WorldWideScience

Sample records for he-3 target system

  1. A liquid He-3 target system for use at intermediate energies

    International Nuclear Information System (INIS)

    Hassell, D.K.; Abegg, R.; Murdoch, B.T.; van Oers, W.J.H.; Soukup, J.

    1981-04-01

    A liquid 3 He target system with remote instrumentation and handling capabilities has been developed for experiments using the 180-525 MeV TRIUMF cyclotron. Helium-3 gas is liquefied by means of a 4 He cryostat into a cylindrical target cell (4.4 cm diameter, 1.6 cm thick) and maintained during operation at approximately 1.6 K. This provides an areal target density of approximately 2.7 x 10 22 He-3 nuclei/cm 2 (128 mg/cm 2 ), suitable for intermediate energy proton scattering. (author)

  2. Expectation values of the e+He(3Se) system

    International Nuclear Information System (INIS)

    Mitroy, J.

    2005-01-01

    Close to converged energies and expectation values for e + He( 3 S e ) are computed using a ground state wave function consisting of 1500 explicitly correlated Gaussians. The best estimate of the e + He( 3 S e ) energy was -2.250 595 08 hartree, which has a binding energy of 0.000 595 08 hartree against dissociation into Ps+He + . The 2γ annihilation rate for the spin doublet state was 5.713x10 9 s -1 . The estimated annihilation rate with the core He + electron was 2.506x10 6 s -1 . The derived enhancement factor for annihilation with the He + (1s) core was 2.29, just over 10% smaller than the enhancement factor derived from analyses of annihilation during e + -He + scattering. The diffuse nature of the wave function, with well separated He + and Ps subsystems, is demonstarted to be on the threshold of satisfying the formal criteria that define a quantum halo state

  3. Contribution to the study of reactions induced by a low-energy He3 beam on a C12 target

    International Nuclear Information System (INIS)

    Schapira, Jean-Paul

    1965-01-01

    This research thesis reports the study concerning which reaction mode will better describe a nucleus in which the excitation energy is between two extremes. Due to experimental considerations and abilities, this study focuses on light target nuclei and carbon 12. The author describes experimental techniques used for angular distributions (targets, detection system), describes the experimental techniques for activation experiments (experimental set-up, targets, measurement of relative efficient cross section, result analysis, measurement of absolute efficient cross section). The author discusses the experimental results (excitation functions and angular distributions) and the interpretation of elastic scattering results (theoretical background, computation approach, analysis of elastic scattering) and the results of the C 12 (He 3 , α)C 11 reaction [fr

  4. The Spin Structure of the Neutron Determined Using a Polarized He-3 Target

    Energy Technology Data Exchange (ETDEWEB)

    Middleton, H

    2004-01-06

    Described is a study of the internal spin structure of the neutron performed by measuring the asymmetry in spin-dependent deep inelastic scattering of polarized electrons from nuclear polarized {sup 3}He. Stanford Linear Accelerator experiment E142's sample of 400 million scattering events collected at beam energies between 19 and 26 GeV led to the most precise measurement of a nucleon spin structure function to date. The {sup 3}He target represents a major advance in polarized target technology, using the technique of spin exchange with optically pumped rubidium vapor to produce a typical {sup 3}He nuclear polarization of 34% in a 30cm long target cell with a gas density of 2.3 x 10{sup 20} cm{sup -3}. The target polarization was measured to {+-}7% using an Adiabatic Fast Passage NMR system calibrated with the thermal equilibrium polarization of the protons in a sample of water. The relatively high polarization and target thickness were the result of the development of large volume glass target cells which had inherent nuclear spin relaxation times for the {sup 3}He gas of as long as 70 hours. A target cell production procedure is presented which focuses on special glass blowing techniques to minimize surface interactions with the {sup 3}He nuclei and careful gas purification and vacuum system procedures to reduce relaxation inducing impurities.

  5. A Precision Measurement of the Neutron Spin Structure Functions Using a Polarized HE-3 Target

    International Nuclear Information System (INIS)

    Smith, T

    2003-01-01

    This thesis describes a precision measurement of the neutron spin dependent structure function, g 1 n (x). The measurement was made by the E154 collaboration at SLAC using a longitudinally polarized, 48.3 GeV electron beam, and a 3 He target polarized by spin exchange with optically pumped rubidium. A target polarization as high as 50% was achieved. The elements of the experiment which pertain to the polarized 3 He target will be described in detail in this thesis. To achieve a precision measurement, it has been necessary to minimize the systematic error from the uncertainty in the target parameters. All of the parameters of the target have been carefully measured, and the most important parameters of the target have been measured using multiple techniques. The polarization of the target was measured using nuclear magnetic resonance techniques, and has been calibrated using both proton NMR and by measuring the shift of the Rb Zeeman resonance frequency due to the 3 He polarization. The fraction of events which originated in the 3 He, as measured by the spectrometers, has been determined using a physical model of the target and the spectrometers. It was also measured during the experiment using a variable pressure 3 He reference cell in place of the polarized 3 He target. The spin dependent structure function g 1 n (z) was measured in the Bjorken x range of 0.014 2 of 5 (GeV/c) 2 . One of the primary motivations for this experiment was to test the Bjorken sum rule. Because the experiment had smaller statistical errors and a broader kinematic coverage than previous experiments, the behavior of the spin structure function g 1 n (x) could be studied in detail at low values of the Bjorken scaling variable x. It was found that g 1 n (x) has a strongly divergent behavior at low values of x, calling into question the methods commonly used to extrapolate the value of g 1 n (x) to low x. The precision of the measurement made by the E154 collaboration at SLAC puts a tighter

  6. A Precision Measurement of the Neutron Spin Structure Functions Using a Polarized HE-3 Target

    Energy Technology Data Exchange (ETDEWEB)

    Smith, T

    2003-11-05

    This thesis describes a precision measurement of the neutron spin dependent structure function, g{sub 1}{sup n}(x). The measurement was made by the E154 collaboration at SLAC using a longitudinally polarized, 48.3 GeV electron beam, and a {sup 3}He target polarized by spin exchange with optically pumped rubidium. A target polarization as high as 50% was achieved. The elements of the experiment which pertain to the polarized {sup 3}He target will be described in detail in this thesis. To achieve a precision measurement, it has been necessary to minimize the systematic error from the uncertainty in the target parameters. All of the parameters of the target have been carefully measured, and the most important parameters of the target have been measured using multiple techniques. The polarization of the target was measured using nuclear magnetic resonance techniques, and has been calibrated using both proton NMR and by measuring the shift of the Rb Zeeman resonance frequency due to the {sup 3}He polarization. The fraction of events which originated in the {sup 3}He, as measured by the spectrometers, has been determined using a physical model of the target and the spectrometers. It was also measured during the experiment using a variable pressure {sup 3}He reference cell in place of the polarized {sup 3}He target. The spin dependent structure function g{sub 1}{sup n}(z) was measured in the Bjorken x range of 0.014 < x < 0.7 with an average Q{sup 2} of 5 (GeV/c){sup 2}. One of the primary motivations for this experiment was to test the Bjorken sum rule. Because the experiment had smaller statistical errors and a broader kinematic coverage than previous experiments, the behavior of the spin structure function g{sub 1}{sup n}(x) could be studied in detail at low values of the Bjorken scaling variable x. It was found that g{sub 1}{sup n}(x) has a strongly divergent behavior at low values of x, calling into question the methods commonly used to extrapolate the value of g

  7. Laser - Polarized HE-3 Target Used for a Precision Measurement of the Neutron Spin Structure

    Energy Technology Data Exchange (ETDEWEB)

    Romalis, M

    2003-11-05

    This thesis describes a precision measurement of the deep inelastic neutron spin structure function g{sub 1}{sup n}(x). The main motivation for the experiment is a test of the Bjorken sum rule. Because of smaller statistical errors and broader kinematic coverage than in previous experiments, we are able to study in detail the behavior of the spin structure function g{sub 1}{sup n}(x) for low values of the Bjorken scaling variable x. We find that it has a strongly divergent behavior, in contradiction to the naive predictions of the Regge theory. This calls into question the methods commonly used for extrapolation of g{sub 1}{sup n}(x) to x = 0. The difference between the proton and the neutron spin structure functions is less divergent at low x, so a test of the Bjorken sum rule is possible. We confirm the sum rule with an accuracy of 8%. The experiment was performed at SLAC using a 50 GeV polarized electron beam and a polarized {sup 3}He target. In this thesis the polarized target is described in detail. We used the technique of Rb optical pumping and Rb-He spin exchange to polarize the {sup 3}He. Because of a novel mechanical design our target had the smallest dilution ever achieved for a high density gas target. Since this is a precision measurement, particular efforts were made to reduce the systematic errors due to the uncertainty in the target parameters. Most important parameters were measured by more than one method. We implemented novel techniques for measuring the thickness of the glass windows of the target, the {sup 3}He density, and the polarization. In particular, one of the methods for measuring the gas density relied on the broadening of the Rb optical absorption lines by collisions with {sup 3}He atoms. The calibration of this technique resulted in the most precise measurements of the pressure broadening parameters for {sup 3}He as well as several other gases, which are described in an Appendix. The polarization of the {sup 3}He was also measured by

  8. The Precision Measurement of the Neutron Spin Structure Function Using Polarized HE-3 Target

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X

    2004-01-05

    Using a 48.6 GeV polarized electron beam scattering off a polarized {sup 3}He target at Stanford Linear Accelerator Centre (SLAC), they measured the neutron spin structure function g{sub 1}{sup n} over kinematic(x) ranging 0.014 < x <0.7 and 1 < Q{sup 2} < 17GeV{sup 2}. The measurement gave the integral result over the neutron spin structure function {integral}{sub 0.014}{sup 0.7} g{sub 1}{sup n}(x)dx = -0.036 {+-} 0.004(stat) {+-} 0.005(syst) at an average Q{sup 2} = 5GeV{sup 2}. Along with the proton results from SLAC E143 experiment (0.03 < x) and SMC experiment (0.014 < x < 0.03), they find the Bjorken sum rule appears to be largely saturated by the data integrated down to x of 0.014. However, they observe relatively large values for g{sub 1}{sup n} at low x. The result calls into question the usual methods (Regge theory) for extrapolating to x = 0 to find the full neutron integral {integral}{sub 0}{sup t} g{sub 1}{sup n}(x) dx, needed for testing the Quark-Parton Model (QMP).

  9. Numerical simulations of heavy fermion systems. From He-3 bilayers to topological Kondo insulators

    International Nuclear Information System (INIS)

    Werner, Jan

    2015-01-01

    In this thesis the results of model calculations based on an extended Periodic Anderson Model are presented. The three particle ring exchange, which is the dominant magnetic exchange process in layered He-3, is included in the model. In addition, the model incorporates the constraint of no double occupancy by taking the limit of large local Coulomb repulsion. By means of Cellular DMFT, the model is investigated for a range of values of the chemical potential μ and inverse temperature β=1/T. The method is a cluster extension to the Dynamical Mean-Field Theory (DMFT), and allows to systematically include non-local correlations beyond the DMFT. The auxiliary cluster model is solved by a hybridization expansion CTQMC cluster solver, which provides unbiased, numerically exact results for the Green's function and other observables of interest. As a first step, the onset of Fermi liquid coherence is studied. At low enough temperature, the self-energy is found to exhibit a linear dependence on Matsubara frequency. Meanwhile, the spin susceptibility crossed over from a Curie-Weiss law to a Pauli law. The heavy fermion state appears at a characteristic coherence scale T coh . While the density is rather high for small filling, for larger filling T coh is increasingly suppressed. This involves a decreasing quasiparticle residue Z∝T coh and an enhanced mass renormalization m * /m∝T coh -1 . Extrapolation leads to a critical filling, where the coherence scale is expected to vanish at a quantum critical point. At the same time, the effective mass diverges. This corresponds to a breakdown of the Kondo effect, which is responsible for the formation of quasiparticles, due to a vanishing of the effective hybridization between the layers. Cellular DMFT simulations are conducted for small clusters of size N c =2 and 3. Furthermore a simple two-band model for two-dimensional topological Kondo insulators is devised, which is based on a single Kramer's doublet coupled to

  10. Numerical simulations of heavy fermion systems. From He-3 bilayers to topological Kondo insulators

    Energy Technology Data Exchange (ETDEWEB)

    Werner, Jan

    2015-03-27

    In this thesis the results of model calculations based on an extended Periodic Anderson Model are presented. The three particle ring exchange, which is the dominant magnetic exchange process in layered He-3, is included in the model. In addition, the model incorporates the constraint of no double occupancy by taking the limit of large local Coulomb repulsion. By means of Cellular DMFT, the model is investigated for a range of values of the chemical potential μ and inverse temperature β=1/T. The method is a cluster extension to the Dynamical Mean-Field Theory (DMFT), and allows to systematically include non-local correlations beyond the DMFT. The auxiliary cluster model is solved by a hybridization expansion CTQMC cluster solver, which provides unbiased, numerically exact results for the Green's function and other observables of interest. As a first step, the onset of Fermi liquid coherence is studied. At low enough temperature, the self-energy is found to exhibit a linear dependence on Matsubara frequency. Meanwhile, the spin susceptibility crossed over from a Curie-Weiss law to a Pauli law. The heavy fermion state appears at a characteristic coherence scale T{sub coh}. While the density is rather high for small filling, for larger filling T{sub coh} is increasingly suppressed. This involves a decreasing quasiparticle residue Z∝T{sub coh} and an enhanced mass renormalization m{sup *}/m∝T{sub coh}{sup -1}. Extrapolation leads to a critical filling, where the coherence scale is expected to vanish at a quantum critical point. At the same time, the effective mass diverges. This corresponds to a breakdown of the Kondo effect, which is responsible for the formation of quasiparticles, due to a vanishing of the effective hybridization between the layers. Cellular DMFT simulations are conducted for small clusters of size N{sub c}=2 and 3. Furthermore a simple two-band model for two-dimensional topological Kondo insulators is devised, which is based on a single

  11. He3 cryostat

    International Nuclear Information System (INIS)

    Novichkova, L.G.; Kulikov, Yu.V.; Stashkova, N.M.

    1992-01-01

    An effective cryostat featuring a one-cycle He 3 refrigerator with a cryosorption pump is described. Gaseous He 3 in contained in a low-pressure vessel having a common wall with a liquid N 2 bath. Due to this, the gas is cooled before sorption and the sorption rate increases approximately by a factor of ten. The cryostat is provided with a needle valve which cuts off the ballast volume of the pipelines from the refrigerator. As a result, the pressure of He 3 vapours increases before condensation and with refrigerator dimensions selected properly, the liquefaction coefficient reaches approximately 80%. Test results of the cryostat and its specifications are presented. (Author)

  12. Opportunities for Polarized He-3 in RHIC and EIC

    Energy Technology Data Exchange (ETDEWEB)

    Aschenauer E.; Deshpande, A.; Fischer, W.; Derbenev, S.; Milner, R.; Roser, T.; Zelenski, A.

    2011-10-01

    The workshop on opportunities for polarized He-3 in RHIC and EIC was targeted at finding practical ways of implementing and using polarized He-3 beams. Polarized He-3 beams will provide the unique opportunity for first measurements, i.e, to a full quark flavor separation measuring single spin asymmetries for p{sup +}, p{sup -} and p{sup 0} in hadron-hadron collisions. In electron ion collisions the combination of data recorded with polarized electron proton/He-3 beams allows to determine the quark flavor separated helicity and transverse momentum distributions. The workshop had sessions on polarized He-3 sources, the physics of colliding polarized He-3 beams, polarimetry, and beam acceleration in the AGS Booster, AGS, RHIC, and ELIC. The material presented at the workshop will allow making plans for the implementation of polarized He-3 beams in RHIC.

  13. Development and testing of a deuterium gas target assembly for neutron production via the H-2(d,n)He-3 reaction at a low-energy accelerator facility

    International Nuclear Information System (INIS)

    Feautrier, D.; Smith, D.L.

    1992-03-01

    This report describes the development and testing of a deuterium gas target intended for use at a low-energy accelerator facility to produce neutrons for basic research and various nuclear applications. The principle source reaction is H-2(d,n)He-3. It produces a nearly mono-energetic group of neutrons. However, a lower-energy continuum neutron spectrum is produced by the H-2(d;n,p)H-2 reaction and also by deuterons which strike various components in the target assembly. The present target is designed to achieve the following objectives: (1) minimize unwanted background neutron production from the target assembly, (2) provide a relatively low level of residual long-term activity within the target components, (3) have the capacity to dissipate up to 150 watts of beam power with good target longevity, and (4) possess a relatively modest target mass in order to minimize neutron scattering from the target components. The basic physical principles that have to be considered in designing an accelerator target are discussed and the major engineering features of this particular target design are outlined. The results of initial performance tests on this target are documented and some conclusions concerning the viability of the target design are presented

  14. HE3 outgassing from four working palladium and uranium beds

    International Nuclear Information System (INIS)

    Souers, P. C.; Coronado, P. R.; Fearon, F. M.; Garza, R. G.; Shaw , J. F.; Stump, R. K.; Tsugawa, R. T.

    1988-01-01

    The He 3 output from two palladium and two uranium beds storing T 2 and D-T was studied as a function of time. Three of the beds were started new and watched for a year; the fourth bed was twelve years old. All four were beds used in routine tritium handling. Initial stoichiometries were PdT/sub 0.3/ and UT/sub 0.7/ so that both operated at similar 1 to 130 kPa pressures. The He 3 from palladium ranged from the 0.002 mo1% lower level of sensitivity to 0.01% for PdT 2 at one year of age. The UT system showed 0.1% He 3 at 4 to 62 days and 0.1 to 10% at longer times, with the first cuts being high in He 3 . The palladium bed with 95 to 97% pure T 2 enriches the output to as high as 97 to 99%. 9 refs., 1 fig., 2 tabs

  15. Contribution to construction and setup of a detection system for the focal plan of the BBS spectrometer. Application to study of the neutron emission decay of the resonant states populated by the reaction (4He,3He) at 42 MeV/u in nuclei 208Pb and 209Pb

    International Nuclear Information System (INIS)

    Plankl-Chabib, Elke

    1999-01-01

    In order to realize an experimental program dedicated to nuclear structure studies we have conceived and constructed at IPN Orsay a detection system for the focal plane of the magnetic spectrometer BBS, installed at the cryogenic cyclotron AGOR of the laboratory KVI (The Netherlands). Two detection units, consisting each of two localization plans of the Cathode Strip Chamber (CSC) type, measure the position and angle of particle trajectory. This information is used for the determination of the reaction parameters at the target by a backtracking procedure. The identification of the reaction products is done by the measurement of their time-of-flight and energy loss. For light ions this task is assumed by plastic scintillators, and for heavy ions by a parallel plan detector (PPAC) and an ionization chamber. This detection system is well adapted to the requirements given by the detection of a large range of ions (protons to 36 Ar at energies of several tenths of MeV/nucleon) as well as the big acceptance, the small dispersion and the aberration of the BBS. The results of the test show the good performances of the detection system. In a first experiment the focal plane detection system was coupled to the neutron multidetector EVEN in order to study the decay of resonant high spin states at high excitation energies by the ( 4 He, 3 He) reaction on 207 Pb and 208 Pb targets. The transfer spectra, inclusive and in coincidence, of the nuclei 208 Pb and 209 Pb show a striking resemblance except for an excitation energy shift which is due to the hole in the last neutron shell of 207 Pb. The resonances at l 8 and l = 9 are clearly populated, in agreement with the predictions of the Bonaccorso-Brink model. A sizeable fraction of the decay of the l = 8 resonance is direct, but at excitation energies higher than 15 MeV (in 208 Pb) the decay is mostly statistical. (author)

  16. Application of the three-body model to the reactions 6Li(3He,t 3He)3He and 6Li(3He,3He3He)3H

    International Nuclear Information System (INIS)

    Haftel, M.I.; Allas, R.G.; Beach, L.A.; Bondelid, R.O.; Petersen, E.L.; Slaus, I.; Lambert, J.M.; Treado, P.A.

