs about the likelihood of intervention. As an app...

  16. Therapeutic Targeting of Telomerase

    Directory of Open Access Journals (Sweden)

    Kathrin Jäger

    2016-07-01

    Full Text Available Telomere length and cell function can be preserved by the human reverse transcriptase telomerase (hTERT, which synthesizes the new telomeric DNA from a RNA template, but is normally restricted to cells needing a high proliferative capacity, such as stem cells. Consequently, telomerase-based therapies to elongate short telomeres are developed, some of which have successfully reached the stage I in clinical trials. Telomerase is also permissive for tumorigenesis and 90% of all malignant tumors use telomerase to obtain immortality. Thus, reversal of telomerase upregulation in tumor cells is a potential strategy to treat cancer. Natural and small-molecule telomerase inhibitors, immunotherapeutic approaches, oligonucleotide inhibitors, and telomerase-directed gene therapy are useful treatment strategies. Telomerase is more widely expressed than any other tumor marker. The low expression in normal tissues, together with the longer telomeres in normal stem cells versus cancer cells, provides some degree of specificity with low risk of toxicity. However, long term telomerase inhibition may elicit negative effects in highly-proliferative cells which need telomerase for survival, and it may interfere with telomere-independent physiological functions. Moreover, only a few hTERT molecules are required to overcome senescence in cancer cells, and telomerase inhibition requires proliferating cells over a sufficient number of population doublings to induce tumor suppressive senescence. These limitations may explain the moderate success rates in many clinical studies. Despite extensive studies, only one vaccine and one telomerase antagonist are routinely used in clinical work. For complete eradication of all subpopulations of cancer cells a simultaneous targeting of several mechanisms will likely be needed. Possible technical improvements have been proposed including the development of more specific inhibitors, methods to increase the efficacy of vaccination

  17. Inflation Targeting and Inflation Persistence

    Institute of Scientific and Technical Information of China (English)

    GEORGE; J.BRATSIOTIS; JAKOB; MADSEN; CHRISTOPHER; MARTIN

    2015-01-01

    This paper argues that the adoption of an inflation target reduces the persistence of inflation.We develop the theoretical literature on inflation persistence by introducing a Taylor Rule for monetary policy into a model of persistence and showing that inflation targets reduce inflation persistence.We investigate changes in the time series properties of inflation in seven countries that introduced inflation targets in the late 1980s or early 1990s.We find that the persistence of inflation is greatly reduced or eliminated following the introduction of inflation targets.

  18. Limits of Inflation Targeting Strategy

    Directory of Open Access Journals (Sweden)

    Aura Niculescu

    2006-03-01

    Full Text Available This paper evaluates the trade-off between output volatility and the variability of the inflation rate around its target (Romanian case. The optimal choice for National Bank of Romania (NBR, in our opinion, is the flexible inflation targeting. For this purpose, NBR must explain the loss function and the optimal monetary policy rule. We then argued that this Romanian authority – NBR – can substantially improve its credibility under inflation targeting policy regime by becoming more accountable and transparent. Is the direct inflation targeting the best choice for the monetary policy regime in Romanian economy?

  19. Data Mining for Target Marketing

    Science.gov (United States)

    Levin, Nissan; Zahavi, Jacob

    Targeting is the core of marketing management. It is concerned with offering the right product/service to the customer at the right time and using the proper channel. In this chapter we discuss how Data Mining modeling and analysis can support targeting applications. We focus on three types of targeting models: continuous-choice models, discrete-choice models and in-market timing models, discussing alternative modeling for each application and decision making. We also discuss a range of pitfalls that one needs to be aware of in implementing a data mining solution for a targeting problem.

  20. Target engagement in lead generation.

    Science.gov (United States)

    Durham, Timothy B; Blanco, Maria-Jesus

    2015-03-01

    The pharmaceutical industry is currently facing multiple challenges, in particular the low number of new drug approvals in spite of the high level of R&D investment. In order to improve target selection and assess properly the clinical hypothesis, it is important to start building an integrated drug discovery approach during Lead Generation. This should include special emphasis on evaluating target engagement in the target tissue and linking preclinical to clinical readouts. In this review, we would like to illustrate several strategies and technologies for assessing target engagement and the value of its application to medicinal chemistry efforts.

  1. Literature evidence in open targets - a target validation platform.

    Science.gov (United States)

    Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

    2017-06-06

    We present the Europe PMC literature component of Open Targets - a target validation platform that integrates various evidence to aid drug target identification and validation. The component identifies target-disease associations in documents and ranks the documents based on their confidence from the Europe PMC literature database, by using rules utilising expert-provided heuristic information. The confidence score of a given document represents how valuable the document is in the scope of target validation for a given target-disease association by taking into account the credibility of the association based on the properties of the text. The component serves the platform regularly with the up-to-date data since December, 2015. Currently, there are a total number of 1168365 distinct target-disease associations text mined from >26 million PubMed abstracts and >1.2 million Open Access full text articles. Our comparative analyses on the current available evidence data in the platform revealed that 850179 of these associations are exclusively identified by literature mining. This component helps the platform's users by providing the most relevant literature hits for a given target and disease. The text mining evidence along with the other types of evidence can be explored visually through https://www.targetvalidation.org and all the evidence data is available for download in json format from https://www.targetvalidation.org/downloads/data .

  2. Transverse target spin asymmetries on a proton target at COMPASS

    CERN Document Server

    Richter, Andreas

    2009-01-01

    Transversity and transverse momentum-dependent parton distribution functions (TMDs) are been measured in semi-inclusive deep inelastic scattering (SIDIS) by using a transversely polarized target at the COMPASS experiment. COMPASS is a fixed target experiment at the CERN M2 beamline, which provides a 160GeV/c polarized m+ beam. In the years 2002-2004 COMPASS has collected data with a transversely polarized deuteron 6LiD target. In 2007, COMPASS has used for the first time a proton NH3 target. To access transversity COMPASS has used three different quark polarimeters: the Collins effect, responsible for an azimuthal asymmetry in the single hadron distribution, azimuthal target spin asymmetries of charged hadron pairs and the transverse polarisation of L hyperons. Beside this also the Sivers asymmetry arising from the correlation between the transverse nucleon spin and the quark intrinsic transverse momentum was measured. European

  3. Radiopharmaceuticals targeting melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Pham, T.Q.; Berghofer, P.; Liu, X.; Greguric, I.; Dikic, B.; Ballantyne, P.; Mattner, F.; Nguyen, V.; Loc' h, C.; Katsifis, A. [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Menai, N.S.W., Sydney (Australia)

    2008-02-15

    Melanoma is one of the most aggressive cancers known with a high rate of mortality and increasing global incidence. So, the development of radiopharmaceuticals for either diagnostic or therapeutic purposes could make enormous contributions to melanoma patient health care. We have been studying melanoma tumours through several targeting mechanisms including melanin or specific receptor based radiopharmaceuticals Structure activity studies indicate that the substitution patterns on radioiodinated benzamides significantly influence the uptake mechanism from melanin to sigma-receptor binding. Furthermore, the position of the iodine as well as the presence of key functional groups and substituents has resulted in compounds with varying degrees of activity uptake and retention in tumours. From these results, a novel molecule 2-(2-(4-(4-iodo benzyl)piperazin-1-yl)-2-oxo-ethyl)isoindoline- 1,3-dione (M.E.L.037) was synthesized, labelled with iodine-123 and evaluated for application in melanoma tumour scintigraphy and radiotherapy. The tumour imaging potential of {sup 123}IM.E.L.037 was studied in vivo in C.57 B.L./ 6 J female mice bearing the B.16 F.0. murine melanoma tumour and in BALB/c nude mice bearing the A.375 human amelanotic melanoma tumour by biodistribution, competition studies and by SPECT imaging. {sup 123}I-M.E.L.037 exhibited high and rapid uptake in the B.16 F.0 melanoma tumour at 1 h (13 % I.D./g) increasing with time to reach 25 % I.D./g at 6 h. A significant uptake was also observed in the eyes (2% I.D., at 3-6 h p.i.) of black mice. No uptake was observed in the tumour or in the eyes of nude mice bearing the A.375 tumour. Due to high uptake and long retention in the tumour and rapid body clearance, standardized uptake values(S.U.V.) of {sup 123}I-M.E.L.037 were 30 and 60, at 24 and 48 h p.i.,respectively. SPECT imaging of mice bearing the B.16 melanoma indicated the radioactivity was predominately located in the tumour followed by the eyes, while no

  4. Dual targeting of peroxisomal proteins

    Directory of Open Access Journals (Sweden)

    Julia eAst

    2013-10-01

    Full Text Available Cellular compartmentalization into organelles serves to separate biological processes within the environment of a single cell. While some metabolic reactions are specific to a single organelle, others occur in more than one cellular compartment. Specific targeting of proteins to compartments inside of eukaryotic cells is mediated by defined sequence motifs. To achieve multiple targeting to different compartments cells use a variety of strategies. Here, we focus on mechanisms leading to dual targeting of peroxisomal proteins. In many instances, isoforms of peroxisomal proteins with distinct intracellular localization are encoded by separate genes. But also single genes can give rise to differentially localized proteins. Different isoforms can be generated by use of alternative transcriptional start sites, by differential splicing or ribosomal read-through of stop codons. In all these cases different peptide variants are produced, of which only one carries a peroxisomal targeting signal. Alternatively, peroxisomal proteins contain additional signals that compete for intracellular targeting. Dual localization of proteins residing in both the cytoplasm and in peroxisomes may also result from use of inefficient targeting signals. The recent observation that some bona fide cytoplasmic enzymes were also found in peroxisomes indicates that dual targeting of proteins to both the cytoplasm and the peroxisome might be more widespread. Although current knowledge of proteins exhibiting only partial peroxisomal targeting is far from being complete, we speculate that the metabolic capacity of peroxisomes might be larger than previously assumed.

  5. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Aletaha, Daniel; Bijlsma, Johannes W J

    2010-01-01

    BACKGROUND: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). OBJECTIVE: /st> To develop recommendations for achieving optimal therapeutic outcomes in RA. METHODS...

  6. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Breedveld, Ferdinand C; Burmester, Gerd R

    2016-01-01

    BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards...

  7. ISOLDE target zone control room

    CERN Multimedia

    2016-01-01

    Operating the ISOLDE target handling robots from the dedicated control room in building 197. Monitors showing the movements of the robots (GPS in this case) in the target zone. The footage shows the actual operation by the operator as well as the different equipment such as camera electronics, camera motor controls, camera monitors and Kuka robot controls touch panel.

  8. Targeting vaccines to dendritic cells

    DEFF Research Database (Denmark)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-01-01

    delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC....

  9. Target recognition by wavelet transform

    CERN Document Server

    Li Zheng Dong; He Wu Liang; Pei Chun Lan; Peng Wen; SongChen; Zheng Xiao Dong

    2002-01-01

    Wavelet transform has an important character of multi-resolution power, which presents pyramid structure, and this character coincides the way by which people distinguish object from coarse to fineness and from large to tiny. In addition to it, wavelet transform benefits to reducing image noise, simplifying calculation, and embodying target image characteristic point. A method of target recognition by wavelet transform is provided

  10. Oxide fiber targets at ISOLDE

    DEFF Research Database (Denmark)

    Köster, U.; Bergmann, U.C.; Carminati, D.

    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 oxide fiber targets are less critical since they may maintain their open structure even when starting to fuse together at so...

  11. The Bering Target Tracking Instrumentation

    DEFF Research Database (Denmark)

    Denver, Troelz; Jørgensen, John Leif; Betto, Maurizio

    2003-01-01

    The key science instrument on the Bering satellite mission is a relative small telescope with an entrance aperture of 300 mm and a focal length between 500 and 1000 mm. The detection of potential targets is performed by one of the target scanning advanced stellar compasses (ASCs). This procedure...... results in a simple prioritized list of right ascension, declination, proper motion and intensity of each prospective target. The telescope itself has a dedicated ASC Camera Head Unit (CHU) mounted on the secondary mirror, largely co-aligned with the telescope. This CHU accurately determines the telescope......'s pointing direction. To achieve fast tracking over a large solid angle, the telescope pointing is achieved by means of a folding mirror in the optical pathway. When a prospective target approaches the telescope FOV, the ASC on the secondary will guide the folding mirror into position such that the target...

  12. Target-Searching on Percolation

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    We study target-searching processes on a percolation, on which a hunter tracks a target by smelling odors it emits. The odor intensity is supposed to be inversely proportional to the distance it propagates. The Monte Carlo simulation is performed on a 2-dimensional bond-percolation above the threshold. Having no idea of the location of the target, the hunter determines its moves only by random attempts in each direction. For lager percolation connectivity p (>~) 0.90, it reveals a scaling law for the searching time versus the distance to the position of the target. The scaling exponent is dependent on the sensitivity of the hunter. For smaller p, the scaling law is broken and the probability of finding out the target significantly reduces. The hunter seems trapped in the cluster of the percolation and can hardly reach the goal.

  13. Ocular toxicity of targeted therapies.

    Science.gov (United States)

    Renouf, Daniel J; Velazquez-Martin, Juan P; Simpson, Rand; Siu, Lillian L; Bedard, Philippe L

    2012-09-10

    Molecularly targeted agents are commonly used in oncology practice, and many new targeted agents are currently being tested in clinical trials. Although these agents are thought to be more specific and less toxic then traditional cytotoxic chemotherapy, they are associated with a variety of toxicities, including ocular toxicity. Many of the molecules targeted by anticancer agents are also expressed in ocular tissues. We reviewed the literature for described ocular toxicities associated with both approved and investigational molecularly targeted agents. Ocular toxicity has been described with numerous approved targeted agents and also seems to be associated with several classes of agents currently being tested in early-phase clinical trials. We discuss the proposed pathogenesis, monitoring guidelines, and management recommendations. It is important for oncologists to be aware of the potential for ocular toxicity, with prompt recognition of symptoms that require referral to an ophthalmologist. Ongoing collaboration between oncologists and ocular disease specialists is critical as the use of molecularly targeted agents continues to expand and novel targeted drug combinations are developed.

  14. Targeting Peace: Understanding UN and EU Targeted Sanctions

    OpenAIRE

    2011-01-01

    In recent years, the international community has increasingly come to abandon the use of comprehensive sanctions in favour of targeted sanctions. Unlike adopting a coercive strategy on entire states, actors like the United Nations (UN) and the European Union (EU) have come to resort to measures that are aimed at individuals, groups and government members. Targeted sanctions involve adopting measures such as asset freezes, travel bans, commodity sanctions, as well as arms embargoes. Eriksson a...

  15. Tracking Target and Spiral Waves

    DEFF Research Database (Denmark)

    Jensen, Flemming G.; Sporring, Jon; Nielsen, Mads

    2002-01-01

    A new algorithm for analyzing the evolution of patterns of spiral and target waves in large aspect ratio chemical systems is introduced. The algorithm does not depend on finding the spiral tip but locates the center of the pattern by a new concept, called the spiral focus, which is defined...... by the evolutes of the actual spiral or target wave. With the use of Gaussian smoothing, a robust method is developed that permits the identification of targets and spirals foci independently of the wave profile. Examples of an analysis of long image sequences from experiments with the Belousov...

  16. Tracking Target and Spiral Waves

    DEFF Research Database (Denmark)

    Jensen, Flemming G.; Sporring, Jon; Nielsen, Mads;

    2002-01-01

    A new algorithm for analyzing the evolution of patterns of spiral and target waves in large aspect ratio chemical systems is introduced. The algorithm does not depend on finding the spiral tip but locates the center of the pattern by a new concept, called the spiral focus, which is defined...... by the evolutes of the actual spiral or target wave. With the use of Gaussian smoothing, a robust method is developed that permits the identification of targets and spirals foci independently of the wave profile. Examples of an analysis of long image sequences from experiments with the Belousov...

  17. After treat-to-target

    DEFF Research Database (Denmark)

    Wakefield, Richard J; D'Agostino, Maria Antonietta; Naredo, Esperanza;

    2012-01-01

    have recently formed a research network - the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted...... defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found...... in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who...

  18. Targeted intraoperative radiotherapy in oncology

    CERN Document Server

    Keshtgar, Mohammed; Wenz, Frederik

    2014-01-01

    Targeted intraoperative radiotherapy is a major advance in the management of cancer patients. With an emphasis on practical aspects, this book offers an ideal introduction to this innovative  technology for clinicians.

  19. Targeted therapy: tailoring cancer treatment

    Institute of Scientific and Technical Information of China (English)

    Min Yan; Quentin Qiang Liu

    2013-01-01

    Targeted therapies include small-molecule inhibitors and monoclonal antibodies,have made treatment more tumor-specific and less toxic,and have opened new possibilities for tailoring cancer treatment.Nevertheless,there remain several challenges to targeted therapies,including molecular identification,drug resistance,and exploring reliable biomarkers.Here,we present several selected signaling pathways and molecular targets involved in human cancers including Aurora kinases,PI3K/mTOR signaling,FOXO-FOXM1 axis,and MDM2/MDM4-p53 interaction.Understanding the molecular mechanisms for tumorigenesis and development of drug resistance will provide new insights into drug discovery and design of therapeutic strategies for targeted therapies.

  20. Orthopedic Health: Targeting Musculoskeletal Pain

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Orthopedic Health Targeting Musculoskeletal Pain Past Issues / Spring 2009 ... Ph.D., Chief of the Cartilage Biology and Orthopaedics Branch, holds a vial containing knee cartilage that ...

  1. "Cavitation in a Mercury Target"

    Energy Technology Data Exchange (ETDEWEB)

    West, C.D.

    2000-09-06

    Recent theoretical work on the formation of bubble nucleation centers by energetic particles leads to some reasonably credible calculations of the maximum negative pressure that might be sustained without bubble formation in the mercury target of the Spallation Neutron Source.

  2. Cavitation in a Mercury Target

    Energy Technology Data Exchange (ETDEWEB)

    West, C.D.

    2000-09-01

    Recent theoretical work on the formation of bubble nucleation centers by energetic particles leads to some reasonably credible calculations of the maximum negative pressure that might be sustained without bubble formation in the mercury target of the Spallation Neutron Source.

  3. Strategically targeting MYC in cancer

    Science.gov (United States)

    Posternak, Valeriya; Cole, Michael D.

    2016-01-01

    MYC is a major driver of cancer cell growth and mediates a transcriptional program spanning cell growth, the cell cycle, metabolism, and cell survival. Many efforts have been made to deliberately target MYC for cancer therapy. A variety of compounds have been generated to inhibit MYC function or stability, either directly or indirectly. The most direct inhibitors target the interaction between MYC and MAX, which is required for DNA binding. Unfortunately, these compounds do not have the desired pharmacokinetics and pharmacodynamics for in vivo application. Recent studies report the indirect inhibition of MYC through the development of two compounds, JQ1 and THZ1, which target factors involved in unique stages of transcription. These compounds appear to have significant therapeutic value for cancers with high levels of MYC, although some effects are MYC-independent. These approaches serve as a foundation for developing novel compounds to pharmacologically target MYC-driven cancers. PMID:27081479

  4. A compendium of ERK targets.

    Science.gov (United States)

    Ünal, Evrim B; Uhlitz, Florian; Blüthgen, Nils

    2017-09-01

    The RAF-MEK-ERK cascade is one of the most studied signaling pathways as it controls many vital cellular programs. There has been an immense amount of effort to determine ERK target proteins involved in regulating these programs. Classical biochemical and genetic approaches have elicited hundreds of direct ERK substrates, and with the advent of phospho-proteomic technologies, numerous studies have expanded the number of ERK target proteins. Here, we compile a comprehensive ERK target phospho-site archive, in which we gathered information from various research studies, and we provide this archive as an online database to form a searchable compendium of ERK targets. © 2017 Federation of European Biochemical Societies.

  5. Gene targeting with retroviral vectors

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, J.; Bernstein, A. (Toronto Univ., ON (Canada))

    1989-04-01

    The authors have designed and constructed integration-defective retroviral vectors to explore their potential for gene targeting in mammalian cells. Two nonoverlapping deletion mutants of the bacterial neomycin resistance (neo) gene were used to detect homologous recombination events between viral and chromosomal sequences. Stable neo gene correction events were selected at a frequency of approximately 1 G418/sup r/ cell per 3 x 10/sup 6/ infected cells. Analysis of the functional neo gene in independent targeted cell clones indicated that unintegrated retroviral linear DNA recombined with the target by gene conversion for variable distances into regions of nonhomology. In addition, transient neo gene correction events which were associated with the complete loss of the chromosomal target sequences were observed. These results demonstrated that retroviral vectors can recombine with homologous chromosomal sequences in rodent and human cells.

  6. 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.

  7. Targeted therapy for pediatric glioma

    NARCIS (Netherlands)

    A.K. Olow

    2015-01-01

    This thesis assesses molecular underpinnings of responses to promising targeted agents for pediatric tumors of Central Nervous System (CNS), incorporating preclinical testing of novel and translatable combination therapies to define the best therapy for each tumor cell specific molecular aberration.

  8. Physics of Automatic Target Recognition

    CERN Document Server

    Sadjadi, Firooz

    2007-01-01

    Physics of Automatic Target Recognition addresses the fundamental physical bases of sensing, and information extraction in the state-of-the art automatic target recognition field. It explores both passive and active multispectral sensing, polarimetric diversity, complex signature exploitation, sensor and processing adaptation, transformation of electromagnetic and acoustic waves in their interactions with targets, background clutter, transmission media, and sensing elements. The general inverse scattering, and advanced signal processing techniques and scientific evaluation methodologies being used in this multi disciplinary field will be part of this exposition. The issues of modeling of target signatures in various spectral modalities, LADAR, IR, SAR, high resolution radar, acoustic, seismic, visible, hyperspectral, in diverse geometric aspects will be addressed. The methods for signal processing and classification will cover concepts such as sensor adaptive and artificial neural networks, time reversal filt...

  9. National Ignition Facility Target Chamber

    Energy Technology Data Exchange (ETDEWEB)

    Wavrik, R W; Cox, J R; Fleming, P J

    2000-10-05

    On June 11, 1999 the Department of Energy dedicated the single largest piece of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL) in Livermore, California. The ten (10) meter diameter aluminum target high vacuum chamber will serve as the working end of the largest laser in the world. The output of 192 laser beams will converge at the precise center of the chamber. The laser beams will enter the chamber in two by two arrays to illuminate 10 millimeter long gold cylinders called hohlraums enclosing 2 millimeter capsule containing deuterium, tritium and isotopes of hydrogen. The two isotopes will fuse, thereby creating temperatures and pressures resembling those found only inside stars and in detonated nuclear weapons, but on a minute scale. The NIF Project will serve as an essential facility to insure safety and reliability of our nation's nuclear arsenal as well as demonstrating inertial fusion's contribution to creating electrical power. The paper will discuss the requirements that had to be addressed during the design, fabrication and testing of the target chamber. A team from Sandia National Laboratories (SNL) and LLNL with input from industry performed the configuration and basic design of the target chamber. The method of fabrication and construction of the aluminum target chamber was devised by Pitt-Des Moines, Inc. (PDM). PDM also participated in the design of the chamber in areas such as the Target Chamber Realignment and Adjustment System, which would allow realignment of the sphere laser beams in the event of earth settlement or movement from a seismic event. During the fabrication of the target chamber the sphericity tolerances had to be addressed for the individual plates. Procedures were developed for forming, edge preparation and welding of individual plates. Construction plans were developed to allow the field construction of the target chamber to occur parallel to other NIF construction activities. This

  10. Target-local Gromov compactness

    CERN Document Server

    Fish, Joel W

    2009-01-01

    We prove a version of Gromov's compactness theorem for pseudo-holomorphic curves which holds locally in the target symplectic manifold. This result applies to sequences of curves with an unbounded number of free boundary components, and in families of degenerating target manifolds which have unbounded geometry (e.g. no uniform energy threshold). Core elements of the proof regard curves as submanifolds (rather than maps) and then adapt methods from the theory of minimal surfaces.

  11. Targeted immunotherapy in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2015-01-01

    In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....

  12. Nanotechnology of emerging targeting systems.

    Science.gov (United States)

    Smith, S S

    2008-09-01

    Recent developments in the design and testing of complex nanoscale payload-carrying systems (i.e. systems with payloads that do not exceed 100 nm in size) are the focus of this brief review. Emerging systems include targeted single-walled nanotubes, viral capsids, dendrimers, gold nanoparticles, milled boron carbide nanoparticles, and protein nucleic acid assemblies. Significant advances are emerging with each of these bionanotechnological approaches to cellular targeting.

  13. Theoretical aspects of inflation targeting

    Directory of Open Access Journals (Sweden)

    Obradović Jelena

    2014-01-01

    Full Text Available Inflation targeting is one of the possible strategies used by central banks during conducting monetary policy. The basic characteristics, advantages and disadvantages of inflation targeting will be presented in this paper. The focus is on the the presentation and interpretation of the understanding of this strategy from the perspective of monetarist and Keynesian theory, the theory of rational expectations, and methodological analysis of the strategy in light of the game theory using payoff matrix.

  14. Target Oriented Drugs against Leishmania.

    Science.gov (United States)

    1980-01-31

    the leishmanial source. Leishmanial strains L32 Leishmania tropica LRC L32 L137 Leishmania tropica LRC L137 L52 Leishmania donovani LRC L52 These...RESOLUTION TEST CHAR] 0REPORT NUMBER I TARGET ORIENTED DRUGS AGAINST LEISHMANIA (First Annual Summary Report) 0URI ZEHAVI, PhD and JOSEPH EL-ON, PhD...GOVT ACCESSION NO. 3. RE PIENT.S CATALOG NUMBER A....*( - ) S. TYPE OF REPORT & PERIOD COVERED TARGET ORIENTED DRUGS AGAINST LEISHMANIA 6 FIRST

  15. Nanotechnology of emerging targeting systems

    Science.gov (United States)

    SMITH, S. S.

    2011-01-01

    Recent developments in the design and testing of complex nanoscale payload-carrying systems (i.e. systems with payloads that do not exceed 100 nm in size) are the focus of this brief review. Emerging systems include targeted single-walled nanotubes, viral capsids, dendrimers, gold nanoparticles, milled boron carbide nanoparticles, and protein nucleic acid assemblies. Significant advances are emerging with each of these bionanotechnological approaches to cellular targeting. PMID:21687833

  16. Oxide fiber targets at ISOLDE

    Energy Technology Data Exchange (ETDEWEB)

    Koester, U. E-mail: ulli.koster@cern.ch; Bergmann, U.C.; Carminati, D.; Catherall, R.; Cederkaell, J.; Correia, J.G.; Crepieux, B.; Dietrich, M.; Elder, K.; Fedoseyev, V.N.; Fraile, L.; Franchoo, S.; Fynbo, H.; Georg, U.; Giles, T.; Joinet, A.; Jonsson, O.C.; Kirchner, R.; Lau, Ch.; Lettry, J.; Maier, H.J.; Mishin, V.I.; Oinonen, M.; Peraejaervi, K.; Ravn, H.L.; Rinaldi, T.; Santana-Leitner, M.; Wahl, U.; Weissman, L

    2003-05-01

    Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxide 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 oxide 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 very intense {sup 6}He beams (order of 10{sup 13} ions per second) via the {sup 9}Be(n,{alpha}) reaction using spallation neutrons.

  17. Killing cells by targeting mitosis.

    Science.gov (United States)

    Manchado, E; Guillamot, M; Malumbres, M

    2012-03-01

    Cell cycle deregulation is a common feature of human cancer. Tumor cells accumulate mutations that result in unscheduled proliferation, genomic instability and chromosomal instability. Several therapeutic strategies have been proposed for targeting the cell division cycle in cancer. Whereas inhibiting the initial phases of the cell cycle is likely to generate viable quiescent cells, targeting mitosis offers several possibilities for killing cancer cells. Microtubule poisons have proved efficacy in the clinic against a broad range of malignancies, and novel targeted strategies are now evaluating the inhibition of critical activities, such as cyclin-dependent kinase 1, Aurora or Polo kinases or spindle kinesins. Abrogation of the mitotic checkpoint or targeting the energetic or proteotoxic stress of aneuploid or chromosomally instable cells may also provide further benefits by inducing lethal levels of instability. Although cancer cells may display different responses to these treatments, recent data suggest that targeting mitotic exit by inhibiting the anaphase-promoting complex generates metaphase cells that invariably die in mitosis. As the efficacy of cell-cycle targeting approaches has been limited so far, further understanding of the molecular pathways modulating mitotic cell death will be required to move forward these new proposals to the clinic.

  18. Radiation target analysis of RNA.

    Science.gov (United States)

    Benstein, S L; Kempner, E

    1996-06-25

    Ribozymes are polynucleotide molecules with intrinsic catalytic activity, capable of cleaving nucleic acid substrates. Large RNA molecules were synthesized containing a hammerhead ribozyme moiety of 52 nucleotides linked to an inactive leader sequence, for total lengths of either 262 or 1226 nucleotides. Frozen RNAs were irradiated with high energy electrons. Surviving ribozyme activity was determined using the ability of the irradiated ribozymes to cleave a labeled substrate. The amount of intact RNA remaining was determined from the same irradiated samples by scanning the RNA band following denaturing gel electrophoresis. Radiation target analyses of these data revealed a structural target size of 80 kDa and a ribozyme activity target size of 15 kDa for the smaller ribozyme, and 319 kDa and 16 kDa, respectively, for the larger ribozyme. The disparity in target size for activity versus structure indicates that, in contrast to proteins, there is no spread of radiation damage far from the primary site of ionization in RNA molecules. The smaller target size for activity indicates that only primary ionizations occurring in the specific active region are effective. This is similar to the case for oligosaccharides. We concluded that the presence of the ribose sugar in the polymer chain restricts radiation damage to a small region and prevents major energy transfer throughout the molecule. Radiation target analysis should be a useful technique for evaluating local RNA:RNA and RNA:protein interactions in vitro.

  19. Target-oriented chaos control

    Energy Technology Data Exchange (ETDEWEB)

    Dattani, Justine [Centre for Mathematical Biology, Department of Mathematical Sciences, University of Bath, Bath BA2 7AY (United Kingdom); Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA (United Kingdom); Blake, Jack C.H. [Centre for Mathematical Biology, Department of Mathematical Sciences, University of Bath, Bath BA2 7AY (United Kingdom); Hilker, Frank M., E-mail: f.hilker@bath.ac.uk [Centre for Mathematical Biology, Department of Mathematical Sciences, University of Bath, Bath BA2 7AY (United Kingdom)

    2011-10-31

    Designing intervention methods to control chaotic behavior in dynamical systems remains a challenging problem, in particular for systems that are difficult to access or to measure. We propose a simple, intuitive technique that modifies the values of the state variables directly toward a certain target. The intervention takes into account the difference to the target value, and is a combination of traditional proportional feedback and constant feedback methods. It proves particularly useful when the target corresponds to the equilibrium of the uncontrolled system, and is available or can be estimated from expert knowledge (e.g. in biology and economy). -- Highlights: → We propose a chaos control method that forces the system to a certain target. → The intervention takes into account the difference to the target value. → It can be seen as a combination of proportional and constant feedback methods. → The method is very robust and highly efficient in the long-term. → It is particularly applicable when suitable target values are known or available.

  20. Unification of automatic target tracking and automatic target recognition

    Science.gov (United States)

    Schachter, Bruce J.

    2014-06-01

    The subject being addressed is how an automatic target tracker (ATT) and an automatic target recognizer (ATR) can be fused together so tightly and so well that their distinctiveness becomes lost in the merger. This has historically not been the case outside of biology and a few academic papers. The biological model of ATT∪ATR arises from dynamic patterns of activity distributed across many neural circuits and structures (including retina). The information that the brain receives from the eyes is "old news" at the time that it receives it. The eyes and brain forecast a tracked object's future position, rather than relying on received retinal position. Anticipation of the next moment - building up a consistent perception - is accomplished under difficult conditions: motion (eyes, head, body, scene background, target) and processing limitations (neural noise, delays, eye jitter, distractions). Not only does the human vision system surmount these problems, but it has innate mechanisms to exploit motion in support of target detection and classification. Biological vision doesn't normally operate on snapshots. Feature extraction, detection and recognition are spatiotemporal. When vision is viewed as a spatiotemporal process, target detection, recognition, tracking, event detection and activity recognition, do not seem as distinct as they are in current ATT and ATR designs. They appear as similar mechanism taking place at varying time scales. A framework is provided for unifying ATT and ATR.

  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. Neuroinflammation: a potential therapeutic target.

    Science.gov (United States)

    Craft, Jeffrey M; Watterson, D Martin; Van Eldik, Linda J

    2005-10-01

    The increased appreciation of the importance of glial cell-propagated inflammation (termed 'neuroinflammation') in the progression of pathophysiology for diverse neurodegenerative diseases, has heightened interest in the rapid discovery of neuroinflammation-targeted therapeutics. Efforts include searches among existing drugs approved for other uses, as well as development of novel synthetic compounds that selectively downregulate neuroinflammatory responses. The use of existing drugs to target neuroinflammation has largely met with failure due to lack of efficacy or untoward side effects. However, the de novo development of new classes of therapeutics based on targeting selective aspects of glia activation pathways and glia-mediated pathophysiologies, versus targeting pathways of quantitative importance in non-CNS inflammatory responses, is yielding promising results in preclinical animal models. The authors briefly review selected clinical and preclinical data that reflect the prevailing approaches targeting neuroinflammation as a pathophysiological process contributing to onset or progression of neurodegenerative diseases. The authors conclude with opinions based on recent experimental proofs of concept using preclinical animal models of pathophysiology. The focus is on Alzheimer's disease, but the concepts are transferrable to other neurodegenerative disorders with an inflammatory component.

  3. Integrin Targeted Delivery of Chemotherapeutics

    Directory of Open Access Journals (Sweden)

    Kai Chen, Xiaoyuan Chen

    2011-01-01

    Full Text Available Targeted delivery of chemotherapeutics is defined in the sense, that is, to maximize the therapeutic index of a chemotherapeutic agent by strictly localizing its pharmacological activity to the site or tissue of action. Integrins are a family of heterodimeric transmembrane glycoproteins involved in a wide range of cell-to-extracellular matrix (ECM and cell-to-cell interactions. As cell surface receptors, integrins readily interact with extracellular ligands and play a vital role in angiogenesis, leukocytes function and tumor development, which sets up integrins as an excellent target for chemotherapy treatment. The peptide ligands containing the arginine-glycine-aspartic acid (RGD, which displays a strong binding affinity and selectivity to integrins, particularly to integrin αvβ3, have been developed to conjugate with various conventional chemotherapeutic agents, such as small molecules, peptides and proteins, and nanoparticle-carried drugs for integtrin targeted therapeutic studies. This review highlights the recent advances in integrin targeted delivery of chemotherapeutic agents with emphasis on target of integrin αvβ3, and describes the considerations for the design of the diverse RGD peptide-chemotherapeutics conjugates and their major applications.