    1977-01-01

    Experimental and theoretical cross sections are presented for the 6 Li( 3 He, 3 He 3 He) 3 H and 6 Li( 3 He,t 3 He) 3 He reactions for the symmetric angle pairs 20 0 -20 0 , 28.3 0 -28.3 0 , and 35 0 -35 0 . The theoretical cross sections are calculated in a three-body model where the trions (i.e., mass-3 nuclei) are treated as elementary particles with 6 Li being a 3 He- 3 H bound state. The trion-trion interaction is represented by S wave separable potentials with the breakup cross sections calculated with the tree-body Haftel-Ebenhoeh code. the Coulomb interaction is taken into account by fitting the separable potential parameters to the trion-trion scattering data and is included approximately in the breakup code. The experimental cross sections are compared with both the plane-wave impulse approximation and the three-body model predictions. The plane-wave impulse approximation predicts both the shapes and magnitudes poorly (10 to 20 times experiment). Without Coulomb corrections the three-body model gives good agreement with experiment for the shapes of the spectra with the magnitudes generally being about 40% of experiment for 6 Li( 3 He, 3 He 3 He) 3 H and about 80% for 6 Li( 3 He,t 3 He) 3 He. The Coulomb corrections improve the magnitudes predicted by the three-body model but not the shapes. It is observed that for these reactions S wave separable potentials describe the breakup data much better than they do the two-body trion-trion scattering data. This result should encourage further three-body treatment of these and similar reactions

  17. The production of He-3 and heavy ion enrichment in He-3-rich flares by electromagnetic hydrogen cyclotron waves

    Science.gov (United States)

    Temerin, M.; Roth, I.

    1992-01-01

    A new model is presented for the production of He-3 and heavy ion enrichments in He-3-rich flares using a direct single-stage mechanism. In analogy with the production of electromagnetic hydrogen cyclotron waves in earth's aurora by electron beams, it is suggested that such waves should exist in the electron acceleration region of impulsive solar flares. Both analytic and test-particle models of the effect of such waves in a nonuniform magnetic field show that these waves can selectively accelerate He-3 and heavy ions to MeV energies in a single-stage process, in contrast to other models which require a two-stage mechanism.

  18. Scattering of 30 MeV He3 from Re185

    Science.gov (United States)

    Garrett, P. E.; Phillips, A. A.; Demand, G. A.; Finlay, P.; Green, K. L.; Leach, K. G.; Schumaker, M. A.; Svensson, C. E.; Wong, J.; Hertenberger, R.; Wirth, H.-F.; Faestermann, T.; Krücken, R.; Burke, D. G.; Bettermann, L.; Braun, N.

    2009-01-01

    The scattering of 30 MeV He3 from a Re185 target has been investigated. The measured elastic scattering is in disagreement with calculations using common optical model parameter sets found in the literature. A new optical model parameter set has been determined that reproduces the data for both the elastic and the inelastic scattering channels.

  19. LANSCE target system performance

    International Nuclear Information System (INIS)

    Russell, G.J.; Gilmore, J.S.; Robinson, H.; Legate, G.L.; Bridge, A.; Sanchez, R.J.; Brewton, R.J.; Woods, R.; Hughes, H.G. III

    1989-01-01

    We measured neutron beam fluxes at LANSCE using gold foil activation techniques. We did an extensive computer simulation of the as-built LANSCE Target/Moderator/Reflector/Shield geometry. We used this mockup in a Monte Carlo calculation to predict LANSCE neutronic performance for comparison with measured results. For neutron beam fluxes at 1 eV, the ratio of measured data to calculated varies from ∼0.6-0.9. The computed 1 eV neutron leakage at the moderator surface is 3.9 x 10 10 n/eV-sr-s-μA for LANSCE high-intensity water moderators. The corresponding values for the LANSCE high-resolution water moderator and the liquid hydrogen moderator are 3.3 and 2.9 x 10 10 , respectively. LANSCE predicted moderator intensities (per proton) for a tungsten target are essentially the same as ISIS predicted moderator intensities for a depleted uranium target. The calculated LANSCE steady state unperturbed thermal (E 13 n/cm 2 -s. The unique LANSCE split-target/flux-trap-moderator system is performing exceedingly well. The system has operated without a target or moderator change for over three years at nominal proton currents of ∼25 μA of 800-MeV protons. (author)

  20. Determination of the π3He3H coupling constant

    International Nuclear Information System (INIS)

    Nichitiu, F.; Sapozhnikov, M.G.

    1977-01-01

    Despersion relations for the real part of the antisymmetric amplitude of the π +-3 He scattering have been used in order to determine the π 3 He 3 H coupling constant. The coupling constant value determined by this method is larger than the elementary pion-nucleon coupling constant, but is in good agreement with the value obtained by another method. The obtained value is f 2 sub(π 3 He 3 H) = 0.12+-0.01. Shown is the importance of using the Coulomb corrections for dispersion relation calculations because the value of π 3 He 3 H coupling constant obtained with corrected total cross sections is larger by about 0.014 than the one obtained without these corrections. The best energy ranges for future π 3 He experiments are commented

  1. Combined He3 cryostats and He3-He4 dilution refrigerators

    International Nuclear Information System (INIS)

    Kovac, L.; Balla, J.

    1974-07-01

    A modular set of equipment was designed, which consists of a 4 He Dewar vessel with a very low evaporation rate, having a pumped 4 He bath in which either a 3 He cryostat or a dilution refrigerator within removable inserts can be placed. Any of them can be simply and rapidly connected to the versatile Dewar, auxiliary 4 He-, vacuum; and 3 He- 4 He systems. Two such sets have already been completed and can be used at temperatures from 1.5K to 0.05K for thermodynamic and neutron diffraction measurements. The performance of all inserts was stable and reliable, differences between the cryostats and runs were small - nearly all within the accuracy of temperature determination. The construction of a lot of parts is identical, allowing rapid manufacture. Assembling and repairs are simple, all parts are easily accessible. (K.A.)

  2. Hard Two-Body Photodisintegration of He3

    Science.gov (United States)

    Pomerantz, I.; Ilieva, Y.; Gilman, R.; Higinbotham, D. W.; Piasetzky, E.; Strauch, S.; Adhikari, K. P.; Aghasyan, M.; Allada, K.; Amaryan, M. J.; Anefalos Pereira, S.; Anghinolfi, M.; Baghdasaryan, H.; Ball, J.; Baltzell, N. A.; Battaglieri, M.; Batourine, V.; Beck, A.; Beck, S.; Bedlinskiy, I.; Berman, B. L.; Biselli, A. S.; Boeglin, W.; Bono, J.; Bookwalter, C.; Boiarinov, S.; Briscoe, W. J.; Brooks, W. K.; Bubis, N.; Burkert, V.; Camsonne, A.; Canan, M.; Carman, D. S.; Celentano, A.; Chandavar, S.; Charles, G.; Chirapatpimol, K.; Cisbani, E.; Cole, P. L.; Contalbrigo, M.; Crede, V.; Cusanno, F.; D'Angelo, A.; Daniel, A.; Dashyan, N.; de Jager, C. W.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Dodge, G. E.; Doughty, D.; Dupre, R.; Dutta, C.; Egiyan, H.; El Alaoui, A.; El Fassi, L.; Eugenio, P.; Fedotov, G.; Fegan, S.; Fleming, J. A.; Fradi, A.; Garibaldi, F.; Geagla, O.; Gevorgyan, N.; Giovanetti, K. L.; Girod, F. X.; Glister, J.; Goetz, J. T.; Gohn, W.; Golovatch, E.; Gothe, R. W.; Griffioen, K. A.; Guegan, B.; Guidal, M.; Guo, L.; Hafidi, K.; Hakobyan, H.; Harrison, N.; Heddle, D.; Hicks, K.; Ho, D.; Holtrop, M.; Hyde, C. E.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jiang, X.; Jo, H. S.; Joo, K.; Katramatou, A. T.; Keller, D.; Khandaker, M.; Khetarpal, P.; Khrosinkova, E.; Kim, A.; Kim, W.; Klein, F. J.; Koirala, S.; Kubarovsky, A.; Kubarovsky, V.; Kuleshov, S. V.; Kvaltine, N. D.; Lee, B.; LeRose, J. J.; Lewis, S.; Lindgren, R.; Livingston, K.; Lu, H. Y.; MacGregor, I. J. D.; Mao, Y.; Martinez, D.; Mayer, M.; McCullough, E.; McKinnon, B.; Meekins, D.; Meyer, C. A.; Michaels, R.; Mineeva, T.; Mirazita, M.; Moffit, B.; Mokeev, V.; Montgomery, R. A.; Moutarde, H.; Munevar, E.; Munoz Camacho, C.; Nadel-Turonski, P.; Nasseripour, R.; Nepali, C. S.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Ostrovidov, A. I.; Pappalardo, L. L.; Paremuzyan, R.; Park, K.; Park, S.; Petratos, G. G.; Phelps, E.; Pisano, S.; Pogorelko, O.; Pozdniakov, S.; Procureur, S.; Protopopescu, D.; Puckett, A. J. R.; Qian, X.; Qiang, Y.; Ricco, G.; Rimal, D.; Ripani, M.; Ritchie, B. G.; Rodriguez, I.; Ron, G.; Rosner, G.; Rossi, P.; Sabatié, F.; Saha, A.; Saini, M. S.; Sarty, A. J.; Sawatzky, B.; Saylor, N. A.; Schott, D.; Schulte, E.; Schumacher, R. A.; Seder, E.; Seraydaryan, H.; Shneor, R.; Smith, G. D.; Sokhan, D.; Sparveris, N.; Stepanyan, S. S.; Stepanyan, S.; Stoler, P.; Subedi, R.; Sulkosky, V.; Taiuti, M.; Tang, W.; Taylor, C. E.; Tkachenko, S.; Ungaro, M.; Vernarsky, B.; Vineyard, M. F.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Wang, Y.; Watts, D. P.; Weinstein, L. B.; Weygand, D. P.; Wojtsekhowski, B.; Wood, M. H.; Yan, X.; Yao, H.; Zachariou, N.; Zhan, X.; Zhang, J.; Zhao, Z. W.; Zheng, X.; Zonta, I.

    2013-06-01

    We have measured cross sections for the γHe3→pd reaction at photon energies of 0.4-1.4 GeV and a center-of-mass angle of 90°. We observe dimensional scaling above 0.7 GeV at this center-of-mass angle. This is the first observation of dimensional scaling in the photodisintegration of a nucleus heavier than the deuteron.

  3. High-momentum response of liquid He3

    International Nuclear Information System (INIS)

    Mazzanti, F.; Polls, A.; Boronat, J.; Casulleras, J.

    2004-01-01

    A final-state-effects formalism suitable to analyze the high-momentum response of Fermi liquids is presented and used to study the dynamic structure function of liquid He 3 . The theory, developed as a natural extension of the Gersch-Rodriguez formalism, incorporates the Fermi statistics explicitly through a new additive term which depends on the semidiagonal two-body density matrix. The use of a realistic momentum distribution, calculated using the diffusion Monte Carlo method, and the inclusion of this additive correction allows for good agreement with available deep-inelastic neutron scattering data

  4. Nova target diagnostics control system

    International Nuclear Information System (INIS)

    Severyn, J.R.

    1985-01-01

    During the past year the Nova target diagnostics control system was finished and put in service. The diagnostics loft constructed to the north of the target room provides the environmental conditions required to collect reliable target diagnostic data. These improvements include equipment cooling and isolation of the power source with strict control of instrumentation grounds to eliminate data corruption due to electromagnetic pulses from the laser power-conditioning system or from target implosion effects

  5. The search for high-energy deuterons in the 3He +3He reaction

    International Nuclear Information System (INIS)

    Pigeon, R.; Slobodrian, R.J.

    1979-01-01

    High-energy deuterons have been detected from the 3 He + 3 He reaction with a system sensitive to cross-sections of 0.6 nb sr -1 . Several tests have permitted to evaluate the small contribution of spurious events. The deuterons are kenematically consistent with the reaction 3 He + 3 He→ 2 H + 4 He + e + +ν, but the measured cross-section at 20deg laboratory is too high for a weak-interaction process; (1.3 +- 0.2) nb sr -1 . It might be due to an interaction of intermediate strength causing the decay of pp pairs ( 3 He) into deuterons. Other alternatives and the implications concerning fusion processes and the production of neutrinos in the sun are discussed in the text

  6. Spallation source neutron target systems

    International Nuclear Information System (INIS)

    Russell, G.; Brown, R.; Collier, M.; Donahue, J.

    1996-01-01

    This is the final report for a two-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The project sought to design a next-generation spallation source neutron target system for the Manuel Lujan, Jr., Neutron Scattering Center (LANSCE) at Los Alamos. It has been recognized for some time that new advanced neutron sources are needed in the US if the country is to maintain a competitive position in several important scientific and technological areas. A recent DOE panel concluded that the proposed Advanced Neutron Source (a nuclear reactor at Oak Ridge National Laboratory) and a high-power pulsed spallation source are both needed in the near future. One of the most technically challenging designs for a spallation source is the target station itself and, more specifically, the target-moderator-reflector arrangement. Los Alamos has demonstrated capabilities in designing, building, and operating high-power spallation-neutron-source target stations. Most of the new design ideas proposed worldwide for target system design for the next generation pulsed spallation source have either been conceived and implemented at LANSCE or proposed by LANSCE target system designers. These concepts include split targets, flux-trap moderators, back scattering and composite moderators, and composite reflectors

  7. Development of targeted radiotherapy systems

    International Nuclear Information System (INIS)

    Ferro, Guillermina; Villarreal, Jose E.; Garcia, Laura; Tendilla, Jose I.; Paredes, Lydia; Murphy, Consuelo A.; Pedraza, Martha

    2001-01-01

    Conventional or external beam radiotherapy, has been a viable alternative for cancer treatment. Although this technique is effective, its use is limited if the patient has multiple malignant lesions (metastases). An alternative approach is based on the design of radiopharmaceuticals that, to be administered in the patient, are directed specifically toward the target cell producing a selective radiation delivery. This treatment is known as targeted radiotherapy. We have summarized and discussed some results related to our investigations on the development of targeted radiotherapy systems, including aspects of internal dosimetry

  8. Comparative measurements between a Li-6 glass and a He-3 high-pressure gas scintillator

    International Nuclear Information System (INIS)

    Priesmeyer, H.G.; Fischer, P.; Harz, U.; Soldner, B.

    1983-01-01

    The He-3 high-pressure gas scintillation neutron detector commercially available as LND 800, has been compated to a Li-6 glass scintillator type NE 912. (n,γ) pulse height discrimination capabilities and neutron detection efficiencies have been determined. The objective of these measurements was to try to improve the Kiel Fast-Chopper TOF detector system by using a gasscintillator, which could cover the neutron beam geometry and by which gamma ray background contributions could be reduced. The time response always meets the requirements of a chopper experiment, but the neutron detection efficiency of the Li-6 glasses now used had to be maintained. (orig./HP) [de

  9. Target raster system at CEBAF

    International Nuclear Information System (INIS)

    Yan, C.; Adderley, P.; Carlini, R.; Cuevas, C.; Vulcan, W.; Wines, R.

    1995-01-01

    A fast raster (FR) system consisting of two Litz cable air-core magnets (x, y) has been installed and tested in the Hall C beam line tunnel, 21 m from the cryogenic target. The system provides a maximum deflection of 0.06 mrad at a frequency range of 15-45 kHz for a 6 GeV electron beam. The FR magnets are driven by a MOSFET bipolar switching power source with a triangle current waveform, the peak-to-peak current is 40 A. (orig.)

  10. Digital signal processing for He3 proportional counter

    International Nuclear Information System (INIS)

    Zeynalov, Sh.S.; Ahmadov, Q.S.

    2010-01-01

    Full text : Data acquisition systems for nuclear spectroscopy have traditionally been based on systems with analog shaping amplifiers followed by analog-to-digital converters. Recently, however, new systems based on digital signal processing make possible to replace the analog shaping and timing circuitry the numerical algorithms to derive properties of the pulse such as its amplitude. DSP is a fully numerical analysis of the detector pulse signals and this technique demonstrates significant advantages over analog systems in some circumstances. From a mathematical point of view, one can consider the signal evolution from the detector to the ADC as a sequence of transformations that can be described by precisely defined mathematical expressions. Digital signal processing with ADCs has the possibility to utilize further information on the signal pulses from radiation detectors. In the experiment each step of the signal generation in the 3He filled proportional counter was described using digital signal processing techniques (DSP). The electronic system has consisted of a detector, a preamplifier and a digital oscilloscope. The pulses from the detector were digitized using a digital storage oscilloscope. This oscilloscope allowed signal digitization with accuracy of 8 bit (256 levels) and with frequency of up to 5 * 10 8 samples/s. As a neutron source was used Cf-252. To obtain detector output current pulse I(t) created by the motions of the ions/electrons pairs was written an algorithm which can easily be programmed using modern computer programming languages.

  11. Study of the He3 breakup reaction and the triton production spectra at 283 MeV

    International Nuclear Information System (INIS)

    Hussain Obid, R.

    1988-01-01

    The breakup of He3 ions at 94MeV/nucleon was studied in inclusive experiments on nuclei ranging from C12 to Pb208, and in coincidence experiments (γd) and (γt) on an A127 target. The inclusive spectra of protons and deuterons show an important contribution of the He3 breakup reaction to the reaction cross section (80%). Analysis of the dependence as a function of A confirms a peripheral mechanism. The coincidence experiment gives a proportion of inelastic breakup in the inclusive cross section of 40 %. Examination of triton spectra reveals that at 94 MeV the dominant reaction is not breakup transfer as at lower energies, but charge exchange. The spectra peak at energies of 20MeV, compatible with the excitation of a mixture of L=1 and L=2 states. The variation of the cross section following an A 1/3 law indicates a peripheral mechanism for the (He3,t) reaction too. The (γ-t) coincidence reaction showing residual nucleus production near the target nucleus reinforces this result [fr

  12. Digital signal processing for He3 proportional counter

    International Nuclear Information System (INIS)

    Ahmadov, Q.S.; Institute of Radiation Problems, ANAS, Baku

    2011-01-01

    Full text: Data acquisition systems for nuclear spectroscopy have traditionally been based on systems with analog shaping amplifiers followed by analog-to-digital converters. Recently, however, new systems based on digital signal processing allow us to replace the analog shaping and timing circuitry the numerical algorithms to derive properties of the pulse such as its amplitude. DSP is a fully numerical analysis of the detector pulse signals and this technique demonstrates significant advantages over analog systems in some circumstances. From a mathematical point of view, one can consider the signal evolution from the detector to the ADC as a sequence of transformations that can be described by precisely defined mathematical expressions.Digital signal processing with ADCs has the possibility to utilize further information on the signal pulses from radiation detectors [1] [2]. In the experiment each step of the signal generation in the 3He filled proportional counter was described using digital signal processing techniques (DSP). The electronic system has consisted of a detector, a preamplifier and a digital oscilloscope. The pulses from the detector were digitized using a OTSZS-02 (250USB)-4 digital storage oscilloscope from ZAO R UDNEV-SHILYAYEV . This oscilloscope allowed signal digitization with accuracy of 8 bit(256 levels) and with frequency of up to 5.10''8 samples/s. As a neutron source was used Cf-252.To obtain detector output current pulse I(t) created by the motions of the ions/electrons pairs was written an algorithm which can easily be programmed using modern computer programming languages

  13. Production of e(+)e(-) pairs in proton-deuteron capture to He-3

    NARCIS (Netherlands)

    Korchin, AY; Van Neck, D; Waroquier, M; Scholten, O; Dieperink, AEL

    1998-01-01

    The process p + d He-3 + gamma * at intermediate energies is described using a covariant and gauge-invariant model, and a realistic pd(3)He vertex, Both photodisintegration of He-3 and proton-deuteron capture with production of e(+)e(-) pairs are studied, and results for cross sections and response

  14. The πHe3H3 coupling constant estimation using the Chew-Low equation

    International Nuclear Information System (INIS)

    Mach, R.; Nichitiu, F.

    1976-01-01

    A semi-phenomenological analysis of the π +- He 3 elastic scattering at 98, 120, 135 and 156 Mev is presented. An information of the πHe 3 H 3 coupling constant using the Chew-Low plot for the P 33 partial wave is obtained. (author)

  15. The πHe3H3 coupling constant estimation using the Chew-Low equation

    International Nuclear Information System (INIS)

    Mach, R.; Nichitiu, F.