  4. CPHD filter derivation for extended targets

    CERN Document Server

    Orguner, Umut

    2010-01-01

    This document derives the CPHD filter for extended targets. Only the update step is derived here. Target generated measurements, false alarms and prior are all assumed to be independent identically distributed cluster processes. We also prove here that the derived CPHD filter for extended targets reduce to PHD filter for extended targets and CPHD filter for standard targets under suitable assumptions.

  5. Ribosome Assembly as Antimicrobial Target

    Directory of Open Access Journals (Sweden)

    Rainer Nikolay

    2016-05-01

    Full Text Available Many antibiotics target the ribosome and interfere with its translation cycle. Since translation is the source of all cellular proteins including ribosomal proteins, protein synthesis and ribosome assembly are interdependent. As a consequence, the activity of translation inhibitors might indirectly cause defective ribosome assembly. Due to the difficulty in distinguishing between direct and indirect effects, and because assembly is probably a target in its own right, concepts are needed to identify small molecules that directly inhibit ribosome assembly. Here, we summarize the basic facts of ribosome targeting antibiotics. Furthermore, we present an in vivo screening strategy that focuses on ribosome assembly by a direct fluorescence based read-out that aims to identify and characterize small molecules acting as primary assembly inhibitors.

  6. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...... take advantage of differentially expressed molecules on the surface of tumor cells, providing effective release of cytotoxic drugs. Several efforts have recently reported the use of diverse molecules as ligands on the surface of nanoparticles to interact with the tumor cells, enabling the effective...... delivery of antitumor agents. Here, we present recent advances in targeted nanoparticles against CRC and discuss the promising use of ligands and cellular targets in potential strategies for the treatment of CRCs....

  7. 3-Bromopyruvate: targets and outcomes.

    Science.gov (United States)

    Shoshan, Maria C

    2012-02-01

    The pyruvate mimetic 3-bromopyruvate (3-BP) is generally presented as an inhibitor of glycolysis and has shown remarkable efficacy in not only preventing tumor growth, but even eradicating existant tumors in animal studies. We here review reported molecular targets of 3-BP and suggest that the very range of possible targets, which pertain to the altered energy metabolism of tumor cells, contributes both to the efficacy and the tumor specificity of the drug. Its in vivo efficacy is suggested to be due to a combination of glycolytic and mitochondrial targets, as well as to secondary effects affecting the tumor microenvironment. The cytotoxicity of 3-BP is less due to pyruvate mimicry than to alkylation of, e.g., key thiols. Alkylation of DNA/RNA has not been reported. More research is warranted to better understand the pharmacokinetics of 3-BP, and its potential toxic effects to normal cells, in particular those that are highly ATP-/mitochondrion-dependent.

  8. Antibiotic drugs targeting bacterial RNAs

    Directory of Open Access Journals (Sweden)

    Weiling Hong

    2014-08-01

    Full Text Available RNAs have diverse structures that include bulges and internal loops able to form tertiary contacts or serve as ligand binding sites. The recent increase in structural and functional information related to RNAs has put them in the limelight as a drug target for small molecule therapy. In addition, the recognition of the marked difference between prokaryotic and eukaryotic rRNA has led to the development of antibiotics that specifically target bacterial rRNA, reduce protein translation and thereby inhibit bacterial growth. To facilitate the development of new antibiotics targeting RNA, we here review the literature concerning such antibiotics, mRNA, riboswitch and tRNA and the key methodologies used for their screening.

  9. Target-Centric Network Modeling

    DEFF Research Database (Denmark)

    Mitchell, Dr. William L.; Clark, Dr. Robert M.

    In Target-Centric Network Modeling: Case Studies in Analyzing Complex Intelligence Issues, authors Robert Clark and William Mitchell take an entirely new approach to teaching intelligence analysis. Unlike any other book on the market, it offers case study scenarios using actual intelligence repor....... Working through these cases, students will learn to manage and evaluate realistic intelligence accounts.......In Target-Centric Network Modeling: Case Studies in Analyzing Complex Intelligence Issues, authors Robert Clark and William Mitchell take an entirely new approach to teaching intelligence analysis. Unlike any other book on the market, it offers case study scenarios using actual intelligence......, and collaborative sharing in the process of creating a high-quality, actionable intelligence product. The case studies reflect the complexity of twenty-first century intelligence issues by dealing with multi-layered target networks that cut across political, economic, social, technological, and military issues...

  10. The SPES direct UCx target

    Science.gov (United States)

    Andrighetto, A.; Antonucci, C.; Barbui, M.; Carturan, S.; Cervellera, F.; Cevolani, S.; Cinausero, M.; Colombo, P.; Dainelli, A.; di Bernardo, P.; Gramegna, F.; Maggioni, G.; Meneghetti, G.; Petrovich, C.; Piga, L.; Prete, G.; Rizzi, V.; Tonezzer, M.; Zafiropoulos, D.; Zanonato, P.

    2007-11-01

    A possible solution for a target system aimed at the production of exotic nuclei as a result of high energy fissions in 238U compounds has been analyzed. The proposed configuration is constituted by a primary proton beam (40 MeV, 0.2 mA) directly impinging on uranium carbide disks inserted within a cylindrical carbon box. This system has been conceived to obtain both a high number of neutron rich atoms (originated from about 1013 fissions/s) and a low power deposition in the target. In order to extract the fission fragments, the box has to be hold at 2000○C. The thermal analysis shows the capability of the thermal radiation to cool the disks with a reasonable margin below the material melting point. Moreover, the analyses of the thermo-mechanical behaviour and of the effusion times confirm the promising features of this target configuration.

  11. A Cryogenic Infrared Calibration Target

    Science.gov (United States)

    Wollack, E. J.; Kinzer, R. E., Jr.; Rinehart, S. A.

    2014-01-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R < or = 0.003, from 800 to 4800/cm (12 - 2 microns ). Upon expanding the spectral range under consideration to 400-10,000/ cm-1 (25 - 1 microns) the observed performance gracefully degrades to R < or = 0.02 at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to approx.4 K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials-Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder-are characterized and presented

  12. Materials considerations in accelerator targets

    Science.gov (United States)

    Peacock, H. B.; Iyer, N. C.; Louthan, M. R.

    1995-09-01

    Future nuclear materials production and/or the burn-up of long lived radioisotopes may be accomplished through the capture of spallation produced neutrons in accelerators. Aluminum clad-lead and/or lead alloys has been proposed as a spallation target. Aluminum was the cladding choice because of the low neutron absorption cross section, fast radioactivity decay, high thermal conductivity, and excellent fabricability. Metallic lead and lead oxide powders were considered for the target core with the fabrication options being casting or powder metallurgy (PM). Scoping tests to evaluate gravity casting, squeeze casting, and casting and swaging processes showed that, based on fabricability and heat transfer considerations, squeeze casting was the preferred option for manufacture of targets with initial core cladding contact. Thousands of aluminum clad aluminum-lithium alloy core targets and control rods for tritium production have been fabricated by coextrusion processes and successfully irradiated in the SRS reactors. Tritium retention in, and release from, the coextruded product was modeled from experimental and operational data. The model assumed that tritium atoms, formed by the 6Li(n,a)3He reaction, were produced in solid solution in the Al-Li alloy. Because of the low solubility of hydrogen isotopes in aluminum alloys, the irradiated Al-Li rapidly became supersaturated in tritium. Newly produced tritium atoms were trapped by lithium atoms to form a lithium tritide. The effective tritium pressure required for trap or tritide stability was the equilibrium decomposition pressure of tritium over a lithium tritide-aluminum mixture. The temperature dependence of tritium release was determined by the permeability of the cladding to tritium and the local equilibrium at the trap sites. The model can be used to calculate tritium release from aluminum clad, aluminum-lithium alloy targets during postulated accelerator operational and accident conditions. This paper describes

  13. [Biotherapy targeting the immune system].

    Science.gov (United States)

    Frenzel, Laurent

    2015-01-01

    The use of monoclonal antibody targeted therapy has changed the management of several diseases, including in hematology and immunology. The panel of the present available biotherapies allows a specific action at various stages of the immune response. Indeed, some of these molecules can target the naive T cell at the immunological synapse or the way of TH1, TH17 and regulatory T cell. Others may be more specific for the B cell and immunoglobulin. Some will even be active on both B and T cells.

  14. Targeted therapies for cutaneous melanoma.

    Science.gov (United States)

    Kee, Damien; McArthur, Grant

    2014-06-01

    Melanoma is resistant to cytotoxic therapy, and treatment options for advanced disease have been limited historically. However, improved understanding of melanoma driver mutations, particularly those involving the mitogen-activated protein kinase pathway, has led to the development of targeted therapies that are effective in this previously treatment-refractory disease. In cutaneous melanomas with BRAF V600 mutations the selective RAF inhibitors, vemurafenib and dabrafenib, and the MEK inhibitor, trametinib, have demonstrated survival benefits. Early signals of efficacy have also been demonstrated with MEK inhibitors in melanomas with NRAS mutations, and KIT inhibitors offer promise in melanomas driven through activation of their target receptor.

  15. Targeting α-synuclein oligomers

    DEFF Research Database (Denmark)

    van Diggelen, Femke

    2017-01-01

    . Although there is currently no cure for PD, αSn oligomers (αSOs) are a potential therapeutic target, but a major drawback it that little is known about the nature of PD-associated αSOs. The scientific literature describes a wide variety of protocols to generate αSOs in vitro, with a subsequent......+/K+ ATPase, V-type ATPase, VDAC, CaMKII and Rab-3A. The identification of these targets is a first step towards unravelling the toxic pathways which are activated upon synaptic binding of extracellularly added αSOs, and hopefully will contribute to the discovery of new disease modifying compounds, which can...

  16. Targeting autophagy in neurodegenerative diseases.

    Science.gov (United States)

    Vidal, René L; Matus, Soledad; Bargsted, Leslie; Hetz, Claudio

    2014-11-01

    The most prevalent neurodegenerative disorders involve protein misfolding and the aggregation of specific proteins. Autophagy is becoming an attractive target to treat neurodegenerative disorders through the selective degradation of abnormally folded proteins by the lysosomal pathway. However, accumulating evidence indicates that autophagy impairment at different regulatory steps may contribute to the neurodegenerative process. Thus, a complex scenario is emerging where autophagy may play a dual role in neurodegenerative diseases by causing the downstream effect of promoting the degradation of misfolded proteins and an upstream effect where its deregulation perturbs global proteostasis, contributing to disease progression. Challenges in the future development of therapeutic strategies to target the autophagy pathway are discussed.

  17. The Bering Autonomous Target Detection

    DEFF Research Database (Denmark)

    Jørgensen, John Leif; Denver, Troelz; Betto, Maurizio

    2003-01-01

    An autonomous asteroid target detection and tracking method has been developed. The method features near omnidirectionality and focus on high speed operations and completeness of search of the near space rather than the traditional faint object search methods, employed presently at the larger...... telescopes. The method has proven robust in operation and is well suited for use onboard spacecraft. As development target for the method and the associated instrumentation the asteroid research mission Bering has been used. Onboard a spacecraft, the autonomous detection is centered around the fully...

  18. Prediction of underwater target strength

    Institute of Scientific and Technical Information of China (English)

    WANG TongQing; Mohammad Amjad

    2001-01-01

    A model as well as its numerical method to calculate target strength of rigid body using Lighthill's acoustic analogy approach which developed from the propeller aircraft sound field study have been presented. The cases of ellipsoid target has been used to demonstrate the approach. The comparison of the numerical results with that of analytical formulation provides a satisfactory check for the validity of the approach. Some reasonable results have been discussed. The advantage of the present model is that it is suitable for any arbitrarily shaped rigid body moving with small Mach number.

  19. Dynamics of aerial target pursuit

    Science.gov (United States)

    Pal, S.

    2015-12-01

    During pursuit and predation, aerial species engage in multitasking behavior that involve simultaneous target detection, tracking, decision-making, approach and capture. The mobility of the pursuer and the target in a three dimensional environment during predation makes the capture task highly complex. Many researchers have studied and analyzed prey capture dynamics in different aerial species such as insects and bats. This article focuses on reviewing the capture strategies adopted by these species while relying on different sensory variables (vision and acoustics) for navigation. In conclusion, the neural basis of these capture strategies and some applications of these strategies in bio-inspired navigation and control of engineered systems are discussed.

  20. Targeting the nuclear RNA exosome

    DEFF Research Database (Denmark)

    Meola, Nicola; Jensen, Torben Heick

    2017-01-01

    Centrally positioned in nuclear RNA metabolism, the exosome deals with virtually all transcript types. This 3'-5' exo- and endo-nucleolytic degradation machine is guided to its RNA targets by adaptor proteins that enable substrate recognition. Recently, the discovery of the 'Poly(A) tail exosome...

  1. Communicating to heterogeneous target groups

    DEFF Research Database (Denmark)

    Pedersen, Karsten

    very often have to communicate to rather heterogeneous target groups that have little more in common than a certain geographical habitat. That goes against most schoolbook teaching in the field of communication, but is none the less the terms with which that kind of communication has to live...

  2. Particle physics using nuclear targets

    Energy Technology Data Exchange (ETDEWEB)

    Ferbel, T.

    1978-01-01

    The use of nuclear targets in particle physics is discussed and some recent results obtained in studies of hadronic interactions on nuclei summarized. In particular experimental findings on inclusive production and on coherent dissociation of mesons and baryons at high energies are presented. 41 references.

  3. High power neutron production targets

    Energy Technology Data Exchange (ETDEWEB)

    Wender, S. [Los Alamos National Lab., NM (United States)

    1996-06-01

    The author describes issues of concern in the design of targets and associated systems for high power neutron production facilities. The facilities include uses for neutron scattering, accelerator driven transmutation, accelerator production of tritium, short pulse spallation sources, and long pulse spallation sources. Each of these applications requires a source with different design needs and consequently different implementation in practise.

  4. Natural products to target inflammation

    NARCIS (Netherlands)

    Allijn, Iris Eva

    2016-01-01

    Chapter 1 Most Western lifestyle diseases such as type 2 diabetes mellitus, cardiovascular disease and cancer have a chronic inflammatory process at its base. Therefore, inflammation is an important therapeutic target. Due to their potency, steroidal drugs dominate the current treatment of

  5. Uranium briquettes for irradiation target

    Energy Technology Data Exchange (ETDEWEB)

    Saliba-Silva, Adonis Marcelo; Garcia, Rafael Henrique Lazzari; Martins, Ilson Carlos; Carvalho, Elita Fontenele Urano de; Durazzo, Michelangelo, E-mail: saliba@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Direct irradiation on targets inside nuclear research or multiple purpose reactors is a common route to produce {sup 99}Mo-{sup 99m}Tc radioisotopes. Nevertheless, since the imposed limits to use LEU uranium to prevent nuclear armament production, the amount of uranium loaded in target meats has physically increased and new processes have been proposed for production. Routes using metallic uranium thin film and UAl{sub x} dispersion have been used for this purpose. Both routes have their own issues, either by bringing difficulties to disassemble the aluminum case inside hot cells or by generating great amount of alkaline radioactive liquid rejects. A potential route might be the dispersion of powders of LEU metallic uranium and nickel, which are pressed as a blend inside a die and followed by pulse electroplating of nickel. The electroplating provides more strength to the briquettes and creates a barrier for gas evolution during neutronic disintegration of {sup 235}U. A target briquette platted with nickel encapsulated in an aluminum case to be irradiated may be an alternative possibility to replace other proposed targets. This work uses pulse Ni-electroplating over iron powder briquette to simulate the covering of uranium by nickel. The following parameters were applied 10 times for each sample: 900Hz, -0.84A/square centimeters with duty cycle of 0.1 in Watts Bath. It also presented the optical microscopy analysis of plated microstructure section. (author)

  6. Targeted therapy using alpha emitters

    Science.gov (United States)

    Vaidyanathan, Ganesan; Zalutsky, Michael R.

    1996-10-01

    Radionuclides such as and which decay by the emission of -particles are attractive for certain applications of targeted radiotherapy. The tissue penetration of and -particles is equivalent to only a few cell diameters, offering the possibility of combining cell-specific targeting with radiation of similar range. Unlike the -particles emitted by radionuclides such as and , -particles are radiation of high linear energy transfer and thus greater biological effectiveness. Several approaches have been explored for targeted radiotherapy with - and -labelled substances including colloids, monoclonal antibodies, metabolic precursors, receptor-avid ligands and other lower molecular weight molecules. An additional agent which exemplifies the promise of -emitting radiopharmaceuticals is meta-[]astatobenzylguanidine. The toxicity of this compound under single-cell conditions, determined both by []thymidine incorporation and by limiting dilution clonogenic assays, for human neuroblastoma cells is of the order of 1000 times higher than that of meta-[]iodobenzylguanidine. For meta-[]astatobenzylguanidine, the value was equivalent to only atoms bound per cell. These results suggest that meta-[]astatobenzylguanidine might be valuable for the targeted radiotherapy of micrometastatic neuroblastomas.

  7. Exploring targeted therapies in oncology

    NARCIS (Netherlands)

    Mom, Constantijne Helene

    2007-01-01

    Targeted therapy in oncology is treatment directed at specific biological pathways and processes that play a critical role in carcinogenesis. Increased knowledge regarding the molecular changes underlying tumor progression and metastatis has resulted in the development of agents that are designed to

  8. Targeted Advertising and Social Status

    NARCIS (Netherlands)

    N. Vikander (Nick)

    2010-01-01

    textabstractThis paper shows how a firm can use non-targeted advertising to exploit consumers' desire for social status. A monopolist sells multiple varieties of a good to consumers who each care about what others believe about his wealth. Advertising allows consumers both to buy different varieties

  9. Bacterial Cytotoxins Target Rho GTPases

    Science.gov (United States)

    Schmidt, Gudula; Aktories, Klaus

    1998-06-01

    Low molecular mass GTPases of the Rho family, which are involved in the regulation of the actin cytoskeleton and in various signal transduction processes, are the eukaryotic targets of bacterial protein toxins. The toxins covalently modify Rho proteins by ADP ribosylation, glucosylation, and deamidation, thereby inactivating and activating the GTPases.

  10. CERN neutrino project on target

    CERN Multimedia

    2005-01-01

    Scientists at CERN announced the completion of the target assembly for the CERN neutrinos to Gran Sasso project, CNGS. On schedule for start-up in May 2006, CNGS will send a beam of neutrinos through the Earth to the Gran Sasso laboratory 730 km away in Italy in a bid to unravel the mysteries of nature's most elusive particles (½ page)

  11. Particle physics using nuclear targets

    Energy Technology Data Exchange (ETDEWEB)

    Ferbel, T.

    1978-01-01

    The use of nuclear targets in particle physics is discussed and some recent results obtained in studies of hadronic interactions on nuclei summarized. In particular experimental findings on inclusive production and on coherent dissociation of mesons and baryons at high energies are presented. 41 references.

  12. Targeted Therapies in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Selen Dogan

    2014-04-01

    Full Text Available Endometrial cancer is the most common genital cancer in developed world. It is generally diagnosed in early stage and it has a favorable prognosis. However, advanced staged disease and recurrences are difficult to manage. There are some common genetic alterations related to endometrial carcinogenesis in similar fashion to other cancers. Personalized medicine, which means selection of best suited treatment for an individual, has gain attention in clinical care of patients in recent years. Targeted therapies were developed as a part of personalized or %u201Ctailored%u201D medicine and specifically acts on a target or biologic pathway. There are quite a number of molecular alteration points in endometrial cancer such as PTEN tumor suppressor genes, DNA mismatch repair genes, PI3K/AKT/mTOR pathway and p53 oncogene which all might be potential candidates for tailored targeted therapy. In recent years targeted therapies has clinical application in ovarian cancer patients and in near future with the advent of new agents these %u201Ctailored%u201D drugs will be in market for routine clinical practice in endometrial cancer patients, in primary disease and recurrences as well.

  13. Aptamers for Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Partha Ray

    2010-05-01

    Full Text Available Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX. SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

  14. Natural products to target inflammation

    NARCIS (Netherlands)

    Allijn, Iris Eva

    2016-01-01

    Chapter 1 Most Western lifestyle diseases such as type 2 diabetes mellitus, cardiovascular disease and cancer have a chronic inflammatory process at its base. Therefore, inflammation is an important therapeutic target. Due to their potency, steroidal drugs dominate the current treatment of inflammat

  15. Tumor targeting via integrin ligands

    Directory of Open Access Journals (Sweden)

    Udaya Kiran eMarelli

    2013-08-01

    Full Text Available Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug delivery systems, and discuss the prospects of such therapies to specifically target tumor cells.

  16. Targeted multi-pinhole SPECT

    NARCIS (Netherlands)

    Branderhorst, W.; Vastenhouw, B.; Van der Have, F.; Blezer, E.L.A.; Bleeker, W.K.; Beekman, F.J.

    2010-01-01

    Purpose: 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

  17. Targeted Therapies for Kidney Cancer

    Science.gov (United States)

    ... The most common side effects seen with this drug include fatigue, rash, diarrhea, increases in blood pressure, and redness, pain, swelling, ... other targets that help cancer cells grow. This drug is taken as a ... effects are nausea, diarrhea, changes in skin or hair color, mouth sores, ...

  18. Manifold knowledge extraction and target recognition

    Science.gov (United States)

    Chao, Cai; Hua, Zhou

    2009-10-01

    Advanced mammalian target identification derived from the perception of target's manifold and measurement manifolddistance. It does not rely on object's segmented accuracy, not depend on target's variety model, and adapt to a range of changes on targets. In this paper, based on the existed manifold learning algorithm, set up a new bionic automatic target recognition model, discussed the targets manifold knowledge acquisition and the knowledge expression architecture, gave a manifold knowledge-based new method for automatic target recognition. Experiments show that the new method has a strong adaptability to targets various transform, and has a very high correctly identification probability.

  19. USING OPTIMAL FEEDBACK CONTROL FOR CHAOS TARGETING

    Institute of Scientific and Technical Information of China (English)

    PENG ZHAO-WANG; ZHONG TING-XIU

    2000-01-01

    Since the conventional open-loop optimal targeting of chaos is very sensitive to noise, a close-loop optimal targeting method is proposed to improve the targeting performance under noise. The present optimal targeting model takes into consideration both precision and speed of the targeting procedure. The parameters, rather than the output, of the targeting controller, are directly optimized to obtain optimal chaos targeting. Analysis regarding the mechanism is given from physics aspect and numerical experiment on the Hénon map is carried out to compare the targeting performance under noise between the close-loop and the open-loop methods.

  20. 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.)

  1. 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.

  2. Emerging targets in human lymphoma: targeting the MYD88 mutation

    Directory of Open Access Journals (Sweden)

    Wang JQ

    2013-08-01

    Full Text Available James Q Wang,* Yogesh S Jeelall,* Keisuke Horikawa* Department of Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia *All authors contributed equally to this manuscript Abstract: B cell neoplasms co-opt the molecular machinery of normal B cells for their survival. Technological advances in cancer genomics has significantly contributed to uncovering the root cause of aggressive lymphomas, revealing a previously unknown link between TLR signaling and B cell neoplasm. Recurrent oncogenic mutations in MYD88 have been found in 39% of the activated B cell-like subtype of diffuse large B cell lymphoma (ABC DLBCL. Interestingly, 29% of ABC DLBCL have a single amino acid substitution of proline for the leucine at position 265 (L265P, and the exact same variant has also been identified in a number of lymphoid malignancies. The MYD88 L265P variant was recently identified in 90% of Wadenstrom's macroglobulinemia patients. These recent developments warrant the need for novel diagnostic tools as well as targeted therapeutics. In this review, we discuss the physiological functions of MYD88 and focus on its role in B cell lymphomas, evaluating the potential for targeting oncogenic MYD88 in lymphoma. Keywords: MYD88, L265P mutation, lymphoma, targeted therapy

  3. CNOOC Lifts 2011 Production Target

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ China National Offshore Oil Corporation (CNOOC), China's top offshore oil and gas producer, has lifted its 2011 production target by up to 11 percent as new projects at home and overseas come on stream.The offshore oil giant, with a market capitalization of about US$105 billion, said in a statement released in late January 2011 that it aimed to produce between 355 and 365 million barrels of oil equivalent (BOE).Oil prices climbed 15 percent in 2010 on the back of expectations that a global economic recovery will drive the demand.Analysts are similarly bullish for 2011, predicting crude prices to trade at around US$100 for the year.CNOOC, the smallest of China's triumvirate of energy companies that also includes CNPC and Sinopee, said it targeted US$8.8 billion in capital expenditure for 2011.

  4. Antihyperlipidemic therapies targeting PCSK9.

    Science.gov (United States)

    Weinreich, Michael; Frishman, William H

    2014-01-01

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

  5. Targeting vaccines to dendritic cells

    DEFF Research Database (Denmark)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-01-01

    to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC...... are considered to play a central role for the provocation of primary immune responses by vaccination. A rational way of improving the potency and safety of new and already existing vaccines could therefore be to direct vaccines specifically to DC. There is a need for developing multifunctional vaccine drug...... delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC....

  6. Endocrine disruptors targeting ERbeta function.

    Science.gov (United States)

    Swedenborg, E; Pongratz, I; Gustafsson, J-A

    2010-04-01

    Endocrine disruptive chemicals (EDCs) circulating in the environment constitute a risk to ecosystems, wildlife and human health. Oestrogen receptor (ER) alpha and beta are targeted by various kinds of EDCs but the molecular mechanisms and long-term consequences of exposure are largely unknown. Some biological effects of EDCs are mediated by the aryl hydrocarbon receptor (AhR), which is a key player in the cellular defence against xenobiotic substances. Adding complexity to the picture, there is also accumulating evidence that AhR-ER pathways have an intricate interplay at multiple levels. In this review, we discuss some EDCs that affect the oestrogen pathway by targeting ERbeta. Furthermore, we describe some effects of AhR activities on the oestrogen system. Mechanisms as well as potential adverse effects on human health are discussed.

  7. Genome engineering with targetable nucleases.

    Science.gov (United States)

    Carroll, Dana

    2014-01-01

    Current technology enables the production of highly specific genome modifications with excellent efficiency and specificity. Key to this capability are targetable DNA cleavage reagents and cellular DNA repair pathways. The break made by these reagents can produce localized sequence changes through inaccurate nonhomologous end joining (NHEJ), often leading to gene inactivation. Alternatively, user-provided DNA can be used as a template for repair by homologous recombination (HR), leading to the introduction of desired sequence changes. This review describes three classes of targetable cleavage reagents: zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR/Cas RNA-guided nucleases (RGNs). As a group, these reagents have been successfully used to modify genomic sequences in a wide variety of cells and organisms, including humans. This review discusses the properties, advantages, and limitations of each system, as well as the specific considerations required for their use in different biological systems.

  8. New therapeutic targets in melanoma.

    Science.gov (United States)

    Martí, R M; Sorolla, A; Yeramian, A

    2012-09-01

    Research into molecular targets for drug development in melanoma is starting to bear fruit. Of the drugs tested to date in patients with metastatic melanoma, those that have yielded the best results are V600E BRAF inhibitors in melanomas carrying the V600E mutation; c-kit tyrosine kinase activity inhibitors in melanomas carrying c-kit mutations; and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, which block the mechanisms involved in immune tolerance. Many problems have yet to be resolved in these areas, however, such as the rapid development of resistance to BRAF and c-kit inhibitors and the lack of biomarkers to predict treatment response in the case of CTLA-4 blockers. We review the results of targeted therapy with these and other drugs in metastatic melanoma and discuss what the future holds for this field. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

  9. Classical scattering from oscillating targets

    Energy Technology Data Exchange (ETDEWEB)

    Papachristou, P.K.; Diakonos, F.K.; Constantoudis, V.; Schmelcher, P.; Benet, L

    2002-12-30

    We study planar classical scattering from an oscillating heavy target whose dynamics defines a five-dimensional phase space. Although the system possesses no periodic orbits, and thus topological chaos is not present, the scattering functions display a variety of structures on different time scales. These structures are due to scattering events with a strong energy transfer from the projectile to the moving disk resulting in low-velocity peaks. We encounter initial conditions for which the projectile exhibits infinitely many bounces with the oscillating disk. Our numerical investigations are supported by analytical results on a specific model with a simple time-law. The observed properties possess universal character for scattering off oscillating targets.

  10. Gastrointestinal hormones and their targets

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2014-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone producing organ in the body. Modern biology makes......, paracrine, spermiocrine secretion etc.), so the same peptide may act as a blood-borne hormone, a neurotransmitter, a local growth factor, or a fertility factor. The molecular targets of each bioactive peptide are specific G-protein coupled receptors expressed in the cell membranes of different target cells...... it feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization...

  11. Recurring Utterances - Targeting a Breakthrough

    Directory of Open Access Journals (Sweden)

    Jacqueline Stark

    2014-05-01

    The most interesting phenomenon is KB’s production of words from former sessions indicating that they are still ‘active’ and the production of completely novel incorrect words. The observable features indicate that immediate auditory processing is possible in the form of repeating target words. However, as soon as KB must retrieve information from the (semantic lexicon, even after being able to correctly ‘repeat’ the target word several times, he responds with a RU, perseveration, or paraphasia. Several of his productions can be characterized as aphasic confabulations which stem from a memory gap. Thus, although KB’s language impairment is severe, his responses across time indicate that step-by-step a breakthrough is being made.

  12. Downstream targets of WRKY33.

    Science.gov (United States)

    Petersen, Klaus; Fiil, Berthe Katrine; Mundy, John; Petersen, Morten

    2008-11-01

    Innate immunity signaling pathways in both animals and plants are regulated by mitogen-activated protein kinase (MAPK) cascades. In a recent publication we show that MPK4 and its substrate MKS1 interact with WRKY33 in vivo, and that WRKY33 is released from complexes with MPK4 upon infection. Transcriptome analysis of a wrky33 loss-of-function mutant identified a subset of defense-related genes as putative targets of WRKY33. These genes include PAD3 and CYP71A13, which encode cytochrome P450 monoxygenases required for synthesis of the antimicrobial phytoalexin camalexin. Chromatin immunoprecipitation confirmed that WRKY33 bound the promoter of PAD3 when plants were inoculated with pathogens. Here we further discuss the involvement of two other targets of WRKY33, NUDT6 and ROF2 in defense responses against invading pathogens.

  13. Downstream targets of WRKY33

    DEFF Research Database (Denmark)

    Petersen, Klaus; Fiil, Berthe Katrine; Mundy, John;

    2008-01-01

    Innate immunity signaling pathways in both animals and plants are regulated by mitogen-activated protein kinase (MAPK) cascades. In a recent publication we show that MPK4 and its substrate MKS1 interact with WRKY33 in vivo, and that WRKY33 is released from complexes with MPK4 upon infection....... Transcriptome analysis of a wrky33 loss-of-function mutant identified a subset of defense-related genes as putative targets of WRKY33. These genes include PAD3 and CYP71A13, which encode cytochrome P450 monoxygenases required for synthesis of the antimicrobial phytoalexin camalexin. Chromatin...... immunoprecipitation confirmed that WRKY33 bound the promoter of PAD3 when plants were inoculated with pathogens. Here we further discuss the involvement of two other targets of WRKY33, NUDT6 and ROF2 in defense responses against invading pathogens....

  14. Targeted Communication and Investor Attention

    OpenAIRE

    Boulland, Romain; Degeorge, François; Ginglinger, Edith

    2012-01-01

    In the spirit of Merton (1987) we find that targeted communication by firms raises investor attention. Continental European firms using English-language commercial press wires to disseminate corporate press releases exhibit less drift and more trading volume after their earnings announcements than firms that do not, consistent with communication on English speaking wires raising investor attention. Continental European firms using English-language commercial press wires also receive more pres...

  15. Cancer Immunotherapy of Targeting Angiogenesis

    Institute of Scientific and Technical Information of China (English)

    JianmeiHou; LingTian; YuquanWei

    2004-01-01

    Tumor growth and metastasis are angiogenesis-dependent. Anti-angiogenic therapy may be a useful approach to cancer therapy. This review discussed tumor angiogenesis and immunotherapy of targeting tumor angiogenesis from two main aspects: (1) active vaccination to induce effective anti-angiogenesis immunity; (2) passive immunotherapy with anti-pro-angiogenic molecules relevant antibody. Evidence from the recent years suggested that anti-angiogenic therapy should be one of the most promising approaches to cancer therapy.

  16. The Automatic Measurement of Targets

    DEFF Research Database (Denmark)

    Höhle, Joachim

    1997-01-01

    The automatic measurement of targets is demonstrated by means of a theoretical example and by an interactive measuring program for real imagery from a réseau camera. The used strategy is a combination of two methods: the maximum correlation coefficient and the correlation in the subpixel range. F...... interactive software is also part of a computer-assisted learning program on digital photogrammetry....

  17. Theranostics Targeting Metastatic Breast Cancer

    Science.gov (United States)

    2016-10-01

    2016. Active Targeting of Cancer Cells, Masaryk University, CZECH REPUBLIC, May 2016. Websites or other Internet sites none Technologies or... trafficking , thus impacting the efficacy of receptor-mediated drug delivery for cancer therapy. These factors include the following: (i) the rate of ligand...The V, Labrie C, Belanger A, Simard J, Lin SX, Pelletier G. Endocrine and intracrine sources of androgens in women : Inhibition of breast cancer and

  18. Nonlinear Acoustic Characterization of Targets

    Science.gov (United States)

    2008-01-01

    matching so as to transmit as much energy as possible into the test object. In addition to this limitation, ultrasound is only able to measure range by...metric arrays for standoff analysis of targets. In 1982, Yoneyama[4] discussed the nonlinear interaction of ultrasound with air as the “scattering of... cavitation effect. This produces a rectification at higher frequencies just as a diode does in an electrical circuit. This natural rectification allows

  19. Electronic warfare target location methods

    CERN Document Server

    Poisel, Richard

    2012-01-01

    Describing the mathematical development underlying current and classical methods of geolocating electronic systems that are emitting, this newly revised and greatly expanded edition of a classic Artech House book offers practical guidance in electronic warfare target location. The Second Edition features a wealth of additional material including new chapters on time delay estimation, direction finding techniques, and the MUSIC algorithm. This practical resource provides you with critical design information on geolocation algorithms, and establishes the fundamentals of existing algorithms as a

  20. Targeting inflammation in metabolic syndrome.

    Science.gov (United States)

    Welty, Francine K; Alfaddagh, Abdulhamied; Elajami, Tarec K

    2016-01-01

    The metabolic syndrome (MetS) is comprised of a cluster of closely related risk factors, including visceral adiposity, insulin resistance, hypertension, high triglyceride, and low high-density lipoprotein cholesterol; all of which increase the risk for the development of type 2 diabetes and cardiovascular disease. A chronic state of inflammation appears to be a central mechanism underlying the pathophysiology of insulin resistance and MetS. In this review, we summarize recent research which has provided insight into the mechanisms by which inflammation underlies the pathophysiology of the individual components of MetS including visceral adiposity, hyperglycemia and insulin resistance, dyslipidemia, and hypertension. On the basis of these mechanisms, we summarize therapeutic modalities to target inflammation in the MetS and its individual components. Current therapeutic modalities can modulate the individual components of MetS and have a direct anti-inflammatory effect. Lifestyle modifications including exercise, weight loss, and diets high in fruits, vegetables, fiber, whole grains, and low-fat dairy and low in saturated fat and glucose are recommended as a first line therapy. The Mediterranean and dietary approaches to stop hypertension diets are especially beneficial and have been shown to prevent development of MetS. Moreover, the Mediterranean diet has been associated with reductions in total and cardiovascular mortality. Omega-3 fatty acids and peroxisome proliferator-activated receptor α agonists lower high levels of triglyceride; their role in targeting inflammation is reviewed. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockers comprise pharmacologic therapies for hypertension but also target other aspects of MetS including inflammation. Statin drugs target many of the underlying inflammatory pathways involved in MetS.

  1. FAST DETECTING TARGET GROUPS IN SAR IMAGES

    Institute of Scientific and Technical Information of China (English)

    Gao Gui; Kuang Gangyao; Jiang Yongmei; Wang Baosun; Gao Sheng

    2006-01-01

    A successful algorithm for detecting target groups is presented. Firstly, A global Constant False Alarm Rate (CFAR) detector is utilized to locate the potential target regions, and then the features are computed for target discrimination based on voting mechanism. Finally, Target groups are extracted. The results of experiments show the validity of this algorithm.

  2. Progress of gene targeting in mouse

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Gene targeting is a powerful approach of study- ing the genefunction in vivo. Specific genetic modifications, including simple gene disruption, point mutations, large chromosomal deletions and rearrangements, targeted incor- poration of foreign genes, could be introduced into the mouse genome by gene targeting. Recent studies make it possible to do the gene targeting with temporal and spatial control.

  3. Targeted therapies in hepatocellular carcinoma.

    Science.gov (United States)

    Bronte, F; Bronte, G; Cusenza, S; Fiorentino, E; Rolfo, C; Cicero, G; Bronte, E; Di Marco, V; Firenze, A; Angarano, G; Fontana, T; Russo, A

    2014-01-01

    The onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients are conflicting. To date various new target drugs are under developed and other biological treatments normally indicated in other malignancies are under investigation also for HCC. These strategies aim to target the different biological pathways implicated in HCC development and progression. The target drugs studied in HCC include anti-VEGF and anti-EGFR monoclonal antibodies, tyrosine kinase inhibitors and mTOR inhibitors. The most important challenge is represented by the best integration of these drugs with standard treatments to achieve improvement in overall survival and quality of life.

  4. 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.

  5. Renal Toxicities of Targeted Therapies.

    Science.gov (United States)

    Abbas, Anum; Mirza, Mohsin M; Ganti, Apar Kishor; Tendulkar, Ketki

    2015-12-01

    With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease.

  6. A Cryogenic Infrared Calibration Target

    CERN Document Server

    Wollack, Edward J; Rinehart, Stephan A

    2014-01-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, $R \\le 0.003$, from $800-4,800\\,{\\rm cm}^{-1}$ $(12-2\\,\\mu$m). Upon expanding the spectral range under consideration to $400-10,000\\,{\\rm cm}^{-1}$ $(25-1\\,\\mu$m) the observed performance gracefully degrades to $R \\le 0.02$ at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to $\\sim4\\,$K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials -- Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder -- are character...

  7. Phenotypic screens targeting neurodegenerative diseases.

    Science.gov (United States)

    Zhang, Minhua; Luo, Guangrui; Zhou, Yanjiao; Wang, Shaohui; Zhong, Zhong

    2014-01-01

    Neurodegenerative diseases affect millions of people worldwide, and the incidences increase as the population ages. Disease-modifying therapy that prevents or slows disease progression is still lacking, making neurodegenerative diseases an area of high unmet medical need. Target-based drug discovery for disease-modifying agents has been ongoing for many years, without much success due to incomplete understanding of the molecular mechanisms underlying neurodegeneration. Phenotypic screening, starting with a disease-relevant phenotype to screen for compounds that change the outcome of biological pathways rather than activities at certain specific targets, offers an alternative approach to find small molecules or targets that modulate the key characteristics of neurodegeneration. Phenotypic screens that focus on amelioration of disease-specific toxins, protection of neurons from degeneration, or promotion of neuroregeneration could be potential fertile grounds for discovering therapeutic agents for neurodegenerative diseases. In this review, we will summarize the progress of compound screening using these phenotypic-based strategies for this area, with a highlight on unique considerations for disease models, assays, and screening methodologies. We will further provide our perspectives on how best to use phenotypic screening to develop drug leads for neurodegenerative diseases.

  8. Mitochondrially targeted fluorescent redox sensors.

    Science.gov (United States)

    Yang, Kylie; Kolanowski, Jacek L; New, Elizabeth J

    2017-04-06

    The balance of oxidants and antioxidants within the cell is crucial for maintaining health, and regulating physiological processes such as signalling. Consequently, imbalances between oxidants and antioxidants are now understood to lead to oxidative stress, a physiological feature that underlies many diseases. These processes have spurred the field of chemical biology to develop a plethora of sensors, both small-molecule and fluorescent protein-based, for the detection of specific oxidizing species and general redox balances within cells. The mitochondrion, in particular, is the site of many vital redox reactions. There is therefore a need to target redox sensors to this particular organelle. It has been well established that targeting mitochondria can be achieved by the use of a lipophilic cation-targeting group, or by utilizing natural peptidic mitochondrial localization sequences. Here, we review how these two approaches have been used by a number of researchers to develop mitochondrially localized fluorescent redox sensors that are already proving useful in providing insights into the roles of reactive oxygen species in the mitochondria.

  9. NEW DRUG TARGETING TREATMENT - GLIVEC

    Institute of Scientific and Technical Information of China (English)

    SUN Xue-mei(孙雪梅); BRADY Ben

    2003-01-01

    This review evaluates the role of Glivec in the treatment of chronic myelogenous leukemia and other malignant tumors. Preclinical and clinical evidence showed that Glivec demonstrated a potent and specific inhibition on BCR-ABL positive leukemias and other malignant tumors in which overexpression of c-kit and PDGFR-β played a major role in their pathogenesis. Glivec has induced complete hematologic responses in up to 98% of patients evaluated in clinical trials. It's a very successful drug that supported the idea of targeted therapy through inhibition of tyrosine kinases. Although it's still in the early stages of clinical development and the resistance to Glivec remains to be a problem needed further study, a great deal has been learned from these research and observation. And with the increasing data, molecular targeting therapy will play much more important role in the treatment of malignant tumors. With the better understanding of the pathogenesis of malignant tumors, well-designed drugs targeting the specific molecular abnormalities with higher efficacy and lower side effect will benefit numerous patients with malignant tumors.

  10. Multisensor Target Detection And Classification

    Science.gov (United States)

    Ruck, Dennis W.; Rogers, Steven K.; Mills, James P.; Kabrisky, Matthew

    1988-08-01

    In this paper a new approach to the detection and classification of tactical targets using a multifunction laser radar sensor is developed. Targets of interest are tanks, jeeps, trucks, and other vehicles. Doppler images are segmented by developing a new technique which compensates for spurious doppler returns. Relative range images are segmented using an approach based on range gradients. The resultant shapes in the segmented images are then classified using Zernike moment invariants as shape descriptors. Two classification decision rules are implemented: a classical statistical nearest-neighbor approach and a multilayer perceptron architecture. The doppler segmentation algorithm was applied to a set of 180 real sensor images. An accurate segmentation was obtained for 89 percent of the images. The new doppler segmentation proved to be a robust method, and the moment invariants were effective in discriminating the tactical targets. Tanks were classified correctly 86 percent of the time. The most important result of this research is the demonstration of the use of a new information processing architecture for image processing applications.

  11. Targeted gene flow for conservation.

    Science.gov (United States)

    Kelly, Ella; Phillips, Ben L

    2016-04-01

    Anthropogenic threats often impose strong selection on affected populations, causing rapid evolutionary responses. Unfortunately, these adaptive responses are rarely harnessed for conservation. We suggest that conservation managers pay close attention to adaptive processes and geographic variation, with an eye to using them for conservation goals. Translocating pre-adapted individuals into recipient populations is currently considered a potentially important management tool in the face of climate change. Targeted gene flow, which involves moving individuals with favorable traits to areas where these traits would have a conservation benefit, could have a much broader application in conservation. Across a species' range there may be long-standing geographic variation in traits or variation may have rapidly developed in response to a threatening process. Targeted gene flow could be used to promote natural resistance to threats to increase species resilience. We suggest that targeted gene flow is a currently underappreciated strategy in conservation that has applications ranging from the management of invasive species and their impacts to controlling the impact and virulence of pathogens.

  12. Therapeutic targets in liver fibrosis.

    Science.gov (United States)

    Fallowfield, Jonathan A

    2011-05-01

    Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points.

  13. Method for forming electrically charged laser targets

    Science.gov (United States)

    Goodman, Ronald K.; Hunt, Angus L.

    1979-01-01

    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.

  14. Classical Geometry and Target Space Duality

    OpenAIRE

    1995-01-01

    This is the written version of lectures presented at Cargese 95. A new formulation for a ``restricted'' type of target space duality in classical two dimensional nonlinear sigma models is presented. The main idea is summarized by the analogy: euclidean geometry is to riemannian geometry as toroidal target space duality is to ``restricted'' target space duality. The target space is not required to possess symmetry. These lectures only discuss the local theory. The restricted target space duali...

  15. Targeted Therapy in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Murray Baron

    2016-10-01

    Full Text Available Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc. The well-known properties of transforming growth factor (TGF-β in promoting collagen synthesis and secretion has led to a small trial of fresolimumab, a human IgG4 monoclonal antibody capable of neutralizing TGF-β. Evidence supporting important roles for interleukin-6 in the pathogenesis of SSc have led to a large trial of tocilizumab in SSc. Soluble guanylate cyclase (sGC is an enzyme that catalyzes the production of cyclic guanosine monophosphate (cGMP upon binding of nitric oxide (NO to the sGC molecule. Processes such as cell growth and proliferation are regulated by cGMP. Evidence that sGC may play a role in SSc has led to a trial of riociguat, a molecule that sensitizes sGC to endogenous NO. Tyrosine kinases (TKs are involved in a wide variety of physiologic and pathological processes including vascular remodeling and fibrogenesis such as occurs in SSc. This has led to a trial of nintedanib, a next-generation tyrosine-kinase (TK inhibitor which targets multiple TKs, in SSc.

  16. Hospitals: Soft Target for Terrorism?

    Science.gov (United States)

    De Cauwer, Harald; Somville, Francis; Sabbe, Marc; Mortelmans, Luc J

    2017-02-01

    In recent years, the world has been rocked repeatedly by terrorist attacks. Arguably, the most remarkable were: the series of four coordinated suicide plane attacks on September 11, 2001 on buildings in New York, Virginia, and Pennsylvania, USA; and the recent series of two coordinated attacks in Brussels (Belgium), on March 22, 2016, involving two bombings at the departure hall of Brussels International Airport and a bombing at Maalbeek Metro Station located near the European Commission headquarters in the center of Brussels. This statement paper deals with different aspects of hospital policy and disaster response planning that interface with terrorism. Research shows that the availability of necessary equipment and facilities (eg, personal protective clothing, decontamination rooms, antidotes, and anti-viral drugs) in hospitals clearly is insufficient. Emergency teams are insufficiently prepared: adequate and repetitive training remain necessary. Unfortunately, there are many examples of health care workers and physicians or hospitals being targeted in both political or religious conflicts and wars. Many health workers were kidnapped and/or killed by insurgents of various ideology. Attacks on hospitals also could cause long-term effects: hospital units could be unavailable for a long time and replacing staff could take several months, further compounding hospital operations. Both physical and psychological (eg, posttraumatic stress disorder [PTSD]) after-effects of a terrorist attack can be detrimental to health care services. On the other hand, physicians and other hospital employees have shown to be involved in terrorism. As data show that some offenders had a previous history with the location of the terror incident, the possibility of hospitals or other health care services being targeted by insiders is discussed. The purpose of this report was to consider how past terrorist incidents can inform current hospital preparedness and disaster response planning

  17. Targeted Radionuclide Therapy of Melanoma.

    Science.gov (United States)

    Norain, Abdullah; Dadachova, Ekaterina

    2016-05-01

    An estimated 60,000 individuals in the United States and 132,000 worldwide are yearly diagnosed with melanoma. Until recently, treatment options for patients with stages III-IV metastatic disease were limited and offered marginal, if any, improvement in overall survival. The situation changed with the introduction of B-RAF inhibitors and anti-cytotoxic T-lymphocyte antigen 4 and anti-programmed cell death protein 1 immunotherapies into the clinical practice. With only some patients responding well to the immune therapies and with very serious side effects and high costs of immunotherapy, there is still room for other approaches for the treatment of metastatic melanoma. Targeted radionuclide therapy of melanoma could be divided into the domains of radioimmunotherapy (RIT), radiolabeled peptides, and radiolabeled small molecules. RIT of melanoma is currently experiencing a renaissance with the clinical trials of alpha-emitter (213)Bi-labeled and beta-emitter (188)Rhenium-labeled monoclonal antibodies in patients with metastatic melanoma producing encouraging results. The investigation of the mechanism of efficacy of melanoma RIT points at killing of melanoma stem cells by RIT and involvement of immune system such as complement-dependent cytotoxicity. The domain of radiolabeled peptides for targeted melanoma therapy has been preclinical so far, with work concentrated on radiolabeled peptide analogues of melanocyte-stimulating hormone receptor and on melanin-binding peptides. The field of radiolabeled small molecule produced radioiodinated benzamides that cross the cellular membrane and bind to the intracellular melanin. The recent clinical trial demonstrated measurable antitumor effects and no acute or midterm toxicities. We are hopeful that the targeted radionuclide therapy of metastatic melanoma would become a clinical reality as a stand-alone therapy or in combination with the immunotherapies such as anti-PD1 programmed cell death protein 1 monoclonal antibodies

  18. Targeted Nanotechnology in Glioblastoma Multiforme

    Science.gov (United States)

    Glaser, Talita; Han, Inbo; Wu, Liquan; Zeng, Xiang

    2017-01-01

    Gliomas, and in particular glioblastoma multiforme, are aggressive brain tumors characterized by a poor prognosis and high rates of recurrence. Current treatment strategies are based on open surgery, chemotherapy (temozolomide) and radiotherapy. However, none of these treatments, alone or in combination, are considered effective in managing this devastating disease, resulting in a median survival time of less than 15 months. The efficiency of chemotherapy is mainly compromised by the blood-brain barrier (BBB) that selectively inhibits drugs from infiltrating into the tumor mass. Cancer stem cells (CSCs), with their unique biology and their resistance to both radio- and chemotherapy, compound tumor aggressiveness and increase the chances of treatment failure. Therefore, more effective targeted therapeutic regimens are urgently required. In this article, some well-recognized biological features and biomarkers of this specific subgroup of tumor cells are profiled and new strategies and technologies in nanomedicine that explicitly target CSCs, after circumventing the BBB, are detailed. Major achievements in the development of nanotherapies, such as organic poly(propylene glycol) and poly(ethylene glycol) or inorganic (iron and gold) nanoparticles that can be conjugated to metal ions, liposomes, dendrimers and polymeric micelles, form the main scope of this summary. Moreover, novel biological strategies focused on manipulating gene expression (small interfering RNA and clustered regularly interspaced short palindromic repeats [CRISPR]/CRISPR associated protein 9 [Cas 9] technologies) for cancer therapy are also analyzed. The aim of this review is to analyze the gap between CSC biology and the development of targeted therapies. A better understanding of CSC properties could result in the development of precise nanotherapies to fulfill unmet clinical needs.

  19. Targeting ECM Disrupts Cancer Progression.

    Science.gov (United States)

    Venning, Freja A; Wullkopf, Lena; Erler, Janine T

    2015-01-01

    Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.

  20. Targeting ECM Disrupts Cancer Progression

    Science.gov (United States)

    Venning, Freja A.; Wullkopf, Lena; Erler, Janine T.

    2015-01-01

    Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression. PMID:26539408

  1. Radar Imaging for Moving Targets

    Science.gov (United States)

    2009-06-01

    solution as scatt (x)  Gk (x ’, x)(x ’)D  inc (x ’)  scatt (x ’) d 3x ’ (3.3) This is a Lippmann- Schwinger equation. It can be observed...boundary conditions for a known target. It is also important to note that there are several aspects to the Lippmann- Schwinger equation: 27 (1...can also be approached using the Lippmann- Schwinger equation as a model for scatt . B. LINEARIZED DATA MODEL (TIME-VARYING SYSTEMS) Besides using

  2. Conotoxins: Molecular and Therapeutic Targets

    Science.gov (United States)

    Lewis, Richard J.

    Marine molluscs known as cone snails produce beautiful shells and a complex array of over 50,000 venom peptides evolved for prey capture and defence. Many of these peptides selectively modulate ion channels and transporters, making them a valuable source of new ligands for studying the role these targets play in normal and disease physiology. A number of conopeptides reduce pain in animal models, and several are now in pre-clinical and clinical development for the treatment of severe pain often associated with diseases such as cancer. Less than 1% of cone snail venom peptides are pharmacologically characterised.

  3. Nondestructive Testing and Target Identification

    Science.gov (United States)

    2016-12-21

    AFRL-AFOSR-VA-TR-2016-0371 Nondestructive Testing and Target Identification David Colton UNIVERSITY OF DELAWARE Final Report 12/20/2016 DISTRIBUTION...PROJECT NUMBER 5e.  TASK NUMBER 5f.  WORK UNIT NUMBER 7.  PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) UNIVERSITY OF DELAWARE 220 HULLIHEN HALL NEWARK...8/98) Prescribed by ANSI Std . Z39.18 Page 1 of 1FORM SF 298 12/21/2016https://livelink.ebs.afrl.af.mil/livelink/llisapi.dll AFOSR Grant FA9550-13-1

  4. Introduction to radar target recognition

    CERN Document Server

    Tait, P

    2006-01-01

    This new text provides an overview of the radar target recognition process and covers the key techniques being developed for operational systems. It is based on the fundamental scientific principles of high resolution radar, and explains how the techniques can be used in real systems, taking into account the characteristics of practical radar system designs and component limitations. It also addresses operational aspects, such as how high resolution modes would fit in with other functions such as detection and tracking. Mathematics is kept to a minimum and the complex techniques and issues are

  5. Zinc metalloproteins as medicinal targets.

    Science.gov (United States)

    Anzellotti, A I; Farrell, N P

    2008-08-01

    Zinc bioinorganic chemistry has emphasized the role of the metal ion on the structure and function of the protein. There is, more recently, an increasing appreciation of the role of zinc proteins in a variety of human diseases. This critical review, aimed at both bioinorganic and medicinal chemists, shows how apparently widely-diverging diseases share the common mechanistic approaches of targeting the essential function of the metal ion to inhibit activity. Protein structure and function is briefly summarized in the context of its clinical relevance. The status of current and potential inhibitors is discussed along with the prospects for future developments (162 references).

  6. Targeting Therapy Resistant Tumor Vessels

    Science.gov (United States)

    2008-08-01

    with ketamine (100 mg/kg i.m.) plus xylazine (10 mg/kg i.m.). In mice used for immunohistochemistry, blood flow and patency of individual tumor...Sprague-Dawley rats and BALB/c mice. Rats were anesthetized with an intraperitoneal injection of 50/50% ketamine -xylaxine, and an intraperitoneal...Pasqualini R, Arap W. Reversal of obesity by targeted ablation of adipose tissue. Nat Med 2004;10:625–32. 47. Zurita AJ, Troncoso P, Cardó-Vila M

  7. The challenge of targeting metastasis.

    Science.gov (United States)

    Fidler, Isaiah J; Kripke, Margaret L

    2015-12-01

    Metastases that are resistant to conventional therapy are the major cause of death from cancer. In most patients, metastasis has already occurred by the time of diagnosis. Thus, the prevention of metastasis is unlikely to be of therapeutic benefit. The biological heterogeneity of metastases presents a major obstacle to treatment. However, the growth and survival of metastases depend on interactions between tumor cells and host homeostatic mechanisms. Targeting these interactions, in addition to the tumor cells, can produce synergistic therapeutic effects against existing metastases.

  8. Assessing protein kinase target similarity

    DEFF Research Database (Denmark)

    Gani, Osman A; Thakkar, Balmukund; Narayanan, Dilip

    2015-01-01

    : focussed chemical libraries, drug repurposing, polypharmacological design, to name a few. Protein kinase target similarity is easily quantified by sequence, and its relevance to ligand design includes broad classification by key binding sites, evaluation of resistance mutations, and the use of surrogate......" of sequence and crystal structure information, with statistical methods able to identify key correlates to activity but also here, "the devil is in the details." Examples from specific repurposing and polypharmacology applications illustrate these points. This article is part of a Special Issue entitled...

  9. Experimental identification of microRNA targets

    DEFF Research Database (Denmark)

    Ørom, Ulf Andersson; Lund, Anders H

    2009-01-01

    microRNAs are small RNAs that regulate protein synthesis post-transcriptionally. Animal microRNAs recognize their targets by incomplete base pairing to sequence motifs most often present in the 3' untranslated region of their target mRNAs. This partial complementarity vastly expands the repertoire...... of potential targets and constitutes a problem for computational target prediction. Although computational analyses have shed light on important aspects of microRNA target recognition, several questions remain regarding how microRNAs can recognize and regulate their targets. Forward experimental approaches...... allow for an unbiased study of microRNA target recognition and may unveil novel, rare or uncommon target binding patterns. In this review we focus on animal microRNAs and the experimental approaches that have been described for identification of their targets....

  10. LIFE Target Fabrication Research Plan Sept 2008

    Energy Technology Data Exchange (ETDEWEB)

    Miles, R; Biener, J; Kucheyev, S; Montesanti, R; Satcher, J; Spadaccini, C; Rose, K; Wang, M; Hamza, A; Alexander, N; Brown, L; Hund, J; Petzoldt, R; Sweet, W; Goodin, D

    2008-11-10

    The target-system for the baseline LIFE fast-ignition target was analyzed to establish a preliminary estimate for the costs and complexities involved in demonstrating the technologies needed to build a prototype LIFE plant. The baseline fast-ignition target upon which this analysis was developed is shown in Figure 1.0-1 below. The LIFE target-system incorporates requirements for low-cost, high throughput manufacture, high-speed, high accuracy injection of the target into the chamber, production of sufficient energy from implosion and recovery and recycle of the imploded target material residue. None of these functions has been demonstrated to date. Existing target fabrication techniques which lead to current 'hot spot' target costs of {approx}$100,000 per target and at a production rate of 2/day are unacceptable for the LIFE program. Fabrication techniques normally used for low-cost, low accuracy consumer products such as toys must be adapted to the high-accuracy LIFE target. This will be challenge. A research program resulting is the demonstration of the target-cycle technologies needed for a prototype LIFE reactor is expected to cost {approx}$51M over the course of 5 years. The effort will result in targets which will cost an estimated $0.23/target at a rep-rate of 20 Hz or about 1.73M targets/day.

  11. Properties of protein drug target classes.

    Directory of Open Access Journals (Sweden)

    Simon C Bull

    Full Text Available Accurate identification of drug targets is a crucial part of any drug development program. We mined the human proteome to discover properties of proteins that may be important in determining their suitability for pharmaceutical modulation. Data was gathered concerning each protein's sequence, post-translational modifications, secondary structure, germline variants, expression profile and drug target status. The data was then analysed to determine features for which the target and non-target proteins had significantly different values. This analysis was repeated for subsets of the proteome consisting of all G-protein coupled receptors, ion channels, kinases and proteases, as well as proteins that are implicated in cancer. Machine learning was used to quantify the proteins in each dataset in terms of their potential to serve as a drug target. This was accomplished by first inducing a random forest that could distinguish between its targets and non-targets, and then using the random forest to quantify the drug target likeness of the non-targets. The properties that can best differentiate targets from non-targets were primarily those that are directly related to a protein's sequence (e.g. secondary structure. Germline variants, expression levels and interactions between proteins had minimal discriminative power. Overall, the best indicators of drug target likeness were found to be the proteins' hydrophobicities, in vivo half-lives, propensity for being membrane bound and the fraction of non-polar amino acids in their sequences. In terms of predicting potential targets, datasets of proteases, ion channels and cancer proteins were able to induce random forests that were highly capable of distinguishing between targets and non-targets. The non-target proteins predicted to be targets by these random forests comprise the set of the most suitable potential future drug targets, and should therefore be prioritised when building a drug development programme.

  12. Targeting FGFR Signaling in Cancer.

    Science.gov (United States)

    Touat, Mehdi; Ileana, Ecaterina; Postel-Vinay, Sophie; André, Fabrice; Soria, Jean-Charles

    2015-06-15

    The fibroblast growth factor signaling pathway (FGFR signaling) is an evolutionary conserved signaling cascade that regulates several basic biologic processes, including tissue development, angiogenesis, and tissue regeneration. Substantial evidence indicates that aberrant FGFR signaling is involved in the pathogenesis of cancer. Recent developments of deep sequencing technologies have allowed the discovery of frequent molecular alterations in components of FGFR signaling among several solid tumor types. Moreover, compelling preclinical models have demonstrated the oncogenic potential of these aberrations in driving tumor growth, promoting angiogenesis, and conferring resistance mechanisms to anticancer therapies. Recently, the field of FGFR targeting has exponentially progressed thanks to the development of novel agents inhibiting FGFs or FGFRs, which had manageable safety profiles in early-phase trials. Promising treatment efficacy has been observed in different types of malignancies, particularly in tumors harboring aberrant FGFR signaling, thus offering novel therapeutic opportunities in the era of precision medicine. The most exciting challenges now focus on selecting patients who are most likely to benefit from these agents, increasing the efficacy of therapies with the development of novel potent compounds and combination strategies, and overcoming toxicities associated with FGFR inhibitors. After examination of the basic and translational research studies that validated the oncogenic potential of aberrant FGFR signaling, this review focuses on recent data from clinical trials evaluating FGFR targeting therapies and discusses the challenges and perspectives for the development of these agents.

  13. Aquaporins as potential drug targets

    Institute of Scientific and Technical Information of China (English)

    Fang WANG; Xue-chao FENG; Yong-ming LI; Hong YANG; Tong-hui MA

    2006-01-01

    The aquaporins (AQP) are a family of integral membrane proteins that selectively transport water and,in some cases,small neutral solutes such as glycerol and urea.Thirteen mammalian AQP have been molecularly identified and localized to various epithelial,endothelial and other tissues.Phenotype studies of transgenic mouse models of AQP knockout,mutation,and in some cases humans with AQP mutations have demonstrated essential roles for AQP in mammalian physiology and pathophysiology,including urinary concentrating function,exocrine glandular fluid secretion,brain edema formation,regulation of intracranial and intraocular pressure,skin hydration,fat metabolism,tumor angiogenesis and cell migration.These studies suggest that AQP may be potential drug targets for not only new diuretic reagents for various forms of pathological water retention,but also targets for novel therapy of brain edema,inflammatory disease,glaucoma,obesity,and cancer.However,potent AQP modulators for in vivo application remain to be discovered.

  14. String theory in target space

    Energy Technology Data Exchange (ETDEWEB)

    Boels, Rutger H.; Hansen, Tobias [II. Institut für Theoretische Physik, Universität Hamburg,Luruper Chaussee 149, D- 22761 Hamburg (Germany)

    2014-06-10

    It is argued that the complete S-matrix of string theory at tree level in a flat background can be obtained from a small set of target space properties, without recourse to the worldsheet description. The main non-standard inputs are (generalised) Britto-Cachazo-Feng-Witten shifts, as well as the monodromy relations for open string theory and the Kawai-Lewellen-Tye relations for closed string theory. The roots of the scattering amplitudes and especially their appearance in the residues at the kinematic poles are central to the story. These residues determine the amplitudes through on-shell recursion relations. Several checks of the formalism are presented, including a computation of the Koba-Nielsen amplitude in the bosonic string. Furthermore the question of target space unitarity is (re-)investigated. For the Veneziano amplitude this question is reduced by Poincaré invariance, unitarity and locality to that of positivity of a particular numerical sum. Interestingly, this analysis produces the main conditions of the no-ghost theorem on dimension and intercept from the first three poles of this amplitude.

  15. Targeting vaccines to dendritic cells.

    Science.gov (United States)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-03-01

    Dendritic cells (DC) are specialized antigen presenting cells (APC) with a remarkable ability to take up antigens and stimulate major histocompatibility complex (MHC)-restricted specific immune responses. Recent discoveries have shown that their role in initiating primary immune responses seems to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC are considered to play a central role for the provocation of primary immune responses by vaccination. A rational way of improving the potency and safety of new and already existing vaccines could therefore be to direct vaccines specifically to DC. There is a need for developing multifunctional vaccine drug delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC.

  16. Tamoxifen Resistance: Emerging Molecular Targets

    Directory of Open Access Journals (Sweden)

    Milena Rondón-Lagos

    2016-08-01

    Full Text Available 17β-Estradiol (E2 plays a pivotal role in the development and progression of breast cancer. As a result, blockade of the E2 signal through either tamoxifen (TAM or aromatase inhibitors is an important therapeutic strategy to treat or prevent estrogen receptor (ER positive breast cancer. However, resistance to TAM is the major obstacle in endocrine therapy. This resistance occurs either de novo or is acquired after an initial beneficial response. The underlying mechanisms for TAM resistance are probably multifactorial and remain largely unknown. Considering that breast cancer is a very heterogeneous disease and patients respond differently to treatment, the molecular analysis of TAM’s biological activity could provide the necessary framework to understand the complex effects of this drug in target cells. Moreover, this could explain, at least in part, the development of resistance and indicate an optimal therapeutic option. This review highlights the implications of TAM in breast cancer as well as the role of receptors/signal pathways recently suggested to be involved in the development of TAM resistance. G protein—coupled estrogen receptor, Androgen Receptor and Hedgehog signaling pathways are emerging as novel therapeutic targets and prognostic indicators for breast cancer, based on their ability to mediate estrogenic signaling in ERα-positive or -negative breast cancer.

  17. Targeted therapies in gastroesophageal cancer.

    Science.gov (United States)

    Kasper, Stefan; Schuler, Martin

    2014-05-01

    Gastroesophageal cancers comprising gastric cancer (GC), and cancers of the distal oesophagus and gastroesophageal junction (GEJ) are a global health threat. In Western populations the incidence of GC is declining which has been attributed to effective strategies of eradicating Helicobacter pylori infection. To the contrary, GEJ cancers are on the rise, with obesity and reflux disease being viewed as major risk factors. During the past decade perioperative chemotherapy, pre- or postoperative radio-chemotherapy, and, in Asian populations, adjuvant chemotherapy have been shown to improve the outcome of patients with advanced GC and GEJ cancers suited for surgery. Less progress has been made in the treatment of metastatic disease. The introduction of trastuzumab in combination with platinum/fluoropyrimidine-based chemotherapy for patients with HER2-positive disease has marked a turning point. Recently, several novel agents targeting growth factor receptors, angiogenic pathways, adhesion molecules and mediators of intracellular signal transduction have been clinically explored. Here we summarise the current status and future developments of molecularly targeted therapies in GC and GEJ cancer.

  18. Seismoelectric imaging of shallow targets

    Science.gov (United States)

    Haines, S.S.; Pride, S.R.; Klemperer, S.L.; Biondi, B.

    2007-01-01

    We have undertaken a series of controlled field experiments to develop seismoelectric experimental methods for near-surface applications and to improve our understanding of seismoelectric phenomena. In a set of off-line geometry surveys (source separated from the receiver line), we place seismic sources and electrode array receivers on opposite sides of a man-made target (two sand-filled trenches) to record separately two previously documented seismoelectric modes: (1) the electromagnetic interface response signal created at the target and (2) the coseismic electric fields located within a compressional seismic wave. With the seismic source point in the center of a linear electrode array, we identify the previously undocumented seismoelectric direct field, and the Lorentz field of the metal hammer plate moving in the earth's magnetic field. We place the seismic source in the center of a circular array of electrodes (radial and circumferential orientations) to analyze the source-related direct and Lorentz fields and to establish that these fields can be understood in terms of simple analytical models. Using an off-line geometry, we create a multifold, 2D image of our trenches as dipping layers, and we also produce a complementary synthetic image through numerical modeling. These images demonstrate that off-line geometry (e.g., crosswell) surveys offer a particularly promising application of the seismoelectric method because they effectively separate the interface response signal from the (generally much stronger) coseismic and source-related fields. ?? 2007 Society of Exploration Geophysicists.

  19. 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.

  20. String theory in target space

    CERN Document Server

    Boels, Rutger H

    2014-01-01

    It is argued that the complete S-matrix of string theory at tree level in a flat background can be obtained from a small set of target space properties, without recourse to the worldsheet description. The main non-standard inputs are (generalised) Britto-Cachazo-Feng-Witten shifts, as well as the monodromy relations for open string theory and the Kawai-Lewellen-Tye relations for closed string theory. The roots of the scattering amplitudes and especially their appearance in the residues at the kinematic poles are central to the story. These residues determine the amplitudes through on-shell recursion relations. Several checks of the formalism are presented, including a computation of the Koba-Nielsen amplitude in the bosonic string. Furthermore the question of target space unitarity is (re-)investigated. For the Veneziano amplitude this question is reduced by Poincare invariance, unitarity and locality to that of positivity of a particular numerical sum. Interestingly, this analysis produces the main condition...