    1975-01-01

    In this paper it is presented an estimation of the πHe 3 H 3 coupling constant using the Chew-Low equation and a semi-phenomenological analysis of the π -+ He 3 elastic differential cross sections at 98, 120, 135 and 156 MeV

  16. Spin Superfluidity and Magnone BEC in He-3

    Science.gov (United States)

    Bunkov, Yury

    2011-03-01

    The spin superfluidity -- superfluidity in the magnetic subsystem of a condensed matter -- is manifested as the spontaneous phase-coherent precession of spins first discovered in 1984 in 3 He-B. This superfluid current of spins -- spin supercurrent -- is one more representative of superfluid currents known or discussed in other systems, such as the superfluid current of mass and atoms in superfluid 4 He; superfluid current of electric charge in superconductors; superfluid current of hypercharge in Standard Model of particle physics; superfluid baryonic current and current of chiral charge in quark matter; etc. Spin superfluidity can be described in terms of the Bose condensation of spin waves -- magnons. We discuss different states of magnon superfluidity with different types of spin-orbit coupling: in bulk 3 He-B; magnetically traped `` Q -balls'' at very low temperatures; in 3 He-A and 3 He-B immerged in deformed aerogel; etc. Some effects in normal 3 He can also be treated as a magnetic BEC of fermi liquid. A very similar phenomena can be observed also in a magnetic systems with dinamical frequensy shift, like MnC03 . We will discuss the main experimental signatures of magnons superfluidity: (i) spin supercurrent, which transports the magnetization on a macroscopic distance more than 1 cm long; (ii) spin current Josephson effect which shows interference between two condensates; (iii) spin current vortex -- a topological defect which is an analog of a quantized vortex in superfluids, of an Abrikosov vortex in superconductors, and cosmic strings in relativistic theories; (iv) Goldstone modes related to the broken U (1) symmetry -- phonons in the spin-superfluid magnon gas; etc. For recent review see Yu. M. Bunkov and G. E. Volovik J. Phys. Cond. Matter. 22, 164210 (2010) This work is partly supported by the Ministry of Education and Science of the Russian Federation (contract N 02.740.11.5217).

  17. A rotating target wheel system for gammasphere

    International Nuclear Information System (INIS)

    Greene, J. P.

    1999-01-01

    A description is given for a low-mass, rotating target wheel to be used within the Gammasphere target chamber. This system was developed for experiments employing high beam currents in order to extend lifetimes of targets using low-melting point target material. The design is based on a previously successful implementation of rotating target wheels for the Argonne Positron Experiment (APEX) as well as the Fragment Mass Analyser (FMA) at ATLAS (Argonne Tandem Linac Accelerator System). A brief history of these rotating target wheel systems is given as well as a discussion on target preparation and performance

  18. Simulations of effusion from ISOL target/ion source systems

    International Nuclear Information System (INIS)

    Mustapha, B.; Nolen, J.A.

    2004-01-01

    Monte Carlo simulations of the low- and high-conductivity Target/Ion Source systems used at Oak Ridge National Laboratory for effusion measurements are performed. Comparisons with the corresponding experimental data for the different geometries are presented and discussed. Independent checks of the simulation using data for simple geometries and using the conductance approach well known in vacuum technology are performed. A simulation-based comparison between the low- and high-conductivity systems is also presented

  19. He 3 -Xe 129 Comagnetometery using Rb 87 Detection and Decoupling

    Science.gov (United States)

    Limes, M. E.; Sheng, D.; Romalis, M. V.

    2018-01-01

    We describe a He 3 -Xe 129 comagnetometer using Rb 87 atoms for noble-gas spin polarization and detection. We use a train of Rb 87 π pulses and σ+/σ- optical pumping to realize a finite-field Rb magnetometer with suppression of spin-exchange relaxation. We suppress frequency shifts from polarized Rb by measuring the He 3 and Xe 129 spin precession frequencies in the dark, while applying π pulses along two directions to depolarize Rb atoms. The plane of the π pulses is rotated to suppress the Bloch-Siegert shifts for the nuclear spins. We measure the ratio of He 3 to Xe 129 spin precession frequencies with sufficient absolute accuracy to resolve Earth's rotation without changing the orientation of the comagnetometer. A frequency resolution of 7 nHz is achieved after integration for 8 h without evidence of significant drift.

  20. Progress in ISOL target-ion source systems

    Energy Technology Data Exchange (ETDEWEB)

    Koester, U. [Institut Laue Langevin, 6 Rue Jules Horowitz, F-38042 Grenoble Cedex 9 (France); ISOLDE, CERN, CH-1211 Geneve 23 (Switzerland)], E-mail: koester@ill.fr; Arndt, O. [HGF VISTARS and Institut fuer Kernchemie, Johannes-Gutenberg Universitaet Mainz, D-55128 Mainz (Germany); Bouquerel, E.; Fedoseyev, V.N. [ISOLDE, CERN, CH-1211 Geneve 23 (Switzerland); Franberg, H. [ISOLDE, CERN, CH-1211 Geneve 23 (Switzerland); Laboratory for Radio- and Environmental Chemistry, Paul Scherrer Institut, CH-5232 Villigen PSI (Switzerland); Joinet, A. [ISOLDE, CERN, CH-1211 Geneve 23 (Switzerland); Centre d' Etude Spatiale des Rayonnements, 9 Av. du Colonel Roche, F-31028 Toulouse Cedex 4 (France); Jost, C. [HGF VISTARS and Institut fuer Kernchemie, Johannes-Gutenberg Universitaet Mainz, D-55128 Mainz (Germany); Kerkines, I.S.K. [Laboratory of Physical Chemistry, National and Kapodistrian University of Athens, Department of Chemistry, Zografou 157 71, GR (Greece); Cherry L. Emerson Center for Scientific Computation and Department of Chemistry, Emory University, Atlanta, GA 30322 (United States); Kirchner, R. [Gesellschaft fuer Schwerionenforschung, Planckstr. 1, D-64291 Darmstadt (Germany)

    2008-10-15

    The heart of every ISOL (isotope separation on-line) facility is its target and ion source system. Its efficiency, selectivity and rapidity is decisive for the production of intense and pure ion beams of short-lived isotopes. Recent progress in ISOL target and ion source technology is discussed at the examples of radioactive ion beams of exotic zinc and tin isotopes that were purified by isothermal chromatography and molecular sideband separation respectively. An outlook is given to which other elements these purification methods are applicable.

  1. Progress in ISOL target-ion source systems

    International Nuclear Information System (INIS)

    Koester, U.; Arndt, O.; Bouquerel, E.; Fedoseyev, V.N.; Franberg, H.; Joinet, A.; Jost, C.; Kerkines, I.S.K.; Kirchner, R.

    2008-01-01

    The heart of every ISOL (isotope separation on-line) facility is its target and ion source system. Its efficiency, selectivity and rapidity is decisive for the production of intense and pure ion beams of short-lived isotopes. Recent progress in ISOL target and ion source technology is discussed at the examples of radioactive ion beams of exotic zinc and tin isotopes that were purified by isothermal chromatography and molecular sideband separation respectively. An outlook is given to which other elements these purification methods are applicable.

  2. A new transfer system for solid targets

    Science.gov (United States)

    Klug, J.; Buckley, K. R.; Zeisler, S. K.; Dodd, M.; Tsao, P.; Hoehr, C.; Economou, C.; Corsaut, J.; Appiah, J. P.; Kovacs, M. S.; Valliant, J. F.; Benard, F.; Ruth, T. J.; Schaffer, P.

    2012-12-01

    As part of a collaborative research project funded by Natural Resources Canada, TRIUMF has designed and manufactured solid target and solid target processing systems for the production of technetium-99m using small medical cyclotrons. The system described herein is capable of transporting the target from a hotcell, where the target is loaded and processed, to the cyclotron and back again. The versatility of the transfer system was demonstrated through the successful installation and operation on the ACSI TR 19 at the BC Cancer Agency, the GE PETtrace cyclotrons at Lawson Health Research (LHRI) and the Centre for Probe Development and Commercialization (CDPC).

  3. Targeting the endocannabinoid system : future therapeutic strategies

    NARCIS (Netherlands)

    Aizpurua-Olaizola, Oier; Elezgarai, Izaskun; Rico-Barrio, Irantzu; Zarandona, Iratxe; Etxebarria, Nestor; Usobiaga, Aresatz

    2017-01-01

    The endocannabinoid system (ECS) is involved in many physiological regulation pathways in the human body, which makes this system the target of many drugs and therapies. In this review, we highlight the latest studies regarding the role of the ECS and the drugs that target it, with a particular

  4. I sup(123) target transfer system

    International Nuclear Information System (INIS)

    Almeida, G.L. de; Rautenberg, F.A.

    1986-01-01

    The construction of target transfer system using a robot into hot cell of IEN cyclotron (Brazilian-CNEN) for sup(123)I production is presented. The system operation is described, and the advantages are shown. (M.C.K.)

  5. 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...

  6. Application of the stabilization method to the molecular states of LiHe3+: Energies and radial couplings

    International Nuclear Information System (INIS)

    Macias, A.; Mendizabal, R.; Pelayo, F.; Riera, A.; Yaez, M.

    1986-01-01

    We have used the stabilization method to perform calculations on autoionizing states of the LiHe 3+ system which are involved in Li 3+ +He collisions. The molecular energies and radial couplings are calculated with use of programs developed at our laboratory. For both short and large internuclear distances, the stabilization treatment is complemented by block-diagonalization techniques. Our calculations allow us to draw conclusions on the conditions under which these methods can be used to calculate energy positions and radial couplings for states that lie in an ionization continuum

  7. He-3, Pierre Morel and Me—Early Work on Anisotropic Superfluidity

    Science.gov (United States)

    Anderson, Philip W.

    2011-08-01

    The idea that there are alternative, anisotropic solutions of BCS equations, which might apply to He-3, surfaced independently in at least three places, one of which was Pierre Morel's thesis project (for the ENS, under me at Bell Labs) I was skeptical of quantitative estimates of transition temperatures and instead focused, with Pierre, on conceptual and experimental properties of such states.

  8. Minority and mode conversion heating in (He-3)-H JET plasmas

    NARCIS (Netherlands)

    Van Eester, D.; Lerche, E.; Johnson, T. J.; Hellsten, T.; Ongena, J.; Mayoral, M. L.; Frigione, D.; Sozzi, C.; Calabro, G.; Lennholm, M.; Beaumont, P.; Blackman, T.; Brennan, D.; Brett, A.; Cecconello, M.; Coffey, I.; Coyne, A.; Crombe, K.; Czarnecka, A.; Felton, R.; Johnson, M. G.; Giroud, C.; Gorini, G.; Hellesen, C.; Jacquet, P.; Kazakov, Y.; Kiptily, V.; Knipe, S.; Krasilnikov, A.; Lin, Y.; Maslov, M.; Monakhov, I.; Noble, C.; Nocente, M.; Pangioni, L.; Proverbio, I.; Stamp, M.; Studholme, W.; Tardocchi, M.; Versloot, T. W.; Vdovin, V.; Whitehurst, A.; Wooldridge, E.; Zoita, V.

    2012-01-01

    Radio frequency (RF) heating experiments have recently been conducted in JET (He-3)-H plasmas. This type of plasmas will be used in ITER's non-activated operation phase. Whereas a companion paper in this same PPCF issue will discuss the RF heating scenario's at half the nominal magnetic

  9. Magnetic confinement system using charged ammonia targets

    International Nuclear Information System (INIS)

    Porter, G.D.; Bogdanoff, A.

    1979-01-01

    A system is described for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory

  10. Shiva and Argus target diagnostics vacuum systems

    International Nuclear Information System (INIS)

    Glaros, S.S.; Mayo, S.E.; Campbell, D.; Holeman, D.

    1978-09-01

    The normal operation of LLL's Argus and Shiva laser irradiation facilities demand a main vacuum system for the target chamber and a separate local vacuum system for each of the larger appendage dianostics. This paper will describe the Argus and Shiva main vacuum systems, their respective auxiliary vacuum systems and the individual diagnostics with their respective special vacuum requirements and subsequent vacuum systems. Our latest approach to automatic computer-controlled vacuum systems will be presented

  11. Jefferson Lab E89-044 experiment: study of the quasi-elastic He3(e,e'p)d reaction in parallel kinematics

    International Nuclear Information System (INIS)

    Penel-Nottaris, E.

    2004-07-01

    The Jefferson Lab Hall A E89-044 experiment has measured the He 3 (e,e'p) reaction cross-sections. The extraction of the longitudinal and transverse response functions for the two-body break-up He 3 (e,e'p)d reaction in parallel kinematics allows the study of the bound proton electromagnetic properties inside the He 3 nucleus and the involved nuclear mechanisms beyond plane waves approximations, for missing momenta of 0 and +- 300 MeV/c and transferred momenta from 0.8 to 4.1 GeV 2 . Preliminary cross-sections have been obtained after calibration of the experimental setup by fitting theoretical models averaged over the experimental phase-space using a Monte-Carlo simulation. The 8% systematic error on cross-sections is linked mainly to the absolute normalization of the target density: the elastic scattering data analysis will allow to reduce this error. The preliminary results show some disagreement with theoretical predictions for the forward angles kinematics around 0 MeV/c missing momenta and sensitivity to final state interactions and He 3 waves functions for missing momenta of 300 MeV/c. The longitudinal and transverse separation should constraint theoretical models more strongly. (author)

  12. A windowless frozen hydrogen target system

    International Nuclear Information System (INIS)

    Knowles, P.E.; Beer, G.A.; Beveridge, J.L.

    1995-06-01

    A cryogenic target system has been constructed in which gaseous mixtures of all three hydrogen isotopes have been frozen onto a thin, 65 mm diameter gold foil. The foil is cooled to 3 K while inside a 70 K radiation shield, all of which is mounted in a vacuum system maintained at 10 -9 torr. Stable multi-layer hydrogen targets of known uniformity and thickness have been maintained for required measurement times of up to several days. To date, hundreds of targets have been successfully used in muon-catalyzed fusion experiments at TRIUMF. (author). 12 refs., 6 figs

  13. Targeting engineering synchronization in chaotic systems

    Science.gov (United States)

    Bhowmick, Sourav K.; Ghosh, Dibakar

    2016-07-01

    A method of targeting engineering synchronization states in two identical and mismatch chaotic systems is explained in detail. The method is proposed using linear feedback controller coupling for engineering synchronization such as mixed synchronization, linear and nonlinear generalized synchronization and targeting fixed point. The general form of coupling design to target any desire synchronization state under unidirectional coupling with the help of Lyapunov function stability theory is derived analytically. A scaling factor is introduced in the coupling definition to smooth control without any loss of synchrony. Numerical results are done on two mismatch Lorenz systems and two identical Sprott oscillators.

  14. The cross section of 3He(3He,2p)4He measured at solar energies

    International Nuclear Information System (INIS)

    Junker, M.; Arpesella, C.; Bellotti, E.; Broggini, C.; Corvisiero, P.; D'Alessandro, A.; Fiorentini, G.; Fubini, A.; Gervino, G.; Greife, U.; Gustavino, C.; Lambert, J.; Prati, P.; Rodney, W.S.; Rolfs, C.; Trautvetter, H.P.; Zavatarelli, S.

    1999-01-01

    We report on the status of the 3 He( 3 He,2p) 4 He experiment at the underground accelerator facility LUNA (Gran Sasso). The lowest projectile energies for the measured cross section correspond already to energies below the center of the solar Gamow peak (E 0 =22 keV). The data provide no evidence for the existence of a hypothetical resonance in the energy range investigated. Although no extrapolation is needed anymore (except for energies at the low-energy tail of the Gamow peak), the data must be corrected for the effects of electron screening, clearly observed the first time for the 3 He( 3 He,2p) 4 He reaction. The effects are however larger than expected and not understood, leading presently to the largest uncertainty on the quoted S(0) value for bare nuclides (= 5.40 MeVb)

  15. 12C(3He,3He n)11C cross section at 910 MeV

    International Nuclear Information System (INIS)

    Aslanides, E.; Fassnacht, P.; Dellacasa, G.; Gallio, M.; Tuyn, J.W.N.

    1981-01-01

    The 12 C( 3 He, 3 He n) 11 C cross section at 910 MeV was measured by using a Ge(Li) gamma spectrometer to determine the disintegration rate and measuring the incident flux by means of a scintillator telescope. Cross sections for the production of 7 Be in C and Al and for the production of 24 Na in Al are then determined using the measured cross section as a monitor

  16. Energy dependence of the 3He(3He,π+)6Li reaction

    International Nuclear Information System (INIS)

    Le Bornec, Y.; Hibou, F.; Bimbot, L.; Hennino, T.; Jourdain, J.C.; Reide, F.; Tatischeff, B.; Willis, N.; Aslanides, E.; Bergdolt, G.; Fassnacht, P.; Racca, C.; Boudard, A.; Bruge, G.; Lugol, J.C.

    1983-01-01

    The 3 He( 3 He, π + ) 6 Li reaction has been studied as a function of energy using the 3 He beam at SATURNE. Cross sections for the 6 Li ground state (1 + ) and 2.18 MeV (3 + ) levels have been obtained at 350, 420, 500 and 600 MeV incident energies at angles THETAsub(π)(lab)=15 0 and 40 0 . These results are compared with two theoretical predictions. (orig.)

  17. Interactions of 29 MeV. He3 particles with light nuclei

    International Nuclear Information System (INIS)

    de la Rubia Pacheco, J.

    1964-01-01

    The interactions of 29 MeV He 3 particles with 32 S , 19 F and 12 C , irradiated in the Nuffield cyclotron (Birmingham University) have been studied using the nuclear emulsion technique. The first excitation levels of 12 C and 32 S have been obtained and the pick-up reaction 12 C (3 H e, 4 H e) 11 C has been studied and used to calculate its Q-values and the first levels of 1 C . (Author) 24 refs

  18. He-3 NMR: from free gas to its encapsulation in fullerene

    Czech Academy of Sciences Publication Activity Database

    Kupka, T.; Stachów, M.; Stobinski, L.; Kaminský, Jakub

    2013-01-01

    Roč. 51, č. 8 (2013), s. 463-468 ISSN 0749-1581 R&D Projects: GA ČR GAP208/11/0105 Grant - others:AV ČR(CZ) M200551205 Institutional support: RVO:61388963 Keywords : He-3 NMR * GIAO * molecular modeling * ab initio * fullerene * SWCNT Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.559, year: 2013

  19. Three-critical phenomena in the He3-He4 mixture

    International Nuclear Information System (INIS)

    Carvalho Filho, C.A.A. de.

    1976-07-01

    A review of the phenomenology of tricritical behaviour in He 3 -He 4 mixtures is made. Starting from a model proposed by Blume, Emery and Griffiths the tricritical transition is investigated by means of the Renormalization Group making use of the Callan-Symanzik equation and usual perturbative methods of Relativistic Quantum Field Theory. Mean-field tricritical exponents and logarithmic corrections are found in a sup(n) unified context. The structure of scaling laws is also studied. (author) [pt

  20. Dimensional crossover of effective orbital dynamics in polar distorted He 3 -A : Transitions to antispacetime

    Science.gov (United States)

    Nissinen, J.; Volovik, G. E.

    2018-01-01

    Topologically protected superfluid phases of He 3 allow one to simulate many important aspects of relativistic quantum field theories and quantum gravity in condensed matter. Here we discuss a topological Lifshitz transition of the effective quantum vacuum in which the determinant of the tetrad field changes sign through a crossing to a vacuum state with a degenerate fermionic metric. Such a transition is realized in polar distorted superfluid He 3 -A in terms of the effective tetrad fields emerging in the vicinity of the superfluid gap nodes: the tetrads of the Weyl points in the chiral A-phase of He 3 and the degenerate tetrad in the vicinity of a Dirac nodal line in the polar phase of He 3 . The continuous phase transition from the A -phase to the polar phase, i.e., the transition from the Weyl nodes to the Dirac nodal line and back, allows one to follow the behavior of the fermionic and bosonic effective actions when the sign of the tetrad determinant changes, and the effective chiral spacetime transforms to antichiral "anti-spacetime." This condensed matter realization demonstrates that while the original fermionic action is analytic across the transition, the effective action for the orbital degrees of freedom (pseudo-EM) fields and gravity have nonanalytic behavior. In particular, the action for the pseudo-EM field in the vacuum with Weyl fermions (A-phase) contains the modulus of the tetrad determinant. In the vacuum with the degenerate metric (polar phase) the nodal line is effectively a family of 2 +1 d Dirac fermion patches, which leads to a non-analytic (B2-E2)3/4 QED action in the vicinity of the Dirac line.