  1. String theory in target space

    Science.gov (United States)

    Boels, Rutger H.; Hansen, Tobias

    2014-06-01

    It is argued that the complete S-matrix of string theory at tree level in a flat background can be obtained from a small set of target space properties, without recourse to the worldsheet description. The main non-standard inputs are (generalised) Britto-Cachazo-Feng-Witten shifts, as well as the monodromy relations for open string theory and the Kawai-Lewellen-Tye relations for closed string theory. The roots of the scattering amplitudes and especially their appearance in the residues at the kinematic poles are central to the story. These residues determine the amplitudes through on-shell recursion relations. Several checks of the formalism are presented, including a computation of the Koba-Nielsen amplitude in the bosonic string. Furthermore the question of target space unitarity is (re-)investigated. For the Veneziano amplitude this question is reduced by Poincaré invariance, unitarity and locality to that of positivity of a particular numerical sum. Interestingly, this analysis produces the main conditions of the no-ghost theorem on dimension and intercept from the first three poles of this amplitude.

  2. Mammalian Target of Rapamycin As a Therapeutic Target in Osteoporosis.

    Science.gov (United States)

    Shen, Gengyang; Ren, Hui; Qiu, Ting; Zhang, Zhida; Zhao, Wenhua; Yu, Xiang; Huang, Jinjing; Tang, Jingjing; Liang, De; Yao, Zhensong; Yang, Zhidong; Jiang, Xiaobing

    2017-08-23

    The mechanistic target of rapamycin (mTOR) plays a key role in sensing and integrating large amounts of environmental cues to regulate organismal growth, homeostasis, and many major cellular processes. Recently, mounting evidences highlight its roles in regulating bone homeostasis, which sheds light on the pathogenesis of osteoporosis. The activation/inhibition of mTOR signaling is reported to positively/negatively regulate bone marrow mesenchymal stem cells (BMSCs)/osteoblasts-mediated bone formation, adipogenic differentiation, osteocytes homeostasis, and osteoclasts-mediated bone resorption, which result in the changes of bone homeostasis, thereby resulting in or protect against osteoporosis. Given the likely importance of mTOR signaling in the pathogenesis of osteoporosis, here we discuss the detailed mechanisms in mTOR machinery and its association with osteoporosis therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. Combinatorial microRNA target predictions

    DEFF Research Database (Denmark)

    Krek, Azra; Grün, Dominic; Poy, Matthew N.

    2005-01-01

    MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3' untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript1, 2, 3. Different combinations of microRNAs are expressed...... in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published micro......RNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results...

  4. Targets and processes for fabricating same

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Jesse D; Malekos, Steven; Le Galloudec, Nathalie; Korgan, Grant; Cowan, Thomas; Sentoku, Yasuhiko

    2016-05-17

    In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

  5. In target yields for EURISOL RIB production

    CERN Document Server

    Ene, D; David, J.-C; Chabod, S

    The goal of this paper is the estimation of the in-target neutron-induced fission fragment productions using the most recent optimized design of the EURISOL converter-fission target assembly.Submitted to EPJA.

  6. Study Identifies New Lymphoma Treatment Target

    Science.gov (United States)

    NCI researchers have identified new therapeutic targets for diffuse large B-cell lymphoma. Drugs that hit these targets are under clinical development and the researchers hope to begin testing them in clinical trials of patients with DLBCL.

  7. Targets culture wastes energy on wrong things.

    Science.gov (United States)

    Fyffe, Theresa

    2016-09-14

    Healthcare targets have been in the news a lot - and not in ways that offer comfortable reading. Missed emergency department waiting-time targets and patients waiting longer for treatments have made headlines.

  8. Targeted therapy: questions to ask your doctor

    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, ...

  9. Terahertz-based target typing.

    Energy Technology Data Exchange (ETDEWEB)

    Lyo, Sungkwun Kenneth; Wanke, Michael Clement; Reno, John Louis; Shaner, Eric Arthur; Grine, Albert D.; Barrick, Todd A.

    2008-09-01

    The purpose of this work was to create a THz component set and understanding to aid in the rapid analysis of transient events. This includes the development of fast, tunable, THz detectors, along with filter components for use with standard detectors and accompanying models to simulate detonation signatures. The signature effort was crucial in order to know the spectral range to target for detection. Our approach for frequency agile detection was to utilize plasmons in the channel of a specially designed field-effect transistor called the grating-gate detector. Grating-gate detectors exhibit narrow-linewidth, broad spectral tunability through application of a gate bias, and no angular dependence in their photoresponse. As such, if suitable sensitivity can be attained, they are viable candidates for Terahertz multi-spectral focal plane arrays.

  10. Synchronous identification of friendly targets

    Science.gov (United States)

    Telle, John M.; Roger, Stutz A.

    1998-01-01

    A synchronous communication targeting system for use in battle. The present invention includes a transceiver having a stabilizing oscillator, a synchronous amplifier and an omnidirectional receiver, all in electrical communication with each other. A remotely located beacon is attached to a blackbody radiation source and has an amplitude modulator in electrical communication with a optical source. The beacon's amplitude modulator is set so that the optical source transmits radiation frequency at approximately the same or lower amplitude than that of the blackbody radiation source to which the beacon is attached. The receiver from the transceiver is adapted to receive frequencies approximately at or below blackbody radiation signals and sends such signals to the synchronous amplifier. The synchronous amplifier then rectifies and amplifies those signals which correspond to the predetermined frequency to therefore identify whether the blackbody radiation source is friendly or not.

  11. Performance Targets and External Benchmarking

    DEFF Research Database (Denmark)

    Friis, Ivar; Hansen, Allan; Vámosi, Tamás S.

    Research on relative performance measures, transfer pricing, beyond budgeting initiatives, target costing, piece rates systems and value based management has for decades underlined the importance of external benchmarking in performance management. Research conceptualises external benchmarking...... the conditions upon which the market mechanism is performing within organizations. This paper aims to contribute to research by providing more insight to the conditions for the use of external benchmarking as an element in performance management in organizations. Our study explores a particular type of external...... towards the conditions for the use of the external benchmarks we provide more insights to some of the issues and challenges that are related to using this mechanism for performance management and advance competitiveness in organizations....

  12. TARGET 2 and Settlement Finality

    Directory of Open Access Journals (Sweden)

    Ivan MANGATCHEV

    2011-03-01

    Full Text Available This article examines how TARGET 2 as system implements the idea of settlement finality regulated by Directive 98/26 EC of the European parliament and of the Council of 19 May 1998 on settlement finality in payment and securities settlement systems (Settlement Finality Directive and Directive 2009/44/EC of the European parliament and of the Council of 6 May 2009 amending Directive 98/26/EC on settlement finality in payment and securities settlement systems and Directive 2002/47/EC on financial collateral arrangements as regards linked systems and credit claims (Directive 2009/44/EC. As the title of the arti and finality of the settlement in this system.

  13. Therapeutic target for protozoal diseases

    Science.gov (United States)

    Rathore, Dharmendar; Jani, Dewal; Nagarkatti, Rana

    2008-10-21

    A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

  14. Purity of targets prepared on Cu substrates

    Science.gov (United States)

    Méens, A.; Rossini, I.; Sens, J. C.

    1993-09-01

    The purity of several elemental self-supporting targets usually prepared by evaporation onto soluble Cu substrates has been studied. The targets were analysed by Rutherford backscattering and instrumental neutron activation analysis. Because of the high percentage of Cu observed in some Si targets, further measurements, including transmission electron microscopy, have been performed on Si targets deposited by e-gun bombardment onto Cu and ion-beam sputtering onto betaine.

  15. Evaluation and validation of drug targets

    Institute of Scientific and Technical Information of China (English)

    Guan-huaDU

    2004-01-01

    Drug target is one of the key factors for discovering and developing new drugs. To find and validate drug targets is a crucial technique required in drug discovery by the strategy of high throughput screening. Based on the knowledge of molecular biology, human genomics and proteomics, it has been predicted that 5000 to 10000 drug targets exist in human. So, it is important orocedure to evaluate and validate the drug targets.

  16. Electrophilic eicosanoids: Signaling and targets.

    Science.gov (United States)

    Pérez-Sala, Dolores

    2011-06-30

    Electrophilic eicosanoids are reactive mediators that arise by non-enzymatic transformations of arachidonic acid or of its products and display varied biological actions. Various electrophilic eicosanoids have shown anti-proliferative and anti-inflammatory effects, which have elicited a great interest in their study as potential therapeutic agents. A key feature of these compounds is their ability to covalently modify proteins, thus altering their structure and function. The modification of several components of the NF-κB pathway contributes to the anti-inflammatory effects of electrophilic eicosanoids, whereas addition to redox-sensitive proteins plays a key role in the antioxidant response. However, electrophilic eicosanoids may also have a dark side, and accumulating evidence points towards their involvement in neurotoxicity and/or neurodegeneration. The ability of some electrophilic eicosanoids to induce protein oligomerization or aggregation through various mechanisms may contribute to these effects. Biochemical and proteomic studies have led to the identification of numerous protein targets for modification by electrophilic eicosanoids, the number of which continues to expand, revealing novel potential functions for these compounds and providing a basis for their pleiotropic effects. The ample number of targets identified, together with the non-enzymatic nature of the modification argue against the potential specificity or regulation of electrophilic eicosanoid action. However, protein modification displays selectivity depending on structural features of the proteins and of the electrophilic compounds as well as on context factors such as cell type and GSH availability. Understanding the factors which control the extent and selectivity of protein modification by electrophilic eicosanoids is therefore essential to elucidate their pathophysiological roles and therapeutic potential in specific settings.

  17. Moringa oleifera Lam: Targeting Chemoprevention.

    Science.gov (United States)

    Karim, Nurul Ashikin Abd; Ibrahim, Muhammad Din; Kntayya, Saie Brindha; Rukayadi, Yaya; Hamid, Hazrulizawati Abd; Razis, Ahmad Faizal Abdull

    2016-01-01

    Moringa oleifera Lam, family Moringaceae, is a perennial plant which is called various names, but is locally known in Malaysia as "murungai" or "kelor". Glucomoringin, a glucosinolate with from M. oleifera is a major secondary metabolite compound. The seeds and leaves of the plant are reported to have the highest amount of glucosinolates. M. oleifera is well known for its many uses health and benefits. It is claimed to have nutritional, medicinal and chemopreventive potentials. Chemopreventive effects of M. oleifera are expected due to the existence of glucosinolate which it is reported to have the ability to induce apoptosis in anticancer studies. Furthermore, chemopreventive value of M. oleifera has been demonstrated in studies utilizing its leaf extract to inhibit the growth of human cancer cell lines. This review highlights the advantages of M. oleifera targeting chemoprevention where glucosinolates could help to slow the process of carcinogenesis through several molecular targets. It is also includes inhibition of carcinogen activation and induction of carcinogen detoxification, anti-inflammatory, anti-tumor cell proliferation, induction of apoptosis and inhibition of tumor angiogenesis. Finally, for synergistic effects of M. oleifera with other drugs and safety, essential for chemoprevention, it is important that it safe to be consumed by human body and works well. Although there is promising evidence about M. oleifera in chemoprevention, extensive research needs to be done due to the expected rise of cancer in coming years and to gain more information about the mechanisms involved in M. oleifera influence, which could be a good source to inhibit several major mechanisms involved in cancer development.

  18. Targeting Cancer with Antisense Oligomers

    Energy Technology Data Exchange (ETDEWEB)

    Hnatowich, DJ

    2008-10-28

    With financial assistance from the Department of Energy, we have shown definitively that radiolabeled antisense DNAs and other oligomers will accumulate in target cancer cells in vitro and in vivo by an antisense mechanism. We have also shown that the number of mRNA targets for our antisense oligomers in the cancer cell types that we have investigated so far is sufficient to provide and antisense image and/or radiotherapy of cancer in mice. These studies have been reported in about 10 publications. However our observation over the past several years has shown that radiolabeled antisense oligomers administered intravenously in their native and naked form will accumulate and be retained in target xenografts by an antisense mechanism but will also accumulate at high levels in normal organs such as liver, spleen and kidneys. We have investigated unsuccessfully several commercially available vectors. Thus the use of radiolabeled antisense oligomers for the imaging of cancer must await novel approaches to delivery. This laboratory has therefore pursued two new paths, optical imaging of tumor and Auger radiotherapy. We are developing a novel method of optical imaging tumor using antisense oligomers with a fluorophore is administered while hybridized with a shorter complementary oligomer with an inhibitor. In culture and in tumored mice that the duplex remains intact and thus nonfluorescent until it encounters its target mRNA at which time it dissociates and the antisense oligomer binds along with its fluorophore to the target. Simultaneous with the above, we have also observed, as have others, that antisense oligomers migrate rapidly and quantitatively to the nucleus upon crossing cell membranes. The Auger electron radiotherapy path results from this observation since the nuclear migration properties could be used effectively to bring and to retain in the nucleus an Auger emitting radionuclide such as 111In or 125I bound to the antisense oligomer. Since the object becomes

  19. Nanoindentation measurements of the mechanical properties of zirconium matrix and hydrides in unirradiated pre-hydrided nuclear fuel cladding

    Science.gov (United States)

    Rico, A.; Martin-Rengel, M. A.; Ruiz-Hervias, J.; Rodriguez, J.; Gomez-Sanchez, F. J.

    2014-09-01

    It is well known that the mechanical properties of the nuclear fuel cladding may be affected by the presence of hydrides. The average mechanical properties of hydrided cladding have been extensively investigated from a macroscopic point of view. In addition, the mechanical and fracture properties of bulk hydride samples fabricated from zirconium plates have also been reported. In this paper, Young's modulus, hardness and yield stress are measured for each phase, namely zirconium hydrides and matrix, of pre-hydrided nuclear fuel cladding. To this end, nanoindentation tests were performed on ZIRLO samples in as-received state, on a hydride blister and in samples with 150 and 1200 ppm of hydrogen homogeneously distributed along the hoop direction of the cladding. The results show that the measured mechanical properties of the zirconium hydrides and ZIRLO matrix (Young's modulus, hardness and yield stress) are rather similar. From the experimental data, the hydride volume fraction in the cladding samples with 150 and 1200 ppm was estimated and the average mechanical properties were calculated by means of the rule of mixtures. These values were compared with those obtained from ring compression tests. Good agreement between the results obtained by both methods was found.

  20. Properties of unirradiated HTGR core support and permanent side reflector graphites: PGX, HLM, 2020, and H-440N

    Energy Technology Data Exchange (ETDEWEB)

    Engle, G.B.

    1977-05-01

    Candidate materials for HTGR core supports and permanent side reflectors--graphite grades 2020 (Stackpole Carbon Company), H-440N (Great Lakes Carbon Corporation), PGX (Union Carbide Corporation), and HLM (Great Lakes Carbon Corporation)--are described and property data are presented. Properties measured are bulk density; tensile properties including ultimate strength, modulus of elasticity, and strain at fracture; flexural strength; compressive properties including ultimate strength, modulus of elasticity, and strain at fracture; and chemical impurity content.

  1. Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

    Science.gov (United States)

    Hill, F. S.; Cox, A. B.; Salmon, Y. L.; Cantu, A. O.; Lucas, J. N.

    1994-01-01

    The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 microgram/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) than that produced by PHA (MI < 0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture.

  2. Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Hill, F.S.; Cantu, A.O.; Lucas, J.N. (Lawrence Livermore National Lab., CA (United States)); Cox, A.B.; Salmon, Y.L. (Air Force Armstrong Lab., Brookes AFB, TX (United States))

    1994-10-01

    The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 [mu]g/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) that that produced by PHA (M1<0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture. (author).

  3. Nanoindentation measurements of the mechanical properties of zirconium matrix and hydrides in unirradiated pre-hydrided nuclear fuel cladding

    Energy Technology Data Exchange (ETDEWEB)

    Rico, A., E-mail: alvaro.rico@urjc.es [DIMME, Departamento de Tecnología Mecánica, Universidad Rey Juan Carlos, c/Tulipán s/n, E-28933 Móstoles, Madrid (Spain); Martin-Rengel, M.A., E-mail: mamartin@mater.upm.es [Departamento de Ciencia de los Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos, Profesor Aranguren SN, E-28040 Madrid (Spain); Ruiz-Hervias, J., E-mail: jesus.ruiz@upm.es [Departamento de Ciencia de los Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos, Profesor Aranguren SN, E-28040 Madrid (Spain); Rodriguez, J. [DIMME, Departamento de Tecnología Mecánica, Universidad Rey Juan Carlos, c/Tulipán s/n, E-28933 Móstoles, Madrid (Spain); Gomez-Sanchez, F.J., E-mail: javier.gomez@amsimulation.com [Advanced Material Simulation, S.L, Madrid (Spain)

    2014-09-15

    It is well known that the mechanical properties of the nuclear fuel cladding may be affected by the presence of hydrides. The average mechanical properties of hydrided cladding have been extensively investigated from a macroscopic point of view. In addition, the mechanical and fracture properties of bulk hydride samples fabricated from zirconium plates have also been reported. In this paper, Young’s modulus, hardness and yield stress are measured for each phase, namely zirconium hydrides and matrix, of pre-hydrided nuclear fuel cladding. To this end, nanoindentation tests were performed on ZIRLO samples in as-received state, on a hydride blister and in samples with 150 and 1200 ppm of hydrogen homogeneously distributed along the hoop direction of the cladding. The results show that the measured mechanical properties of the zirconium hydrides and ZIRLO matrix (Young’s modulus, hardness and yield stress) are rather similar. From the experimental data, the hydride volume fraction in the cladding samples with 150 and 1200 ppm was estimated and the average mechanical properties were calculated by means of the rule of mixtures. These values were compared with those obtained from ring compression tests. Good agreement between the results obtained by both methods was found.

  4. Kinetic analysis for non-isothermal decomposition of un-irradiated and gamma-irradiated anhydrous cadmium nitrate

    Energy Technology Data Exchange (ETDEWEB)

    Culas, S.; Samuel, J. [Mar Ivanios College, Kerala (India). Dept. of Chemistry

    2014-04-01

    The thermal decomposition of untreated and γ-irradiated samples of anhydrous cadmium nitrate was performed under non-isothermal conditions at different heating rates (5, 10, 15 and 20 C min{sup -1}). The results showed that the decomposition proceeds in one major step with the formation of cadmium oxide as solid residue. The data were analysed by using both isoconversional and non-isoconversional methods. The activation energy was calculated by various model-free isoconversional methods: Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose (KAS) and Friedman (FR) methods. Irradiation enhances the decomposition and the effect increases with the irradiation dose. The activation energy decreases on irradiation. The appropriate conversion model for the thermal decomposition process selected by means of the master-plot method agrees with phase boundary reaction with spherical symmetry (R3 mechanism) for both untreated and irradiated salts at all heating rates. (orig.)

  5. Unirradiated cells rescue cells exposed to ionizing radiation: Activation of NF-κB pathway in irradiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Lam, R.K.K. [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); Han, Wei [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); State Key Laboratory in Marine Pollution, City University of Hong Kong (Hong Kong)

    2015-12-15

    Highlights: • Rescue effect was observed in both irradiated and HeLa and NIH/3T3 cells. • Novel setup and procedures to separate the rescue signals and the bystander signals. • Confirmed activation of NF-κB pathway in rescue effect using activation inhibitor. • Confirmed activation of NF-κB pathway in rescue effect using anti-NF-κB p65 antibody. - Abstract: We studied the involvement of NF-κB pathway activation in the rescue effect in HeLa and NIH/3T3 cells irradiated by α particles. Firstly, upon irradiation by 5 cGy of α particles, for both cell lines, the numbers of 53BP1 foci/cell at 12 h post-irradiation were significantly smaller when only 2.5% of the cell population was irradiated as compared to 100% irradiation, which demonstrated the rescue effect. Secondly, we studied the effect of NF-κB on the rescue effect through the use of the NF-κB activation inhibitor BAY-11-7082. Novel experimental setup and procedures were designed to prepare the medium (CM) which had conditioned the bystander cells previously partnered with irradiated cells, to ensure physical separation between rescue and bystander signals. BAY-11-7082 itself did not inflict DNA damages in the cells or have effects on activation of the NF-κB response pathway in the irradiated cells through direct irradiation. The rescue effect was induced in both cell lines by the CM, which was abrogated if BAY-11-7082 was added to the CM. Thirdly, we studied the effect of NF-κB on the rescue effect through staining for phosphorylated NF-κB (p-NF-κB) expression using the anti-NF-κB p65 (phospho S536) antibody. When the fraction of irradiated cells dropped from 100% to 2.5%, the p-NF-κB expression in the cell nuclei of irradiated NIH/3T3 cells increased significantly, while that in the cell nuclei of irradiated HeLa cells also increased although not significantly. Moreover, the p-NF-κB expression in the cell nuclei of irradiated HeLa cells and NIH/3T3 cells treated with CM also increased significantly.

  6. Studies of release properties of ISOLDE targets

    CERN Document Server

    Peräjärvi, K; Fedosseev, V; Joinet, A; Köster, U; Lau, C; Lettry, Jacques; Ravn, H L; Santana-Leitner, M

    2003-01-01

    Off-line release rates of Be, Mg, S, Mn and Kr from refractory materials were studied. Mn yields were determined from a ZrO2 target and Kr yields from a SrO and ZrO2 targets. A Monte Carlo code to optimize ISOLDE targets was introduced.

  7. Target manifold formation using a quadratic SDF

    Science.gov (United States)

    Hester, Charles F.; Risko, Kelly K. D.

    2013-05-01

    Synthetic Discriminant Function (SDF) formulation of correlation filters provides constraints for forming target subspaces for a target set. In this paper we extend the SDF formulation to include quadratic constraints and use this solution to form nonlinear manifolds in the target space. The theory for forming these manifolds will be developed and demonstrated with data.

  8. Behavioral targeting: a European legal perspective

    NARCIS (Netherlands)

    Zuiderveen Borgesius, F.

    2013-01-01

    Behavioral targeting, or online profiling, is a hotly debated topic. Much of the collection of personal information on the Internet is related to behavioral targeting, although research suggests that most people don't want to receive behaviorally targeted advertising. The World Wide Web Consortium i

  9. 40 CFR 35.9020 - Planning targets.

    Science.gov (United States)

    2010-07-01

    ... STATE AND LOCAL ASSISTANCE Financial Assistance for the National Estuary Program § 35.9020 Planning targets. The EPA Assistant Administrator for Water develops planning targets each year to help each... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Planning targets. 35.9020 Section...

  10. Behavioral targeting: a European legal perspective

    NARCIS (Netherlands)

    Zuiderveen Borgesius, F.

    2013-01-01

    Behavioral targeting, or online profiling, is a hotly debated topic. Much of the collection of personal information on the Internet is related to behavioral targeting, although research suggests that most people don't want to receive behaviorally targeted advertising. The World Wide Web Consortium i

  11. Improved Targeting of Cancers with Nanotherapeutics

    DEFF Research Database (Denmark)

    Foster, Christian; Watson, Andre; Kaplinsky, Joseph John;

    2017-01-01

    Targeted cancer nanotherapeutics offers numerous opportunities for the selective uptake of toxic chemotherapies within tumors and cancer cells. The unique properties of nanoparticles, such as their small size, large surface-to-volume ratios, and the ability to achieve multivalency of targeting...... ligands on their surface, provide superior advantages for nanoparticle-based drug delivery to a variety of cancers. This review highlights various key concepts in the design of targeted nanotherapeutics for cancer therapy, and discusses physicochemical parameters affecting nanoparticle targeting, along...... with recent developments for cancer-targeted nanomedicines....

  12. Targeting nominal income growth or inflation?

    DEFF Research Database (Denmark)

    Jensen, Henrik

    2002-01-01

    Within a simple New Keynesian model emphasizing forward-looking behavior of private agents, I evaluate optimal nominal income growth targeting versus optimal inflation targeting. When the economy is mainly subject to shocks that do not involve monetary policy trade-offs for society, inflation...... targeting is preferable. Otherwise, nominal income growth targeting may be superior because it induces inertial policy making, which improves the inflation-output-gap trade-off. Somewhat paradoxically, inflation targeting may be relatively less favorable the more society dislikes inflation, and the more...... persistent are the effects of inflation-generating shocks...

  13. Targeted alpha therapy for cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Barry J [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Raja, Chand [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Rizvi, Syed [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Li Yong [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Tsui, Wendy [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Zhang, David [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Song, Emma [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Qu, C F [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Kearsley, John [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Graham, Peter [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Thompson, John [Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown 2050 NSW (Australia)

    2004-08-21

    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The {sup 213}Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 {mu

  14. The trajectory of the target probability effect.

    Science.gov (United States)

    Hon, Nicholas; Yap, Melvin J; Jabar, Syaheed B

    2013-05-01

    The effect of target probability on detection times is well-established: Even when detection accuracy is high, lower probability targets are detected more slowly than higher probability ones. Although this target probability effect on detection times has been well-studied, one aspect of it has remained largely unexamined: How the effect develops over the span of an experiment. Here, we investigated this issue with two detection experiments that assessed different target probability ratios. Conventional block segment analysis and linear mixed-effects modeling converged on two key findings. First, we found that the magnitude of the target probability effect increases as one progresses through a block of trials. Second, we found, by examining the trajectories of the low- and high-probability targets, that this increase in effect magnitude was driven by the low-probability targets. Specifically, we found that low-probability targets were detected more slowly as a block of trials progressed. Performance to high-probability targets, on the other hand, was largely invariant across the block. The latter finding is of particular interest because it cannot be reconciled with accounts that propose that the target probability effect is driven by the high-probability targets.

  15. Targeting tumor suppressor genes for cancer therapy.

    Science.gov (United States)

    Liu, Yunhua; Hu, Xiaoxiao; Han, Cecil; Wang, Liana; Zhang, Xinna; He, Xiaoming; Lu, Xiongbin

    2015-12-01

    Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics.

  16. Design and Implementation of SCSI Target Emulator

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A SCSI target emulator is used in a storage area network (SAN) environment to simulate the behavior of a SCSI target for processing and responding to I/O requests issued by initiators. The SCSI target emulator works with general storage devices with multiple transport protocols. The target emulator utilizes a protocol conversion module that translates the SCSI protocols to a variety of storage devices and implements the multi-RAID-level configuration and storage visualization functions. Moreover, the target emulator implements RAM caching, multi-queuing, and request merging to effectively improve the I/O response speed of the general storage devices. The throughput and average response times of the target emulator for block sizes of 4 KB to 128 KB are 150% faster for reads and 67% faster for writes than the existing emulator. With a block size of 16 KB, the I/O latency of the target emulator is only about 20% that of the existing emulator.

  17. Infrared signature generation of airborne targets

    Science.gov (United States)

    Whalen, Michael R.

    1993-08-01

    This report proposes a generic methodology for generating infrared signatures of airborne targets. The various issues, assumptions and simplifications utilized in signature studies are outlines to insure baseline consistency among future models and evaluation tools. More specifically, the target is characterized on a component level, and the at-aperture signature is generated by the correct inclusion of atmospheric transmission. While the technique and general concepts may apply to all airborne targets, this study places emphasis on cruise missiles and related targets due to their low contrast. For these targets, the background signature becomes more important as both the emitted target radiance and the reflected background radiance contribute to the overall signature. Example target signatures generated using the proposed methodology will be presented following the discussion of signature modeling.

  18. Targeting hedgehog in hematologic malignancy.

    Science.gov (United States)

    Irvine, David A; Copland, Mhairi

    2012-03-08

    The Hedgehog pathway is a critical mediator of embryonic patterning and organ development, including hematopoiesis. It influences stem cell fate, differentiation, proliferation, and apoptosis in responsive tissues. In adult organisms, hedgehog pathway activity is required for aspects of tissue maintenance and regeneration; however, there is increasing awareness that abnormal hedgehog signaling is associated with malignancy. Hedgehog signaling is critical for early hematopoietic development, but there is controversy over its role in normal hematopoiesis in adult organisms where it may be dispensable. Conversely, hedgehog signaling appears to be an important survival and proliferation signal for a spectrum of hematologic malignancies. Furthermore, hedgehog signaling may be critical for the maintenance and expansion of leukemic stem cells and therefore provides a possible mechanism to selectively target these primitive cell subpopulations, which are resistant to conventional chemotherapy. Indeed, phase 1 clinical trials of hedgehog pathway inhibitors are currently underway to test this hypothesis in myeloid leukemias. This review covers: (1) the hedgehog pathway and its role in normal and malignant hematopoiesis, (2) the recent development of clinical grade small molecule inhibitors of the pathway, and (3) the potential utility of hedgehog pathway inhibition as a therapeutic strategy in hemato-oncology.

  19. Drug targeting through pilosebaceous route.

    Science.gov (United States)

    Chourasia, Rashmi; Jain, Sanjay K

    2009-10-01

    Local skin targeting is of interest for the pharmaceutical and the cosmetic industry. A topically applied substance has basically three possibilities to penetrate into the skin: transcellular, intercellular, and follicular. The transfollicular path has been largely ignored because hair follicles constitute only 0.1% of the total skin. The hair follicle is a skin appendage with a complex structure containing many cell types that produce highly specialised proteins. The hair follicle is in a continuous cycle: anagen is the hair growth phase, catagen the involution phase and telogen is the resting phase. Nonetheless, the hair follicle has great potential for skin treatment, owing to its deep extension into the dermis and thus provides much deeper penetration and absorption of compounds beneath the skin than seen with the transdermal route. In the case of skin diseases and of cosmetic products, delivery to sweat glands or to the pilosebaceous unit is essential for the effectiveness of the drug. Increased accumulation in the pilosebaceous unit could treat alopecia, acne and skin cancer more efficiently and improve the effect of cosmetic substances and nutrients. Therefore, we review herein various drug delivery systems, including liposomes, niosomes, microspheres, nanoparticles, nanoemulsions, lipid nanocarriers, gene therapy and discuss the results of recent researches. We also review the drugs which have been investigated for pilosebaceous delivery.

  20. Terrorist targeting and energy security

    Energy Technology Data Exchange (ETDEWEB)

    Toft, Peter; Duero, Arash; Bieliauskas, Arunas [Institute of Energy, Joint Research Center of the European Commission, P.O. Box 2, 1755 ZG Petten (Netherlands)

    2010-08-15

    Sudden, short-term disruptions seriously endangering energy security can be triggered by a variety of events - among them attacks by terrorists. This study investigates terrorist attack practices against energy infrastructures and discusses how we may understand them. Our results indicate that attacks against energy infrastructures are comparatively few. Also, we find no strong connection between the ideologies of various terrorist groups and their proclivity to attack. In addition, the highly disproportionate number of attacks in a handful of countries highlights the strong geographic concentration of attacks. To explain these findings, we analyze terrorist targeting incentives including intimidation levels, symbolism, attack feasibility, and concerns for stakeholders. We argue that terrorists in general have comparatively few incentives to attack energy supply infrastructures based on our assessment of these factors. Moreover, higher levels of terrorist incidents in states more prone to internal violent conflict may suggest stronger incentives to attack energy infrastructures. When outlining energy security policies, the low frequency of worldwide attacks coupled with the high concentration of attacks in certain unstable countries should be taken into consideration. Energy importing countries could benefit from developing strategies to increase stability in key energy supply and/or transit countries facing risks of internal instability. (author)

  1. 26 CFR 1.430(d)-1 - Determination of target normal cost and funding target.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Determination of target normal cost and funding target. 1.430(d)-1 Section 1.430(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... of target normal cost and funding target. (a) In general—(1) Overview. This section sets forth rules...

  2. 26 CFR 1.338-1 - General principles; status of old target and new target.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false General principles; status of old target and new target. 1.338-1 Section 1.338-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... of old target and new target. (a) In general—(1) Deemed transaction. Elections are available under...

  3. Double-layered target and identification method of individual target correlated with evaporation residues

    Energy Technology Data Exchange (ETDEWEB)

    Kaji, D., E-mail: daiya@riken.jp; Morimoto, K.

    2015-08-21

    A double-layered target system and an identification method (target ID) for individual targets mounted on a rotating wheel using correlation with evaporation residues were newly developed for the study of superheavy elements (SHE). The target system can be used in three modes: conventional single-layered mode, double-layered mode, and energy-degrader mode. The target ID method can be utilized for masking a target, measuring an excitation function without changing the beam energy from the accelerator, and searching for SHE nuclides using multiple targets during a single irradiation.

  4. Target injection methods for inertial fusion energy

    Energy Technology Data Exchange (ETDEWEB)

    Petzoldt, R.W.; Moir, R.W.

    1994-06-01

    We have studied four methods to inject IFE targets: the gas gun, electrostatic accelerator, induction accelerator, and rail gun. We recommend a gas gun for indirect drive targets because they can support a gas pressure load on one end and can slide along the gun barrel without damage. With the gas gun, the amount of gas required for each target (about 10 to 100 mg) is acceptable; for other types of targets, a sabot would be necessary. A cam and poppet valve arrangement is recommended for gas flow control. An electrostatic accelerator is attractive for use with lightweight spherical direct drive targets. Since there is no physical contact between the target and the injector, there will be no wear of either component during the injection process. An induction accelerator has an advantage of no electrical contact between the target and the injector. Physical contact is not even necessary, so the wear should be minimal. It requires a cylindrical conductive target sleeve which is a substantial added mass. A rail gun is a simpler device than an electrostatic accelerator or induction accelerator. It requires electrical contact between the target and the rails and may have a significant wear rate. The wear in a vacuum could be reduced by use of a solid lubricant such as MoS{sub 2}. The total required accuracy of target injection, tracking and beam pointing of {plus_minus}0.4 mm appears achievable but will require development and experimental verification.

  5. 3 MW solid rotating target design

    Science.gov (United States)

    McManamy, T.; Rennich, M.; Gallmeier, F.; Ferguson, P.; Janney, J.