  1. Evolution of nuclear weapon-produced tritium and its decay product He-3 in the Mediterranean Sea, 1952-2011

    Energy Technology Data Exchange (ETDEWEB)

    Roether, Wolfgang [IUP Univ. Bremen (Germany)

    2015-07-01

    After 1952, tritium in the Mediterranean Sea (Med) rose 100-fold up to a 30 TU peak in 1965 (1 TU = [H-3/H] . 10{sup 18}) and thereafter declined to about 1 TU in 2011. This resulted in a strong supply of its stable daughter He-3, concentrated in the 1960s. Terrigenic He being low in He-3 due to a predominantly crustal origin allowed precise determination of the tritiugenic He-3 (± 0.7% in delta He-3). The highest He-3 was found off the Tyrrhenian Sea in 1983 (delta He-3 ∝ 16%). The principle input into the subsurface waters occurs in the Eastern Med by way of the Levantine Intermediate Water (LIW), which moves as a high-salinity core westward toward the Strait of Gibraltar. The observations demonstrate strong longitudinal flow dispersion. As tritium-He-3 ages are biased toward times of strong input, one finds an age increase with calendar year of observation, attributed to fast flow contributions showing up first. A realistic estimate for transfer from the LIW source up to the Western Med is 22 years. Especially in the East, He-3 lately decreased distinctly, in response to the reduced He-3 generation.

  2. Target system materials and engineering problems

    International Nuclear Information System (INIS)

    Fischer, W.E.

    1989-01-01

    This paper discusses the common problems of target design. As a model for the discussion, the author considers a spallation source which is fed by a high power proton beam of the order of one megawatt. The materials used for the target station and particularly for the spallation target itself depend on whether the source is built for pulsed, modulated or continuous operation. The difference of materials used is mainly determined by the neutronics considerations. Depending on the choice of materials for the target systems, the characters of material problems met, are of somewhat different nature. It is recognized that for each target version quite specific difficulties have to be overcome. On the other hand, there is a whole set of problems which is common to all target versions. These are: heat load in region of proton beam interactions; thermal stress and cycling; and radiation damage. It is shown that solutions to the whole package of problems up to a beam power of 0 (1MW) have been found. The whole effort concentrates onto the region of the first few centimeters of beam penetration. Two solutions have been proposed: (1) Keep the power of proton beam limited and produce neutrons elsewhere in the target. and (2) Dilute the power by moving mechanically the target and the window. 8 refs., 11 figs

  3. Coherent π- production in He3 + Li6 → π- + X at 303 MeV/N

    International Nuclear Information System (INIS)

    Hiller, B.; Pirner, H.J.; Heidelberg Univ.

    1982-01-01

    The production of pions by the He 3 nucleus is calculated in the Weizsaecker-Williams approximation. The pion cloud of the He 3 nucleus acts like a beam of pions scattering incoherently on the Li 6 nucleus. The size and energy dependence of the observed π-cross section at 0 0 degrees is in good agreement with this theoretical model. (orig.)

  4. Targeting the Thioredoxin System for Cancer Therapy.

    Science.gov (United States)

    Zhang, Junmin; Li, Xinming; Han, Xiao; Liu, Ruijuan; Fang, Jianguo

    2017-09-01

    Thioredoxin (Trx) and thioredoxin reductase (TrxR) are essential components of the Trx system which plays pivotal roles in regulating multiple cellular redox signaling pathways. In recent years TrxR/Trx have been increasingly recognized as an important modulator of tumor development, and hence targeting TrxR/Trx is a promising strategy for cancer treatment. In this review we first discuss the structural details of TrxR, the functions of the Trx system, and the rational of targeting TrxR/Trx for cancer treatment. We also highlight small-molecule TrxR/Trx inhibitors that have potential anticancer activity and review their mechanisms of action. Finally, we examine the challenges of developing TrxR/Trx inhibitors as anticancer agents and perspectives for selectively targeting TrxR/Trx. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Lowest vibrational states of 4He3He+: Non-Born-Oppenheimer calculations

    International Nuclear Information System (INIS)

    Stanke, Monika; Bubin, Sergiy; Kedziera, Dariusz; Molski, Marcin; Adamowicz, Ludwik

    2007-01-01

    Very accurate quantum mechanical calculations of the first five vibrational states of the 4 He 3 He + molecular ion are reported. The calculations have been performed explicitly including the coupling of the electronic and nuclear motions [i.e., without assuming the Born-Oppenheimer (BO) approximation]. The nonrelativistic non-BO wave functions were used to calculate the α 2 relativistic mass velocity, Darwin, and spin-spin interaction corrections. For the lowest vibrational transition, whose experimental energy is established with high precision, the calculated and the experimental results differ by only 0.16 cm -1

  6. Recent Advances in Aptamers Targeting Immune System.

    Science.gov (United States)

    Hu, Piao-Ping

    2017-02-01

    The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.

  7. Measurement of Double-Polarization Asymmetries in the Quasielastic He3→(e → ,e'd ) Process

    Science.gov (United States)

    Mihovilovič, M.; Jin, G.; Long, E.; Zhang, Y.-W.; Allada, K.; Anderson, B.; Annand, J. R. M.; Averett, T.; Boeglin, W.; Bradshaw, P.; Camsonne, A.; Canan, M.; Cates, G. D.; Chen, C.; Chen, J. P.; Chudakov, E.; De Leo, R.; Deng, X.; Deltuva, A.; Deur, A.; Dutta, C.; El Fassi, L.; Flay, D.; Frullani, S.; Garibaldi, F.; Gao, H.; Gilad, S.; Gilman, R.; Glamazdin, O.; Golak, J.; Golge, S.; Gomez, J.; Hansen, O.; Higinbotham, D. W.; Holmstrom, T.; Huang, J.; Ibrahim, H.; de Jager, C. W.; Jensen, E.; Jiang, X.; Jones, M.; Kang, H.; Katich, J.; Khanal, H. P.; Kievsky, A.; King, P.; Korsch, W.; LeRose, J.; Lindgren, R.; Lu, H.-J.; Luo, W.; Marcucci, L. E.; Markowitz, P.; Meziane, M.; Michaels, R.; Moffit, B.; Monaghan, P.; Muangma, N.; Nanda, S.; Norum, B. E.; Pan, K.; Parno, D.; Piasetzky, E.; Posik, M.; Punjabi, V.; Puckett, A. J. R.; Qian, X.; Qiang, Y.; Qui, X.; Riordan, S.; Saha, A.; Sauer, P. U.; Sawatzky, B.; Schiavilla, R.; Schoenrock, B.; Shabestari, M.; Shahinyan, A.; Širca, S.; Skibiński, R.; John, J. St.; Subedi, R.; Sulkosky, V.; Tobias, W. A.; Tireman, W.; Urciuoli, G. M.; Viviani, M.; Wang, D.; Wang, K.; Wang, Y.; Watson, J.; Wojtsekhowski, B.; Witała, H.; Ye, Z.; Zhan, X.; Zhang, Y.; Zheng, X.; Zhao, B.; Zhu, L.; Jefferson Lab Hall A Collaboration

    2014-12-01

    We present a precise measurement of double-polarization asymmetries in the He3→(e → ,e'd ) reaction. This particular process is a uniquely sensitive probe of hadron dynamics in 3He and the structure of the underlying electromagnetic currents. The measurements have been performed in and around quasielastic kinematics at Q2=0.25 (GeV /c )2 for missing momenta up to 270 MeV /c . The asymmetries are in fair agreement with the state-of-the-art calculations in terms of their functional dependencies on pm and ω , but are systematically offset. Beyond the region of the quasielastic peak, the discrepancies become even more pronounced. Thus, our measurements have been able to reveal deficiencies in the most sophisticated calculations of the three-body nuclear system, and indicate that further refinement in the treatment of their two-and/or three-body dynamics is required.

  8. Fusion blankets for catalyzed D--D and D--He3 reactors

    International Nuclear Information System (INIS)

    Fillo, J.A.; Powell, J.R.

    1977-01-01

    Blanket designs are presented for catalyzed D-D (Cat-D) and D-He 3 fusion reactors. Because of relatively low neutron wall loads and the flexibility due to non-tritium breeding, blankets potentially should operate for reactor life-times of approximately 30 years. Unscheduled replacement of failed blanket modules should be relatively rapid, due to very low residual activity, by operators working either through access ports in the shield (option 1) or directly in the plasma chamber (option 2). Cat-D blanket designs are presented for high (approximately 30%) and low (approximately 12%) β noncircular Tokamak reactors. The blankets are thick graphite screens, operating at high temperature to anneal radiation damage; the deposited neutron and gamma energy is thermally radiated along internal cavities and conducted to a bank of internal SiC coolant tubes (approximately 4 cm. ID) containing high pressure helium. In the D-He 3 Tokamak reactor design, the blanket consists of multiple layers (e.g., three) of thin (approximately 10 cm.) high strength aluminum (e.g., SAP), modular plates, cooled by organic terphynyl coolant

  9. Conceptual design study of IFMIF target system

    International Nuclear Information System (INIS)

    Kato, Y.; Nakamura, H.; Ida, M.; Maekawa, H.; Katsuta, H.; Hua, T.; Cevolani, S.

    1997-01-01

    IFMIF-CDA (International Fusion Materials Irradiation Facility - Conceptual Design Activity) had been carried out during 1995 and 1996, under the auspices of the IEA. The mission of this facility is to provide an accelerator based deuterium-lithium (D-Li) neutron source to test the candidate materials of radiation - resistant and low - activation materials up to about a full lifetime of anticipated use in fusion energy reactors. The neutrons of about 14 MeV are obtained by the stripping reaction of the deuteron of Max. 40 MeV with target lithium. Total deuteron beam current is about 250 mA and beam footprint is 20 cm x 5 cm on the free surface of lithium jet. In this report general characteristics of the target lithium system and the results of thermal and flow analysis for the target lithium jet are described. (author)

  10. A Context Dependent Automatic Target Recognition System

    Science.gov (United States)

    Kim, J. H.; Payton, D. W.; Olin, K. E.; Tseng, D. Y.

    1984-06-01

    This paper describes a new approach to automatic target recognizer (ATR) development utilizing artificial intelligent techniques. The ATR system exploits contextual information in its detection and classification processes to provide a high degree of robustness and adaptability. In the system, knowledge about domain objects and their contextual relationships is encoded in frames, separating it from low level image processing algorithms. This knowledge-based system demonstrates an improvement over the conventional statistical approach through the exploitation of diverse forms of knowledge in its decision-making process.

  11. Preparation of targets using electron gun systems

    International Nuclear Information System (INIS)

    Maier-Komor, P.

    1975-01-01

    Most targets of isotopes with very low vapor pressure can only be fabricated by vacuum deposition using an electron gun system or a heavy ion sputtering system. Heavy ion sputtering is a very new technique with many unsolved problems. Therefore it seems to be easier to work with an electron gun. Different commercially available electron guns, which are all designed for the high evaporation rates used in industry, are examined for their qualification in processing small amounts of material as used in fabrication of isotope targets. Electron backscattering and the associated efficiency of the electron beam power is strongly dependent on the atomic number Z of the evaporant and the incident angle of the electron beam on the surface of the evaporant. This dependence leads also to the undesired effects to the target layers from electrons and ions. Some precautions are necessary against the effects of the electrons and ions, which are formed in the plasma directly over the beam impact point. Beam power and beam density have to be chosen to get a constant evaporation rate and a low enough condensation rate in order not to overheat the target substrates. To evaporate some metals it may be helpful to pulse the electron beam

  12. Preliminary conceptual design of target system. Pt. 1. System configuration

    Energy Technology Data Exchange (ETDEWEB)

    Hino, Ryutaro; Haga, Katsuhiro; Kaminaga, Masanori [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment] [and others

    1997-07-01

    In the 21st century, neutron is expected to play a very important role in the fields of structural biology, nuclear physics, material science if a very high-intensity neutron source will be built because of its superior nature as an probe to investigate material structure and its function. The Japan Atomic Energy Research Institute has launched the Neutron Science Project for construction and utilization of a high-intensity spallation neutron source coupled with a proton accelerator. In the project, a neutron scattering facility is planned to be constructed in an early stage. Development of a 5MW spallation neutron source is one of the most difficult technical challenges in this project. A two-step development plan of the target was established to construct a 5MW-target station In the 1st step, a 1.5MW target will be constructed to develop 5MW target technology. The preliminary conceptual design was conducted to clarify the specifications of the target system of 1.5MW and 5MW including system layout, scale etc. This report describes (1) a design policy, (2) a layout of system consisting of the target, remote-handling devices, bio-shieldings etc., (3) specifications of components and facilities such as cooling systems for target and moderators, beam-port shutter and air conditioning system, (4) overhaul procedures by remote-handling devices, (5) safety assessment, and (6) necessary R and D items derived from the design activity. (author)

  13. Tumour targeting with systemically administered bacteria.

    LENUS (Irish Health Repository)

    Morrissey, David

    2012-01-31

    Challenges for oncology practitioners and researchers include specific treatment and detection of tumours. The ideal anti-cancer therapy would selectively eradicate tumour cells, whilst minimising side effects to normal tissue. Bacteria have emerged as biological gene vectors with natural tumour specificity, capable of homing to tumours and replicating locally to high levels when systemically administered. This property enables targeting of both the primary tumour and secondary metastases. In the case of invasive pathogenic species, this targeting strategy can be used to deliver genes intracellularly for tumour cell expression, while non-invasive species transformed with plasmids suitable for bacterial expression of heterologous genes can secrete therapeutic proteins locally within the tumour environment (cell therapy approach). Many bacterial genera have been demonstrated to localise to and replicate to high levels within tumour tissue when intravenously (IV) administered in rodent models and reporter gene tagging of bacteria has permitted real-time visualisation of this phenomenon. Live imaging of tumour colonising bacteria also presents diagnostic potential for this approach. The nature of tumour selective bacterial colonisation appears to be tumour origin- and bacterial species- independent. While originally a correlation was drawn between anaerobic bacterial colonisation and the hypoxic nature of solid tumours, it is recently becoming apparent that other elements of the unique microenvironment within solid tumours, including aberrant neovasculature and local immune suppression, may be responsible. Here, we consider the pre-clinical data supporting the use of bacteria as a tumour-targeting tool, recent advances in the area, and future work required to develop it into a beneficial clinical tool.

  14. Mercury erosion experiments for spallation target system

    International Nuclear Information System (INIS)

    Kinoshita, Hidetaka; Kaminaga, Masanori; Haga, Katsuhiro; Hino, Ryutaro

    2003-01-01

    The Japan Atomic Energy Research Institute (JAERI) and the High Energy Accelerator Research Organization (KEK) are promoting a plan to construct the spallation neutron source at the Tokai Research Establishment, JAERI, under the High-Intensity Proton Accelerator Project (J-PARC). A mercury circulation system has been designed so as to supply mercury to the target stably under the rated flow rate of 41 m 3 /hr. Then, it was necessary to confirm a mercury pump performance from the viewpoint of making the mercury circulation system feasible, and more, to investigate erosion rate under the mercury flow as well as an amount of mercury remained on the surface after drain from the viewpoints of mechanical strength relating to the lifetime and remote handling of mercury components. The mercury pump performance was tested under the mercury flow conditions by using an experimental gear pump, which had almost the same structure as a practical mercury pump to be expected in the mercury circulation system, and the erosion rates in a mercury pipeline as well as the amount of mercury remained on the surface were also investigated. The discharged flow rates of the experimental gear pump increased linearly with the rotation speed, so that the gear pump would work as the flow meter. Erosion rates obtained under the mercury velocity less than 1.6 m/s was found to be so small that decrease of pipeline wall thickness would be 390 μm after 30-year operation under the rated mercury velocity of 0.7 m/s. For the amount of remaining mercury on the pipeline, remaining rates of weight and volume were estimated at 50.7 g/m 2 and 3.74 Hg-cm 3 /m 2 , respectively. Applying these remaining rates of weight and volume to the mercury target, the remaining mercury was estimated at about 106.5 g and 7.9 cm 3 . Radioactivity of this remaining mercury volume was found to be three-order lower than that of the target casing. (author)

  15. Development of IFE target systems on the NIF

    International Nuclear Information System (INIS)

    Schultz, K.R.; Fagaly, R.L.; Bernat, T.; Meier, W.; Petzoldt, R.; Foreman, L.

    1995-01-01

    The Target Systems session of the Workshop on NIF Experiments for IFE developed a list of critical issues for inertial fusion energy (IFE) target systems, and considered the potential of the National Ignition Facility (NIF) to help in the resolution of these issues and in the development of IFE target systems. This paper describes the IFE Target System issues, categorized into target fabrication issues and target transport issues, describes potential NIF IFE target systems experiments, considers the impact of these experiments on the NIF and discusses the development required before these experiments could be done. Most target systems issues must be resolved by development in the laboratory, not in the NIF, and some must be resolved before the NIF can be successful. However, experiments done in the NIF could play a valuable role in developing target systems for IFE. These experiments should have modest impact on the basic design of the NIF, but could require several hundred dedicated, high yield shots

  16. Magnetic biosensor system to detect biological targets

    KAUST Repository

    Li, Fuquan; Gooneratne, Chinthaka Pasan; Kosel, Jü rgen

    2012-01-01

    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

  17. Investigation of the behaviour of both dead time and observed counting rates of He-3 gas filled neutron detector

    Energy Technology Data Exchange (ETDEWEB)

    Adib, M.; Eid, Y.; Abdel Kawy, A.; Maayouf, R.M.A.; Shuriet, G.M.; Hamouda, I.

    1981-01-01

    The behaviour of the dead time of He-3 detector, operating at both the proportional and the corona discharge regions, is investigated as a function of the neutron reaction rate inside the detector. The applied experimental method makes use of the fluctuations, due to the detector dead time in the observed counting rates from Poisson's distribution. In order to check the validity of the experimental method used in the present work, the dead time of BF/sub 3/ neutron detectors with different efficiencies (due to different enrichement in B-10) were determined. It is shown that the observed counting rate from the He-3 detector operating at the proportional region for neutron reaction rates ranging from 8 x 10/sup 3/ to 2.5 x 10/sup 4/ reaction/sec decreases with the increase of the neutron reaction rate. Such behaviour was not observed when operating the He-3 detector at the corona discharge region.

  18. Investigation of the behaviour of both dead time and observed counting rates of He-3 gas filled neutron detector

    International Nuclear Information System (INIS)

    Adib, M.; Eid, Y.; Abdel Kawy, A.; Maayouf, R.M.A.; Shuriet, G.M.; Hamouda, I.

    1981-01-01

    The behaviour of the dead time of He-3 detector, operating at both the proportional and the corona discharge regions, is investigated as a function of the neutron reaction rate inside the detector. The applied experimental method makes use of the fluctuations, due to the detector dead time in the observed counting rates from Poisson's distribution. In order to check the validity of the experimental method used in the present work, the dead time of BF 3 neutron detectors with different efficiencies (due to different enrichement in B-10) were determined. It is shown that the observed counting rate from the He-3 detector operating at the proportional region for neutron reaction rates ranging from 8 x 10 3 to 2.5 x 10 4 reaction/sec decreases with the increase of the neutron reaction rate. Such behaviour was not observed when operating the He-3 detector at the corona discharge region. (orig.) [de

  19. Automation in irradiating target systems for cyclotrons

    International Nuclear Information System (INIS)

    Araujo, Sumair G.; Sciani, Valdir; Almeida, Rosemeire S.

    2000-01-01

    Nowadays, two cyclotron are being operated at IPEN-CNEN/SP: one model CV-28, capable of accelerating p, d, 3 He 4 and α, with energies of 24, 14, 36 and 28 MeV, respectively, and beam currents up to 30 μA; the other one, model cyclone 30, accelerates protons with energy of 30 MeV and currents up to 350 μ A. Both have the objective of irradiating targets both for radioisotope production for use in Nuclear Medicine, such as 67 Ga, 201 Tl, 111 In, 123 I, 18 F, and general research. The development of irradiating systems completely automatized was the objective of this work, always aiming to reduce the radiation exposition dose to the workers and to increasing the reliability of use of these systems, because very high activities are expected in these processes. In the automation, a Programmable Logical Controller (PLC) was used connected to a feedback net, to manage all the variables involved in the irradiation processes. The program of the PLC was developed using Simatic Step Seven (S7), Software from Siemens, where all the steps are supervised in screens at a microcomputer. The assembling and sequence of leading were developed using the software from Unisoft, that keeps the operator informed about the work being carried out, at any time. (author)

  20. Study of Interaction of Low-Energy Antiprotons with H$^{2}$,He$^{3}$,He$^{4}$,Ne-Nuclei Using a Streamer Chamber in Magnetic Field

    CERN Multimedia

    2002-01-01

    The aim of this experiment is the systematic study of the interaction between low-energy antiprotons and the H|2,~He|3,~He|4,~Ne-nuclei using a self shunted streamer chamber in a magnetic field exposed to the antiproton beam of the LEAR facility. The properties of the self shunted streamer chamber, which allows the use of the filling gas (hydrogen, helium, neon at a pressure of l~atm) as a target, permit to carry out experiments also in the very low-energy region. \\\\ \\\\ The experimental apparatus is suitable for a large programme of measurements. We plan to measure the @*H|2 cross section and the spectator momentum distributions at @* momenta lower than 250~MeV/c, where data are lacking. It is interesting to study for the first time the @*He|3 and @*He|4 interactions measuring the cross sections and the emitted particle distributions. Among other things the knowledge of the branching ratio of the @*He|4 annihilation channels clarifies some open cosmological questions. The study of the process of nuclear absor...