    2010-03-01

    A rotating solid target design concept is being developed for potential use at the second SNS target station (STS). A long pulse beam (˜1 ms) at 1.3 GeV and 20 Hz is planned with power levels at or above 1 MW. Since the long pulse may give future opportunities for higher power, this study is looking at 3 MW to compare the performance of a solid rotating target to a mercury target. Unlike the case for stationary solid targets at such powers this study indicates that a rotating solid target, when used with large coupled hydrogen moderators, has neutronic performance equal to or better than that with a mercury target, and the solid target has a greatly increased lifetime. Design studies have investigated water cooled tungsten targets with tantalum cladding approximately 1.2 m in diameter, and 70 mm thick. Operating temperatures are low (plane, top and bottom surface cooling. In case of cooling system failure, the diameter gives enough surface area to remove the decay heat by radiation to the surrounding reflector assemblies while keeping the peak temperatures below approximately 700 °C. This temperature should mitigate potential loss of coolant accidents and subsequent steam, tungsten interaction which has a threshold of approximately 800 °C. Design layouts for the sealing systems and potential target station concepts have been developed.

  6. Target injection methods for inertial fusion energy

    Science.gov (United States)

    Petzoldt, Ronald W.; Moir, Ralph W.

    1994-06-01

    We have studied four methods to inject IFE targets: the gas gun, electrostatic accelerator, induction accelerator, and rail gun. We recommend a gas gun for indirect drive targets because they can support a gas pressure load on one end and can slide along the gun barrel without damage. With the gas gun, the amount of gas required for each target (about 10 to 100 mg) is acceptable; for other types of targets, a sabot would be necessary. A cam and poppet valve arrangement is recommended for gas flow control. An electrostatic accelerator is attractive for use with lightweight spherical direct drive targets. Since there is no physical contact between the target and the injector, there will be no wear of either component during the injection process. An induction accelerator has an advantage of no electrical contact between the target and the injector. Physical contact is not even necessary, so the wear should be minimal. It requires a cylindrical conductive target sleeve which is a substantial added mass. A rail gun is a simpler device than an electrostatic accelerator or induction accelerator. It requires electrical contact between the target and the rails and may have a significant wear rate. The wear in a vacuum could be reduced by use of a solid lubricant such as MoS2. The total required accuracy of target injection, tracking and beam pointing of +/- 0.4 mm appears achievable but will require development and experimental verification.

  7. Fluid mechanics aspects of magnetic drug targeting.

    Science.gov (United States)

    Odenbach, Stefan

    2015-10-01

    Experiments and numerical simulations using a flow phantom for magnetic drug targeting have been undertaken. The flow phantom is a half y-branched tube configuration where the main tube represents an artery from which a tumour-supplying artery, which is simulated by the side branch of the flow phantom, branches off. In the experiments a quantification of the amount of magnetic particles targeted towards the branch by a magnetic field applied via a permanent magnet is achieved by impedance measurement using sensor coils. Measuring the targeting efficiency, i.e. the relative amount of particles targeted to the side branch, for different field configurations one obtains targeting maps which combine the targeting efficiency with the magnetic force densities in characteristic points in the flow phantom. It could be shown that targeting efficiency depends strongly on the magnetic field configuration. A corresponding numerical model has been set up, which allows the simulation of targeting efficiency for variable field configuration. With this simulation good agreement of targeting efficiency with experimental data has been found. Thus, the basis has been laid for future calculations of optimal field configurations in clinical applications of magnetic drug targeting. Moreover, the numerical model allows the variation of additional parameters of the drug targeting process and thus an estimation of the influence, e.g. of the fluid properties on the targeting efficiency. Corresponding calculations have shown that the non-Newtonian behaviour of the fluid will significantly influence the targeting process, an aspect which has to be taken into account, especially recalling the fact that the viscosity of magnetic suspensions depends strongly on the magnetic field strength and the mechanical load.

  8. Therapeutic targeting of replicative immortality.

    Science.gov (United States)

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. Copyright © 2015 The Authors

  9. Mitochondria: a target for bacteria.

    Science.gov (United States)

    Lobet, Elodie; Letesson, Jean-Jacques; Arnould, Thierry

    2015-04-01

    Eukaryotic cells developed strategies to detect and eradicate infections. The innate immune system, which is the first line of defence against invading pathogens, relies on the recognition of molecular patterns conserved among pathogens. Pathogen associated molecular pattern binding to pattern recognition receptor triggers the activation of several signalling pathways leading to the establishment of a pro-inflammatory state required to control the infection. In addition, pathogens evolved to subvert those responses (with passive and active strategies) allowing their entry and persistence in the host cells and tissues. Indeed, several bacteria actively manipulate immune system or interfere with the cell fate for their own benefit. One can imagine that bacterial effectors can potentially manipulate every single organelle in the cell. However, the multiple functions fulfilled by mitochondria especially their involvement in the regulation of innate immune response, make mitochondria a target of choice for bacterial pathogens as they are not only a key component of the central metabolism through ATP production and synthesis of various biomolecules but they also take part to cell signalling through ROS production and control of calcium homeostasis as well as the control of cell survival/programmed cell death. Furthermore, considering that mitochondria derived from an ancestral bacterial endosymbiosis, it is not surprising that a special connection does exist between this organelle and bacteria. In this review, we will discuss different mitochondrial functions that are affected during bacterial infection as well as different strategies developed by bacterial pathogens to subvert functions related to calcium homeostasis, maintenance of redox status and mitochondrial morphology.

  10. Memory for found targets interferes with subsequent performance in multiple-target visual search.

    Science.gov (United States)

    Cain, Matthew S; Mitroff, Stephen R

    2013-10-01

    Multiple-target visual searches--when more than 1 target can appear in a given search display--are commonplace in radiology, airport security screening, and the military. Whereas 1 target is often found accurately, additional targets are more likely to be missed in multiple-target searches. To better understand this decrement in 2nd-target detection, here we examined 2 potential forms of interference that can arise from finding a 1st target: interference from the perceptual salience of the 1st target (a now highly relevant distractor in a known location) and interference from a newly created memory representation for the 1st target. Here, we found that removing found targets from the display or making them salient and easily segregated color singletons improved subsequent search accuracy. However, replacing found targets with random distractor items did not improve subsequent search accuracy. Removing and highlighting found targets likely reduced both a target's visual salience and its memory load, whereas replacing a target removed its visual salience but not its representation in memory. Collectively, the current experiments suggest that the working memory load of a found target has a larger effect on subsequent search accuracy than does its perceptual salience.

  11. Protection Related to High-power Targets

    CERN Document Server

    Plum, M.A.

    2016-01-01

    Target protection is an important part of machine protection. The beam power in high-intensity accelerators is high enough that a single wayward pulse can cause serious damage. Today's high-power targets operate at the limit of available technology, and are designed for a very narrow range of beam parameters. If the beam pulse is too far off centre, or if the beam size is not correct, or if the beam density is too high, the target can be seriously damaged. We will start with a brief introduction to high-power targets and then move to a discussion of what can go wrong, and what are the risks. Next we will discuss how to control the beam-related risk, followed by examples from a few different accelerator facilities. We will finish with a detailed example of the Oak Ridge Spallation Neutron Source target tune up and target protection.

  12. Liquid Hydrogen Target for the COMPASS experiment

    CERN Document Server

    Bremer, J; Duday-Chanat, L; Geyer, R; Mallot, G K; Pirotte, O; Vullierme, B

    2014-01-01

    A liquid hydrogen target has been developed for the COMPASS experiment at CERN. The target has a diameter of 40 mm and a length of 2.5 meter, creating an active volume of about 3 liter of liquid hydrogen. The cylindrical part of the target wall is formed by a Kapton® foil strip, wound and glued to a thickness of 0.125 mm. The Kapton® foil is used to minimize the energy loss of the particles, scattered or created within the target volume, crossing the target boundary. The two end-caps enclosing the target volume have been fabricated from Mylar®. The system is cooled with a 30 W at 20 K cryocooler, delivering the cooling capacity for the cool-down as well as for the continuous operation of the system.

  13. Attentional processing of multiple targets and distractors.

    Science.gov (United States)

    Munneke, Jaap; Fait, Elisa; Mazza, Veronica

    2013-11-01

    We assessed the functioning of attention when multiple relevant objects are intermingled with multiple distractors, measuring two electrophysiological subcomponents of the N2pc that have been associated, respectively, with target selection and distractor suppression: the target negativity (Nt) and the distractor positivity (Pd). To this aim, we orthogonally manipulated the number of targets and distractors in an enumeration task. The Nt was modulated by target, but not distractor numerosity, suggesting that an increase in target numerosity leads to an increase in attentional resources needed to form individual representations of the targets. In contrast, the number of distractors did not differentially alter the Pd. We hypothesize that distractors sharing similar visual features can be processed (and possibly suppressed) as a set, without the need for individuation.

  14. Neutronic characterization of the MEGAPIE target

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, Stefano [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France)], E-mail: Stefano.panebianco@cea.fr; Berg, Klara [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); David, Jean-Christophe [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Eid, Mohamed [CEA/DEN/DM2S/SERMA, Centre de Saclay, F-91194 Gif-sur-Yvette (France); Filges, Uwe; Groeschel, Friedrich [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Guertin, Arnaud [SUBATECH, Ecole des Mines, F-44307 Nantes (France); Konobeyev, Alexander Yu [Forschungszentrum Karlsruhe, IRS, D-76021 Karlsruhe (Germany); Latge, Christian [CEA/DEN/DTN/DIR, Centre de Cadarache, F-13108 Saint-Paul-lez-Durance (France); Lemaire, Sebastien [CEA, DAM Ile de France, F-91297 Bruyeres le Chatel (France); Leray, Sylvie; Letourneau, Alain [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Luethy, Markus [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Michel-Sendis, Franco [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Scazzi, Selene [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Stankunas, Gediminas [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Thiolliere, Nicolas [SUBATECH, Ecole des Mines, F-44307 Nantes (France); Tobler, Leonhard; Zanini, Luca [Paul Scherrer Institut, CH-5232 Villigen (Switzerland)

    2009-04-15

    The MEGAPIE project aimed to design, build and operate a liquid metal spallation neutron target of about 1 MW beam power in the SINQ facility at the Paul Scherrer Institut (Villigen, Switzerland). This project is an important step in the roadmap towards the demonstration of the accelerator driven system (ADS) concept and high power liquid metal targets in general. Following the design phase, an experimental program was defined to provide a complete characterization of the facility by performing a 'mapping' of the neutron flux at different points, from the center of the target to the beam lines. The neutronic performance of the target was studied using different experimental techniques with the goals of validating the Monte Carlo codes used in the design of the target; additionally, the performance was compared with the solid lead targets used before and after the MEGAPIE experiment.

  15. Neutronic characterization of the MEGAPIE target

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, Stefano; David, Jean-Christophe; Leray, Sylvie; Letourneau, Alain; Michel-Sendis, Franco; Stankunas, Gediminas [CEA/IRFU, Gif-sur-Yvette (France); Berg, Klara; Filges, Uwe; Groeschel, Friedrich; Luethy, Markus; Scazzi, Selene; Tobler, Leonhard; Zanini, Luca [PSI, Villigen (Switzerland); Eid, Mohamed [CEA/DEN/DM2S/SERMA, Gif-sur-Yvette (France); Guertin, Arnaud; Thiolliere, Nicolas [SUBATECH, Nantes (France); Konobeyev, Alexander Yu. [FZK/IRS, Karlsruhe (Germany); Latge, Christian [CEA/DEN/DTN/DIR, St. Paul Lez Durance (France); Lemaire, Sebastien [CEA/DAM/DCSA/SCGA, Bruyeres-le-Chatel (France)

    2008-07-01

    The MEGAPIE project aimed to design, build and operate a liquid metal spallation neutron target of 1 MW beam power in the SINQ facility at the Paul Scherrer Institut (Villigen, Switzerland). The project is an important step in the road-map towards the demonstration of the Accelerator Driven System (ADS) concept and high power liquid metal targets in general. Following the design phase, an experimental program was defined to provide a complete characterization of the facility by performing a 'mapping' of the neutron flux at different points, from the center of the target to the beam lines. The neutronic performance of the target was studied using different experimental techniques with the goals of validating the Monte Carlo codes used in the design of the target; additionally, the performance was compared with the solid lead targets used before and after the MEGAPIE experiment. (authors)

  16. Development on dynamic nuclear polarized targets

    CERN Document Server

    Penttila, S I

    2002-01-01

    Our interest in understanding the spin content of the nucleon has left its marks on the recent development of the dynamic nuclear polarized (DNP) targets. This can be seen from the targets developed at CERN and SLAC for the measurement of the polarized spin structure functions in deep inelastic scattering. The results of the experiments indicated that less than 30% of the nucleon spin is carried by the quarks. This unpredicted small value initiated planning of new polarized target experiments to determine the gluon polarization on the nucleon using polarized real photons and polarized /sup 6/LiD targets. In several facilities very intense polarized photon beams are available at a wide energy range. During the next few years these photon beams with DNP targets will be used to test the fundamental GDH sum rule. Other DNP target developments are also discussed. (61 refs).

  17. Application of VNIIRS for target tracking

    Science.gov (United States)

    Blasch, Erik; Kahler, Bart

    2015-05-01

    The Motion Imagery Standards Board (MISB) has created the Video National Imagery Interpretability Rating Scale (VNIIRS). VNIIRS extends NIIRS to scene characterization from streaming video to include object recognition of various targets for a given size. To apply VNIIRs for target tracking, there is a need to understand the operating conditions of the sensor type, environmental phenomenon, and target behavior (SET). In this paper, we explore VNIIRS for target tracking given the sensor resolution to support the relative tracking performance using track success. The relative assessment can be used in relation to the absolute target size associated with the VNIIRS. In a notional analysis, we determine the issues and capabilities of using VNIIRS video quality ratings to determine track success. The outcome of the trade study is an experiment to understand how to use VNIIRS can support target tracking evaluation.

  18. Inflation targeting and product market deregulation

    OpenAIRE

    Moretti, Laura

    2012-01-01

    I evaluate the effect of inflation targeting on inflation and how it interacts with product market deregulation during the disinflationary process in the 1990s. Using a sample of 21 OECD countries, I show that, after controlling for product market deregulation, the effect of inflation targeting is quantitatively important and statistically significant. Moreover, product market deregulation also matters in particular in countries that adopted an inflation targeting regime. I propose a New Keyn...

  19. Novel Acoustic Scattering Processes for Target Discrimination

    Science.gov (United States)

    2014-12-31

    Scattering Processes for Target Discrimination 5a. CONTRACT NUMBER 5b. GRANT NUMBER N000141010093 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Marston...10-1-0093 December 2014 Novel Acoustic Scattering Processes for Target Discrimination Philip L. Marston, Principal Investigator Physics and...Target Discrimination (2010) Philip L. Marston Physics and Astronomy Dept., Washington State University, Pullman, WA 99164-2814 phone: (509) 335

  20. Moller Polarimetry with Atomic Hydrogen Targets

    Energy Technology Data Exchange (ETDEWEB)

    Chudakov, Eugene [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Luppov, V. [University of Michigan Spin Physics Center, Ann Arbor, MI (United States)

    2012-06-01

    A proposal to use polarized atomic hydrogen gas as the target for electron beam polarimetry based on the Moller scattering is described. Such a gas, stored in an ultra-cold magnetic trap, would provide a target of practically 100\\% polarized electrons. It is conceivable to reach a $\\sim$0.3\\% systematic accuracy of the beam polarimetry with such a target. Feasibility studies for the CEBAF electron beam have been performed.

  1. From monetary to exchange rate targets

    Directory of Open Access Journals (Sweden)

    M.J. ARTIS

    2013-12-01

    Full Text Available This paper was presented at the Fourth International Seminar on European Economic and Monetary Union, held in Copenhagen in March of 1981. The author takes up the theoretical issues in the framework of both static and dynamic analysis. He argues, on the basis of the criterion of minimising the variance of prices around their target value, that an exchange-rate target outperforms a monetary target under most conceivable types of disturbances in a static analysis. 

  2. Main Development Targets for CNOOC in 2000

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    @@ In order to obtain stable reserves and create scope economic management, the China National Offshore Oil Corporation (CNOOC) officially put forward the main development target and main sci-tech sector target of the Ninth Five-Year Plan in July, 1995. These targets aim to make CNOOC as an international group corporation,including exploration and development of oil and gas,refining, petrochemicals, chemical fertilizer, power generation, unitizing sales network of up and down stream.

  3. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2017-07-14

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  4. Target Capture during Mos1 Transposition*

    Science.gov (United States)

    Pflieger, Aude; Jaillet, Jerôme; Petit, Agnès; Augé-Gouillou, Corinne; Renault, Sylvaine

    2014-01-01

    DNA transposition contributes to genomic plasticity. Target capture is a key step in the transposition process, because it contributes to the selection of new insertion sites. Nothing or little is known about how eukaryotic mariner DNA transposons trigger this step. In the case of Mos1, biochemistry and crystallography have deciphered several inverted terminal repeat-transposase complexes that are intermediates during transposition. However, the target capture complex is still unknown. Here, we show that the preintegration complex (i.e., the excised transposon) is the only complex able to capture a target DNA. Mos1 transposase does not support target commitment, which has been proposed to explain Mos1 random genomic integrations within host genomes. We demonstrate that the TA dinucleotide used as the target is crucial both to target recognition and in the chemistry of the strand transfer reaction. Bent DNA molecules are better targets for the capture when the target DNA is nicked two nucleotides apart from the TA. They improve strand transfer when the target DNA contains a mismatch near the TA dinucleotide. PMID:24269942

  5. Methodological foundations of target market enterprise orientation

    National Research Council Canada - National Science Library

    N.V. Karpenko

    2012-01-01

    In the article the author determines the importance of target market orientation maintenance which content is based on marketing principles and envisages the interrelationship of market segmentation...

  6. 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

  7. Target studies for surface muon production

    Science.gov (United States)

    Berg, F.; Desorgher, L.; Fuchs, A.; Hajdas, W.; Hodge, Z.; Kettle, P.-R.; Knecht, A.; Lüscher, R.; Papa, A.; Rutar, G.; Wohlmuther, M.

    2016-02-01

    Meson factories are powerful drivers of diverse physics programs. With beam powers already in the MW-regime attention has to be turned to target and beam line design to further significantly increase surface muon rates available for experiments. For this reason we have explored the possibility of using a neutron spallation target as a source of surface muons by performing detailed Geant4 simulations with pion production cross sections based on a parametrization of existing data. While the spallation target outperforms standard targets in the backward direction by more than a factor 7 it is not more efficient than standard targets viewed under 90°. Not surprisingly, the geometry of the target plays a large role in the generation of surface muons. Through careful optimization, a gain in surface muon rate of between 30% and 60% over the standard "box-like" target used at the Paul Scherrer Institute could be achieved by employing a rotated slab target. An additional 10% gain could also be possible by utilizing novel target materials such as, e.g., boron carbide.

  8. Selective targeting of epigenetic reader domains.

    Science.gov (United States)

    Greschik, Holger; Schüle, Roland; Günther, Thomas

    2017-05-01

    Epigenetic regulators including writers, erasers, and readers of chromatin marks have been implicated in numerous diseases and are therefore subject of intense academic and pharmaceutical research. While several small-molecule inhibitors targeting writers or erasers are either approved drugs or are currently being evaluated in clinical trials, the targeting of epigenetic readers has lagged behind. Proof-of-principle that epigenetic readers are also relevant drug targets was provided by landmark discoveries of selective inhibitors targeting the BET family of acetyl-lysine readers. More recently, high affinity chemical probes for non-BET acetyl- and methyl-lysine reader domains have also been developed. Areas covered: This article covers recent advances with the identification and validation of inhibitors and chemical probes targeting epigenetic reader domains. Issues related to epigenetic reader druggability, quality requirements for chemical probes, interpretation of cellular action, unexpected cross-talk, and future challenges are also discussed. Expert opinion: Chemical probes provide a powerful means to unravel biological functions of epigenetic readers and evaluate their potential as drug targets. To yield meaningful results, potency, selectivity, and cellular target engagement of chemical probes need to be stringently validated. Future chemical probes will probably need to fulfil additional criteria such as strict target specificity or the targeting of readers within protein complexes.

  9. Target-tracking algorithm for omnidirectional vision

    Science.gov (United States)

    Cai, Chengtao; Weng, Xiangyu; Fan, Bing; Zhu, Qidan

    2017-05-01

    Omnidirectional vision with the advantage of a large field-of-view overcomes the problem that a target is easily lost due to the narrow sight of perspective vision. We improve a target-tracking algorithm based on discriminative tracking features in several aspects and propose a target-tracking algorithm for an omnidirectional vision system. (1) An elliptical target window expression model is presented to represent the target's outline, which can adapt to the deformation of an object and reduce background interference. (2) The background-weighted linear RGB histogram target feature is introduced, which decreases the weight of the background feature. (3) The Bhattacharyya coefficients-based feature identification method is employed, which reduces the computation time of the tracking algorithm. (4) An adaptive target scale and orientation measurement method is applied to adapt to severe deformations of the target's outline. (5) A model update strategy is put forward, which is based on similarity measurements to achieve an effective and accurate model update. The experimental results show the proposed algorithm can achieve better performance than the state-of-the-art algorithms when using omnidirectional vision to perform long-term target-tracking tasks.

  10. ISAC target operation with high proton currents

    CERN Document Server

    Dombsky, M; Schmor, P; Lane, M

    2003-01-01

    The TRIUMF-ISAC facility target stations were designed for ISOL target irradiations with up to 100 mu A proton beam currents. Since beginning operation in 1998, ISAC irradiation currents have progressively increased from initial values of approx 1 mu A to present levels of up to 40 mu A on refractory metal foil targets. In addition, refractory carbide targets have operated at currents of up to 15 mu A for extended periods. The 1-40 mu A operational regime is achieved by tailoring each target to the thermal requirements dictated by material properties such as beam power deposition, thermal conductivity and maximum operating temperature of the target material. The number of heat shields on each target can be varied in order to match the effective emissivity of the target surface for the required radiative power dissipation. Targets of different thickness, surface area and volume have been investigated to study the effect of diffusion and effusion delays on the yield of radioisotopes. For yields of short-lived p...

  11. On Training Targets for Supervised Speech Separation

    Science.gov (United States)

    Wang, Yuxuan; Narayanan, Arun; Wang, DeLiang

    2014-01-01

    Formulation of speech separation as a supervised learning problem has shown considerable promise. In its simplest form, a supervised learning algorithm, typically a deep neural network, is trained to learn a mapping from noisy features to a time-frequency representation of the target of interest. Traditionally, the ideal binary mask (IBM) is used as the target because of its simplicity and large speech intelligibility gains. The supervised learning framework, however, is not restricted to the use of binary targets. In this study, we evaluate and compare separation results by using different training targets, including the IBM, the target binary mask, the ideal ratio mask (IRM), the short-time Fourier transform spectral magnitude and its corresponding mask (FFT-MASK), and the Gammatone frequency power spectrum. Our results in various test conditions reveal that the two ratio mask targets, the IRM and the FFT-MASK, outperform the other targets in terms of objective intelligibility and quality metrics. In addition, we find that masking based targets, in general, are significantly better than spectral envelope based targets. We also present comparisons with recent methods in non-negative matrix factorization and speech enhancement, which show clear performance advantages of supervised speech separation. PMID:25599083

  12. Target tracking based on frequency spectrum amplitude

    Institute of Scientific and Technical Information of China (English)

    Guo Huidong; Zhang Xinhua; Xia Zhijun

    2006-01-01

    The amplitude of frequency spectrum can be integrated with probabilistic data association (PDA) to distinguish the target with clutter echoes, especially in low SNR underwater environment. A new target-tracking algorithm is presented which adopts the amplitude of frequency spectrum to improve target tracking in clutter. The probabilistic density distribution of frequency spectrum amplitude is analyzed. By simulation, the results show that the algorithm is superior to PDA. This approach enhances stability for the association probability and increases the performance of target tracking.

  13. Two target localization using passive monopulse radar

    KAUST Repository

    Jardak, Seifallah

    2016-02-19

    The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localization and tracking purposes. Many works focused on accurately localizing one or two targets laying within a narrow beam centered around the monopulse antenna boresight direction. In this work, however, a new approach uses the outputs of a four quadrant antenna receiver to rapidly localize two point targets present in the hemisphere. A second set of antennas can be required to localize two targets sharing the same elevation or azimuth angles. To combine the outputs of both antenna sets and enhance the estimation performance of the algorithm, two methods are presented and compared.

  14. Predicting the Reliability of Drug-target Interaction Predictions with Maximum Coverage of Target Space.

    Science.gov (United States)

    Peón, Antonio; Naulaerts, Stefan; Ballester, Pedro J

    2017-06-19

    Many computational methods to predict the macromolecular targets of small organic molecules have been presented to date. Despite progress, target prediction methods still have important limitations. For example, the most accurate methods implicitly restrict their predictions to a relatively small number of targets, are not systematically validated on drugs (whose targets are harder to predict than those of non-drug molecules) and often lack a reliability score associated with each predicted target. Here we present a systematic validation of ligand-centric target prediction methods on a set of clinical drugs. These methods exploit a knowledge-base covering 887,435 known ligand-target associations between 504,755 molecules and 4,167 targets. Based on this dataset, we provide a new estimate of the polypharmacology of drugs, which on average have 11.5 targets below IC50 10 µM. The average performance achieved across clinical drugs is remarkable (0.348 precision and 0.423 recall, with large drug-dependent variability), especially given the unusually large coverage of the target space. Furthermore, we show how a sparse ligand-target bioactivity matrix to retrospectively validate target prediction methods could underestimate prospective performance. Lastly, we present and validate a first-in-kind score capable of accurately predicting the reliability of target predictions.

  15. The drug target genes show higher evolutionary conservation than non-target genes.

    Science.gov (United States)

    Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

    2016-01-26

    Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

  16. Inflation Targeting in Emerging Market Countries

    OpenAIRE

    Frederic S. Mishkin

    2000-01-01

    This paper outlines what inflation targeting involves for emerging market/transition countries and discusses the advantages and disadvantages of this monetary policy strategy. The discussion suggests that although inflation targeting is not a panacea and may not be appropriate for many emerging market countries, it can be a highly useful monetary policy strategy in a number of them.

  17. Mathematical modelling of magnetically targeted drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Grief, Andrew D. [Theoretical Mechanics, School of Mathematical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)]. E-mail: andrew.grief@nottingham.ac.uk; Richardson, Giles [Theoretical Mechanics, School of Mathematical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)]. E-mail: giles.richardson@nottingham.ac.uk

    2005-05-15

    A mathematical model for targeted drug delivery using magnetic particles is developed. This includes a diffusive flux of particles arising from interactions between erythrocytes in the microcirculation. The model is used to track particles in a vessel network. Magnetic field design is discussed and we show that it is impossible to specifically target internal regions using an externally applied field.

  18. A rotating target for Ra production

    NARCIS (Netherlands)

    Sohani, M.; Wilschut, H. W.

    2012-01-01

    A target wheel with pyrolytic graphite targets is designed and constructed at the TRI mu P facility to boost the production rate of Ra isotopes. Simulation, design properties and production results are discussed. (C) 2012 Elsevier B.V. All rights reserved.

  19. ISOLDE target zone control room HD

    CERN Multimedia

    2016-01-01

    Operating the ISOLDE target handling robots from the dedicated control room in building 197. Monitors showing the movements of the robots (GPS in this case) in the target zone. The footage shows the actual operation by the operator as well as the different equipment such as camera electronics, camera motor controls, camera monitors and Kuka robot controls touch panel.

  20. Target Tracking and Interception by Aggressive Honeybees

    Science.gov (United States)

    2010-08-01

    targets can hinder, prevent or endanger attacks to the centrally-located targets. Figure 15. Percentage of strikes (totalling 100%) to each of the...adjusted, 53  to minimize the drag that is produced by the medium through which they move. For example, 54  sharks , tuna and mackerel possess fusiform shapes

  1. 28 CFR 55.17 - Targeting.

    Science.gov (United States)

    2010-07-01

    ... REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.17 Targeting. The term...). “Targeting” refers to a system in which the minority language materials or assistance required by the Act are... targeting system will normally fulfill the Act's minority language requirements if it is designed...

  2. Refocusing vibrating targets in SAR images

    Science.gov (United States)

    Wang, Qi; Santhanam, Balu; Pepin, Matthew; Atwood, Tom; Hayat, Majeed M.

    2012-06-01

    In synthetic-aperture radar (SAR) returned signals, ground-target vibrations introduce a phase modulation that is linearly proportional to the vibration displacement. Such modulation, termed the micro-Doppler effect, introduces ghost targets along the azimuth direction in reconstructed SAR images that prevents SAR from forming focused images of the vibrating targets. Recently, a discrete fractional Fourier transform (DFrFT) based method was developed to estimate the vibration frequencies and instantaneous vibration accelerations of the vibrating targets from SAR returned signals. In this paper, a demodulation-based algorithm is proposed to reconstruct focused SAR images of vibrating targets by exploiting the estimation results of the DFrFT-based vibration estimation method. For a single-component harmonic vibration, the history of the vibration displacement is first estimated from the estimated vibration frequency and the instantaneous vibration accelerations. Then a reference signal whose phase is modulated by the estimated vibration displacement with a delay of 180 degree is constructed. After that, the SAR phase history from the vibration target is multiplied by the reference signal and the vibration-induced phase modulation is canceled. Finally, the SAR image containing the re-focused vibration target is obtained by applying the 2-D Fourier transform to the demodulated SAR phase history. This algorithm is applied to simulated SAR data and successfully reconstructs the SAR image containing the re-focused vibrating target.

  3. 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.

  4. Target Studies for Surface Muon Production

    CERN Document Server

    Berg, F; Fuchs, A; Hajdas, W; Hodge, Z; Kettle, P -R; Knecht, A; Lüscher, R; Papa, A; Rutar, G; Wohlmuther, M

    2015-01-01

    Meson factories are powerful drivers of diverse physics programmes. With beam powers already in the MW-regime attention has to be turned to target and beam line design to further significantly increase surface muon rates available for experiments. For this reason we have explored the possibility of using a neutron spallation target as a source of surface muons by performing detailed Geant4 simulations with pion production cross sections based on a parametrization of existing data. While the spallation target outperforms standard targets in the backward direction by more than a factor 7 it is not more efficient than standard targets viewed under 90{\\deg}. Not surprisingly, the geometry of the target plays a large role in the generation of surface muons. Through careful optimization, a gain in surface muon rate of between 30 - 60% over the standard "box-like" target used at the Paul Scherrer Institute could be achieved by employing a rotated slab target. An additional 10% gain could also be possible by utilizin...

  5. Inflation targeting and interest rate policy

    NARCIS (Netherlands)

    Verhagen, W.H.

    2001-01-01

    The thesis contains a collection of papers on issues in inflation targeting and its implications for the way interest rates are set. In this respect, the first part deals with two largely positive issues: the effect of inflation forecast targeting on the term structure of interest rates and the impl

  6. Waiting-time targets. Early learners.

    Science.gov (United States)

    Moore, Alison

    2007-04-05

    Thirteen 'early achiever' sites have volunteered to deliver the new 18-week target ahead of schedule. The sites have highlighted recurring issues for trusts aiming for 18 weeks: orthopaedics, audiology, endoscopy and some smaller specialties have all proved challenging. The target should be seen as a vital step towards a 'no unnecessary delay' system of working and thinking.

  7. What "helps" tumors evade vascular targeting treatment?

    Institute of Scientific and Technical Information of China (English)

    SI Zhi-chao; LIU Jie

    2008-01-01

    Objective To throw a light on the possible factors which might induce resistance of vascular targeting treatment in tumors by reviewing the recent publications in the field of tumor angiogenesis and vascular targeting treatment.Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1971 to January 2008. The search terms were "angiogenesis", "vascular targeting treatment" and "endothelial progenitor cells".Study selection Articles involved in the possible influence factors during angiogenesis and vascular targeting treatment were selected, including angiogenic or anti-angiogenic mechanism, tumor vasculature, tumor cells, cancer stem cells and endothelial progenitor cells.Results As a promising strategy vascular targeting treatment still has experimental and clinical setbacks which may term tumor vasculature's resistance to anti-angiogenesis agents. There are several possible explanations for such a resistance that might account for clinical and preclinical failures of anti-angiogenic treatment against tumor.Proangiogenic effect of hypoxia, normal tumor vasculature, escape of tumor cells and tumor vasculogenesis are included.This review reveals some clues which might be helpful to direct future research in order to remove obstacles to vascular targeting treatment.Conclusions Generally and undoubtedly vascular targeting treatment remains a promising strategy. But we still have to realize the existence of a challenging future. Further research is required to enhance our knowledge of vascular targeting treatment strategy before it could make a more substantial success.

  8. The History of Target-Controlled Infusion

    NARCIS (Netherlands)

    Struys, Michel M. R. F.; De Smet, Tom; Glen, John (Iain) B.; Vereecke, Hugo E. M.; Absalom, Anthony R.; Schnider, Thomas W.

    Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted (target) drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical

  9. Targeted inhibition of tumor growth and angiogenesis

    NARCIS (Netherlands)

    van der Meel, R.

    2013-01-01

    Two main strategies have been pursued for the development of an effective and targeted anti-cancer treatment. The first strategy comprised the generation of a targeted nanomedicine for the inhibition of tumor cell proliferation by blocking growth factor receptor pathways. The epidermal growth factor

  10. Inflation targeting and interest rate policy

    NARCIS (Netherlands)

    Verhagen, W.H.

    2001-01-01

    The thesis contains a collection of papers on issues in inflation targeting and its implications for the way interest rates are set. In this respect, the first part deals with two largely positive issues: the effect of inflation forecast targeting on the term structure of interest rates and the

  11. Prodrug applications for targeted cancer therapy.

    Science.gov (United States)

    Giang, Irene; Boland, Erin L; Poon, Gregory M K

    2014-09-01

    Prodrugs are widely used in the targeted delivery of cytotoxic compounds to cancer cells. To date, targeted prodrugs for cancer therapy have achieved great diversity in terms of target selection, activation chemistry, as well as size and physicochemical nature of the prodrug. Macromolecular prodrugs such as antibody-drug conjugates, targeted polymer-drug conjugates and other conjugates that self-assemble to form liposomal and micellar nanoparticles currently represent a major trend in prodrug development for cancer therapy. In this review, we explore a unified view of cancer-targeted prodrugs and highlight several examples from recombinant technology that exemplify the prodrug concept but are not identified as such. Recombinant "prodrugs" such as engineered anthrax toxin show promise in biological specificity through the conditionally targeting of multiple cellular markers. Conditional targeting is achieved by structural complementation, the spontaneous assembly of engineered inactive subunits or fragments to reconstitute functional activity. These complementing systems can be readily adapted to achieve conditionally bispecific targeting of enzymes that are used to activate low-molecular weight prodrugs. By leveraging strengths from medicinal chemistry, polymer science, and recombinant technology, prodrugs are poised to remain a core component of highly focused and tailored strategies aimed at conditionally attacking complex molecular phenotypes in clinically relevant cancer.