  1. Use of the TFTR prototype charge exchange neutral analyzer for fast He3++ diagnostics during ICRF heating on PLT

    International Nuclear Information System (INIS)

    Medley, S.S.

    1981-07-01

    The Charge Exchange Neutral Analyzer (CENA) for TFTR is designed to measure singly charged ion species of atomic mass A = 1, 2, and 3 simultaneously with up to 75 energy channels per mass and an energy range of 0.5 3 charge exchange neutrals makes the analyzer of particular interest for recently proposed fast He 3 ++ diagnostics during ICRF heating on PLT

  2. Measurement of the fluxes of galactic cosmic ray H-2 and He-3 in 1972--1973

    International Nuclear Information System (INIS)

    Teegarden, B.J.; Vonrosenvinge, T.T.; Mcdonald, F.B.; Trainor, J.H.; Webber, W.R.

    1975-04-01

    If a nearby source of low-energy helium is present, which has traversed a relatively small amount of matter and thus has not caused the production of a significant amount of H-2 or He-3, then these abundance ratios will be suppressed, particularly at low energies. This seems to be the most likely explanation for low ratios. (Author)

  3. Precise measurement of magnetic field gradients from free spin precession signals of He-3 and Xe-129 magnetometers

    NARCIS (Netherlands)

    Allmendinger, Fabian; Blümler, Peter; Doll, Michael; Grasdijk, Oliver; Heil, Werner; Jungmann, Klaus; Karpuk, Sergej; Krause, Hans-Joachim; Offenhäuser, Andreas; Repetto, Maricel; Schmidt, Ulrich; Sobolev, Yuri; Tullney, Kathlyne; Willmann, Lorenz; Zimmer, Stefan

    2017-01-01

    We report on precise measurements of magnetic field gradients extracted from transverse relaxation rates of precessing spin samples. The experimental approach is based on the free precession of gaseous, nuclear spin polarized He-3 and (12)9Xe atoms in a spherical cell inside a magnetic guiding field

  4. 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.

  5. Nanomedicine: Drug Delivery Systems and Nanoparticle Targeting

    International Nuclear Information System (INIS)

    Youn, Hye Won; Kang, Keon Wook; Chung, Jun Key; Lee, Dong Soo

    2008-01-01

    Applications of nanotechnology in the medical field have provided the fundamentals of tremendous improvement in precise diagnosis and customized therapy. Recent advances in nanomedicine have led to establish a new concept of theragnosis, which utilizes nanomedicines as a therapeutic and diagnostic tool at the same time. The development of high affinity nanoparticles with large surface area and functional groups multiplies diagnostic and therapeutic capacities. Considering the specific conditions related to the disease of individual patient, customized therapy requires the identification of disease target at the cellular and molecular level for reducing side effects and enhancing therapeutic efficiency. Well-designed nanoparticles can minimize unnecessary exposure of cytotoxic drugs and maximize targeted localization of administrated drugs. This review will focus on major pharmaceutical nanomaterials and nanoparticles as key components of designing and surface engineering for targeted theragnostic drug development

  6. Target system neutronics study for NXGENS

    International Nuclear Information System (INIS)

    Willis, C.; Muhrer, G.

    2007-01-01

    The Materials Test Station (MTS) [E. Pitcher, G. Muhrer, H. Trellue, Neutronics Assessment of the LANSCE Materials Test Station as an Irradiation Facility for the JIMO Space Reactor, LA-CP-04-0903.], a spallation target station, planned for construction at the Los Alamos Neutron Science Center (LANSCE), will provide the opportunity to test the prototype of a long-pulse spallation source neutron scattering instrument (NXGENS). In this paper, we present the target-moderator neutronics optimization study that was performed in support of NXGENS

  7. Repetitive output laser system and method using target reflectivity

    International Nuclear Information System (INIS)

    Johnson, R.R.

    1978-01-01

    An improved laser system and method for implosion of a thermonuclear fuel pellet is described in which that portion of a laser pulse reflected by the target pellet is utilized in the laser system to initiate a succeeding target implosion, and in which the energy stored in the laser system to amplify the initial laser pulse, but not completely absorbed thereby, is used to amplify succeeding laser pulses initiated by target refγlection

  8. A beam sweeping system for the Fermilab antiproton production target

    International Nuclear Information System (INIS)

    Bieniosek, F.M.

    1993-08-01

    In the Main Injector era beam intensities high enough to damage the antiproton production target will be available. In order to continue to operate with a tightly-focused primary beam spot on the target, and thus maintain yield, it will be necessary to spread the hot spot on the target by use of a beam sweeping system. This report summarizes the requirements for such a system, and addresses the issues involved in the design of a sweeping system

  9. Detection technique of targets for missile defense system

    Science.gov (United States)

    Guo, Hua-ling; Deng, Jia-hao; Cai, Ke-rong

    2009-11-01

    Ballistic missile defense system (BMDS) is a weapon system for intercepting enemy ballistic missiles. It includes ballistic-missile warning system, target discrimination system, anti-ballistic-missile guidance systems, and command-control communication system. Infrared imaging detection and laser imaging detection are widely used in BMDS for surveillance, target detection, target tracking, and target discrimination. Based on a comprehensive review of the application of target-detection techniques in the missile defense system, including infrared focal plane arrays (IRFPA), ground-based radar detection technology, 3-dimensional imaging laser radar with a photon counting avalanche photodiode (APD) arrays and microchip laser, this paper focuses on the infrared and laser imaging detection techniques in missile defense system, as well as the trends for their future development.

  10. A Gas Target with a Tritium Gas Handling System

    Energy Technology Data Exchange (ETDEWEB)

    Holmqvist, B; Wiedling, T

    1963-12-15

    A detailed description is given of a simple tritium gas target and its tritium gas filling system, and how to put it into operation. By using the T (p,n) He reaction the gas target has been employed for production of monoenergetic fast neutrons of well defined energy and high intensity. The target has been operated successfully for a long time.

  11. Feasibility of target communities in a Dutch brook valley system

    NARCIS (Netherlands)

    Prins, AH; Bekker, RM

    As a reaction to the ongoing deterioration of nature conservation interest in The Netherlands, an offensive nature strategy was formulated in the 1990 Nature Policy Plan. In this Plan, target communities and target plant species are mentioned. For the 'Drentse A brook valley system', target

  12. Tumor target amplification: Implications for nano drug delivery systems.

    Science.gov (United States)

    Seidi, Khaled; Neubauer, Heidi A; Moriggl, Richard; Jahanban-Esfahlan, Rana; Javaheri, Tahereh

    2018-04-10

    Tumor cells overexpress surface markers which are absent from normal cells. These tumor-restricted antigenic signatures are a fundamental basis for distinguishing on-target from off-target cells for ligand-directed targeting of cancer cells. Unfortunately, tumor heterogeneity impedes the establishment of a solid expression pattern for a given target marker, leading to drastic changes in quality (availability) and quantity (number) of the target. Consequently, a subset of cancer cells remains untargeted during the course of treatment, which subsequently promotes drug-resistance and cancer relapse. Since target inefficiency is only problematic for cancer treatment and not for treatment of other pathological conditions such as viral/bacterial infections, target amplification or the generation of novel targets is key to providing eligible antigenic markers for effective targeted therapy. This review summarizes the limitations of current ligand-directed targeting strategies and provides a comprehensive overview of tumor target amplification strategies, including self-amplifying systems, dual targeting, artificial markers and peptide modification. We also discuss the therapeutic and diagnostic potential of these approaches, the underlying mechanism(s) and established methodologies, mostly in the context of different nanodelivery systems, to facilitate more effective ligand-directed cancer cell monitoring and targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. The Nuclotron internal target control and data acquisition system

    Energy Technology Data Exchange (ETDEWEB)

    Isupov, A.Yu., E-mail: isupov@moonhe.jinr.ru [Joint Institute for Nuclear Research, Dubna 141980 (Russian Federation); Krasnov, V.A.; Ladygin, V.P.; Piyadin, S.M.; Reznikov, S.G. [Joint Institute for Nuclear Research, Dubna 141980 (Russian Federation)

    2013-01-11

    The new control system of the Nuclotron (JINR, Dubna) internal target is described in both hardware and software aspects. The CAMAC hardware is based on the use of the standard CAMAC modules developed and manufactured at JINR. The internal target control and data acquisition (IntTarg CDAQ) system software is implemented using the ngdp framework under the Unix-like operating system (OS) FreeBSD to allow easy network distribution of the online data collected from internal target and accompanying detectors, as well as the internal target remote control.

  14. Monetary targeting and financial system characteristics : An empirical analysis

    NARCIS (Netherlands)

    Samarina, A..

    2012-01-01

    This paper investigates how reforms and characteristics of the financial system affect the likelihood of countries to abandon their strategy of monetary targeting. Apart from financial system characteristics, we include macroeconomic, fiscal, and institutional factors potentially associated with

  15. The NA50 segmented target and vertex recognition system

    International Nuclear Information System (INIS)

    Bellaiche, F.; Cheynis, B.; Contardo, D.; Drapier, O.; Grossiord, J.Y.; Guichard, A.; Haroutunian, R.; Jacquin, M.; Ohlsson-Malek, F.; Pizzi, J.R.

    1997-01-01

    The NA50 segmented target and vertex recognition system is described. The segmented target consists of 7 sub-targets of 1-2 mm thickness. The vertex recognition system used to determine the sub-target where an interaction has occured is based upon quartz elements which produce Cerenkov light when traversed by charged particles from the interaction. The geometrical arrangement of the quartz elements has been optimized for vertex recognition in 208 Pb-Pb collisions at 158 GeV/nucleon. A simple algorithm provides a vertex recognition efficiency of better than 85% for dimuon trigger events collected with a 1 mm sub-target set-up. A method for recognizing interactions of projectile fragments (nuclei and/or groups of nucleons) is presented. The segmented target allows a large target thickness which together with a high beam intensity (∼10 7 ions/s) enables high statistics measurements. (orig.)

  16. Vision-Based Target Finding and Inspection of a Ground Target Using a Multirotor UAV System.

    Science.gov (United States)

    Hinas, Ajmal; Roberts, Jonathan M; Gonzalez, Felipe

    2017-12-17

    In this paper, a system that uses an algorithm for target detection and navigation and a multirotor Unmanned Aerial Vehicle (UAV) for finding a ground target and inspecting it closely is presented. The system can also be used for accurate and safe delivery of payloads or spot spraying applications in site-specific crop management. A downward-looking camera attached to a multirotor is used to find the target on the ground. The UAV descends to the target and hovers above the target for a few seconds to inspect the target. A high-level decision algorithm based on an OODA (observe, orient, decide, and act) loop was developed as a solution to address the problem. Navigation of the UAV was achieved by continuously sending local position messages to the autopilot via Mavros. The proposed system performed hovering above the target in three different stages: locate, descend, and hover. The system was tested in multiple trials, in simulations and outdoor tests, from heights of 10 m to 40 m. Results show that the system is highly reliable and robust to sensor errors, drift, and external disturbance.

  17. Active Multimodal Sensor System for Target Recognition and Tracking.

    Science.gov (United States)

    Qu, Yufu; Zhang, Guirong; Zou, Zhaofan; Liu, Ziyue; Mao, Jiansen

    2017-06-28

    High accuracy target recognition and tracking systems using a single sensor or a passive multisensor set are susceptible to external interferences and exhibit environmental dependencies. These difficulties stem mainly from limitations to the available imaging frequency bands, and a general lack of coherent diversity of the available target-related data. This paper proposes an active multimodal sensor system for target recognition and tracking, consisting of a visible, an infrared, and a hyperspectral sensor. The system makes full use of its multisensor information collection abilities; furthermore, it can actively control different sensors to collect additional data, according to the needs of the real-time target recognition and tracking processes. This level of integration between hardware collection control and data processing is experimentally shown to effectively improve the accuracy and robustness of the target recognition and tracking system.

  18. Establishment of protein delivery systems targeting podocytes.

    Directory of Open Access Journals (Sweden)

    Wen Chih Chiang

    2010-07-01

    Full Text Available Podocytes are uniquely structured cells that are critical to the kidney filtration barrier. Their anatomic location on the outer side of the glomerular capillaries expose podocytes to large quantities of both plasma and urinary components and thus are reachable for drug delivery. Recent years have made clear that interference with podocyte-specific disease pathways can modulate glomerular function and influence severity and progression of glomerular disease.Here, we describe studies that show efficient transport of proteins into the mammalian cells mouse 3T3 fibroblasts and podocytes, utilizing an approach termed profection. We are using synthetic lipid structures that allow the safe packing of proteins or antibodies resulting in the subsequent delivery of protein into the cell. The uptake of lipid coated protein is facilitated by the intrinsic characteristic of cells such as podocytes to engulf particles that are physiologically retained in the extracellular matrix. Profection of the restriction enzyme MunI in 3T3 mouse fibroblasts caused an increase in DNA degradation. Moreover, purified proteins such as beta-galactosidase and the large GTPase dynamin could be profected into podocytes using two different profection reagents with the success rate of 95-100%. The delivered beta-galactosidase enzyme was properly folded and able to cleave its substrate X-gal in podocytes. Diseased podocytes are also potential recipients of protein cargo as we also delivered fluorophore labeled IgG into puromycin treated podocytes. We are currently optimizing our protocol for in vivo profection.Protein transfer is developing as an exciting tool to study and target highly differentiated cells such as podocytes.

  19. A two-cassette reporter system for assessing target gene translation and target gene product inclusion body formation

    DEFF Research Database (Denmark)

    2016-01-01

    The present invention relates to a dual cassette reporter system capable of assessing target gene translation and target gene product folding. The present invention further relates to vectors and host cells comprising the dual cassette reporter system. In addition the invention relates to the use...... of the dual cassette reporter system for assessing target gene translation and target gene product folding....

  20. System for measuring the proton polarization in a polarized target

    International Nuclear Information System (INIS)

    Karnaukhov, I.M.; Lukhanin, A.A.; Telegin, Yu.N.; Trotsenko, V.I.; Chechetenko, V.F.

    1984-01-01

    The system for measuring the proton polarization in a polarized target representing the high-sensitivity nuclear magnetic resonance (NMR) is described Q-meter with series connection and a circuit for measuring system resonance characteristic is used for NMR-absorption signal recording. Measuring coil is produced of a strip conductor in order to obtain uniform system sensitivity to polarization state in all target volume and improve signal-to-noise ratio. Polarization measuring system operates ion-line with the M-6000 computer. The total measuring error for the value of free proton polarization in target taking into account the error caused by local depolarization of working substance under irradiation by high-intense photon beam is <= 6%. Long-term application of the described system for measuring the proton polarization in the LUEh-20000 accelerator target used in the pion photoproduction experiments has demonstrated its high reliability

  1. The evaluation study of high performance gas target system

    International Nuclear Information System (INIS)

    Hur, Min Goo; Yang, Seung Dae; Kim, Sang Wook

    2008-06-01

    The object of this study is a improvement of a gas target and targetry for increasing the radioisotope production yields. The main results are as follows 1. Improvement of beam entrance of the gas target : In this work, deep hole grid was designed for improvement of beam entrance. Using FEM(Finite Elements Method) analysis, it was verified that this design is more effective than the old one. 2. Improvement of target gas loading and withdrawing system : For the targetry, Helium gas and vacuum lines was installed for evaluating the production yields. Using these lines, it was proved that the recovery yields was improved and the residual impurity was reduced. 3. Improvement of target cooling efficiency : In case of the cylindrical target, it is more effective to use short length of target cavity for the high production yields. For improving the cooling efficiency, cooling fin was suggested to the target design. It is more effective to put the cooling fins inside the target cavity for the suppressed target pressure and density reduction effect during the proton beam irradiation. In conclusion, the target with fins inside the target cavity was better for high current irradiation and mass RI production

  2. The evaluation study of high performance gas target system

    Energy Technology Data Exchange (ETDEWEB)

    Hur, Min Goo; Yang, Seung Dae; Kim, Sang Wook

    2008-06-15

    The object of this study is a improvement of a gas target and targetry for increasing the radioisotope production yields. The main results are as follows 1. Improvement of beam entrance of the gas target : In this work, deep hole grid was designed for improvement of beam entrance. Using FEM(Finite Elements Method) analysis, it was verified that this design is more effective than the old one. 2. Improvement of target gas loading and withdrawing system : For the targetry, Helium gas and vacuum lines was installed for evaluating the production yields. Using these lines, it was proved that the recovery yields was improved and the residual impurity was reduced. 3. Improvement of target cooling efficiency : In case of the cylindrical target, it is more effective to use short length of target cavity for the high production yields. For improving the cooling efficiency, cooling fin was suggested to the target design. It is more effective to put the cooling fins inside the target cavity for the suppressed target pressure and density reduction effect during the proton beam irradiation. In conclusion, the target with fins inside the target cavity was better for high current irradiation and mass RI production.

  3. Unmanned Aircraft Systems (UAS) Sensor and Targeting

    Science.gov (United States)

    2010-07-27

    Identify an uncoiled garden hose lying on the ground. 8.2 Identify specific type of truck crop being grown (e.g., tomatoes, peppers, lettuce ). 8.2... lettuce ). (NIIRS 8.2) Detect scoring of poppy bulbs. (NIIRS 8.5) Detect tubing (approximately 1-inch diameter) for drip irrigation systems. (NIIR5 8.5...trial can be presented as a time history for each axis. A sample is shown in Figures C.1-3 and C.1-4. TOP 07-1-003 27 July 2010 C-2

  4. Treat-to-target in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    van Vollenhoven, Ronald F; Mosca, Marta; Bertsias, George

    2014-01-01

    guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology...

  5. Targeting herpesvirus reliance of the chemokine system

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; Kledal, Thomas N

    2006-01-01

    the infection. However, since both virus and host exist, the organisms struggle must reach an ecological equilibrium. Among the best-studied interactions between viruses and the host immune system are those between herpesviruses and their hosts. Herpesviruses are known to devote a significant part...... of their large genomes on immuno-modulatory genes, some encoding chemokines or chemokine receptors. These genes, which may be dispensable for viral replication in vitro, are highly important for viral growth in vivo, for viral dissemination and disease progression. Indeed, all beta and gamma-herpesviruses have...... chemokine receptors seems to be their constitutive activity. The biological function of the constitutive activity is still unclear, but it has become clear that the receptors are involved in important parts of the viral lifecycle in vivo, and that the receptor signaling is involved in gamma-herpesvirus...

  6. Multiple operating system rotation environment moving target defense

    Science.gov (United States)

    Evans, Nathaniel; Thompson, Michael

    2016-03-22

    Systems and methods for providing a multiple operating system rotation environment ("MORE") moving target defense ("MTD") computing system are described. The MORE-MTD system provides enhanced computer system security through a rotation of multiple operating systems. The MORE-MTD system increases attacker uncertainty, increases the cost of attacking the system, reduces the likelihood of an attacker locating a vulnerability, and reduces the exposure time of any located vulnerability. The MORE-MTD environment is effectuated by rotation of the operating systems at a given interval. The rotating operating systems create a consistently changing attack surface for remote attackers.

  7. Quantum criticality in He3 bi-layers and heavy fermion compounds

    International Nuclear Information System (INIS)

    Benlagra, A.

    2009-11-01

    Despite intense experimental as well as theoretical efforts the understanding of physical phenomena peculiar to heavy fermion compounds remains one of the major problems in condensed matter physics; this research thesis considers the recently proposed theoretical approaches to describe the critical regime properties. This approach is based on the following idea: critical modes which are responsible for this regime are non-magnetic and are associated to the destruction of the Kondo effect between localized magnetic impurities and travelling conduction electrons at the quantum critical point. The author derives an analytic expression for the free energy within this model by using the Luttinger-Ward functional approach within the frame of the Eliashberg theory. The obtained expressions are transparently including the effect of critical fluctuations, integrated in a self-coherent way. The behaviour of different thermodynamic quantities is then deduced from these expressions. The result is compared with recent experiments on heavy fermion compounds as well as on a Helium-3 bilayer system adsorbed on graphite substrate in order to test the validity of such a model. Strengths and drawbacks of the model are outlined

  8. Development of a higher power cooling system for lithium targets.

    Science.gov (United States)

    Phoenix, B; Green, S; Scott, M C; Bennett, J R J; Edgecock, T R

    2015-12-01

    The accelerator based Boron Neutron Capture Therapy beam at the University of Birmingham is based around a solid thick lithium target cooled by heavy water. Significant upgrades to Birmingham's Dynamitron accelerator are planned prior to commencing a clinical trial. These upgrades will result in an increase in maximum achievable beam current to at least 3 mA. Various upgrades to the target cooling system to cope with this increased power have been investigated. Tests of a phase change coolant known as "binary ice" have been carried out using an induction heater to provide a comparable power input to the Dynamitron beam. The experimental data shows no improvement over chilled water in the submerged jet system, with both systems exhibiting the same heat input to target temperature relation for a given flow rate. The relationship between the cooling circuit pumping rate and the target temperature in the submerged jet system has also been tested. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Optimizing moderation of He-3 neutron detectors for shielded fission sources

    Energy Technology Data Exchange (ETDEWEB)

    Rees, Lawrence B., E-mail: Lawrence_Rees@byu.edu [Department of Physics and Astronomy, Brigham Young University, Provo, UT 84602 (United States); Czirr, J. Bart, E-mail: czirr@juno.com [Department of Physics and Astronomy, Brigham Young University, Provo, UT 84602 (United States)

    2012-11-01

    The response of a {sup 3}He neutron detector is highly dependent on the amount of moderator incorporated into the detector system. If there is too little moderation, neutrons will not react with the {sup 3}He. If there is too much moderation, neutrons will not reach the {sup 3}He. In applications for portal or border monitors where {sup 3}He detectors are used to interdict illicit importation of plutonium, the fission source is always shielded to some extent. Since the energy distribution of neutrons emitted from the source depends on the amount and type of shielding present, the optimum placement of moderating material around {sup 3}He tubes is a function of shielding. In this paper, we use Monte Carlo techniques to model the response of {sup 3}He tubes placed in polyethylene boxes for moderation. To model the shielded fission neutron source, we use a point {sup 252}Cf source placed in the center of polyethylene spheres of varying radius. Detector efficiency as a function of box geometry and shielding is explored. We find that increasing the amount of moderator behind and to the sides of the detector generally improves the detector response, but that incremental benefits are minimal if the thickness of the polyethylene moderator is greater than about 5-7 cm. The thickness of the moderator in front of the {sup 3}He tubes, however, is very important. For bare sources, about 4-5 cm of moderator is optimum, but as the shielding increases, the optimum thickness of this moderator decreases to 0.5-1 cm. Similar conclusions can be applied to polyethylene boxes employing two {sup 3}He tubes. Two-tube boxes with front moderators of non-uniform thickness may be useful for detecting neutrons over a wide energy range.

  10. A tritium target system for μCF

    International Nuclear Information System (INIS)

    Zmeskal, J.; Ackerbauer, P.; Durham, W.B.; Heard, H.C.; Neumann, W.; Bossy, H.

    1990-12-01

    An apparatus has been constructed for the safe handling of tritium as part of a series of muon-catalyzed fusion experiments. The equipment was designed to handle 100 kCi of tritium. The main parts of this system are the oil-free high vacuum and transfer system, and the quadrupole mass analyzer for a direct determination of the target content. The system was used successfully for five continuous periods of operation of over one month each. A new target system was constructed at Lawrence Livermore National Laboratory (LLNL) for ultimate use at Paul Scherrer Institute (PSI) to investigate the high temperature and high pressure region. 9 refs., 4 figs

  11. Cryogenic control system of the large COMPASS polarized target

    CERN Document Server

    Gautheron, F; Baum, G; Berglund, P; Doshita, N; Görtz, S; Gustafsson, K K; Horikawa, N; Kisselev, Yu V; Koivuniemi, J H; Kondo, K; Meyer, Werner T; Reicherz, G

    2004-01-01

    The dilution refrigerator used to cool the large COMPASS polarized target is monitored through a PC running LabVIEW trademark 6.1 under Windows 2000 trademark . About 60 parameters of the target (temperatures, pressures, flow rates) are continuously plotted and checked. They are periodically recorded in an Oracle trademark database and in a data file. An alarm for every parameter can be individually activated and optionally connected to a GSM (Global System for Mobile Communication) delivery message system. A web server receives and publishes the online status of the target with online tables and graphics on a dedicated COMPASS polarized target information web site. A Siemens programmable logic controller (PLC) powered by an uninterruptable source keeps the cryogenic system safe and stable during the long beam periods by controlling valves and interlocks. This safety feature protects the dilution refrigerator against potential damages in case of power failure.

  12. The evaluation study for gas target system in cyclotron

    International Nuclear Information System (INIS)

    Hur, Min Goo; Yang, Seung Dae; Kim, Sang Wook

    2009-06-01

    The object of this study is an improvement of a gas target and targetry for increasing the radioisotope production yields. The main results are as follows 1. Improvement of beam entrance of the gas target : In this work, the deep hole grid and the hex grid are compared for improvement of beam entrance. Using FEM analysis, it was verified that the hex grid design is more effective than the hole grid. 2. Improvement of target gas loading and withdrawing system : For the targetry, two type of mixture gas (N 2 +H 2 /N 2 +O 2 ) lines was installed for CH 4 /CO 2 production. Use the mixture gas than the He gas, it was proved that the recovery yields was improved and the residual impurity was reduced. 3. Compare the target yields : For improving the cooling efficiency, cooling fin was suggested to the target design. Also, we tested the production yield variation with impurity of the mixture gas. It is more effective to put the cooling fins inside the target cavity for the suppressed target pressure and density reduction effect during the proton beam irradiation. In conclusion, the target with fins inside the target cavity was better for high current irradiation and mass RI production

  13. The Research Progress of Targeted Drug Delivery Systems

    Science.gov (United States)

    Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

    2017-06-01

    Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

  14. IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

    Science.gov (United States)

    Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

    2017-11-01

    The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  15. Zeeman relaxation of MnH (X7Σ+) in collisions with He3: Mechanism and comparison with experiment

    Science.gov (United States)

    Turpin, F.; Stoecklin, T.; Halvick, Ph.

    2011-03-01

    We present a theoretical study of the Zeeman relaxation of the magnetically trappable lowest field seeking state of MnH (7Σ) in collisions with He3. We analyze the collisional Zeeman transition mechanism as a function of the final diatomic state and its variation as a function of an applied magnetic field. We show that as a result of this mechanism the levels with ΔMj>2 give negligible contributions to the Zeemam relaxation cross section. We also compare our results to the experimental cross sections obtained from the buffer-gas cooling and magnetic trapping of this molecule and investigate the dependence of the Zeeman relaxation cross section on the accuracy of the three-body interaction at ultralow energies.

  16. Measuring Neutron Spectrum at MIT Research Reactor Utilizing He-3 Bonner Cylinder Approach with an Unfolding Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Leder, A. [MIT; Anderson, A. J. [Chicago U., KICP; Billard, J. [Lyon, IPN; Figueroa-Feliciano, E. [Northwestern U.; Formaggio, J. A. [MIT; Hasselkus, C. [Wisconsin U., Madison; Newman, E. [MIT; Palladino, K. [Wisconsin U., Madison; Phuthi, M. [MIT; Winslow, L. [MIT; Zhang, L. [MIT

    2017-10-02

    The Ricochet experiment seeks to measure Coherent (neutral-current) Elastic Neutrino-Nucleus Scattering using dark-matter-style detectors with sub-keV thresholds placed near a neutrino source, such as the MIT (research) Reactor (MITR), which operates at 5.5 MW generating approximately 2.2e18 neutrinos/second at the core. Currently, Ricochet is characterizing the backgrounds at MITR, the main component of which comes in the form of neutrons emitted from the core simultaneous with the neutrino signal. To characterize this background, we wrapped a Bonner cylinder around a He-3 thermal neutron detector, whose data was then unfolded to produce a neutron energy spectrum across several orders of magnitude. We discuss the resulting spectrum and its implications for deploying Ricochet in the future at the MITR site as well as the feasibility of reducing this background level via the addition of polyethylene shielding around the detector setup.

  17. Maintenance Effectiveness and Target Observation System and its ERP Interface

    International Nuclear Information System (INIS)

    Soon, Han Seong; Kim, Gi Yong; Seo, Mi Ro; Jeong, Hun Jong; Choi, Kwang Hee; Hong, Sung Yull

    2005-01-01

    Maintenance effectiveness and target observation system (MENTOS) is a maintenance rule (MR) implementation software for plant personnel to collect, edit, store, and analyze all information required for the MR implementation. Potential users and the developers of MENTOS have decided that MENTOS is implemented in the ERP system of KHNP. This article describes MENTOS briefly and introduces the ERP interface of MENTOS

  18. [Research and application of microcontroller system for target controlled infusion].

    Science.gov (United States)

    Cheng, Yuke; Dou, Jianhong; Zhang, Xingan; Wang, Ruosong

    2005-08-01

    This paper presents a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extending power and easy manipulation. It has been used in the clinical anesthesia.

  19. Developing conservation targets in social-ecological systems

    Directory of Open Access Journals (Sweden)

    Phillip S. Levin

    2015-12-01

    Full Text Available The development of targets is foundational in conservation. Although progress has been made in setting targets, the diverse linkages among ecological and social components make target setting for coupled social-ecological systems extremely challenging. Developing integrated social-ecological targets is difficult because it forces policy makers to consider how management actions propagate throughout social-ecological systems, and because ultimately it is society, not scientists, that defines targets. We developed an interdisciplinary approach for identifying management targets and illustrate this approach using an example motivated by Puget Sound, USA. Our approach blends ecological modeling with empirical social science to articulate trade-offs and reveal societal preferences for different social-ecological states. The framework aims to place information in the hands of decision makers and promote discussion in the appropriate forums. Our ultimate objective is to encourage the informed participation of citizens in the development of social-ecological targets that reflect their values while also protecting key ecosystem attributes.

  20. A Secure and Privacy-Preserving Targeted Ad-System

    Science.gov (United States)

    Androulaki, Elli; Bellovin, Steven M.

    Thanks to its low product-promotion cost and its efficiency, targeted online advertising has become very popular. Unfortunately, being profile-based, online advertising methods violate consumers' privacy, which has engendered resistance to the ads. However, protecting privacy through anonymity seems to encourage click-fraud. In this paper, we define consumer's privacy and present a privacy-preserving, targeted ad system (PPOAd) which is resistant towards click fraud. Our scheme is structured to provide financial incentives to all entities involved.

  1. TARGET - NEW PAYMENT SYSTEM FOR THE EURO AREA

    Directory of Open Access Journals (Sweden)

    ELENA VIOLETA DRĂGOI

    2015-04-01

    Full Text Available At EU level, the funds transfer systems have undergone significant changes starting with the introduction of euro. The launch of the euro, the emergence of new technologies, introduction of financial innovations and the globalization have led to reorganization of funds transfer systems` infrastructure. The paper aims to offer an analysis of actual payment system for Euro area, a trans-European funds transfer system with gross settlement in real-time for payments in euro TARGET- to increase economical and operational efficiency of payments and also to reduce the risks in the electronic funds transfer system by creating efficient and secure payment systems.

  2. System for measuring of proton polarization in polarized target

    International Nuclear Information System (INIS)

    Derkach, A.Ya.; Lukhanin, A.A.; Karnaukhov, I.M.; Kuz'menko, V.S.; Telegin, Yu.N.; Trotsenko, V.I.; Chechetenko, V.F.

    1981-01-01

    Measurement system of proton polarization in the target, which uses the method of nuclear magnetic resonance is described. To record the signal of NMR-absorption a parallel Q-meter of voltage with analogous subtraction of resonance characteristics of measurement circuit is used. To obtain gradual sensitivity of the system to polarization state in the whole volume of the target the measurement coils is made of tape conductor. The analysis and mathematical modelling of Q-meter are carried out. Corrections for nonlinearity and dispersion are calculated. Key diagrams of the main electron blocks of Q-meter are presented. The system described operates on line with the M6000 computer. Total error of measurement of polarization value of free protons in the target does not exceed 6% [ru

  3. Radiation effects in IFMIF Li target diagnostic systems

    International Nuclear Information System (INIS)

    Molla, J.; Vila, R.; Shikama, T.; Horiike, H.; Simakov, S.; Ciotti, M.; Ibarra, A.

    2009-01-01

    Diagnostics for the lithium target will be crucial for the operation of IFMIF. Several parameters as the lithium temperature, target thickness or wave pattern must be monitored during operation. Radiation effects may produce malfunctioning in any of these diagnostics due to the exposure to high radiation fields. The main diagnostic systems proposed for the operation of IFMIF are reviewed in this paper from the point of view of radiation damage. The main tools for the assessment of the performance of these diagnostics are the neutronics calculations by using specialised codes and the information accumulated during the last decades on the radiation effects in functional materials, components and diagnostics for ITER. This analysis allows to conclude that the design of some of the diagnostic systems must be revised to assure the high availability required for the target system.

  4. Target isolation system, high power laser and laser peening method and system using same

    Science.gov (United States)

    Dane, C. Brent; Hackel, Lloyd A.; Harris, Fritz

    2007-11-06

    A system for applying a laser beam to work pieces, includes a laser system producing a high power output beam. Target delivery optics are arranged to deliver the output beam to a target work piece. A relay telescope having a telescope focal point is placed in the beam path between the laser system and the target delivery optics. The relay telescope relays an image between an image location near the output of the laser system and an image location near the target delivery optics. A baffle is placed at the telescope focal point between the target delivery optics and the laser system to block reflections from the target in the target delivery optics from returning to the laser system and causing damage.

  5. Target plane imaging system for the Nova laser

    International Nuclear Information System (INIS)

    Swift, C.D.; Bliss, E.S.; Jones, W.A.; Reeves, R.J.; Seppala, L.G.; Shelton, R.T.; VanArsdall, P.J.

    1985-01-01

    The Nova laser, in operation since December 1984, is capable of irradiating targets with light at 1.05 μm, 0.53 μm, and 0.35 μm. Correct alignment of these harmonic beams uses a system called a target plane imager (TPI). It is a large microscope (four meters long, weighing one thousand kilograms) that relays images from the target chamber center to a video optics module located on the outside of the chamber. Several modes of operation are possible including: near-field viewing and far-field viewing at three magnifications and three wavelengths. In addition, the entire instrument can be scanned in X,Y,Z to examine various planes near chamber center. Performance of this system and its computer controls will be described

  6. System of measurement of proton polarization in a polarized target

    Energy Technology Data Exchange (ETDEWEB)

    Karnaukov, I.M.; Chechetenko, V.F.; Lukhanin, A.A.; Telegin, Y.N.; Trotsenko, V.I.

    1985-05-01

    This paper describes a nuclear magnetic resonance spectrometer with high sensitivity. The signal of NMR absorption is recorded by a Q-meter with a series circuit and a circuit for compensation of the resonance characteristic of the measuring circuit. In order to ensure uniform sensitivity of the system to the state of polarization throughout the volume of the target and to enhance the S/N ration the measuring coil is made of a flat conductor. The polarization-measuring system works on-line with an M-6000 computer. The total error of measurement of the polarization of free protons in a target with allowance for the error due to local depolarization of free protons in a target with allowance for the error due to local depolarization of the working substance under irradiation with an intense photon beam is less than or equal to 6%.

  7. Polymer-Based Novel Lung Targeted Delivery Systems.

    Science.gov (United States)

    Elmowafy, Enas; Osman, Rihab; Ishak, Rania A H

    2017-01-01

    Due to its unique features, the respiratory tract had received great attention as a promising non-invasive route for drug administration to achieve both local and systemic effects. Efforts spent to tailor systems able to overcome the lung defence mechanisms and biological barriers are followed in this review. Aerodynamic diameter, morphology, lung deposition and drug release profiles are the main criteria describing the selected new smart lung targeted delivery systems. Novel systems such as nanoparticles, nano-embedded-in microparticles (NEM), small microparticles (MP), large porous particles (LPP), PulmospheresTM and polymeric micelles are used to passively target different areas in the respiratory tract. The most common preparation methods are outlined in the article. Special emphasis was given to the characteristics of the polymers used to fabricate the developed systems. Efforts made to prepare systems using chitosan (CS), alginate (alg), hyaluronic acid (HA), gelatin and albumin as examples of natural polymers and poly lactic-co-glycolic acid (PLGA) and poly(Ɛ-caprolactone) (PCL) as synthetic polymers were compiled. The continuous development and work in the area of lung targeting resulted in the development of engineered smart platforms with the capability to carry small drug molecules, proteins and genes to treat a variety of local and systemic diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Activity of Nanobins Targeted to the Urokinase Plasminogen Activator System

    Science.gov (United States)

    Hankins, Patrick Leon

    While innovations in nanotechnology have resulted in numerous medical advancements for the treatment of cancer, there remains an urgent unmet need for safe and efficient molecular platforms that facilitate the delivery of potent therapeutics to solid tumors. Nanoscale formulations help to overcome the poor bioavailability and systemic organ toxicity associated with many small molecule drugs. Of these nanoparticle drug delivery systems, the greatest clinical successes to date have employed simple nanoscale lipid bilayer assemblies which encase large payloads of chemotherapeutic. While the nanobin platform we have developed has seen initial success through the passive accumulation into tumors, actively targeting nanobins to tumor specific antigens has the potential to increase the therapeutic index of these nanoparticle drugs. We have identified the urokinase plasminogen activator (uPA) and its cell surface bound receptor (uPAR) as ideal targets for drug delivery due to their selective overexpression in metastatic cancers and their important role in tumor progression. From a panel of monoclonal antibodies targeted to uPA and uPAR, we have selected ATN291 and ATN658 as lead candidates for nanobin targeting based on their tumor cell binding and ability to be internalized by cells. A novel method of conjugating antibodies to liposomes was developed for our nanobin platform that preserves the high binding affinity and specificity of these antibodies. We evaluated these uPA- and uPAR-targeted nanobins in several xenograft tumor models and found that they were well-tolerated over a wide range of doses and demonstrated significantly increased antitumor efficacy over untargeted nanobins in multiple tumor types. Preliminary studies suggest that uPA-targeted nanobins are readily internalized by tumor cells, and we believe this is the mechanism for their increased antitumor effect. A method for radiolabeling nanobins with gallium-67 was developed, and preliminary SPECT

  9. Targeting the orexinergic system: Mainly but not only for sleep ...

    African Journals Online (AJOL)

    Orexin receptors belong to the big family of G protein coupled receptors (GPCRs) that constitute the main targets in the modern pharmacological approaches. Although the orexinergic system is involved in a variety of processes, treating sleep-wakefulness disorders such as narcolepsy and insomnia, remains the main ...

  10. Microcomputer-aided monitor for liquid hydrogen target system

    International Nuclear Information System (INIS)

    Kitami, T.; Watanabe, K.

    1983-03-01

    A microcomputer-aided monitor for a liquid hydrogen target system has been designed and tested. Various kinds of input data such as temperature, pressure, vacuum, etc. are scanned in a given time interval. Variation with time in any four items can be displayed on CRT and, if neccessary, printed out on a sheet of recording paper. (author)

  11. Petawatt laser and target irradiation system at LLNL

    International Nuclear Information System (INIS)

    Pennington, D.M.; Perry, M.D.; Britten, J.A.; Brown, C.G.; Herman, S.; Homer, J.; Miller, J.L.; Stuart, B.C.; Tietbohl, G.; Van Lue, J.; Yanovsky, V.

    1997-01-01

    In May, 1996, we demonstrated the production over a petawatt of peak power in the Nova/Petawatt Laser Facility, generating 620 J in ∼ 430 fs. Results of the first focused irradiance tests, and recent deployment of a novel targeting system will be presented

  12. Treat-to-target in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Mosca, Marta; Boumpas, Dimitrios T; Bruce, Ian N

    2013-01-01

    on May 8, 2012 to discuss whether a treat-to-target approach could be applied in the treatment of systemic lupus erythematosus (SLE) (T2T/SLE), define a research agenda, and establish a plan for moving forward. In the present paper, observations raised at the meeting and literature data on potential...