  12. Targeted toxins in brain tumor therapy.

    Science.gov (United States)

    Li, Yan Michael; Hall, Walter A

    2010-11-01

    Targeted toxins, also known as immunotoxins or cytotoxins, are recombinant molecules that specifically bind to cell surface receptors that are overexpressed in cancer and the toxin component kills the cell. These recombinant proteins consist of a specific antibody or ligand coupled to a protein toxin. The targeted toxins bind to a surface antigen or receptor overexpressed in tumors, such as the epidermal growth factor receptor or interleukin-13 receptor. The toxin part of the molecule in all clinically used toxins is modified from bacterial or plant toxins, fused to an antibody or carrier ligand. Targeted toxins are very effective against cancer cells resistant to radiation and chemotherapy. They are far more potent than any known chemotherapy drug. Targeted toxins have shown an acceptable profile of toxicity and safety in early clinical studies and have demonstrated evidence of a tumor response. Currently, clinical trials with some targeted toxins are complete and the final results are pending. This review summarizes the characteristics of targeted toxins and the key findings of the important clinical studies with targeted toxins in malignant brain tumor patients. Obstacles to successful treatment of malignant brain tumors include poor penetration into tumor masses, the immune response to the toxin component and cancer heterogeneity. Strategies to overcome these limitations are being pursued in the current generation of targeted toxins.

  13. Targeted Toxins in Brain Tumor Therapy

    Directory of Open Access Journals (Sweden)

    Walter A. Hall

    2010-11-01

    Full Text Available Targeted toxins, also known as immunotoxins or cytotoxins, are recombinant molecules that specifically bind to cell surface receptors that are overexpressed in cancer and the toxin component kills the cell. These recombinant proteins consist of a specific antibody or ligand coupled to a protein toxin. The targeted toxins bind to a surface antigen or receptor overexpressed in tumors, such as the epidermal growth factor receptor or interleukin-13 receptor. The toxin part of the molecule in all clinically used toxins is modified from bacterial or plant toxins, fused to an antibody or carrier ligand. Targeted toxins are very effective against cancer cells resistant to radiation and chemotherapy. They are far more potent than any known chemotherapy drug. Targeted toxins have shown an acceptable profile of toxicity and safety in early clinical studies and have demonstrated evidence of a tumor response. Currently, clinical trials with some targeted toxins are complete and the final results are pending. This review summarizes the characteristics of targeted toxins and the key findings of the important clinical studies with targeted toxins in malignant brain tumor patients. Obstacles to successful treatment of malignant brain tumors include poor penetration into tumor masses, the immune response to the toxin component and cancer heterogeneity. Strategies to overcome these limitations are being pursued in the current generation of targeted toxins.

  14. Targeted Magnetic Hyperthermia for Lung Cancer

    Science.gov (United States)

    2013-09-01

    O R R EC TE D PR O O F 928 were evident. In contrast, MRI scans of treated mice showed 929 no signs of intra-thoracic lung cancer (Fig. 4). The...mice that received SPIO-loaded nanoemulsion 1010 (either targeted or non-targeted) appeared hypointense, in- 1011 dicating SPIO accumulation in these

  15. Carbohydrate plasma expanders for passive tumor targeting

    DEFF Research Database (Denmark)

    Hoffmann, Stefan; Caysa, Henrike; Kuntsche, Judith

    2013-01-01

    The objective of this study was to investigate the suitability of carbohydrate plasma volume expanders as a novel polymer platform for tumor targeting. Many synthetic polymers have already been synthesized for targeted tumor therapy, but potential advantages of these carbohydrates include...

  16. Technical Design Report, Second Target Station

    Energy Technology Data Exchange (ETDEWEB)

    Galambos, John D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Anderson, David E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bechtol, D. [HDR, Inc., Chattanooga, TN (United States); Bethea, Katie L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Brown, N. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Carden, W. F. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Chae, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Clark, A. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Counce, Deborah M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Craft, K. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Crofford, Mark T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Collins, Richard M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cousineau, Sarah M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Curry, Douglas E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cutler, Roy I. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dayton, Michael J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dean, Robert A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Deibele, Craig E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Doleans, Marc [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dye, T. [HDR, Inc., Chattanooga, TN (United States); Eason, Bob H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Eckroth, James A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Fincrock, C. [HDR, Inc., Chattanooga, TN (United States); Fritts, S. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Gallmeier, Franz X. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gawne, Ken R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hartman, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Herwig, Kenneth W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hess, S. [HDR, Inc., Chattanooga, TN (United States); Holmes, Jeffrey A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Horak, Charlie M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Howell, Matthew P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Iverson, Erik B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jacobs, Lorelei L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jones, Larry C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Johnson, B. [HDR, Inc., Chattanooga, TN (United States); Johnson, S. [HDR, Inc., Chattanooga, TN (United States); Kasemir, Kay [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kim, Sang-Ho [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Laughon, Gregory J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lu, W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mahoney, Kelly L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mammosser, John [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); McManamy, T. [McManamy Consulting, Inc., Knoxville, TN (United States); Michilini, M. [HDR, Inc., Chattanooga, TN (United States); Middendorf, Mark E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); O' Neal, Ed [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nemec, B. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Peters, Roy Cecil [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Plum, Michael A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Reagan, G. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Remec, Igor [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Rennich, Mark J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Riemer, Bernie [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Saethre, Robert B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Schubert, James Phillip [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Shishlo, Andrei P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Smith, C. Craig [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Strong, William Herb [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tallant, Kathie M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tennant, David Alan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Thibadeau, Barbara M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Trumble, S. [HDR, Inc., Chattanooga, TN (United States); Trotter, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wang, Z. [Institute of Modern Physics (IMP), Chinese Academy of Sciences (China); Webb, Steven B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Williams, Derrick C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); White, Karen S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Zhao, Jinkui [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-01-01

    The Second Target Station (STS) is a proposed upgrade for SNS. It includes a doubling of the accelerator power and an additional instrument hall. The new instrument hall will receive a 467 kW 10 Hz beam. The parameters and preliminary design aspects of the STS are presented for the accelerator, target systems, instrument hall, instruments and civil construction aspects.

  17. Population ageing and public finance targets

    OpenAIRE

    Heikki Oksanen

    2003-01-01

    The paper incorporates intergenerational fairness into a framework to analyse long-term sustainability of public finances under population ageing. It establishes a link between ageing-related public expenditure projections and public finance targets, thereby clarifying the connection between pension reforms and general government budget balance and debt targets.

  18. NIF Target Assembly Metrology Methodology and Results

    Energy Technology Data Exchange (ETDEWEB)

    Alger, E. T. [General Atomics, San Diego, CA (United States); Kroll, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Dzenitis, E. G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Montesanti, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hughes, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Swisher, M. [IAP, Livermore, CA (United States); Taylor, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Segraves, K. [IAP, Livermore, CA (United States); Lord, D. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Castro, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Edwards, G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-01-01

    During our inertial confinement fusion (ICF) experiments at the National Ignition Facility (NIF) we require cryogenic targets at the 1-cm scale to be fabricated, assembled, and metrologized to micron-level tolerances. During assembly of these ICF targets, there are physical dimensmetrology is completed using optical coordinate measurement machines that provide repeatable measurements with micron precision, while also allowing in-process data collection for absolute accuracy in assembly. To date, 51 targets have been assembled and metrologized, and 34 targets have been successfully fielded on NIF relying on these metrology data. In the near future, ignition experiments on NIF will require tighter tolerances and more demanding target assembly and metrology capability. Metrology methods, calculations, and uncertainty estimates will be discussed. Target diagnostic port alignment, target position, and capsule location results will be reviewed for the 2009 Energetics Campaign. The information is presented via control charts showing the effect of process improvements that were made during target production. Certain parameters, including capsule position, met the 2009 campaign specifications but will have much tighter requirements in the future. Finally, in order to meet these new requirements assembly process changes and metrology capability upgrades will be necessary.

  19. Performance Targets and External Market Prices

    DEFF Research Database (Denmark)

    Hansen, Allan; Friis, Ivar; Vámosi, Tamás S.

    In this paper we explore the processes of ‘bringing the market inside the firm’ to set performance targets and benchmark production workers productivity. We analyze attempts to use external suppliers’ bids in target setting in a Danish manufacturing company. The case study illustrates how...... the implementation of external market information in target setting – well known in transfer pricing, relative performance evaluation, beyond budgeting, target costing, piece rates systems and value based management – relate to challenging motivation and information problem. The analysis and discussion of those...... problems, in particular those related to accounting for the internal performance (that are going to be compared with the external target), calculating the ‘inside’ costs and defining controllability, contributes to the management accounting as well as the piece-rate literature....

  20. Design of the NIF Cryogenic Target System

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, C; Baltz, J; Malsbury, T; Atkinson, D; Brugmann, V; Coffield, F; Edwards, O; Haid, B; Locke, S; Shiromizu, S; Skulina, K

    2008-06-10

    The United States Department of Energy has embarked on a campaign to conduct credible fusion ignition experiments on the National Ignition Facility (NIF) at the Lawrence Livermore National Laboratory in 2010. The target assembly specified for this campaign requires the formation of a deuterium/tritium (DT) fuel ice layer in a 2 mm diameter capsule at the center of a 9 mm long by 5 mm diameter cylinder, called a hohlraum. The ice layer must be formed and maintained at temperatures below 20 K. At laser shot time, the target is positioned at the center of the NIF target chamber, aligned to the laser beams and held stable to less than 7 {micro}m rms. We have completed the final design of the Cryogenic Target System and are integrating the devices necessary to create, characterize and position the cryogenic target for ignition experiments. These designs, with supporting analysis and prototype test results, will be presented.

  1. Progress on LMJ targets for ignition

    Energy Technology Data Exchange (ETDEWEB)

    Cherfils-Clerouin, C; Boniface, C; Bonnefille, M; Dattolo, E; Galmiche, D; Gauthier, P; Giorla, J; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Masson-Laborde, P E; Monteil, M C; Poggi, F; Seytor, P; Wagon, F; Willien, J L, E-mail: catherine.cherfils@cea.f [CEA, DAM, DIF, F-91297 Arpajon (France)

    2009-12-15

    Targets designed to produce ignition on the Laser Megajoule (LMJ) are being simulated in order to set specifications for target fabrication. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4 MJ and 380 TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-ball shaped cocktail hohlraum; with these improvements, a target based on the 240-beam A1040 capsule can be included in the 160-beam laser energy-power space. Robustness evaluations of these different targets shed light on critical points for ignition, which can trade off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

  2. The Jefferson Lab frozen spin target

    Energy Technology Data Exchange (ETDEWEB)

    Keith, C.D., E-mail: ckeith@jlab.org [Thomas Jefferson National Accelerator Facility, Newport News, VA 23606 (United States); Brock, J.; Carlin, C.; Comer, S.A.; Kashy, D. [Thomas Jefferson National Accelerator Facility, Newport News, VA 23606 (United States); McAndrew, J. [School of Physics, University of Edinburgh, Edinburgh (United Kingdom); Meekins, D.G.; Pasyuk, E.; Pierce, J.J.; Seely, M.L. [Thomas Jefferson National Accelerator Facility, Newport News, VA 23606 (United States)

    2012-08-21

    A frozen spin polarized target, constructed at Jefferson Lab for use inside a large acceptance spectrometer, is described. The target has been utilized for photoproduction measurements with polarized tagged photons of both longitudinal and circular polarization. Protons in TEMPO-doped butanol were dynamically polarized to approximately 90% outside the spectrometer at 5 T and 200-300 mK. Photoproduction data were acquired with the target inside the spectrometer at a frozen-spin temperature of approximately 30 mK with the polarization maintained by a thin, superconducting coil installed inside the target cryostat. A 0.56 T solenoid was used for longitudinal target polarization and a 0.50 T dipole for transverse polarization. Spin-lattice relaxation times as high as 4000 h were observed. We also report polarization results for deuterated propanediol doped with the trityl radical OX063.

  3. Exploiting novel molecular targets in gastrointestinal cancers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Novel molecular targets are being discovered as we learn more about the aberrant processes underlying various cancers. Efforts to translate this knowledge are starting to impact on the care of patients with gastrointestinal cancers. The epidermal growth factor receptor (EGFR) pathway and angiogenesis have been targeted successfully in colorectal cancer with cetuximab, panitunumab and bevacizumab. Similarly, EGFR-targeting with erlotinib yielded significant survival benefit in pancreatic cancer when combined with gemcitabine. The multi-targeting approach with sorafenib has made it the first agent to achieve significant survival benefit in hepatocellular carcinoma. Efforts to exploit the dysregulated Akt/mTOR pathway in GI cancer therapy are ongoing. These molecular targets can be disrupted by various approaches, including the use of monoclonal antibody to intercept extracellular ligands and disrupt receptor-ligand binding, and small molecule inhibitors that interrupt the activation of intracellular kinases.

  4. Radiochemical aspects of liquid mercury spallation targets

    CERN Document Server

    Neuhausen, Joerg; Eichler, Bernd; Eller, Martin; Horn, Susanne; Schumann, Dorothea; Stora, Thierry

    2012-01-01

    Liquid metal spallation targets using mercury as target material are used in state-of-the-art high power pulsed neutron sources that have been constructed in the USA and Japan within the last decade. Similar target concepts were also proposed for next generation ISOL, beta-beam and neutrino facilities. A large amount of radioactivity will be induced in the liquid metal during operation caused by the interaction of the target material with the intense proton beam. This radioactivity - carried by a wide range of radioisotopes of all the elements of the periodic table from hydrogen up to thallium - must be considered for the assessment of safe operation and maintenance procedures as well as for a final disposal of the used target material and components. This report presents an overview on chemical investigations performed in our laboratory that deal with the behavior of radionuclides in proton irradiated mercury samples. The solubility of elements in mercury was calculated using thermodynamical data obtained by...

  5. The Jefferson Lab Frozen Spin Target

    Energy Technology Data Exchange (ETDEWEB)

    Christopher Keith, James Brock, Christopher Carlin, Sara Comer, David Kashy, Josephine McAndrew, David Meekins, Eugene Pasyuk, Joshua Pierce, Mikell Seely

    2012-08-01

    A frozen spin polarized target, constructed at Jefferson Lab for use inside a large acceptance spectrometer, is described. The target has been utilized for photoproduction measurements with polarized tagged photons of both longitudinal and circular polarization. Protons in TEMPO-doped butanol were dynamically polarized to approximately 90% outside the spectrometer at 5 T and 200-300 mK. Photoproduction data were acquired with the target inside the spectrometer at a frozen-spin temperature of approximately 30 mK with the polarization maintained by a thin, superconducting coil installed inside the target cryostat. A 0.56 T solenoid was used for longitudinal target polarization and a 0.50 T dipole for transverse polarization. Spin relaxation times as high as 4000 hours were observed. We also report polarization results for deuterated propanediol doped with the trityl radical OX063.

  6. Delayed neutrons measurement at the MEGAPIE target

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, S.; Bokov, P.; Dore, D.; Letourneau, A.; Prevost, A.; Ridikas, D. [CEA Saclay, Dept. d' Astrophysique de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee (DSM/DAPNIA/SPhN), 91- Gif sur Yvette (France); Ledoux, X. [CEA Bruyeres-le-Chatel (CEA DIF, DPTA/SPN), 91 (France). Dept. de Physique Theorique et Appliquee

    2008-07-01

    In the framework of the Neutronic and Nuclear Assessment Task Group of the MEGAPIE experiment we measured the delayed neutron (DN) flux at the top of the target. The measurement was proposed mainly for radioprotection purposes since the DN flux at the top of the target has been estimated to be of the same order of magnitude as the prompt neutron flux. Given the strong model-dependence of DN predictions, the measurement of DN contribution to the total neutron activity at the top of the target was thus desired. Moreover, this measurement is complementary to the DN experiments performed at PNPI (Gatchina) on solid lead and bismuth targets. The DN measurement at MEGAPIE was performed during the start-up phase of the target. In this paper we present a detailed description of the experimental setup and some preliminary results on decay spectra. (authors)

  7. Delayed neutrons measurement at the MEGAPIE target

    CERN Document Server

    Panebianco, Stefano; Dore, Diane; Ledoux, Xavier; Letourneau, Alain; Prevost, Aurelien; Ridikas, Danas

    2007-01-01

    In the framework of the Neutronic and Nuclear Assessment Task Group of the MEGAPIE experiment we measured the delayed neutron (DN) flux at the top of the target. The measurement was proposed mainly for radioprotection purposes since the DN flux at the top of the target has been estimated to be of the same order of magnitude as the prompt neutron flux. Given the strong model-dependence of DN predictions, the measurement of DN contribution to the total neutron activity at the top of the target was thus desired. Moreover, this measurement is complementary to the DN experiments performed at PNPI (Gatchina) on solid lead and bismuth targets. The DN measurement at MEGAPIE was performed during the start-up phase of the target. In this paper we present a detailed description of the experimental setup and some preliminary results on decay spectra.

  8. Epicardial fat: a new cardiovascular therapeutic target.

    Science.gov (United States)

    Iacobellis, Gianluca

    2016-04-01

    Epicardial fat is the visceral fat depot of the heart. Given its rapid metabolism, organ fat specificity and simple objective measurability, epicardial fat can serve as target for pharmaceutical agents targeting the adipose tissue. Epicardial fat has shown to significantly respond to thiazolidinediones, glucagon like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors and statins. Epicardial fat may represent a measurable risk factor and modifiable therapeutic target. Targeted pharmaceutical interventions may allow the epicardial fat to resume its physiological role. A drug-induced browning effect on epicardial fat suggests the development of pharmacological strategies to increase energy consumption. The potential of modulating the epicardial fat transcriptome with targeted pharmacological agents can open new avenues in the pharmacotherapy of cardio-metabolic diseases.

  9. Targeted Radionuclide Therapy of Human Tumors

    Directory of Open Access Journals (Sweden)

    Sergey V. Gudkov

    2015-12-01

    Full Text Available Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

  10. Cooperative target convergence using multiple agents

    Energy Technology Data Exchange (ETDEWEB)

    Kwok, K.S.; Driessen, B.J.

    1997-10-01

    This work considers the problem of causing multiple (100`s) autonomous mobile robots to converge to a target and provides a follow-the-leader approach to the problem. Each robot has only a limited-range sensor for sending the target and also larger but also limited-range robot-to-robot communication capability. Because of the small amount of information available to the robots, a practical approach to improve convergence to the target is to have a robot follow the robot with the best quality of information. Specifically, each robot emits a signal that informs in-range robots what its status is. A robot has a status value of 0 if it is itself in range of the target. A robot has a status of 1 if it is not in range of the target but is in communication range of a robot that is in range of the target. A robot has a status of 2 if it is not in range of the target but is within range of another robot that has status 1, and so on. Of all the mobile robots that any given robot is in range of, it follows the one with the best status. The emergent behavior is the ant-like trails of robots following each other toward the target. If the robot is not in range of another robot that is either in range of the target or following another robot, the robot will assign-1 to its quality-of-information, and will execute an exhaustive search. The exhaustive search will continue until it encounters either the target or another robot with a nonnegative quality-of-information. The quality of information approach was extended to the case where each robot only has two-bit signals informing it of distance to in-range robots.

  11. Ecosystem Targets - Defining target levels for ecosystem components: a socio-ecological approach

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Ecological indicators can facilitate Ecosystem-based Management, but only if targets for indicators exist. Because targets are an expression of the desired state of...

  12. Search for Two Categories of Target Produces Fewer Fixations to Target-Color Items

    Science.gov (United States)

    Menneer, Tamaryn; Stroud, Michael J.; Cave, Kyle R.; Li, Xingshan; Godwin, Hayward J.; Liversedge, Simon P.; Donnelly, Nick

    2012-01-01

    Searching simultaneously for metal threats (guns and knives) and improvised explosive devices (IEDs) in X-ray images is less effective than 2 independent single-target searches, 1 for metal threats and 1 for IEDs. The goals of this study were to (a) replicate this dual-target cost for categorical targets and to determine whether the cost remains…

  13. COMPASS polarized target for Drell-Yan

    CERN Document Server

    Pešek, M

    2014-01-01

    In the COMPASS Drell–Yan experiment the pion beam with momen tum of 190 GeV/ c and in- tensity up to 10 8 pions/s will interact with transversely polarized proton t arget producing muon pair via Drell–Yan process. The solid-state NH 3 will be polarized by dynamic nuclear polar- ization. Maximum polarization reached during data taking i s expected to be up to 90%. The non-interacting beam and other particles produced inside t he target will be stopped in the hadron absorber after the target. Two target cells, sepparated by a 20 cm gap in between, each 55 cm long and 4 cm in diameter give the target material volume about 691 cm 3 . The target platform needs to be moved by 2.3 m in upstream dire ction from the position used in previous experiments in order to accomodate the absorber. D uring the beam time higher radiation is expected in the area of the control room. Thus a new target r emote control system is needed. The target magnet is undergoing a substantial upgrade. Drell–Yan data taking is expected t...

  14. Novel Targeted Therapies for Metastatic Melanoma.

    Science.gov (United States)

    Iams, Wade T; Sosman, Jeffrey A; Chandra, Sunandana

    Oncogene-targeted therapy is a major component of precision oncology, and although patients with metastatic melanoma have experienced improved outcomes with this strategy, there are a number of potential therapeutic targets currently under study that may further increase the drug armamentarium for this patient population. In this review, we discuss the landscape of targeted therapies for patients with advanced melanoma, focusing on oncogene mutation-specific targets. In patients with typical BRAF V600-mutant melanoma, combination BRAF and MEK inhibition has surpassed outcomes compared with monotherapy with BRAF or MEK inhibition alone, and current strategies seek to address inevitable resistance mechanisms. For patients with NRAS-mutant melanoma, MEK inhibitor monotherapy and combined MEK and CDK4/6 inhibition are burgeoning strategies; for patients with KIT-mutant melanoma, tyrosine kinase inhibition is being leveraged, and for NF-1-mutant melanoma, mTOR and MEK inhibition is being actively evaluated. In patients with atypical, non-V600 BRAF-mutant melanoma, MEK inhibitor monotherapy is the potential novel targeted approach on the horizon. For advanced uveal melanoma, novel targets such as IMCgp100 and glembatumumab have shown activity in early studies. We review additional strategies that remain in the preclinical and early clinical pipeline, so there is much hope for the future of targeted agents for distinct molecular cohorts of patients with advanced melanoma.

  15. Isochoric Heating of Reduced Mass Targets

    Energy Technology Data Exchange (ETDEWEB)

    Akli, Kramer [The Ohio State Univ., Columbus, OH (United States)

    2015-11-13

    This report summarizes the experimental results of a study aimed at achieving star-like plasmas in the laboratory by isochrically heating solid-density targets with intense lasers. Of special interest is the investigation of spatial/temporal temperature and density gradients and their dependence on the target geometry and mass. The investigation was carried out in two phases. In the first phase, solid targets with variable transverse and longitudinal dimensions were investigated. We found that electron beam recirculation is enhanced for reduced mass targets. As a result, the temperature gradients are minimized for these targets yielding more uniform temperature hot plasmas. In the second phase, reduced mass targets were irradiated with intense ultra-short laser pulses. Bright monochromatic x-rays and broadband Extreme ultraviolet radiation (EUV or XUV) emissions were achieved by optimizing the electrostatic sheath fields surrounding the target. The study also revealed that this laser-driven source of radiation has a small source size, short duration, and high photon fluxes suitable for point projection radiography and for probing matter under extreme environments.

  16. Discovery of functional antibodies targeting ion channels.

    Science.gov (United States)

    Wilkinson, Trevor C I; Gardener, Matthew J; Williams, Wendy A

    2015-04-01

    Ion channels play critical roles in physiology and disease by modulation of cellular functions such as electrical excitability, secretion, cell migration, and gene transcription. Ion channels represent an important target class for drug discovery that has been largely addressed, to date, using small-molecule approaches. A significant opportunity exists to target these channels with antibodies and alternative formats of biologics. Antibodies display high specificity and affinity for their target antigen, and they have the potential to target ion channels very selectively. Nevertheless, isolating antibodies to this target class is challenging due to the difficulties in expression and purification of ion channels in a format suitable for antibody drug discovery in addition to the complexity of screening for function. In this article, we will review the current state of ion channel biologics discovery and the progress that has been made. We will also highlight the challenges in isolating functional antibodies to these targets and how these challenges may be addressed. Finally, we also illustrate successful approaches to isolating functional monoclonal antibodies targeting ion channels by way of a number of case studies drawn from recent publications.

  17. Target Injector and Sabot Remover for IFE

    Science.gov (United States)

    Yoshida, Hiroki; Kameyama, Nobukazu

    2012-10-01

    Target injectors for IFE are required to inject targets to the reactor center at a velocity of over 100 m/s with accuracy of several millimeters. A target injector system with a magnetic sabot remover is developed to demonstrate injection of polystyrene targets. A typical target used in this study is 4.0 mm in diameter and 0.8 mg in weight. It is inserted in to an aluminum sabot that is 9.2 mm in outer diameter and 40 mm in length. They are accelerated together by a pneumatic gun. Before injection into the reactor, the sabot is removed for laser irradiation. The sabot remover is composed of Neodymium magnets array that generates Lorentz force as a result of interaction between the magnets' field and induced current on the sabot. The Neodymium magnets are 14 mm at inner diameter and 316 mT on its surface. The magnetic array is designed and optimized its magnets number for complete target extraction. The theoretically and experimentally confirmed deceleration rate of the sabot is 60.2 m/s/s per one meter. The targets are shot into the vacuum chamber after extraction from the sabot at accelerated velocity of 30 m/s. The experimentally obtained injection accuracy is 5.3 mm in horizontal direction and 4.8 mm in vertical direction.

  18. Laval nozzles for cluster-jet targets

    Energy Technology Data Exchange (ETDEWEB)

    Hergemoeller, Ann-Katrin; Bonaventura, Daniel; Grieser, Silke; Koehler, Esperanza; Taeschner, Alexander; Khoukaz, Alfons [Institut fuer Kernphysik, Westfaelische Wilhelms-Universitaet Muenster, 48149 Muenster (Germany)

    2014-07-01

    Cluster-jet targets are highly suited as internal targets for storage ring experiments. Here the target beam itself is produced by the expansion of pre-cooled gases within fine Laval nozzles. With such targets high and constant target beam thicknesses can be achieved and adjusted continuously during operation. At the prototype cluster-jet target for the PANDA experiment, which was built up and set successfully into operation at the University of Muenster, density structures within the cluster beam directly behind the nozzle have been observed. Therefore, a tilting system was installed, allowing for an adjustment of the nozzle system relative to the experimental setup. With this installation target densities of more than 2 x 10{sup 15} atoms/cm{sup 2} at a distance of 2.1 m behind the nozzle were achieved. To study the impact of the Laval nozzle geometry on the beam structures and the achievable density, an improved nozzle production method was established. With this technique it is possible to produce with high efficiency fine micrometer-sized nozzles with variable geometries, e.g. different opening angles, opening diameters or lengths of the exit trumpet. The method for the production of Laval nozzles are presented, and new perspectives are discussed.

  19. The cluster-jet target for PANDA

    Energy Technology Data Exchange (ETDEWEB)

    Hergemoeller, Ann-Katrin; Koehler, Esperanza; Grieser, Silke; Taeschner, Alexander; Ortjohann, Hans-Werner; Bonaventura, Daniel; Khoukaz, Alfons [Muenster Univ. (Germany). Inst. fuer Kernphysik

    2013-07-01

    A cluster-jet target will be the first one of two planned internal targets for the PANDA experiment at FAIR. At the University of Muenster the target prototype was built up in complete PANDA geometry and successfully set into operation. Areal target densities of more than 2 x 10{sup 15} atoms/cm{sup 2} at a distance of 2.1 m behind the nozzle were achieved by the installation of a new tilting system. This device allows for an adjustment of the nozzle relative to the experimental setup. The thickness is reproducible, constant in time, and variable over several orders of magnitude by the adjustment of the stagnation pressure and temperature before the nozzle. Depending on the experimental program the target beam size and shape should be variable and should guarantee a low residual gas background. That can be realized with the application of special shaped skimmers for the target beam preparation. The cluster beam shape can be visualized by a new monitoring system based on a Micro Channel Plate. This enables a direct observation of an ionized cluster beam at a phosphor screen in combination with a CCD camera. In this presentation an overview of the cluster-jet target, various special features, and images of the cluster beam is presented and discussed.

  20. Improving pharmacological targeting of AKT in melanoma.

    Science.gov (United States)

    Kuzu, Omer F; Gowda, Raghavendra; Sharma, Arati; Noory, Mohammad A; Dinavahi, Saketh S; Kardos, Gregory; Drabick, Joseph J; Robertson, Gavin P

    2017-09-28

    Targeting AKT with pharmacological agents inhibiting this protein in the melanoma clinic is ineffective. This is a major contradiction considering the substantial preclinical data suggesting AKT as an effective target. Various approaches have been undertaken to unravel this contradiction and drug combinations sought that could resolve this concern. We have shown that genetic targeting AKT3 or WEE1 can be effective for inhibiting tumor growth in preclinical animal models. However, no one has examined whether combining pharmacological agents targeting each of these enzymes could be more effective than inhibiting each alone and enhance the efficacy of targeting AKT in melanoma. This report shows that combining the AKT inhibitors (AZD5363 or MK1775) with the WEE1 inhibitor, AZD5363, can synergistically kill cultured melanoma cells and decrease melanoma tumor growth by greater than 90%. Co-targeting AKT and WEE1 led to enhanced deregulation of the cell cycle and DNA damage repair pathways by modulating the transcription factors p53 and FOXM1, as well as the proteins whose expression is regulated by these two proteins. Thus, this study identifies a unique combination of pharmacological agents and the ratio needed for efficacy that could be used to potentially improve the therapeutic effectiveness of targeting AKT in the clinic. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Multiplexed modular genetic targeting of quantum dots.

    Science.gov (United States)

    Saurabh, Saumya; Beck, Lauren E; Maji, Suvrajit; Baty, Catherine J; Wang, Yi; Yan, Qi; Watkins, Simon C; Bruchez, Marcel P

    2014-11-25

    While DNA-directed nanotechnology is now a well-established platform for bioinspired nanoscale assembly in vitro, the direct targeting of various nanomaterials in living biological systems remains a significant challenge. Hybrid biological systems with integrated and targeted nanomaterials may have interesting and exploitable properties, so methods for targeting various nanomaterials to precise biological locations are required. Fluorescence imaging has benefited from the use of nanoparticles with superior optical properties compared to fluorescent organic dyes or fluorescent proteins. While single-particle tracking (SPT) in living cells with genetically encoded proteins is limited to very short trajectories, the high photon output of genetically targeted and multiplexed quantum dots (QDs) would enable long-trajectory analysis of multiple proteins. However, challenges with genetic targeting of QDs limit their application in these experiments. In this report, we establish a modular method for targeting QD nanoparticles selectively to multiple genetically encoded tags by precomplexing QD-streptavidin conjugates with cognate biotinylated hapten molecules. This approach enables labeling and SPT of multiple genetically encoded proteins on living cells at high speed and can label expressed proteins in the cytosol upon microinjection into living cells. While we demonstrate labeling with three distinct QD conjugates, the approach can be extended to other specific hapten-affinity molecule interactions and alternative nanoparticles, enabling precise directed targeting of nanoparticles in living biological systems.

  2. Folate targeted polymeric 'green' nanotherapy for cancer

    Science.gov (United States)

    Narayanan, Sreeja; Binulal, N. S.; Mony, Ullas; Manzoor, Koyakutty; Nair, Shantikumar; Menon, Deepthy

    2010-07-01

    The concept of 'green' chemotherapy by employing targeted nanoparticle mediated delivery to enhance the efficacy of phytomedicines is reported. Poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating a well known nutraceutical namely, grape seed extract (GSE)—'NanoGSE'—was prepared by a nanoprecipitation technique. The drug-loaded nanoparticles of size ~ 100 nm exhibited high colloidal stability at physiological pH. Molecular receptor targeting of this nanophytomedicine against folate receptor over-expressing cancers was demonstrated in vitro by conjugation with a potential cancer targeting ligand, folic acid (FA). Fluorescence microscopy and flow cytometry data showed highly specific cellular uptake of FA conjugated NanoGSE on folate receptor positive cancer cells. Studies were also conducted to investigate the efficiency of targeted (FA conjugated) versus non-targeted (non-FA conjugated) nanoformulations in causing cancer cell death. The IC50 values were lowered by a factor of ~ 3 for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This in vitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a 'green' approach.

  3. Design of the LBNF Beamline Target Station

    Energy Technology Data Exchange (ETDEWEB)

    Tariq, S. [Fermilab; Ammigan, K. [Fermilab; Anderson, K.; ; Buccellato, S. A. [Fermilab; Crowley, C. F. [Fermilab; Hartsell, B. D. [Fermilab; Hurh, P. [Fermilab; Hylen, J. [Fermilab; Kasper, P. [Fermilab; Krafczyk, G. E. [Fermilab; Lee, A. [Fermilab; Lundberg, B. [Fermilab; Reitzner, S. D. [Fermilab; Sidorov, V. [Fermilab; Stefanik, A. M. [Fermilab; Tropin, I. S. [Fermilab; Vaziri, K. [Fermilab; Williams, K. [Fermilab; Zwaska, R. M. [Fermilab; Densham, C. [RAL, Didcot

    2016-10-01

    The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-filled decay pipe where they decay into muons and neutrinos. The target and horns are encased in actively cooled steel and concrete shielding in a chamber called the target chase. The reference design chase is filled with air, but nitrogen and helium are being evaluated as alternatives. A replaceable beam window separates the decay pipe from the target chase. The facility is designed for initial operation at 1.2 MW, with the ability to upgrade to 2.4 MW, and is taking advantage of the experience gained by operating Fermilab’s NuMI facility. We discuss here the design status, associated challenges, and ongoing R&D and physics-driven component optimization of the Target Station.