  13. Preferential lentiviral targeting of astrocytes in the central nervous system.

    Directory of Open Access Journals (Sweden)

    Michael Fassler

    Full Text Available The ability to visualize and genetically manipulate specific cell populations of the central nervous system (CNS is fundamental to a better understanding of brain functions at the cellular and molecular levels. Tools to selectively target cells of the CNS include molecular genetics, imaging, and use of transgenic animals. However, these approaches are technically challenging, time consuming, and difficult to control. Viral-mediated targeting of cells in the CNS can be highly beneficial for studying and treating neurodegenerative diseases. Yet, despite specific marking of numerous cell types in the CNS, in vivo selective targeting of astrocytes has not been optimized. In this study, preferential targeting of astrocytes in the CNS was demonstrated using engineered lentiviruses that were pseudotyped with a modified Sindbis envelope and displayed anti-GLAST IgG on their surfaces as an attachment moiety. Viral tropism for astrocytes was initially verified in vitro in primary mixed glia cultures. When injected into the brains of mice, lentiviruses that displayed GLAST IgG on their surface, exhibited preferential astrocyte targeting, compared to pseudotyped lentiviruses that did not incorporate any IgG or that expressed a control isotype IgG. Overall, this approach is highly flexible and can be exploited to selectively target astrocytes or other cell types of the CNS. As such, it can open a window to visualize and genetically manipulate astrocytes or other cells of the CNS as means of research and treatment.

  14. Thermal hydraulics of accelerator driven system windowless targets

    Directory of Open Access Journals (Sweden)

    Bruno ePanella

    2015-07-01

    Full Text Available The study of the fluid dynamics of the windowless spallation target of an Accelerator Driven System (ADS is presented. Several target mockup configurations have been investigated: the first one was a symmetrical target, that was made by two concentric cylinders, the other configurations are not symmetrical. In the experiments water has been used as hydraulic equivalent to lead-bismuth eutectic fluid. The experiments have been carried out at room temperature and flow rate up to 24 kg/s. The fluid velocity components have been measured by an ultrasound technique. The velocity field of the liquid within the target region either for the approximately axial-symmetrical configuration or for the not symmetrical ones as a function of the flow rate and the initial liquid level is presented. A comparison of experimental data with the prediction of the finite volume FLUENT code is also presented. Moreover the results of a 2D-3D numerical analysis that investigates the effect on the steady state thermal and flow fields due to the insertion of guide vanes in the windowless target unit of the EFIT project ADS nuclear reactor are presented, by analysing both the cold flow case (absence of power generation and the hot flow case (nominal power generation inside the target unit.

  15. Multi-Stage System for Automatic Target Recognition

    Science.gov (United States)

    Chao, Tien-Hsin; Lu, Thomas T.; Ye, David; Edens, Weston; Johnson, Oliver

    2010-01-01

    A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feedforward back-propagation neural network (NN) is then trained to classify each feature vector and to remove false positives. The system parameter optimizations process has been developed to adapt to various targets and datasets. The objective was to design an efficient computer vision system that can learn to detect multiple targets in large images with unknown backgrounds. Because the target size is small relative to the image size in this problem, there are many regions of the image that could potentially contain the target. A cursory analysis of every region can be computationally efficient, but may yield too many false positives. On the other hand, a detailed analysis of every region can yield better results, but may be computationally inefficient. The multi-stage ATR system was designed to achieve an optimal balance between accuracy and computational efficiency by incorporating both models. The detection stage first identifies potential ROIs where the target may be present by performing a fast Fourier domain OT-MACH filter-based correlation. Because threshold for this stage is chosen with the goal of detecting all true positives, a number of false positives are also detected as ROIs. The verification stage then transforms the regions of interest into feature space, and eliminates false positives using an

  16. Ex vivo investigation of magnetically targeted drug delivery system

    International Nuclear Information System (INIS)

    Yoshida, Y.; Fukui, S.; Fujimoto, S.; Mishima, F.; Takeda, S.; Izumi, Y.; Ohtani, S.; Fujitani, Y.; Nishijima, S.

    2007-01-01

    In conventional systemic drug delivery the drug is administered by intravenous injection; it then travels to the heart from where it is pumped to all regions of the body. When the drug is aimed at a small target region, this method is extremely inefficient and leads to require much larger doses than those being necessary. In order to overcome this problem a number of targeted drug delivery methods are developed. One of these, magnetically targeted drug delivery system (MT-DDS) will be a promising way, which involves binding a drug to small biocompatible magnetic particles, injecting these into the blood stream and using a high gradient magnetic field to pull them out of suspension in the target region. In the present paper, we describe an ex vivo experimental work. It is also reported that navigation and accumulation test of the magnetic particles in the Y-shaped glass tube was performed in order to examine the threshold of the magnetic force for accumulation. It is found that accumulation of the magnetic particles was succeeded in the blood vessel when a permanent magnet was placed at the vicinity of the blood vessel. This result indicates the feasibility of the magnetically drug targeting in the blood vessel

  17. LANSCE (Los Alamos Neutron Scattering Center) target system performance

    International Nuclear Information System (INIS)

    Russell, G.J.; Gilmore, J.S.; Robinson, H.; Legate, G.L.; Bridge, A.; Sanchez, R.J.; Brewton, R.J.; Woods, R.; Hughes, H.G. III

    1989-01-01

    The authors measured neutron beam fluxes at LANSCE using gold foil activation techniques. They did an extensive computer simulation of the as-built LANSCE Target/Moderator/Reflector/Shield geometry. They used this mockup in a Monte Carlo calculation to predict LANSCE neutronic performance for comparison with measured results. For neutron beam fluxes at 1 eV, the ratio of measured data to calculated varies from ∼0.6-0.9. The computed 1 eV neutron leakage at the moderator surface is 3.9 x 10 10 n/eV-sr-s-μA for LANSCE high-intensity water moderators. The corresponding values for the LANSCE high-resolution water moderator and the liquid hydrogen moderator are 3.3 and 2.9 x 10 10 , respectively. LANSCE predicted moderator intensities (per proton) for a tungsten target are essentially the same as ISIS predicted moderator intensities for a depleted uranium target. The calculated LANSCE steady state unperturbed thermal (E 13 n/cm 2 -s. The unique LANSCE split-target/flux-trap-moderator system is performing exceedingly well. The system has operated without a target or moderator change for over three years at nominal proton currents of 25 μA of 800-MeV protons. 17 refs., 8 figs., 3 tabs

  18. Treat-to-target in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Mosca, Marta; Boumpas, Dimitrios T; Bruce, Ian N

    2013-01-01

    Multiple clinical trials performed over twenty years in the treatment of rheumatoid arthritis (RA) have clearly demonstrated that patients have better outcomes if their disease activity at each time-point for follow-up includes a pre-specified target. A European SLE expert panel met in Zurich...... on May 8, 2012 to discuss whether a treat-to-target approach could be applied in the treatment of systemic lupus erythematosus (SLE) (T2T/SLE), define a research agenda, and establish a plan for moving forward. In the present paper, observations raised at the meeting and literature data on potential...

  19. Neural Network Target Identification System for False Alarm Reduction

    Science.gov (United States)

    Ye, David; Edens, Weston; Lu, Thomas T.; Chao, Tien-Hsin

    2009-01-01

    A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feed forward back propagation neural network (NN) is then trained to classify each feature vector and remove false positives. This paper discusses the test of the system performance and parameter optimizations process which adapts the system to various targets and datasets. The test results show that the system was successful in substantially reducing the false positive rate when tested on a sonar image dataset.

  20. Analysis of an XADS Target with the System Code TRACE

    International Nuclear Information System (INIS)

    Jaeger, Wadim; Sanchez Espinoza, Victor H.; Feng, Bo

    2008-01-01

    Accelerator-driven systems (ADS) present an option to reduce the radioactive waste of the nuclear industry. The experimental Accelerator-Driven System (XADS) has been designed to investigate the feasibility of using ADS on an industrial scale to burn minor actinides. The target section lies in the middle of the subcritical core and is bombarded by a proton beam to produce spallation neutrons. The thermal energy produced from this reaction requires a heat removal system for the target section. The target is cooled by liquid lead-bismuth-eutectics (LBE) in the primary system which in turn transfers the heat via a heat exchanger (HX) to the secondary coolant, Diphyl THT (DTHT), a synthetic diathermic fluid. Since this design is still in development, a detailed investigation of the system is necessary to evaluate the behavior during normal and transient operations. Due to the lack of experimental facilities and data for ADS, the analyses are mostly done using thermal hydraulic codes. In addition to evaluating the thermal hydraulics of the XADS, this paper also benchmarks a new code developed by the NRC, TRACE, against other established codes. The events used in this study are beam power switch-on/off transients and a loss of heat sink accident. The obtained results from TRACE were in good agreement with the results of various other codes. (authors)

  1. Exploding pusher targets for the SHIVA laser system

    International Nuclear Information System (INIS)

    Rosen, M.D.; Larsen, J.T.; Nuckolls, J.H.

    1977-01-01

    The first targets for the 20 TW SHIVA laser system were designed. They are simple glass micro-balloons, approximately 300 μm in diameter and 2 μm thick, filled with D-T gas. Using LASNEX, whose model physics was utilized successfully for ARGUS targets, we optimize for both gain and yield. The target behaves as an exploding pusher. Different simple analytic models for the physics of this mode are presented, and are tested by comparing their scaling predictions, at constant absorbed power, with those demonstrated by LASNEX. Emphasis is placed on successful prediction of the basic quantities of peak ion temperature and compression, rather than neutron yield or n tau

  2. Emerging drugs which target the renin-angiotensin-aldosterone system.

    Science.gov (United States)

    Steckelings, Ulrike Muscha; Paulis, Ludovit; Unger, Thomas; Bader, Michael

    2011-12-01

    The renin-angiotensin-aldosterone system (RAAS) is already the most important target for drugs in the cardiovascular system. However, still new developments are underway to interfere with the system on different levels. The novel strategies to interfere with RAAS aim to reduce the synthesis of the two major RAAS effector hormones, angiotensin (Ang) II and aldosterone, or interfere with their receptors, AT1 and mineralocorticoid receptor, respectively. Moreover, novel targets have been identified in RAAS, such as the (pro)renin receptor, and molecules, which counteract the classical actions of Ang II and are therefore beneficial in cardiovascular diseases. These include the AT2 receptor and the ACE2/Ang-(1-7)/Mas axis. The search for drugs activating these tissue-protective arms of RAAS is therefore the most innovative field in RAAS pharmacology. Most of the novel pharmacological strategies to inhibit the classical RAAS need to prove their superiority above the existing treatment in clinical trials and then have to compete against these now quite cheap drugs in a competitive market. The newly discovered targets have functions beyond the cardiovascular system opening up novel therapeutic areas for drugs interfering with RAAS components.

  3. IFMIF-CDA technical workshop on lithium target system. Proceedings

    International Nuclear Information System (INIS)

    1995-09-01

    An intense neutron source, International Fusion Materials Irradiation Facility (IFMIF) is planned under the collaborative program by International Energy Agency (IEA), and the Conceptual Design Activity (CDA) started in February 1995. US, Japan and EU are responsible to take a lead in coordinating accelerator, target and test cell design, respectively. In order to exchange the current results of the study and to coordinate the activities for the design integration, the first technical workshop on the lithium target system was held in the period of July 18-21 at the Tokai Research Establishment of the JAERI. This publication summarizes the materials presented in this meeting. The presentations and discussions were organized with the identified CDA tasks. It was confirmed that the reference design of the IFMIF target based on the previous studies under FMIT and ESNIT, elaborated to meet IFMIF parameters, is reasonable and feasible. It was pointed out that the interface between accelerator and test cell subsystems should be carefully investigated to avoid technical conflicts. Some design options such as nozzle, backwall and lithium jet geometry, lithium purity control, and lithium vapor control, based on the current technology were proposed to improve the integral target system function, and further R and D studies were suggested for design integration. (author)

  4. Constraints in distortion-invariant target recognition system simulation

    Science.gov (United States)

    Iftekharuddin, Khan M.; Razzaque, Md A.

    2000-11-01

    Automatic target recognition (ATR) is a mature but active research area. In an earlier paper, we proposed a novel ATR approach for recognition of targets varying in fine details, rotation, and translation using a Learning Vector Quantization (LVQ) Neural Network (NN). The proposed approach performed segmentation of multiple objects and the identification of the objects using LVQNN. In this current paper, we extend the previous approach for recognition of targets varying in rotation, translation, scale, and combination of all three distortions. We obtain the analytical results of the system level design to show that the approach performs well with some constraints. The first constraint determines the size of the input images and input filters. The second constraint shows the limits on amount of rotation, translation, and scale of input objects. We present the simulation verification of the constraints using DARPA's Moving and Stationary Target Recognition (MSTAR) images with different depression and pose angles. The simulation results using MSTAR images verify the analytical constraints of the system level design.

  5. Microchimeric cells in systemic lupus erythematosus: targets or innocent bystanders?

    Science.gov (United States)

    Stevens, A M

    2006-01-01

    During pregnancy maternal and fetal cells commute back and forth leading to fetal microchimerism in the mother and maternal microchimerism in the child that can persist for years after the birth. Chimeric fetal and maternal cells can be hematopoietic or can differentiate into somatic cells in multiple organs, potentially acting as targets for 'autoimmunity' and so have been implicated in the pathogenesis of autoimmune diseases that resemble graft-versus-host disease after stem cell transplantation. Fetal cells have been found in women with systemic lupus erythematosus, both in the blood and a target organ, the kidney, suggesting that they may be involved in pathogenesis. Future studies will address how the host immune system normally tolerates maternal and fetal cells or how the balance may change during autoimmunity.

  6. Cnidarian Neurotoxic Peptides Affecting Central Nervous System Targets.

    Science.gov (United States)

    Lazcano-Pérez, Fernando; Hernández-Guzmán, Ulises; Sánchez-Rodríguez, Judith; Arreguín-Espinosa, Roberto

    2016-01-01

    Natural products from animal venoms have been used widely in the discovery of novel molecules with particular biological activities that enable their use as potential drug candidates. The phylum Cnidaria (jellyfish, sea anemones, corals zoanthids, hydrozoans, etc.) is the most ancient venomous phylum on earth. Its venoms are composed of a complex mixture of peptidic compounds with neurotoxic and cytolitic properties that have shown activity on mammalian systems despite the fact that they are naturally targeted against fish and invertebrate preys, mainly crustaceans. For this reason, cnidarian venoms are an interesting and vast source of molecules with a remarkable activity on central nervous system, targeting mainly voltage-gated ion channels, ASIC channels, and TRPV1 receptors. In this brief review, we list the amino acid sequences of most cnidarian neurotoxic peptides reported to date. Additionally, we propose the inclusion of a new type of voltage-gated sea anemone sodium channel toxins based on the most recent reports.

  7. Magnetron co-sputtering system for coating ICF targets

    International Nuclear Information System (INIS)

    Hsieh, E.J.; Meyer, S.F.; Halsey, W.G.; Jameson, G.T.; Wittmayer, F.J.

    1981-01-01

    Fabrication of Inertial Confinement Fusion (ICF) targets requires deposition of various types of coatings on microspheres. The mechanical strength, and surface finish of the coatings are of concern in ICF experiments. The tensile strength of coatings can be controlled through grain refinement, selective doping and alloy formation. We have constructed a magnetron co-sputtering system to produce variable density profile coatings with high tensile strength on microspheres

  8. Design and implementation of typical target image database system

    International Nuclear Information System (INIS)

    Qin Kai; Zhao Yingjun

    2010-01-01

    It is necessary to provide essential background data and thematic data timely in image processing and application. In fact, application is an integrating and analyzing procedure with different kinds of data. In this paper, the authors describe an image database system which classifies, stores, manages and analyzes database of different types, such as image database, vector database, spatial database, spatial target characteristics database, its design and structure. (authors)

  9. Circular Orbit Target Capture Using Space Tether-Net System

    Directory of Open Access Journals (Sweden)

    Guang Zhai

    2013-01-01

    Full Text Available The space tether-net system for on-orbit capture is proposed in this paper. In order to research the dynamic behaviors during system deployment, both free and nonfree deployment dynamics in circular orbit are developed; the system motion with respect to Local Vertical and Local Horizontal frame is also researched with analysis and simulation. The results show that in the case of free deployment, the capture net follows curve trajectories due to the relative orbit dynamic perturbation, and the initial deployment velocities are planned by state transformation equations for static and floating target captures; in the case of non-free deployment, the system undergoes an altitude libration along the Local Vertical, and the analytical solutions that describe the attitude libration are obtained by using variable separation and integration. Finally, the dynamics of postdeployment system is also proved marginally stable if the critical initial conditions are satisfied.

  10. Large-space cluster model calculations for the 3He(3He,2p)4He and 3H(3H,2n)4He reactions

    International Nuclear Information System (INIS)

    Csoto, Attila; Langanke, Karlheinz

    1999-01-01

    The 3 He( 3 He, 2p) 4 He and 3 H( 3 H, 2n) 4 He reactions are studied in a microscopic cluster model. We search for resonances in the 3 He+ 3 He and 4 He + p + p channels using methods that treat the two- and three-body resonance asymptotics correctly. Our results show that the existence of a low-energy resonance or virtual state, which could influence the 7 Be and 8 B solar neutrino fluxes, is rather unlikely. Our calculated 3 He( 3 He, 2p) 4 He and 3 H( 3 H, 2n) 4 He cross sections are in a good general agreement with the experimental data

  11. DNA repair systems as targets of cadmium toxicity

    International Nuclear Information System (INIS)

    Giaginis, Constantinos; Gatzidou, Elisavet; Theocharis, Stamatios

    2006-01-01

    Cadmium (Cd) is a heavy metal and a potent carcinogen implicated in tumor development through occupational and environmental exposure. Recent evidence suggests that proteins participating in the DNA repair systems, especially in excision and mismatch repair, are sensitive targets of Cd toxicity. Cd by interfering and inhibiting these DNA repair processes might contribute to increased risk for tumor formation in humans. In the present review, the information available on the interference of Cd with DNA repair systems and their inhibition is summarized. These actions could possibly explain the indirect contribution of Cd to mutagenic effects and/or carcinogenicity

  12. Targeted multidrug delivery system to overcome chemoresistance in breast cancer

    Directory of Open Access Journals (Sweden)

    Tang Y

    2017-01-01

    Full Text Available Yuan Tang,1 Fariborz Soroush,1 Zhaohui Tong,2 Mohammad F Kiani,1 Bin Wang1,3 1Department of Mechanical Engineering, Temple University, Philadelphia, PA, 2Department of Agricultural and Biological Engineering, University of Florida, Gainesville, FL, 3Department of Biomedical Engineering, Widener University, Chester, PA, USA Abstract: Chemotherapy has been widely used in breast cancer patients to reduce tumor size. However, most anticancer agents cannot differentiate between cancerous and normal cells, resulting in severe systemic toxicity. In addition, acquired drug resistance during the chemotherapy treatment further decreases treatment efficacy. With the proper treatment strategy, nanodrug carriers, such as liposomes/immunoliposomes, may be able to reduce undesired side effects of chemotherapy, to overcome the acquired multidrug resistance, and to further improve the treatment efficacy. In this study, a novel combinational targeted drug delivery system was developed by encapsulating antiangiogenesis drug bevacizumab into liposomes and encapsulating chemotherapy drug doxorubicin (DOX into immunoliposomes where the human epidermal growth factor receptor 2 (HER2 antibody was used as a targeting ligand. This novel combinational system was tested in vitro using a HER2 positive and multidrug resistant breast cancer cell line (BT-474/MDR, and in vivo using a xenograft mouse tumor model. In vitro cell culture experiments show that immunoliposome delivery led to a high cell nucleus accumulation of DOX, whereas free DOX was observed mostly near the cell membrane and in cytoplasm due to the action of P-gp. Combining liposomal bevacizumab with immunoliposomal DOX achieved the best tumor growth inhibition and the lowest toxicity. Tumor size decreased steadily within a 60-day observation period indicating a potential synergistic effect between DOX and bevacizumab through the targeted delivery. Our findings clearly indicate that tumor growth was significantly

  13. A computational framework for modeling targets as complex adaptive systems

    Science.gov (United States)

    Santos, Eugene; Santos, Eunice E.; Korah, John; Murugappan, Vairavan; Subramanian, Suresh

    2017-05-01

    Modeling large military targets is a challenge as they can be complex systems encompassing myriad combinations of human, technological, and social elements that interact, leading to complex behaviors. Moreover, such targets have multiple components and structures, extending across multiple spatial and temporal scales, and are in a state of change, either in response to events in the environment or changes within the system. Complex adaptive system (CAS) theory can help in capturing the dynamism, interactions, and more importantly various emergent behaviors, displayed by the targets. However, a key stumbling block is incorporating information from various intelligence, surveillance and reconnaissance (ISR) sources, while dealing with the inherent uncertainty, incompleteness and time criticality of real world information. To overcome these challenges, we present a probabilistic reasoning network based framework called complex adaptive Bayesian Knowledge Base (caBKB). caBKB is a rigorous, overarching and axiomatic framework that models two key processes, namely information aggregation and information composition. While information aggregation deals with the union, merger and concatenation of information and takes into account issues such as source reliability and information inconsistencies, information composition focuses on combining information components where such components may have well defined operations. Since caBKBs can explicitly model the relationships between information pieces at various scales, it provides unique capabilities such as the ability to de-aggregate and de-compose information for detailed analysis. Using a scenario from the Network Centric Operations (NCO) domain, we will describe how our framework can be used for modeling targets with a focus on methodologies for quantifying NCO performance metrics.