  4. Hypersonic sliding target tracking in near space

    Directory of Open Access Journals (Sweden)

    Xiang-yu Zhang

    2015-12-01

    Full Text Available To improve the tracking accuracy of hypersonic sliding target in near space, the influence of target hypersonic movement on radar detection and tracking is analyzed, and an IMM tracking algorithm is proposed based on radial velocity compensating and cancellation processing of high dynamic biases under the earth centered earth fixed (ECEF coordinate. Based on the analysis of effect of target hypersonic movement, a measurement model is constructed to reduce the filter divergence which is caused by the model mismatch. The high dynamic biases due to the target hypersonic movement are approximately compensated through radial velocity estimation to achieve the hypersonic target tracking at low systematic biases in near space. The high dynamic biases are further eliminated by the cancellation processing of different radars, in which the track association problem can be solved when the dynamic biases are low. An IMM algorithm based on constant acceleration (CA, constant turning (CT and Singer models is used to achieve the hypersonic sliding target tracking in near space. Simulation results show that the target tracking in near space can be achieved more effectively by using the proposed algorithm.

  5. 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

  6. ZFN-Site searches genomes for zinc finger nuclease target sites and off-target sites

    Directory of Open Access Journals (Sweden)

    Iseli Christian

    2011-05-01

    Full Text Available Abstract Background Zinc Finger Nucleases (ZFNs are man-made restriction enzymes useful for manipulating genomes by cleaving target DNA sequences. ZFNs allow therapeutic gene correction or creation of genetically modified model organisms. ZFN specificity is not absolute; therefore, it is essential to select ZFN target sites without similar genomic off-target sites. It is important to assay for off-target cleavage events at sites similar to the target sequence. Results ZFN-Site is a web interface that searches multiple genomes for ZFN off-target sites. Queries can be based on the target sequence or can be expanded using degenerate specificity to account for known ZFN binding preferences. ZFN off-target sites are outputted with links to genome browsers, facilitating off-target cleavage site screening. We verified ZFN-Site using previously published ZFN half-sites and located their target sites and their previously described off-target sites. While we have tailored this tool to ZFNs, ZFN-Site can also be used to find potential off-target sites for other nucleases, such as TALE nucleases. Conclusions ZFN-Site facilitates genome searches for possible ZFN cleavage sites based on user-defined stringency limits. ZFN-Site is an improvement over other methods because the FetchGWI search engine uses an indexed search of genome sequences for all ZFN target sites and possible off-target sites matching the half-sites and stringency limits. Therefore, ZFN-Site does not miss potential off-target sites.

  7. Tumor targeting using liposomal antineoplastic drugs

    Science.gov (United States)

    Huwyler, Jörg; Drewe, Jürgen; Krähenbühl, Stephan

    2008-01-01

    During the last years, liposomes (microparticulate phospholipid vesicles) have been used with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumor drugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research. PMID:18488413

  8. BRVAAF and performance analysis for target detection

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    A bistatic range-velocity-acceleration ambiguity function (BRVAAF) is proposed. The model of radar measurements of an accelerating target involving the time delay, Doppler frequency and Doppler rate is given. The relationships between these measurements and the parameters of the bistatic geometry, target position, velocity and acceleration are derived. Moreover, the effects of the bistatic geometry factors on these measurements are analyzed. Besides, the two relationships of the bistatic integration loss and the bistatic optimum integration time with these factors are built and their change trends are described respectively. This research is helpful to analyze the influences of the bistatic geometry factors on the target detection and signal processing.

  9. Resource implications of a national health target

    DEFF Research Database (Denmark)

    Jones, Peter; Sopina, Liza Elizaveta; Ashton, Toni

    2014-01-01

    of clinical/service managers in ED throughout New Zealand determined the type and cost of resources used for the target. Responses to the target were classified according to their impact in ED, the hospital and the community. Quantifiable resource changes were assigned a financial value and grouped......, with estimated total expenditure of over NZ$52 m. The majority of expenditure occurred in ED (60.8%) and hospital (38.7%) with little spent in the community. New staff accounted for 76.5% of expenditure. Per capita expenditure in the ED was associated with improved target performance (r = 0.48, P = 0...

  10. Automatic Target Detection Using Wavelet Transform

    Directory of Open Access Journals (Sweden)

    Ganesan L

    2004-01-01

    Full Text Available Automatic target recognition (ATR involves processing images for detecting, classifying, and tracking targets embedded in a background scene. This paper presents an algorithm for detecting a specified set of target objects embedded in visual images for an ATR application. The developed algorithm employs a novel technique for automatically detecting man-made and non-man-made single, two, and multitargets from nontarget objects, located within a cluttered environment by evaluating nonoverlapping image blocks, where block-by-block comparison of wavelet cooccurrence feature is done. The results of the proposed algorithm are found to be satisfactory.

  11. Conducting monetary policy with inflation targets

    OpenAIRE

    George A. Kahn; Klara Parrish

    1998-01-01

    Since the early 1990s, a number of central banks have adopted numerical inflation targets as a guide for monetary policy. The targets are intended to help central banks achieve and maintain price stability by specifying an explicit goal for monetary policy based on a given time path for a particular measure of inflation. In some cases the targets are expressed as a range for inflation over time, while in other cases they are expressed as a path for the inflation rate itself. The measure of in...

  12. Automated High Throughput Drug Target Crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Rupp, B

    2005-02-18

    The molecular structures of drug target proteins and receptors form the basis for 'rational' or structure guided drug design. The majority of target structures are experimentally determined by protein X-ray crystallography, which as evolved into a highly automated, high throughput drug discovery and screening tool. Process automation has accelerated tasks from parallel protein expression, fully automated crystallization, and rapid data collection to highly efficient structure determination methods. A thoroughly designed automation technology platform supported by a powerful informatics infrastructure forms the basis for optimal workflow implementation and the data mining and analysis tools to generate new leads from experimental protein drug target structures.

  13. Characteristics of Hostile and Friendly Takeover Targets

    OpenAIRE

    Randall Morck; Andrei Shleifer; Vishny, Robert W.

    1987-01-01

    Compared to an average Fortune 500 firm, a target of a hostile takeover is smaller, older, has a lower Tobin's Q, invests less of its income, and is growing more slowly. The low Q seems to be an industry-specific rather than a firm-specific effect. In addition, a hostile target is less likely to be run by a member of the founding family, and has lower officer ownership, than the average firm. In contrast, a target of a friendly acquisitions is smaller and younger than an average Fortune 500 f...

  14. Antiproton production target of the AA

    CERN Multimedia

    Photographic Service

    1980-01-01

    The target rods were initially of tungsten, later of iridium. Diameters were around 3 mm and the lengths 60-110 mm. The rod is embedded in graphite, pressed into an aluminium body with cooling fins for forced air cooling. The 26 GeV proton beam from the PS was focused to the dimension of the rod. To aim precisely at its centre, the target was fitted with a scintillator screen, with circles at every 5 mm radius. Both scintillator and target had to stand pulses of 1.4E13 protons every 4.8 s, without interruption for many months.

  15. Novel targeted therapies for eosinophilic disorders

    Science.gov (United States)

    Wechsler, Michael E.; Fulkerson, Patricia C.; Bochner, Bruce S.; Gauvreau, Gail M.; Gleich, Gerald J.; Henkel, Tim; Kolbeck, Roland; Mathur, Sameer K.; Ortega, Hector; Patel, Jatin; Prussin, Calman; Renzi, Paolo; Rothenberg, Marc E.; Roufosse, Florence; Simon, Dagmar; Simon, Hans-Uwe; Wardlaw, Andrew; Weller, Peter F.; Klion, Amy D.

    2013-01-01

    Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. HESs are chronic disorders with significant morbidity and mortality. Although the availability of targeted chemotherapeutic agents, including imatinib, has improved quality of life and survival in some patients with HESs, additional agents with increased efficacy and decreased toxicity are sorely needed. The purpose of this review is to provide an overview of eosinophil biology with an emphasis on potential targets of pharmacotherapy and to provide a summary of potential eosinophil-targeting agents, including those in development, in clinical trials, or approved for other disorders. PMID:22935585

  16. LINEAR SEARCH FOR A BROWNIAN TARGET MOTION

    Institute of Scientific and Technical Information of China (English)

    A. B. El-Rayes; Abd El-Moneim A. Mohamed; Hamdy M. Abou Gabal

    2003-01-01

    A target is assumed to move according to a Brownian motion on the real line.The searcher starts from the origin and moves in the two directions from the starting point.The object is to detect the target.The purpose of this paper is to find the conditions under which the expected value of the first meeting time of the searcher and the target is finite,and to show the existence of a search plan which made this expected value minimum.

  17. Stereotactic radiosurgery: a "targeted" therapy for cancer

    Institute of Scientific and Technical Information of China (English)

    Ming Zeng; Liang-Fu Han

    2012-01-01

    The developments of medicine always follow innovations in science and technology.In the past decade,such innovations have made cancer-related targeted therapies possible.In general,the term "targeted therapy" has been used in reference to cellular and molecular level oriented therapies.However,improvements in the delivery and planning of traditional radiation therapy have also provided cancer patients more options for "targeted" treatment,notably stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT).In this review,the progress and controversies of SRS and SBRT are discussed to show the role of stereotactic radiation therapy in the ever evolving multidisciplinary care of cancer patients.

  18. Targets for a Neutral Kaon Beam

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Christopher [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States)

    2016-04-01

    A secondary beam of neutral Kaons is under consideration for Hall D at Jefferson Lab to perform spectroscopic studies of hyperons produced by K 0 L particles scattering from proton and deuteron targets. The proposed physics program would utilize the GlueX detector package currently installed in Hall D. This contribution looks at potential targets for use in the new facility, paying close attention to the existing infrastructure of GlueX and Hall D. Unpolarized cryotargets of liquid hydrogen and deuerium, as well as polarized solid targets of protons and deuterons are examined.

  19. Molecular targeting for malignant gliomas (Review).

    Science.gov (United States)

    Kondo, Yasuko; Hollingsworth, Emporia F; Kondo, Seiji

    2004-05-01

    With tendency to invade rapidly in the brain, malignant gliomas are very resistant to conventional therapies including radiation and chemotherapy. Recent advances in genetic and molecular techniques have made it possible to define characteristic molecular profiles of malignant gliomas. Based on the list of the molecules closely related to glioblastoma tissues, we reviewed strategies targeting them. Target molecules extensively studied include EGFR, PTEN, telomerase and signal pathway modulators for Ras/Raf/MAPK and PI3K/Akt/mTOR pathways. Therapies targeting specific molecules may result in killing tumor cells effectively while keeping normal cells intact.

  20. Target Cultural Issues in College English Teaching

    Institute of Scientific and Technical Information of China (English)

    WAN Xin

    2016-01-01

    With the passage time, China has been playing a increasingly important role in world stage, so what a current college English classroom needs is not a mere mastery of English language, but an overall understanding of target culture. In order to at-tain this goal, analysis concerning the current situation of target cultural teaching in college English teaching classroom should be done, and suggestions about target cultural teaching in college English teaching classroom should be put forward. By doing so, students will not only improve their linguistic competence, but also will enhance their inter-cultural performance.

  1. Wavelet-based technique for target segmentation

    Science.gov (United States)

    Sadjadi, Firooz A.

    1995-07-01

    Segmentation of targets embedded in clutter obtained by IR imaging sensors is one of the challenging problems in automatic target recognition (ATR). In this paper a new texture-based segmentation technique is presented that uses the statistics of 2D wavelet decomposition components of the lcoal sections of the image. A measure of statistical similarity is then used to segment the image and separate the target from the background. This technique is applied on a set of real sequential IR imagery and has shown to produce a high degree of segmentation accuracy across varying ranges.

  2. Diagnostics for High Power Targets and Dumps

    CERN Document Server

    Gschwendtner, E

    2012-01-01

    High power targets are generally used for neutrino, antiproton, neutron and secondary beam production whereas dumps are needed in beam waste management. In order to guarantee an optimized and safe use of these targets and dumps, reliable instrumentation is needed; the diagnostics in high power beams around targets and dumps is reviewed. The suite of beam diagnostics devices used in such extreme environments is discussed, including their role in commissioning and operation. The handling and maintenance of the instrumentation components in high radiation areas is also addressed.

  3. Performance Simulations of Moving Target Search Algorithms

    Directory of Open Access Journals (Sweden)

    Peter K. K. Loh

    2009-01-01

    Full Text Available The design of appropriate moving target search (MTS algorithms for computer-generated bots poses serious challenges as they have to satisfy stringent requirements that include computation and execution efficiency. In this paper, we investigate the performance and behaviour of existing moving target search algorithms when applied to search-and-capture gaming scenarios. As part of the investigation, we also introduce a novel algorithm known as abstraction MTS. We conduct performance simulations with a game bot and moving target within randomly generated mazes of increasing sizes and reveal that abstraction MTS exhibits competitive performance even with large problem spaces.

  4. Radar automatic target recognition (ATR) and non-cooperative target recognition (NCTR)

    CERN Document Server

    Blacknell, David

    2013-01-01

    The ability to detect and locate targets by day or night, over wide areas, regardless of weather conditions has long made radar a key sensor in many military and civil applications. However, the ability to automatically and reliably distinguish different targets represents a difficult challenge. Radar Automatic Target Recognition (ATR) and Non-Cooperative Target Recognition (NCTR) captures material presented in the NATO SET-172 lecture series to provide an overview of the state-of-the-art and continuing challenges of radar target recognition. Topics covered include the problem as applied to th

  5. Targeted molecular trait stacking in cotton through targeted double-strand break induction.

    Science.gov (United States)

    D'Halluin, Kathleen; Vanderstraeten, Chantal; Van Hulle, Jolien; Rosolowska, Joanna; Van Den Brande, Ilse; Pennewaert, Anouk; D'Hont, Kristel; Bossut, Martine; Jantz, Derek; Ruiter, Rene; Broadhvest, Jean

    2013-10-01

    Recent developments of tools for targeted genome modification have led to new concepts in how multiple traits can be combined. Targeted genome modification is based on the use of nucleases with tailor-made specificities to introduce a DNA double-strand break (DSB) at specific target loci. A re-engineered meganuclease was designed for specific cleavage of an endogenous target sequence adjacent to a transgenic insect control locus in cotton. The combination of targeted DNA cleavage and homologous recombination-mediated repair made precise targeted insertion of additional trait genes (hppd, epsps) feasible in cotton. Targeted insertion events were recovered at a frequency of about 2% of the independently transformed embryogenic callus lines. We further demonstrated that all trait genes were inherited as a single genetic unit, which will simplify future multiple-trait introgression.

  6. TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery.

    Directory of Open Access Journals (Sweden)

    Yi-An Chen

    Full Text Available Prioritising candidate genes for further experimental characterisation is a non-trivial challenge in drug discovery and biomedical research in general. An integrated approach that combines results from multiple data types is best suited for optimal target selection. We developed TargetMine, a data warehouse for efficient target prioritisation. TargetMine utilises the InterMine framework, with new data models such as protein-DNA interactions integrated in a novel way. It enables complicated searches that are difficult to perform with existing tools and it also offers integration of custom annotations and in-house experimental data. We proposed an objective protocol for target prioritisation using TargetMine and set up a benchmarking procedure to evaluate its performance. The results show that the protocol can identify known disease-associated genes with high precision and coverage. A demonstration version of TargetMine is available at http://targetmine.nibio.go.jp/.

  7. Consumer responses to ethnic targeted marketing

    NARCIS (Netherlands)

    A.-S.I.A. Lenoir (Anne-Sophie); S. Puntoni (Stefano)

    2014-01-01

    markdownabstract__Abstract__ Marketing is impacted more than ever by demographic change, to the extent that practitioners targeting ethnic groups should re-think their approach depending upon the strength with which different generations identify with their cultural heritage.

  8. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Barnkob, Mike Stein

    2014-01-01

    cancer immunotherapies has yet to be fulfilled. The insufficient efficacy of existing treatments can be attributed to a number of biological and technical issues. In this review, we detail the current limitations of immunotherapy target selection and design, and review computational methods to streamline...... therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes...... and co-targets for single-epitope and multi-epitope strategies. We provide examples of application to the well-known tumor antigen HER2 and suggest bioinformatics methods to ameliorate therapy resistance and ensure efficient and lasting control of tumors....

  9. Therapeutic Approaches to Target Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, Arlhee, E-mail: arlhee@cim.sld.cu; Leon, Kalet [Department of Systems Biology, Center of Molecular Immunology, 216 Street, PO Box 16040, Atabey, Havana 11600 (Cuba)

    2011-08-15

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC.

  10. IMS Mitigation Target Areas - 2010 [ds673

    Data.gov (United States)

    California Department of Resources — Mitigation Target Areas (MTA) were developed by the California Department of Fish and Game for the Interim Mitigation Strategy (IMS). The MTAs are an identification...

  11. Enhancing proton acceleration by using composite targets

    Energy Technology Data Exchange (ETDEWEB)

    Bulanov, S. S.; Esarey, E.; Schroeder, C. B.; Bulanov, S. V.; Esirkepov, T. Zh.; Kando, M.; Pegoraro, F.; Leemans, W. P.

    2015-07-10

    Efficient laser ion acceleration requires high laser intensities, which can only be obtained by tightly focusing laser radiation. In the radiation pressure acceleration regime, where the tightly focused laser driver leads to the appearance of the fundamental limit for the maximum attainable ion energy, this limit corresponds to the laser pulse group velocity as well as to another limit connected with the transverse expansion of the accelerated foil and consequent onset of the foil transparency. These limits can be relaxed by using composite targets, consisting of a thin foil followed by a near critical density slab. Such targets provide guiding of a laser pulse inside a self-generated channel and background electrons, being snowplowed by the pulse, compensate for the transverse expansion. The use of composite targets results in a significant increase in maximum ion energy, compared to a single foil target case.

  12. "UCx fission targets oxidation test stand"

    CERN Document Server

    Lacroix, Rachel

    2014-01-01

    "Set up a rig dedicated to the oxidation of UCx and define a procedure for repeatable, reliable and safe method for converting UC2 fission targets into an acceptable uranium carbide oxide waste for subsequent disposal by the Swiss Authorities."

  13. Characterizing Health Information for Different Target Audiences.

    Science.gov (United States)

    Sun, Yueping; Hou, Zhen; Hou, Li; Li, Jiao

    2015-01-01

    Different groups of audiences in health care: health professionals and health consumers, each have different information needs. Health monographs targeting different audiences are created by leveraging readers' background knowledge. The NCI's Physician Data Query (PDQ®) Cancer Information Summaries provide parallel cancer information and education resources with different target audiences. In this paper, we used targeted audience-specific cancer information PDQs to measure characteristic differences on the element level between audiences. In addition, we compared vocabulary coverage. Results show a significant difference between the professional and patient version of cancer monographs in both content organization and vocabulary. This study provides a new view to assess targeted audience-specific health information, and helps editors to improve the quality and readability of health information.

  14. Magnetic biosensor system to detect biological targets

    KAUST Repository

    Li, Fuquan

    2012-09-01

    Magneto-resistive sensors in combination with magnetic beads provide sensing platforms, which are small in size and highly sensitive. These platforms can be fully integrated with microchannels and electronics to enable devices capable of performing complex tasks. Commonly, a sandwich method is used that requires a specific coating of the sensor\\'s surface to immobilize magnetic beads and biological targets on top of the sensor. This paper concerns a micro device to detect biological targets using magnetic concentration, magnetic as well as mechanical trapping and magnetic sensing. Target detection is based on the size difference between bare magnetic beads and magnetic beads with targets attached. This method remedies the need for a coating layer and reduces the number of steps required to run an experiment. © 2012 IEEE.

  15. Discovering the 'Magic' of Target Marketing.

    Science.gov (United States)

    Grier, Linda J.; Ackenbom, Charles R.

    1988-01-01

    Describes target marketing of children's summer camps, emphasizing the benefits of collaborative advertising campaigns. Discusses the scope and economics of four model campaigns. Outlines the design, implementation, and evaluation of collaborative marketing projects. (SV)

  16. Logarithm Laws and Shrinking Target Properties

    Indian Academy of Sciences (India)

    J S Athreya

    2009-09-01

    We survey some of the recent developments in the study of logarithm laws and shrinking target properties for various families of dynamical systems. We discuss connections to geometry, diophantine approximation and probability theory.

  17. Enhancing proton acceleration by using composite targets

    CERN Document Server

    Bulanov, S S; Schroeder, C B; Bulanov, S V; Esirkepov, T Zh; Kando, M; Pegoraro, F; Leemans, W P

    2015-01-01

    Efficient laser ion acceleration requires high laser intensities, which can only be obtained by tightly focusing laser radiation. In the radiation pressure acceleration regime, where the tightly focused laser driver leads to the appearance of the fundamental limit for the maximum attainable ion energy, this limit corresponds to the laser pulse group velocity as well as to another limit connected with the transverse expansion of the accelerated foil and consequent onset of the foil transparency. These limits can be relaxed by using composite targets, consisting of a thin foil followed by a near critical density slab. Such targets provide guiding of a laser pulse inside a self-generated channel and background electrons, being snowplowed by the pulse, compensate for the transverse expansion. The use of composite targets results in a significant increase in maximum ion energy, compared to a single foil target case.

  18. Target Visualization at the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Potter, Daniel Abraham [Univ. of California, Davis, CA (United States)

    2011-01-01

    As the National Ignition Facility continues its campaign to achieve ignition, new methods and tools will be required to measure the quality of the targets used to achieve this goal. Techniques have been developed to measure target surface features using a phase-shifting diffraction interferometer and Leica Microsystems confocal microscope. Using these techniques we are able to produce a detailed view of the shell surface, which in turn allows us to refine target manufacturing and cleaning processes. However, the volume of data produced limits the methods by which this data can be effectively viewed by a user. This paper introduces an image-based visualization system for data exploration of target shells at the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. It aims to combine multiple image sets into a single visualization to provide a method of navigating the data in ways that are not possible with existing tools.

  19. Magnetized Target Fusion Driven by Plasma Liners

    Science.gov (United States)

    Thio, Y. C. Francis; Cassibry, Jason; Eskridge, Richard; Kirkpatrick, Ronald C.; Knapp, Charles E.; Lee, Michael; Martin, Adam; Smith, James; Wu, S. T.; Rodgers, Stephen L. (Technical Monitor)

    2001-01-01

    For practical applications of magnetized target fusion, standoff drivers to deliver the imploding momentum flux to the target plasma remotely are required. Quasi-spherically converging plasma jets have been proposed as standoff drivers for this purpose. The concept involves the dynamic formation of a quasi-spherical plasma liner by the merging of plasma jets, and the use of the liner so formed to compress a spheromak or a field reversed configuration (FRC). Theoretical analysis and computer modeling of the concept are presented. It is shown that, with the appropriate choice of the flow parameters in the liner and the target, the impact between the liner and the target plasma can be made to be shockless in the liner or to generate at most a very weak shock in the liner. Additional information is contained in the original extended abstract.

  20. Nuclear Targeting Terms for Engineers and Scientists

    Energy Technology Data Exchange (ETDEWEB)

    St Ledger, John W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-02-01

    The Department of Defense has a methodology for targeting nuclear weapons, and a jargon that is used to communicate between the analysts, planners, aircrews, and missile crews. The typical engineer or scientist in the Department of Energy may not have been exposed to the nuclear weapons targeting terms and methods. This report provides an introduction to the terms and methodologies used for nuclear targeting. Its purpose is to prepare engineers and scientists to participate in wargames, exercises, and discussions with the Department of Defense. Terms such as Circular Error Probable, probability of hit and damage, damage expectancy, and the physical vulnerability system are discussed. Methods for compounding damage from multiple weapons applied to one target are presented.

  1. The expected radiation damage of CSNS target

    Science.gov (United States)

    Yin, W.; Yu, Q. Z.; Lu, Y. L.; Wang, S. L.; Tong, J. F.; Liang, T. J.

    2012-12-01

    The radiation damage to the tungsten target and its SS316 vessel for Chinese Spallation Neutron Source (CSNS) has been estimated with a Monte-Carlo simulation code MCNPX2.5.0. We compare the effects on the radiation damage due to two different proton beam profiles: a uniform distribution and a Gaussian distribution. We also discuss the dependence of the radiation damage estimation on different physics models. The results show the peak displacement productions in vessel and the fourth target plate are 2.5 and 5.5 dpa/y, respectively, under a Gaussian proton beam. The peak helium productions in the vessel and the fourth target are 305 and 353 appm/y, respectively, under the same proton beam. Based on these results and the allowable dpa values we have estimated the lifetime of the tungsten target and its vessel.

  2. Fabrication of Simple Step-Target

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>Step-target was used to measure the shock velocity. If we can measure the shock velocity and particle velocity together, we get one point in the shock compress line. If we measure a series of shock velocity

  3. WTS - Risk Based Resource Targeting (RBRT) -

    Data.gov (United States)

    Department of Transportation — The Risk Based Resource Targeting (RBRT) application supports a new SMS-structured process designed to focus on safety oversight of systems and processes rather than...

  4. Observer's Interface for Solar System Target Specification

    Science.gov (United States)

    Roman, Anthony; Link, Miranda; Moriarty, Christopher; Stansberry, John A.

    2016-10-01

    When observing an asteroid or comet with HST, it has been necessary for the observer to manually enter the target's orbital elements into the Astronomer's Proposal Tool (APT). This allowed possible copy/paste transcription errors from the observer's source of orbital elements data. In order to address this issue, APT has now been improved with the capability to identify targets in and then download orbital elements from JPL Horizons. The observer will first use a target name resolver to choose the intended target from the Horizons database, and then download the orbital elements from Horizons directly into APT. A manual entry option is also still retained if the observer does not wish to use elements from Horizons. This new capability is available for HST observing, and it will also be supported for JWST observing. The poster shows examples of this new interface.

  5. Targeted therapies in upper gastrointestinal cancer

    NARCIS (Netherlands)

    Kordes, S.

    2016-01-01

    Upper gastrointestinal (GI) cancers, as esophageal, gastric and pancreatic cancer, are still highly lethal diseases, in spite of advances in surgery, radiotherapy, chemotherapy and specific targeted therapy. Especially when patients are diagnosed with locally advanced or metastasized disease, upper

  6. Polarization measurement in the COMPASS polarized target

    CERN Document Server

    Kondo, K; Baum, G; Berglund, P; Doshita, N; Gautheron, F; Görtz, S; Hasegawa, T; Horikawa, N; Ishimoto, S; Iwata, T; Kisselev, Yu V; Koivuniemi, J H; Le Goff, J M; Magnon, A; Meyer, W; Reicherz, G; Matsuda, T

    2004-01-01

    Continuous wave nuclear magnetic resonance (NMR) is used to determine the target polarization in the COMPASS experiment. The system is made of the so-called Liverpool Q-meters, Yale-cards, and VME modules for data taking and system controlling. In 2001 the NMR coils were embedded in the target material, while in 2002 and 2003 the coils were mounted on the outer surface of the target cells to increase the packing factor of the material. Though the error of the measurement became larger with the outer coils than with the inner coils, we have performed stable measurements throughout the COMPASS run time for 3 years. The maximum polarization was +57% and -53% as the average in the target cells.

  7. New Cholesterol Fighting Meds Target Key Gene

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_165942.html New Cholesterol Fighting Meds Target Key Gene Two trials show ... New gene-based therapies appear to significantly decrease cholesterol levels in people, and could even cut down ...

  8. Targeting influenza virosomes to ovarian carcinoma cells

    NARCIS (Netherlands)

    Mastrobattista, E; Schoen, P; Wilschut, J; Crommelin, DJA; Storm, G

    2001-01-01

    Reconstituted influenza virus envelopes (virosomes) containing the viral hemagglutinin (HA) have attracted attention as delivery vesicles for cytosolic drug delivery as they possess membrane fusion activity. Here, we show that influenza virosomes can be targeted towards ovarian carcinoma cells (OVCA

  9. Gas production in the MEGAPIE spallation target

    Energy Technology Data Exchange (ETDEWEB)

    Thiolliere, N. [SUBATECH, EMN-IN2P3/CNRS-Universite, Nantes, F-44307 (France); Zanini, L. [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); David, J. C. [CEA Saclay, Irfu/SPhN, 91191 Gif Sur Yvette (France); Eikenberg, J. [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Guertin, A. [SUBATECH, EMN-IN2P3/CNRS-Universite, Nantes, F-44307 (France); Konobeyev, A. Y. [Institut fuer Reaktorsicherheit, FZK GmbH, 76021 Karlsruhe (Germany); Lemaire, S. [CEA Bruyeres-le-Chatel, DAM Ile de France, 91297 Arpajon Cedex (France); Panebianco, S. [CEA Saclay, Irfu/SPhN, 91191 Gif Sur Yvette (France)

    2011-07-01

    The Megawatt Pilot Experiment (MEGAPIE) project was started in 2000 to design, build and operate a liquid Lead-Bismuth Eutectic (LBE) spallation neutron target at the power level of 1 MW. The target was irradiated for four months in 2006 at the Paul Scherrer Inst. in Switzerland. Gas samples were extracted in various phases of operation and analyzed by {gamma} spectroscopy leading to the determination of the main radioactive isotopes released from the LBE. Comparison with calculations performed using several validated codes (MCNPX2.5.0/CINDER'90, FLUKA/ORIHET and SNT) yields the ratio between simulated in-target isotope production rates and experimental amount released at any given time. This work underlines the weak points of spallation models for some released isotopes. Also, results provide relevant information for safety and radioprotection in an Accelerator Driven System (ADS) and more particularly for the gas management in a spallation target dedicated to neutron production facilities. (authors)

  10. Hard target LIDAR calibration for SO2

    CSIR Research Space (South Africa)

    Du Plessis, A

    2006-01-01

    Full Text Available Presentation on hard target LIDAR calibration for SO2. This project aimed at measuring the concentration of the atmospheric pollutants such as gases and mobile laser system for remote detection...

  11. Parametric estimation of ultra wideband radar targets

    Institute of Scientific and Technical Information of China (English)

    Fan Ping; Jing Zhanrong

    2009-01-01

    Based on the analysis of impulse response properties, a scattering model of ultra wideband (UWB) radar targets is developed to estimate the target parameters exactly. With this model, two algorithms of multiple signal classification (MUSIC), and matrix pencil (MP), are introduced to calculate the scattering center parame-ters of targets and their performances are compared. The simulation experiments show that there are no differ-ences in the estimation precision of MUSIC and MP methods when the signal-to-noise ratio (SNR) is larger than 13 dB. However, the MP method has a better performance than that of MUSIC method when the SNR is smaller than 13 dB. Besides, the time consuming of MP method is leas than that of MUSIC method. Therefore, the MP algorithm is preferred for the parametric estimation of UWB radar targets.

  12. Does target viewing time influence perceived reachability?

    Science.gov (United States)

    Gabbard, Carl; Ammar, Diala

    2007-09-01

    This study examined the influence of target viewing time on perceived (estimates of) reachability. Right-handed participants were asked to judge the simulated reachability of midline targets using their dominant limb in viewing conditions of 150 ms, 500 ms, 1 s and 2 s. Responses were compared to actual maximum reach. In reference to percent error, interestingly, the 150 ms condition revealed the least error at peripersonal targets and the most inaccuracy with distal (extrapersonal) targets. This condition was also distinct with a significant overestimation bias -- a common observation in earlier studies. However, with increasing viewing time this bias was reduced. These data provide evidence that 150 ms is effective for estimating reach within one's general peripersonal workspace. However, with judgments distal from that point, more time enhanced accuracy, with 500 ms and 1 s being optimal. Overall results are discussed relative to perceptual effectiveness in programming reaching movements.

  13. Potential targets for lung squamous cell carcinoma

    Science.gov (United States)

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  14. Targeted ocean sampling guidance for tropical cyclones

    Science.gov (United States)

    Chen, Sue; Cummings, James A.; Schmidt, Jerome M.; Sanabia, Elizabeth R.; Jayne, Steven R.

    2017-05-01

    A 3-D variational ocean data assimilation adjoint approach is used to examine the impact of ocean observations on coupled tropical cyclone (TC) model forecast error for three recent hurricanes: Isaac (2012), Hilda (2015), and Matthew (2016). In addition, this methodology is applied to develop an innovative ocean observation targeting tool validated using TC model simulations that assimilate ocean temperature observed by Airborne eXpendable Bathy Thermographs and Air-Launched Autonomous Micro-Observer floats. Comparison between the simulated targeted and real observation data assimilation impacts reveals a positive maximum mean linear correlation of 0.53 at 400-500 m, which implies some skill in the targeting application. Targeted ocean observation regions from these three hurricanes, however, show that the largest positive impacts in reducing the TC model forecast errors are sensitive to the initial prestorm ocean conditions such as the location and magnitude of preexisting ocean eddies, storm-induced ocean cold wake, and model track errors.

  15. Kansas Water Quality Action Targeting System (KATS)

    Data.gov (United States)

    Kansas Data Access and Support Center — This system is a revision of the original KATS system developed in 1990 as a tool to aid resource managers target Kansas valuable and vulnerable water resources for...

  16. Ion channels: molecular targets of neuroactive insecticides.

    Science.gov (United States)

    Raymond-Delpech, Valérie; Matsuda, Kazuhiko; Sattelle, Benedict M; Rauh, James J; Sattelle, David B

    2005-11-01

    Many of the insecticides in current use act on molecular targets in the insect nervous system. Recently, our understanding of these targets has improved as a result of the complete sequencing of an insect genome, i.e., Drosophila melanogaster. Here we examine the recent work, drawing on genetics, genomics and physiology, which has provided evidence that specific receptors and ion channels are targeted by distinct chemical classes of insect control agents. The examples discussed include, sodium channels (pyrethroids, p,p'-dichlorodiphenyl-trichloroethane (DDT), dihydropyrazoles and oxadiazines); nicotinic acetylcholine receptors (cartap, spinosad, imidacloprid and related nitromethylenes/nitroguanidines); gamma-aminobutyric acid (GABA) receptors (cyclodienes, gamma-BHC and fipronil) and L-glutamate receptors (avermectins). Finally, we have examined the molecular basis of resistance to these molecules, which in some cases involves mutations in the molecular target, and we also consider the future impact of molecular genetic technologies in our understanding of the actions of neuroactive insecticides.

  17. Targeting the Neural Microenvironment in Prostate Cancer

    Science.gov (United States)

    2016-10-01

    Award Number: W81XWH-14-1-0505 TITLE: Targeting the Neural Microenvironment in Prostate Cancer PRINCIPAL INVESTIGATOR: Michael Ittmann MD PhD...CONTRACT NUMBER Targeting the Neural Microenvironment in Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0505 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...tumor microenvironment plays an important role in the initiation and progression of PCa. One important component of this microenvironment is nerves

  18. Targeting Discoidin Domain Receptors in Prostate Cancer

    Science.gov (United States)

    2016-08-01

    1 AWARD NUMBER: W81XWH-15-1-0226 TITLE: Targeting Discoidin Domain Receptors in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Rafael Fridman...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-15-1-0226 Targeting Discoidin Domain Receptors in Prostate Cancer 5b. GRANT NUMBER W81XWH-15...DDRs in prostate cancer . During the first funding period, we conducted immunohistochemical studies by staining a 200 case Grade/Stage tissue

  19. Orbital Evasive Target Tracking and Sensor Management

    Science.gov (United States)

    2012-03-30

    orbits to simulate the space resource management for situation awareness. We adopted NASA’s General Mission Analysis Tool ( GMAT ) for space target...realistic satellite orbits to simulate the space resource management for situation awareness. We adopted NASA’s General Mission Analysis Tool ( GMAT ...Analysis Tool ( GMAT ) for space target tracking with multiple space borne observers. The results indicate that the game theoretic approach is more effective

  20. Recent Development of Anticancer Therapeutics Targeting Akt

    OpenAIRE

    Morrow, John K.; Du-Cuny, Lei; Chen, Lu; Meuillet, Emmanuelle J.; Eugene A Mash; Powis, Garth; Zhang, Shuxing

    2011-01-01

    The serine/threonine kinase Akt has proven to be a significant signaling target, involved in various biological functions. Because of its cardinal role in numerous cellular responses, Akt has been implicated in many human diseases, particularly cancer. It has been established that Akt is a viable and feasible target for anticancer therapeutics. Analysis of all Akt kinases reveals conserved homology for an N-terminal regulatory domain, which contains a pleckstrin-homology (PH) domain for cellu...

  1. Classification of Radar Targets Using Invariant Features

    Science.gov (United States)

    2007-11-02

    deployed for a stationary target to extract scattering centers from the raw SAR radar data (also known as the Video Phase History or VPH ), and these...center on the target. These scattering center tracks are subtracted from the VPH to generate the residual VPH , and more scattering centers are...successively extracted until an acceptable amount of the VPH is characterized. The multiple sensors generate multiple two-dimensional views, and the 3D MAGI

  2. Definitions of radioisotope thick target yields

    Energy Technology Data Exchange (ETDEWEB)

    Otuka, Naohiko [International Atomic Energy Agency, Wien (Austria). Nuclear Data Section; Takacs, Sandor [Hungarian Academy of Science, Debrecen (Hungary). Inst. of Nuclear Research

    2015-05-01

    Definitions of thick target yields are reviewed in relation to their documentation for the experimental nuclear reaction data library (database). Researchers reporting experimental thick target yields are urged to define their yields clearly with an appropriate unit in order to compile them in the experimental data library (EXFOR) in a consistent manner, and also to properly utilise them for comparison with other experimental and evaluated yields.

  3. An analytical high value target acquisition model

    OpenAIRE

    Becker, Kevin J.

    1986-01-01

    Approved for public release; distribution is unlimited An Analytical High Value Target (HVT) acquisition model is developed for a generic anti-ship cruise missile system. the target set is represented as a single HVT within a field of escorts. The HVT's location is described by a bivariate normal probability distribution. the escorts are represented by a spatially homogeneous Poisson random field surrounding the HVT. Model output consists of the probability that at least one missile of...

  4. Targeting Prostate Cancer with Multifunctional Nanoparticles

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0487 TITLE: Targeting Prostate Cancer with Multifunctional Nanoparticles PRINCIPAL INVESTIGATOR: Darryl Martin...Targeting Prostate Cancer with Multifunctional Nanoparticles 5b. GRANT NUMBER W81XWH-14-1-0487 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Darryl...claudin-3 and claudin-4 are expressed in subsets of aggressive prostate cancer. Finally, we produced our first two batches of nanoparticles during year

  5. The Evolution of Air Force Targeting

    Science.gov (United States)

    2012-12-01

    the idea of the “strategic” application of air power. German Zeppelin raids on London in 1917 are probably the first known uses of air forces beyond...bombardment led to an increasing emphasis on targeting. Then- Maj Donald Wilson, an instructor at the ACTS, believed that attack- ing a few critical targets...the organic industrial, economic, and civic systems that maintained the life of the enemy nation itself.13 This doctrine led to an even greater

  6. SPATIAL TARGETING STRATEGIES FOR LAND CONSERVATION

    OpenAIRE

    David A. Newburn; Berck, Peter; Merenlender, Adina

    2004-01-01

    Purchasing development rights is a major mechanism for the protection of environmental quality and landscape amenities. This paper provides a targeting strategy for protecting multiple environmental benefits that takes into account land costs and probability of land use conversion. We compare two strategies. Subject to a budget constraint on parcel purchases, the standard strategy is to target parcels with the highest ratio of environmental benefits to land costs. The standard strategy select...

  7. Targeted therapies in gynecologic cancers and melanoma.

    Science.gov (United States)

    Ortega, Eugenia; Marti, Rosa M; Yeramian, Andree; Sorolla, Anabel; Dolcet, Xavier; Llobet, David; Abal, Leandro; Santacana, Maria; Pallares, Judit; Llombart-Cussac, Antonio; Matias-Guiu, Xavier

    2008-11-01

    The article reviews the main molecular pathology alterations of endometrial and ovarian carcinomas and melanoma. Several promising drugs targeting the genes most frequently altered in these tumors are under consideration. The most promising signaling pathways to be targeted for therapies in these tumors are the tyrosine kinase receptor (EGFR, HER2, c-KIT), the RAS/B-RAF/MAPK, the PI3K-mTOR, and apoptosis signaling pathways.

  8. The History of Target-Controlled Infusion.

    Science.gov (United States)

    Struys, Michel M R F; De Smet, Tom; Glen, John Iain B; Vereecke, Hugo E M; Absalom, Anthony R; Schnider, Thomas W

    2016-01-01

    Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted ("target") drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical and regulatory issues addressed in prototype development. We also describe the launch of the current clinically available systems.

  9. Probe Array Correction With Strong Target Interactions

    Science.gov (United States)

    2012-08-01

    measurements, bistatic scattering cross section, array mutual impedances, Lorentz reciprocity theorem 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...ABSTRACT: SAR 18. NUMBER OF PAGES 50 19a. NAME OF RESPONSIBLE PERSON (Monitor) a. REPORT Unclassified b. ABSTRACT Unclassified c. THIS...fields scattered by a target. The measurements are made with the objective of estimating the far zone bistatic scattering from the target using

  10. Artifacts in Radar Imaging of Moving Targets

    Science.gov (United States)

    2012-09-01

    leads to the wrong object localization and defocusing on the image. For SAR , a moving target’s physical location varies throughout the imaging...Imaging, Synthetic Aperture Radar, Bistatic Radar, Multistatic Radar, Moving Targets, Backprojection 15. NUMBER OF PAGES 133 16. PRICE CODE 17...broadening and range errors were introduced by target motion. This leads to incorrect object localization and defocusing on the image. For SAR , a

  11. Inflation targeting and disinflation in Serbia

    OpenAIRE

    Savić, Nebojša; Pitić, Goran; Nedeljković, Milan

    2016-01-01

    This paper provides a brief overview of the existing monetary policy strategies and their advantages and weaknesses. The analysis highlights the strengths of the flexible inflation targeting regime and its role in disinflation processes in countries with high inflation history. It then focuses on Serbia and discusses monetary policy instruments within the flexible inflation targeting regime which have spurred the stabilization of inflation at a low level over the past three years. In addition...

  12. A high-power target experiment

    CERN Document Server

    Kirk, H G; Ludewig, H; Palmer, Robert; Samulyak, V; Simos, N; Tsang, Thomas; Bradshaw, T W; Drumm, Paul V; Edgecock, T R; Ivanyushenkov, Yury; Bennett, Roger; Efthymiopoulos, Ilias; Fabich, Adrian; Haseroth, H; Haug, F; Lettry, Jacques; Hayato, Y; Yoshimura, Koji; Gabriel, Tony A; Graves, Van; Spampinato, P; Haines, John; McDonald, Kirk T

    2005-01-01

    We describe an experiment designed as a proof-of-principle test for a target system capable of converting a 4 MW proton beam into a high-intensity muon beam suitable for incorporation into either a neutrino factory complex or a muon collider. The target system is based on exposing a free mercury jet to an intense proton beam in the presence of a high strength solenoidal field.

  13. New targets for drug discovery against malaria.

    Directory of Open Access Journals (Sweden)

    Guido Santos

    Full Text Available A mathematical model which predicts the intraerythrocytic stages of Plasmodium falciparum infection was developed using data from malaria-infected mice. Variables selected accounted for levels of healthy red blood cells, merozoite (Plasmodium asexual phase infected red blood cells, gametocyte (Plasmodium sexual phase infected red blood cells and a phenomenological variable which accounts for the mean activity of the immune system of the host. The model built was able to reproduce the behavior of three different scenarios of malaria. It predicts the later dynamics of malaria-infected humans well after the first peak of parasitemia, the qualitative response of malaria-infected monkeys to vaccination and the changes observed in malaria-infected mice when they are treated with antimalarial drugs. The mathematical model was used to identify new targets to be focused on drug design. Optimization methodologies were applied to identify five targets for minimizing the parasite load; four of the targets thus identified have never before been taken into account in drug design. The potential targets include: 1 increasing the death rate of the gametocytes, 2 decreasing the invasion rate of the red blood cells by the merozoites, 3 increasing the transformation of merozoites into gametocytes, 4 decreasing the activation of the immune system by the gametocytes, and finally 5 a combination of the previous target with decreasing the recycling rate of the red blood cells. The first target is already used in current therapies, whereas the remainders are proposals for potential new targets. Furthermore, the combined target (the simultaneous decrease of the activation of IS by gRBC and the decrease of the influence of IS on the recycling of hRBC is interesting, since this combination does not affect the parasite directly. Thus, it is not expected to generate selective pressure on the parasites, which means that it would not produce resistance in Plasmodium.

  14. On Training Targets for Supervised Speech Separation

    OpenAIRE

    Wang, Yuxuan; Narayanan, Arun; Wang, DeLiang

    2014-01-01

    Formulation of speech separation as a supervised learning problem has shown considerable promise. In its simplest form, a supervised learning algorithm, typically a deep neural network, is trained to learn a mapping from noisy features to a time-frequency representation of the target of interest. Traditionally, the ideal binary mask (IBM) is used as the target because of its simplicity and large speech intelligibility gains. The supervised learning framework, however, is not restricted to the...

  15. Inflation targeting and disinflation in Serbia

    OpenAIRE

    Savić, Nebojša; Pitić, Goran; Nedeljković, Milan

    2016-01-01

    This paper provides a brief overview of the existing monetary policy strategies and their advantages and weaknesses. The analysis highlights the strengths of the flexible inflation targeting regime and its role in disinflation processes in countries with high inflation history. It then focuses on Serbia and discusses monetary policy instruments within the flexible inflation targeting regime which have spurred the stabilization of inflation at a low level over the past three years. In addition...

  16. Bayesian target tracking based on particle filter

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    For being able to deal with the nonlinear or non-Gaussian problems, particle filters have been studied by many researchers. Based on particle filter, the extended Kalman filter (EKF) proposal function is applied to Bayesian target tracking. Markov chain Monte Carlo (MCMC) method, the resampling step, etc novel techniques are also introduced into Bayesian target tracking. And the simulation results confirm the improved particle filter with these techniques outperforms the basic one.

  17. Target-related neologism formation in jargonaphasia.

    Science.gov (United States)

    Christman, S S

    1994-01-01

    Neologistic demisyllables produced by three subjects with jargonaphasia (Christman, 1990, 1992) were compared to target demisyllables to determine whether phonological patterns underlying target-related neology could be captured by the Sonority Sequencing Principle independently of phonotactics. Results revealed that substitution errors replaced most intended segments with obstruents, despite the absence of phonotactic restrictions that might have conditioned the errors. Findings suggest a default pattern of segment selection to which the phonological system reverts when normal processing is otherwise blocked.

  18. Targeting ESR1-Mutant Breast Cancer

    Science.gov (United States)

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0359 TITLE: Targeting ESR1-Mutant Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Sarat Chandarlapaty CONTRACTING...31 Aug 2015 4. TITLE AND SUBTITLE Targeting ESR1-Mutant Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0359 5c. PROGRAM ELEMENT...mutations found in breast cancer using both structural and cell based assays. We have now have evidence for the effects of the most recurrent

  19. Qualitative differential games with two targets

    Science.gov (United States)

    Getz, W. M.; Leitmann, G.

    1977-01-01

    So-called differential games of kind (qualitative games) were considered involving two or more players each of whom possesses a target toward which he wished to steer the response of a dynamical system that was under the control of all players. Sufficient conditions were derived, which assure termination on a particular player's target. In general, these conditions were constructive in that they permited construction of a winning (terminating) strategy for a player. The theory is illustrated by a pursuit-evasion problem.

  20. Achieving target refraction after cataract surgery.

    Science.gov (United States)

    Simon, Shira S; Chee, Yewlin E; Haddadin, Ramez I; Veldman, Peter B; Borboli-Gerogiannis, Sheila; Brauner, Stacey C; Chang, Kenneth K; Chen, Sherleen H; Gardiner, Matthew F; Greenstein, Scott H; Kloek, Carolyn E; Chen, Teresa C

    2014-02-01

    To evaluate the difference between target and actual refraction after phacoemulsification and intraocular lens implantation at an academic teaching institution's Comprehensive Ophthalmology Service. Retrospective study. We examined 1275 eye surgeries for this study. All consecutive cataract surgeries were included if they were performed by an attending or resident surgeon from January through December 2010. Postoperative refractions were compared with preoperative target refractions. Patients were excluded if they did not have a preoperative target refraction documented or if they did not have a recorded postoperative manifest refraction within 90 days. The main outcome measure was percentage of cases achieving a postoperative spherical equivalent ± 1.0 diopter (D) of target spherical equivalent. We performed 1368 cataract surgeries from January through December of 2010. Of these, 1275 (93%) had sufficient information for analysis. Of the included cases, 94% (1196 of 1275) achieved ± 1.0 D of target refraction by 90 days after cataract surgery. This paper establishes a new benchmark for a teaching hospital, where 94% of patients achieved within 1.0 D of target refraction after cataract surgery. The refractive outcomes after cataract surgery at this academic teaching institution were higher than average international benchmarks. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  1. Update on the targeted therapy of melanoma.

    Science.gov (United States)

    Johnson, Douglas B; Sosman, Jeffrey A

    2013-06-01

    Melanoma is the most aggressive of the cutaneous malignancies, causing more than 9,000 deaths in the past year in the United States. Historically, systemic therapies have been largely ineffective, because melanoma is usually resistant to cytotoxic chemotherapy. However, during the past few years, several targeted therapies have proved effective in this challenging disease. These recent advances have been facilitated by an improved understanding of the driving genetic aberrations of melanoma, particularly mutations in the mitogen-activated protein kinase (MAPK) pathway. Vemurafenib, a BRAF inhibitor, demonstrated an overall survival advantage in phase III trials and is an appropriate option for first-line therapy in metastatic BRAF mutant melanoma. Dabrafenib, another BRAF inhibitor, and trametinib, a MEK inhibitor, also have been shown to be effective in phase III trials for BRAF mutant melanoma and may be additional treatment options as monotherapy or in combination pending regulatory approval. Additionally, imatinib is a promising targeted therapy for patients whose tumors harbor a KIT mutation in exons 11 and 13. Although these targeted agents cause objective responses and clinical benefit in patients with metastatic melanoma, resistance invariably develops. New targets and strategies to overcome acquired resistance are urgently needed. Furthermore, no effective targeted therapy has been developed for NRAS mutant tumors or in melanomas with as yet unknown driver mutations. In this review, we discuss current molecular targeted treatment options and promising ongoing research to develop new strategies to treat melanoma.

  2. The SPES High Power ISOL production target

    Science.gov (United States)

    Andrighetto, A.; Corradetti, S.; Ballan, M.; Borgna, F.; Manzolaro, M.; Scarpa, D.; Monetti, A.; Rossignoli, M.; Silingardi, R.; Mozzi, A.; Vivian, G.; Boratto, E.; De Ruvo, L.; Sattin, N.; Meneghetti, G.; Oboe, R.; Guerzoni, M.; Margotti, A.; Ferrari, M.; Zenoni, A.; Prete, G.

    2016-11-01

    SPES (Selective Production of Exotic Species) is a facility under construction at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro), aimed to produce intense neutron-rich radioactive ion beams (RIBs). These will be obtained using the ISOL (Isotope Separation On-Line) method, bombarding a uranium carbide target with a proton beam of 40MeV energy and currents up to 200μA. The target configuration was designed to obtain a high number of fissions, up to 1013 per second, low power deposition and fast release of the produced isotopes. The exotic isotopes generated in the target are ionized, mass separated and re-accelerated by the ALPI superconducting LINAC at energies of 10AMeV and higher, for masses in the region of A = 130 amu , with an expected rate on the secondary target up to 109 particles per second. In this work, recent results on the R&D activities regarding the SPES RIB production target-ion source system are reported.

  3. Achieving the Renewable Energy Target for Jamaica

    Directory of Open Access Journals (Sweden)

    Abdullahi Olabode ABDULKADRI

    2014-05-01

    Full Text Available ieving the Renewable Energy Target for Jamaica Abstract: The high cost of energy in Jamaica, one of the highest in the Caribbean region, is usually cited as a hindrance to industrial development and efficiency, especially in the manufacturing sector. High energy cost is also considered to be a national energy security issue and the government is taking steps to ensure adequate supply of energy at affordable prices. In the current National Development Plan, the government has set a target for renewable energy sources to supply 20% of the country's energy need by the year 2030. Using a linear programing model of energy planning, we examine how realistically this target could be achieved. Our findings indicate that the 20% renewable energy target is technically achievable with the optimal plan showing a mixture of wind power, hydropower and bagasse power but no solar power. However, when the timeline for investment in new generating capacities that will ensure the attainment of the target is considered, it becomes highly improbable that the target will be met. This study fills the gap that exists in evidence-based analysis of energy policy in Jamaica.

  4. Rotating target wheel for the FMA

    Energy Technology Data Exchange (ETDEWEB)

    Back, B.B.; Davids, C.N.; Falout, J. [and others

    1995-08-01

    In anticipation of high intensity beams that will be available from the PII-ECR source injector to ATLAS, a new rotating target wheel was developed for the sliding seal chamber at the FMA. The wheel is 9 inch in diameter and contains up to ten targets. The rotation of the wheel is achieved by a DC motor, a ferrofluidic feedthrough, and a gear mechanism that allows both target rotation and changing the target angle relative to the beam. The nominal rotation speed is 1000 RPM, although higher speeds can be achieved if necessary. The assembly is equipped with an absolute encoder which is read out via a newly developed CAMAC module. This module provides the following main functions: (1) a TTL signal to be used for sweeping the beam when a target frame is about to pass through the beam, (2) a read-out of the target position that can be included in the data event structure, (3) programmable set points for the beam-off signal. The system is presently being tested and will be used in experiments scheduled for March 1995.

  5. PROS AND CONS OF INFLATION TARGETING STRATEGY

    Directory of Open Access Journals (Sweden)

    Mihaela SUDACEVSCHI

    2011-12-01

    Full Text Available The purpose of this paper is to define the inflation targeting strategy and its characteristics. Inflation targeting is a monetary policy strategy in which the central bank projected estimates and makes public, or “target” inflation rate and then, attempts to steer actual inflation towards the target through the use of interest rate changes and other monetary tools. Early proposals of monetary systems targeting the price level or the inflation rate, rather then exchange rate, followed the general crisis of the gold standard after the World War I. Inflation is usually measured as the change of prices for consumer goods, called Consumer Price Index (CPI. Inflation targeting assumes that this figure accurately represents growth or money supply, but is not always the case. The most serious exception occurs when factors external to the national economy are the cause of the price increase. A more essential objection to the strategy of inflation targeting is that it does not really comprise a specific set of monetary policy recommendation would traditional monetarism did, but just constitutes an explicit statement of the aims of the monetary authority.

  6. Discovering drug targets through the web.

    Science.gov (United States)

    Wishart, David S

    2007-03-01

    Traditionally, drug-target discovery is a "wet-bench" experimental process, depending on carefully designed genetic screens, biochemical tests and cellular assays to identify proteins and genes that are associated with a particular disease or condition. However, recent advances in DNA sequencing, transcript profiling, protein identification and protein quantification are leading to a flood of genomic and proteomic data that is, or potentially could be, linked to disease data. The quantity of data generated by these high throughput methods is forcing scientists to re-think the way they do traditional drug-target discovery. In particular it is leading them more and more towards identifying potential drug targets using computers. In fact, drug-target identification is now being done as much on the desk-top as on the bench-top. This review focuses on describing how drug-target discovery can be done in silico (i.e. via computer) using a variety of bioinformatic resources that are freely available on the web. Specifically, it highlights a number of web-accessible sequence databases, automated genome annotation tools, text mining tools; and integrated drug/sequence databases that can be used to identify drug targets for both endogenous (genetic and epigenetic) diseases as well as exogenous (infectious) diseases.

  7. Game theoretic sensor management for target tracking

    Science.gov (United States)

    Shen, Dan; Chen, Genshe; Blasch, Erik; Pham, Khanh; Douville, Philip; Yang, Chun; Kadar, Ivan

    2010-04-01

    This paper develops and evaluates a game-theoretic approach to distributed sensor-network management for target tracking via sensor-based negotiation. We present a distributed sensor-based negotiation game model for sensor management for multi-sensor multi-target tacking situations. In our negotiation framework, each negotiation agent represents a sensor and each sensor maximizes their utility using a game approach. The greediness of each sensor is limited by the fact that the sensor-to-target assignment efficiency will decrease if too many sensor resources are assigned to a same target. It is similar to the market concept in real world, such as agreements between buyers and sellers in an auction market. Sensors are willing to switch targets so that they can obtain their highest utility and the most efficient way of applying their resources. Our sub-game perfect equilibrium-based negotiation strategies dynamically and distributedly assign sensors to targets. Numerical simulations are performed to demonstrate our sensor-based negotiation approach for distributed sensor management.

  8. Test of a High Power Target Design

    CERN Multimedia

    2002-01-01

    %IS343 :\\\\ \\\\ A high power tantalum disc-foil target (RIST) has been developed for the proposed radioactive beam facility, SIRIUS, at the Rutherford Appleton Laboratory. The yield and release characteristics of the RIST target design have been measured at ISOLDE. The results indicate that the yields are at least as good as the best ISOLDE roll-foil targets and that the release curves are significantly faster in most cases. Both targets use 20 -25 $\\mu$m thick foils, but in a different internal geometry.\\\\ \\\\Investigations have continued at ISOLDE with targets having different foil thickness and internal geometries in an attempt to understand the release mechanisms and in particular to maximise the yield of short lived isotopes. A theoretical model has been developed which fits the release curves and gives physical values of the diffusion constants.\\\\ \\\\The latest target is constructed from 2 $\\mu$m thick tantalum foils (mass only 10 mg) and shows very short release times. The yield of $^{11}$Li (half-life of ...

  9. Screening closing scenarios for tactical targets

    Science.gov (United States)

    Sefcik, Jason A.; Lee, Harry C.; Olson, Teresa L. P.

    2002-07-01

    The first step in an automatic image target acquisition system is determining the location of candidate objects. Screening for targets must also be done within a tactical scenario timeframe. The screening process must only require a portion of the processing workload since other algorithms must execute in the same time frame. The detection of these candidate objects is allocated to two functions within the same algorithm. The first is a pre-screener and other is a clutter rejection component that will categorize the object nomination into target or non-target classes. This paper describes a screener that meets the necessary requirements for tactical operations. It uses the magnitude and direction of the image gradient. Locations are nominated by looking at local neighborhoods in this gradient space. Regions of interest are then selected and various features are extracted. These features are selected both for their information content and their ease of calculation. Using a Bayes approach, target candidates are selected as plausible targets of interest.

  10. Allegany Ballistics Lab: sensor test target system

    Science.gov (United States)

    Eaton, Deran S.

    2011-06-01

    Leveraging the Naval Surface Warfare Center, Indian Head Division's historical experience in weapon simulation, Naval Sea Systems Command commissioned development of a remote-controlled, digitally programmable Sensor Test Target as part of a modern, outdoor hardware-in-the-loop test system for ordnance-related guidance, navigation and control systems. The overall Target system design invokes a sciences-based, "design of automated experiments" approach meant to close the logistical distance between sensor engineering and developmental T&E in outdoor conditions over useful real world distances. This enables operating modes that employ broad spectrum electromagnetic energy in many a desired combination, variably generated using a Jet Engine Simulator, a multispectral infrared emitter array, optically enhanced incandescent Flare Simulators, Emitter/Detector mounts, and an RF corner reflector kit. As assembled, the recently tested Sensor Test Target prototype being presented can capably provide a full array of useful RF and infrared target source simulations for RDT&E use with developmental and existing sensors. Certain Target technologies are patent pending, with potential spinoffs in aviation, metallurgy and biofuels processing, while others are variations on well-established technology. The Sensor Test Target System is planned for extended installation at Allegany Ballistics Laboratory (Rocket Center, WV).

  11. 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.

  12. Targeting Signaling Pathways in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Johannes Haybaeck

    2013-05-01

    Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are relevant for ovarian tumorigenesis. The understanding of these molecular pathways is essential for the development of novel therapeutic strategies. Purpose: We want to give an overview on the molecular genetic changes of the histopathological types of OC and their role as putative therapeutic targets. In Depth Review of Existing Data: In 2012, the vascular endothelial growth factor (VEGF inhibitor, bevacizumab, was approved for OC treatment. Bevacizumab has shown promising results as single agent and in combination with conventional chemotherapy, but its target is not distinctive when analyzed before treatment. At present, mammalian target of rapamycin (mTOR inhibitors, poly-ADP-ribose polymerase (PARP inhibitors and components of the EGFR pathway are in the focus of clinical research. Interestingly, some phytochemical substances show good synergistic effects when used in combination with chemotherapy. Conclusion: Ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative options to bevacizumab available for OC patients. Novel targets which can be assessed before therapy to predict efficacy are needed. The assessment of therapeutic targets is continuously improved by molecular pathological analyses on tumor tissue. A careful selection of patients for personalized treatment will help to reduce putative side effects and toxicity.

  13. Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

    Science.gov (United States)

    Yang, Ye; Zhang, Jianyun; Yao, Yijun

    2017-01-01

    Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

  14. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

    Science.gov (United States)

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

  15. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models

    Science.gov (United States)

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com.

  16. Modeling target erosion during reactive sputtering

    Energy Technology Data Exchange (ETDEWEB)

    Strijckmans, K., E-mail: Koen.Strijckmans@ugent.be; Depla, D.

    2015-03-15

    Highlights: • The erosion of a target is simulated with the RSD2013 software during reactive magnetron sputtering. • The influence of redeposition on the target state and on the hysteresis is explained. • The racetrack formation along the hysteresis and as function of the redeposition is quantified. • Comparison of the racetrack and the sputter profile shows clear differences. - Abstract: The influence of the reactive sputter conditions on the racetrack and the sputter profile for an Al/O{sub 2} DC reactive sputter system is studied by modeling. The role of redeposition, i.e. the deposition of sputtered material back on the target, is therefore taken into account. The used model RSD2013 is capable of simulating the effect of redeposition on the target condition in a spatial resolved way. Comparison between including and excluding redeposition in the RSD2013 model shows that the in-depth oxidation profile of the target differs. Modeling shows that it is important to distinguish between the formed racetrack, i.e. the erosion depth profile, and the sputter profile. The latter defines the distribution of the sputtered atoms in the vacuum chamber. As the target condition defines the sputter yield, it does determine the racetrack and the sputter profile of the planar circular target. Both the shape of the racetrack and the sputter profile change as function of the redeposition fraction as well as function of the oxygen flow change. Clear asymmetries and narrowing are observed for the racetrack shape. Similar effects are noticed for the sputter profile but to a different extent. Based on this study, the often heard misconception that the racetrack shape defines the distribution of the sputtered atoms during reactive sputtering is proven to be wrong.

  17. Normalization for triple-target microarray experiments

    Directory of Open Access Journals (Sweden)

    Magniette Frederic

    2008-04-01

    Full Text Available Abstract Background Most microarray studies are made using labelling with one or two dyes which allows the hybridization of one or two samples on the same slide. In such experiments, the most frequently used dyes are Cy3 and Cy5. Recent improvements in the technology (dye-labelling, scanner and, image analysis allow hybridization up to four samples simultaneously. The two additional dyes are Alexa488 and Alexa494. The triple-target or four-target technology is very promising, since it allows more flexibility in the design of experiments, an increase in the statistical power when comparing gene expressions induced by different conditions and a scaled down number of slides. However, there have been few methods proposed for statistical analysis of such data. Moreover the lowess correction of the global dye effect is available for only two-color experiments, and even if its application can be derived, it does not allow simultaneous correction of the raw data. Results We propose a two-step normalization procedure for triple-target experiments. First the dye bleeding is evaluated and corrected if necessary. Then the signal in each channel is normalized using a generalized lowess procedure to correct a global dye bias. The normalization procedure is validated using triple-self experiments and by comparing the results of triple-target and two-color experiments. Although the focus is on triple-target microarrays, the proposed method can be used to normalize p differently labelled targets co-hybridized on a same array, for any value of p greater than 2. Conclusion The proposed normalization procedure is effective: the technical biases are reduced, the number of false positives is under control in the analysis of differentially expressed genes, and the triple-target experiments are more powerful than the corresponding two-color experiments. There is room for improving the microarray experiments by simultaneously hybridizing more than two samples.

  18. Layout optimization for multilayer overlay targets

    Science.gov (United States)

    Binns, L. A.; Smith, N. P.; Ausschnitt, C. P.; Morningstar, J.; Muth, W.; Schneider, J.; Yerdon, R.

    2006-03-01

    A novel overlay target developed by IBM and Accent Optical Technologies, Blossom, allows simultaneous overlay measurements of multiple layers (currently, up to 28) with a single target. This is achieved by a rotationally symmetric arrangement of small (4 micron) targets in a 50 micron square area, described more fully in a separate paper. In this paper, we examine the lessons learned in developing and testing the Blossom design. We start by examining proximity effects; the spacing of adjacent targets means that both the precision-like Total Measurement Uncertainty (TMU) and accuracy of a measurement can be affected by proximity of features. We use a mixture of real and modelled data to illustrate this problem, and find that the layout of Blossom reduces the proximity-induced bias. However, we do find that in certain cases proximity effects can increase the TMU of a particular measurement. The solution is to ensure that parts of the target that interact detrimentally are maximally separated. We present a solution to this, viewing the problem as a constrained Travelling Salesman Problem. We have imposed some global constraints, for example printing front-end and back-end layers on separate targets, and consistency with the overlay measurement strategy. Initially, we assume that pairwise measurements are either critical or non-critical, and optimize the layout so that the critical layers are both not placed adjacent to any prior or intermediate-layer features. We then build upon this structure, to consider the effect of low-energy implants (that cannot be seen once processed) and site re-use possibilities. Beyond this, we also investigate the impact of more strategic optimizations, for example, tuning the number of features on each layer. In each case, we present on-product performance data achieved, and modelled data on some additional target variants / extreme cases.

  19. Transorbital target localization in the porcine model

    Science.gov (United States)

    DeLisi, Michael P.; Mawn, Louise A.; Galloway, Robert L.

    2013-03-01

    Current pharmacological therapies for the treatment of chronic optic neuropathies such as glaucoma are often inadequate due to their inability to directly affect the optic nerve and prevent neuron death. While drugs that target the neurons have been developed, existing methods of administration are not capable of delivering an effective dose of medication along the entire length of the nerve. We have developed an image-guided system that utilizes a magnetically tracked flexible endoscope to navigate to the back of the eye and administer therapy directly to the optic nerve. We demonstrate the capabilities of this system with a series of targeted surgical interventions in the orbits of live pigs. Target objects consisted of NMR microspherical bulbs with a volume of 18 μL filled with either water or diluted gadolinium-based contrast, and prepared with either the presence or absence of a visible coloring agent. A total of 6 pigs were placed under general anesthesia and two microspheres of differing color and contrast content were blindly implanted in the fat tissue of each orbit. The pigs were scanned with T1-weighted MRI, image volumes were registered, and the microsphere containing gadolinium contrast was designated as the target. The surgeon was required to navigate the flexible endoscope to the target and identify it by color. For the last three pigs, a 2D/3D registration was performed such that the target's coordinates in the image volume was noted and its location on the video stream was displayed with a crosshair to aid in navigation. The surgeon was able to correctly identify the target by color, with an average intervention time of 20 minutes for the first three pigs and 3 minutes for the last three.

  20. Protein Targeting to the Plastid of Euglena.

    Science.gov (United States)

    Durnford, Dion G; Schwartzbach, Steven D

    2017-01-01

    The lateral transfer of photosynthesis between kingdoms through endosymbiosis is among the most spectacular examples of evolutionary innovation. Euglena, which acquired a chloroplast indirectly through an endosymbiosis with a green alga, represents such an example. As with other endosymbiont-derived plastids from eukaryotes, there are additional membranes that surround the organelle, of which Euglena has three. Thus, photosynthetic genes that were transferred from the endosymbiont to the host nucleus and whose proteins are required in the new plastid, are now faced with targeting and plastid import challenges. Early immunoelectron microscopy data suggested that the light-harvesting complexes, photosynthetic proteins in the thylakoid membrane, are post-translationally targeted to the plastid via the Golgi apparatus, an unexpected discovery at the time. Proteins targeted to the Euglena plastid have complex, bipartite presequences that direct them into the endomembrane system, through the Golgi apparatus and ultimately on to the plastid, presumably via transport vesicles. From transcriptome sequencing, dozens of plastid-targeted proteins were identified, leading to the identification of two different presequence structures. Both have an amino terminal signal peptide followed by a transit peptide for plastid import, but only one of the two classes of presequences has a third domain-the stop transfer sequence. This discovery implied two different transport mechanisms; one where the protein was fully inserted into the lumen of the ER and another where the protein remains attached to, but effectively outside, the endomembrane system. In this review, we will discuss the biochemical and bioinformatic evidence for plastid targeting, discuss the evolution of the targeting system, and ultimately provide a working model for the targeting and import of proteins into the plastid of Euglena.