  14. Target diagnostic system for the National Ignition Facility (NIF)

    International Nuclear Information System (INIS)

    Leeper, R.J.; Chandler, G.A.; Cooper, G.W.; Derzon, M.S.

    1996-01-01

    A review of recent progress on the design of a diagnostic system proposed for ignition target experiments on the National Ignition Facility (NIF) will be presented. This diagnostic package contains an extensive suite of optical, x-ray, gamma-ray, and neutron diagnostics that enable measurements of the performance of both direct and indirect driven NIF targets. The philosophy used in designing all of the diagnostics in the set has emphasized redundant and independent measurement of fundamental physical quantities relevant to the operation of the NIF target. A unique feature of these diagnostics is that they are being designed to be capable of operating, in the high radiation, EMP, and debris backgrounds expected on the NIF facility. The diagnostic system proposed can be categorized into three broad areas: laser characterization, hohlraum characterization, and capsule performance diagnostics. The operating principles of a representative instrument from each class of diagnostic employed in this package will be summarized and illustrated with data obtained in recent prototype diagnostic tests

  15. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  16. Environmental Management System Objectives & Targets Results Summary - FY 2015.

    Energy Technology Data Exchange (ETDEWEB)

    Vetter, Douglas W

    2016-02-01

    Sandia National Laboratories (SNL) Environmental Management System is the integrated approach for members of the workforce to identify and manage environmental risks. Each Fiscal Year (FY) SNL performs an analysis to identify environmental aspects, and the environmental programs associated with them are charged with the task of routinely monitoring and measuring the objectives and targets that are established to mitigate potential impacts of SNL's operations on the environment. An annual summary of the results achieved towards meeting established Sandia Corporation and SNL Site-specific objectives and targets provides a connection to, and rational for, annually revised environmental aspects. The purpose of this document is to summarize the results achieved and documented in FY 2015.

  17. Why Targeted Therapies are Necessary for Systemic Lupus Erythematosus

    Science.gov (United States)

    Durcan, Laura; Petri, Michelle

    2016-01-01

    Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side-effects. Current management strategies rely heavily on non-specific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic pre-clinical data and promising early phase studies have ultimately been disappointing in phase III randomized controlled studies. Recent efforts have focused on B cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated including interferon alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective. PMID:27497251

  18. Targeted electrohydrodynamic printing for micro-reservoir drug delivery systems

    International Nuclear Information System (INIS)

    Hwang, Tae Heon; Kim, Jin Bum; Yang, Da Som; Ryu, WonHyoung; Park, Yong-il

    2013-01-01

    Microfluidic drug delivery systems consisting of a drug reservoir and microfluidic channels have shown the possibility of simple and robust modulation of drug release rate. However, the difficulty of loading a small quantity of drug into drug reservoirs at a micro-scale limited further development of such systems. Electrohydrodynamic (EHD) printing was employed to fill micro-reservoirs with controlled amount of drugs in the range of a few hundreds of picograms to tens of micrograms with spatial resolution of as small as 20 µm. Unlike most EHD systems, this system was configured in combination with an inverted microscope that allows in situ targeting of drug loading at micrometer scale accuracy. Methylene blue and rhodamine B were used as model drugs in distilled water, isopropanol and a polymer solution of a biodegradable polymer and dimethyl sulfoxide (DMSO). Also tetracycline-HCl/DI water was used as actual drug ink. The optimal parameters of EHD printing to load an extremely small quantity of drug into microscale drug reservoirs were investigated by changing pumping rates, the strength of an electric field and drug concentration. This targeted EHD technique was used to load drugs into the microreservoirs of PDMS microfluidic drug delivery devices and their drug release performance was demonstrated in vitro. (paper)

  19. Pathogenic inflammation and its therapeutic targeting in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Timothy Andrew Gottschalk

    2015-10-01

    Full Text Available Systemic Lupus Erythematosus (SLE, lupus is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues including skin, kidneys and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. Over many years, clinical trials in SLE have focused on agents that control B and T lymphocyte activation, and, with the single exception of an agent known as Belimumab which targets the B cell survival factor BAFF, they have been disappointing. At present, standard therapy for SLE with mild disease is the agent hydroxychloroquine. During disease flares, steroids are often used, while the more severe manifestations with major organ involvement warrant potent, broad-spectrum immuno-suppression with cyclophosphamide or mycophenolate. Current treatments have severe and dose-limiting toxicities and thus a more specific therapy targeting a causative factor or signaling pathway would be greatly beneficial in SLE treatment. Moreover, the ability to control inflammation alongside B cell activation may be a superior approach for disease control. There has been a recent focus on the innate immune system and associated inflammation, which has uncovered key players in driving the pathogenesis of SLE. Delineating some of these intricate inflammatory mechanisms has been possible with studies using spontaneous mouse mutants and genetically engineered mice. These strains, to varying degrees, exhibit hallmarks of the human disease and therefore have been utilized to model human SLE and to test new drugs. Developing a better understanding of the initiation and perpetuation of disease in SLE may uncover suitable novel targets for therapeutic intervention. Here we discuss the involvement of inflammation in SLE disease pathogenesis, with a focus on several key proinflammatory cytokines and myeloid growth factors, and

  20. Pathogenic Inflammation and Its Therapeutic Targeting in Systemic Lupus Erythematosus

    Science.gov (United States)

    Gottschalk, Timothy A.; Tsantikos, Evelyn; Hibbs, Margaret L.

    2015-01-01

    Systemic lupus erythematosus (SLE, lupus) is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues, including skin, kidneys, and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. Over many years, clinical trials in SLE have focused on agents that control B- and T-lymphocyte activation, and, with the single exception of an agent known as belimumab which targets the B-cell survival factor BAFF, they have been disappointing. At present, standard therapy for SLE with mild disease is the agent hydroxychloroquine. During disease flares, steroids are often used, while the more severe manifestations with major organ involvement warrant potent, broad-spectrum immunosuppression with cyclophosphamide or mycophenolate. Current treatments have severe and dose-limiting toxicities and thus a more specific therapy targeting a causative factor or signaling pathway would be greatly beneficial in SLE treatment. Moreover, the ability to control inflammation alongside B-cell activation may be a superior approach for disease control. There has been a recent focus on the innate immune system and associated inflammation, which has uncovered key players in driving the pathogenesis of SLE. Delineating some of these intricate inflammatory mechanisms has been possible with studies using spontaneous mouse mutants and genetically engineered mice. These strains, to varying degrees, exhibit hallmarks of the human disease and therefore have been utilized to model human SLE and to test new drugs. Developing a better understanding of the initiation and perpetuation of disease in SLE may uncover suitable novel targets for therapeutic intervention. Here, we discuss the involvement of inflammation in SLE disease pathogenesis, with a focus on several key proinflammatory cytokines and myeloid growth factors, and review the known

  1. The new control system of the SPS target sector

    CERN Document Server

    Carlier, E; Mecredy, N; O'Leary, J

    1999-01-01

    The SPS, the Super Proton Synchrotron at CERN, is an accelerator originally designed and commissioned in 1976 for protons. The control system of the SPS target stations, beam absorbers and other aperture limiting devices was developed in the seventies. It was mainly based on home made electronics and equipment dependent software. With time, this electronics has become obsolete, difficult to maintain in operation and not suitable for integration into a modern control system. In 1997, a project was set up to modernise the electronics and the related software. The new control system is largely based on standard industrial hardware and software components. SIEMENS Simatic S7-300 programmable logic controllers have been used as equipment controllers and connected through PROFIBUS to a Windows-NT front-end PC running the SIEMENS WinCC SCADA package which acts as local controller and remote access gateway. This fully industrial solution has been successfully integrated into the actual SPS accelerator control infrast...

  2. Micro-NRA and micro-3HIXE with He-3 microbeam on samples exposed in ASDEX Upgrade and Pilot-PSI machines

    NARCIS (Netherlands)

    Kelemen, M.; Zaloznik, A.; Vavpetic, P.; Pecovnik, M.; Pelicon, P.; Hakola, A.; Lahtinen, A.; Karhunen, J.; Piip, K.; van der Meiden, H. J.; Paris, P.; Laan, M.; Krieger, K.; Oberkofler, M.; Markelj, S.; ASDEX Upgrade team,

    2017-01-01

    Micro nuclear reaction analysis (micro-NRA) exploiting the nuclear reaction D(He-3,p)He-4 was used for post-mortem analyses of special marker samples, exposed to deuterium plasma inside ASDEX Upgrade (AUG) tokamak and to the deuterium plasma jet in the Pilot-PSI linear plasma gun. Lateral

  3. The cosmic-ray He-3/He-4 ratio from 200 MeV per nucleon(-1) to 3.7 GeV per nucleon(-1)

    DEFF Research Database (Denmark)

    Reimer, O.; Menn, W.; Hof, M.

    1998-01-01

    by their mass using the velocity versus magnetic rigidity technique. The measured He-3/He-4 ratios are corrected to the top of the atmosphere, and a comparison with previous data is given. The observed isotopic composition is found to be generally consistent with the predictions of a standard leaky box model...

  4. Target-Tracking Camera for a Metrology System

    Science.gov (United States)

    Liebe, Carl; Bartman, Randall; Chapsky, Jacob; Abramovici, Alexander; Brown, David

    2009-01-01

    An analog electronic camera that is part of a metrology system measures the varying direction to a light-emitting diode that serves as a bright point target. In the original application for which the camera was developed, the metrological system is used to determine the varying relative positions of radiating elements of an airborne synthetic aperture-radar (SAR) antenna as the airplane flexes during flight; precise knowledge of the relative positions as a function of time is needed for processing SAR readings. It has been common metrology system practice to measure the varying direction to a bright target by use of an electronic camera of the charge-coupled-device or active-pixel-sensor type. A major disadvantage of this practice arises from the necessity of reading out and digitizing the outputs from a large number of pixels and processing the resulting digital values in a computer to determine the centroid of a target: Because of the time taken by the readout, digitization, and computation, the update rate is limited to tens of hertz. In contrast, the analog nature of the present camera makes it possible to achieve an update rate of hundreds of hertz, and no computer is needed to determine the centroid. The camera is based on a position-sensitive detector (PSD), which is a rectangular photodiode with output contacts at opposite ends. PSDs are usually used in triangulation for measuring small distances. PSDs are manufactured in both one- and two-dimensional versions. Because it is very difficult to calibrate two-dimensional PSDs accurately, the focal-plane sensors used in this camera are two orthogonally mounted one-dimensional PSDs.

  5. Solute carrier transporters: potential targets for digestive system neoplasms.

    Science.gov (United States)

    Xie, Jing; Zhu, Xiao Yan; Liu, Lu Ming; Meng, Zhi Qiang

    2018-01-01

    Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues of digestive systems and mediate specific uptake of small molecule substrates in facilitative manner. Given the important role of SLC proteins in maintaining normal functions of digestive system, dysregulation of these protein in digestive system neoplasms may deliver biological and clinical significance that deserves systemic studies. In this review, we critically summarized the recent advances in understanding the role of SLC proteins in digestive system neoplasms. We highlighted that several SLC subfamilies, including metal ion transporters, transporters of glucose and other sugars, transporters of urea, neurotransmitters and biogenic amines, ammonium and choline, inorganic cation/anion transporters, transporters of nucleotide, amino acid and oligopeptide organic anion transporters, transporters of vitamins and cofactors and mitochondrial carrier, may play important roles in mediating the initiation, progression, metastasis, and chemoresistance of digestive system neoplasms. Proteins in these SLC subfamilies may also have diagnostic and prognostic values to particular cancer types. Differential expression of SLC proteins in tumors of digestive system was analyzed by extracting data from human cancer database, which revealed that the roles of SLC proteins may either be dependent on the substrates they transport or be tissue specific. In addition, small molecule modulators that pharmacologically regulate the functions of SLC proteins were discussed for their possible application in the treatment of digestive system neoplasms. This review highlighted the potential of SLC family proteins as drug target for the treatment of digestive system neoplasms.

  6. False targets vs. redundancy in homogeneous parallel systems

    International Nuclear Information System (INIS)

    Levitin, Gregory; Hausken, Kjell

    2009-01-01

    System defense against natural threats and disasters that have a stochastic nature includes providing redundancy and protecting system elements. The defense against strategic intentional attacks can also include deploying false targets aimed at misleading the attacker. Distribution of the available resources among different defensive means is an important problem that arises in organizing the defense of complex civil infrastructures, industrial systems or military objects. The article considers defense resource allocation in a system exposed to external intentional attack. The expected damage caused by the attack is evaluated as system unsupplied demand. The defender distributes its limited resource between deploying redundant genuine elements and false elements, both of which are targets of attack. The attacker attacks a subset of the elements and distributes its limited resource evenly among the attacked elements. Two cases are considered: in the first one the number of attacked elements and the vulnerability of each genuine element are fixed and the defense resource distribution is determined as a solution of an optimization problem; in the second one the number of attacked elements is the attacker's free choice variable and the element's vulnerability depends on a contest determined by the defender's and attacker's resources allocated to each element. The defender's optimal resource distribution strategy is determined as a solution of a two-period minmax game. It is shown that the optimal number of genuine elements decreases monotonically with the growth of the element cost and vulnerability, whereas the optimal number of false elements demonstrates non-monotonic behavior. The contest intensity is an important factor influencing the optimal defense resource distribution. It cannot be ignored when the defense strategy is determined, and it thus also impacts the attack strategy

  7. Endocannabinoid System: A Multi-Facet Therapeutic Target.

    Science.gov (United States)

    Kaur, Rimplejeet; Ambwani, Sneha R; Singh, Surjit

    2016-01-01

    the therapeutic targets for both cannabinoid receptor agonists and antagonists. One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that act selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted. Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids. In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as "protective" and "disease inducing substance", time-dependent changes in the expression of cannabinoid receptors.

  8. Challenges in thermal and hydraulic analysis of ADS target systems

    International Nuclear Information System (INIS)

    Groetzbach, G.; Batta, A.; Lefhalm, C.-H.; Otic, I.

    2004-01-01

    The liquid metal cooled spallation targets of Accelerator Driven nuclear reactor Systems obey high thermal loads; in addition some flow and cooling conditions are of a prototypical character; in contrast the operating conditions for the engaged materials are narrow; thus, the target development requires a very careful analysis by experimental and numerical means. Especially the cooling of the steel window, which is heated by the proton beam, needs special care. Some of the main goals of the experimental and numerical analyses of the thermal dynamics of those systems are discusses. The prediction of locally detached flows and of flows with larger recirculation areas suffers from insufficient turbulence modeling; this has to be compensated by using prototypical model experiments, e.g. with water, to select the adequate models and numerical schemes. The well known problems with the Reynolds analogy in predicting the heat transfer in liquid metals requires always prototypic liquid metal experiments to select and adapt the turbulent heat flux models. The uncertainties in liquid metal experiments cannot be neglected; so it is necessary to perform CFD calculations and experiments always hand in hand and to develop improve turbulent heat flux models. One contribution to an improved 3 or 4-equation model is deduced from recent Direct Numerical Simulation (DNS) data. (author)

  9. Target Diagnostic Control System Implementation for the National Ignition Facility

    International Nuclear Information System (INIS)

    Shelton, R.T.; Kamperschroer, J.H.; Lagin, L.J.; Nelson, J.R.; O'Brien, D.W.

    2010-01-01

    The extreme physics of targets shocked by NIF's 192-beam laser are observed by a diverse suite of diagnostics. Many diagnostics are being developed by collaborators at other sites, but ad hoc controls could lead to unreliable and costly operations. A Diagnostic Control System (DCS) framework for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost Windows XP processor and Java application. Each instrument is aggregated with others as needed in the supervisory system to form an integrated diagnostic. The Java framework provides data management, control services and operator GUI generation. DCS instruments are reusable by replication with reconfiguration for specific diagnostics in XML. Advantages include minimal application code, easy testing, and high reliability. Collaborators save costs by assembling diagnostics with existing DCS instruments. This talk discusses target diagnostic instrumentation used on NIF and presents the DCS architecture and framework.

  10. CHAOS: An SDN-Based Moving Target Defense System

    Directory of Open Access Journals (Sweden)

    Yuan Shi

    2017-01-01

    Full Text Available Moving target defense (MTD has provided a dynamic and proactive network defense to reduce or move the attack surface that is available for exploitation. However, traditional network is difficult to realize dynamic and active security defense effectively and comprehensively. Software-defined networking (SDN points out a brand-new path for building dynamic and proactive defense system. In this paper, we propose CHAOS, an SDN-based MTD system. Utilizing the programmability and flexibility of SDN, CHAOS obfuscates the attack surface including host mutation obfuscation, ports obfuscation, and obfuscation based on decoy servers, thereby enhancing the unpredictability of the networking environment. We propose the Chaos Tower Obfuscation (CTO method, which uses the Chaos Tower Structure (CTS to depict the hierarchy of all the hosts in an intranet and define expected connection and unexpected connection. Moreover, we develop fast CTO algorithms to achieve a different degree of obfuscation for the hosts in each layer. We design and implement CHAOS as an application of SDN controller. Our approach makes it very easy to realize moving target defense in networks. Our experimental results show that a network protected by CHAOS is capable of decreasing the percentage of information disclosure effectively to guarantee the normal flow of traffic.

  11. Automated Navigation System based on Weapon-Target Assignment

    Directory of Open Access Journals (Sweden)

    Mohammad Khairudin

    2011-12-01

    Full Text Available Operating of weapon on the tank is mostly by manually. It is not desired performance for a critical operation. An automatic control system is required to operate the weapon with the target while maintaining the accuracy. In this paper has designed an automatic weapon control system using object image proccessing. Various an image processing methods used to improve the weapon accuracy to obtain the intended target. The method used in digital image processing is the Camshift motion tracking method. This method is compared with the Lucas Canade motion tracking method. This comparison is conducted to found more precise results between the two methods. Results of object image processing are used to control the direction of the weapon that towards the desired goal. The results show that the implementation of the Lucas Canade motion tracking method using fire simulation tools have been successful. The performance of the Lucas Canade motion tracking methods is better than the CamShift method. Using Lucas Canade method for weapon controller is accordance with the purposes.

  12. Cooling System for the Merit High-Power Target Experiment

    CERN Document Server

    Haug, F; Silva, P; Pezzeti, M; Pavlov, O; Pirotte, O; Metselaar, J; Efthymiopoulos, I; Fabich, A; Lettry, J; Kirk, H G; McDonald, K T; Titus, P; Bennett, J R J

    2010-01-01

    MERIT is a proof-of-principle experiment of a target station suitable as source for future muon colliders or neutrino factories. When installed at the CERN (European Organization for Nuclear Research) PS (Proton Synchrotron)complex fast-extracted high-intensity proton beams intercepted a free mercury jet inside a normal-conducting, pulsed 15-T capture solenoid magnet cooled with liquid nitrogen. Up to 25 MJ of Joule heat was dissipated in the magnet during a pulse. The fully automated, remotely controlled cryogenic system of novel design permitted the transfer of nitrogen by the sole means of differential pressures inside the vessels. This fast cycling system permitted several hundred tests in less than three weeks during the 2007 data taking campaign.

  13. Zebrafish neurotransmitter systems as potential pharmacological and toxicological targets.

    Science.gov (United States)

    Rico, E P; Rosemberg, D B; Seibt, K J; Capiotti, K M; Da Silva, R S; Bonan, C D

    2011-01-01

    Recent advances in neurobiology have emphasized the study of brain structure and function and its association with numerous pathological and toxicological events. Neurotransmitters are substances that relay, amplify, and modulate electrical signals between neurons and other cells. Neurotransmitter signaling mediates rapid intercellular communication by interacting with cell surface receptors, activating second messenger systems and regulating the activity of ion channels. Changes in the functional balance of neurotransmitters have been implicated in the failure of central nervous system function. In addition, abnormalities in neurotransmitter production or functioning can be induced by several toxicological compounds, many of which are found in the environment. The zebrafish has been increasingly used as an animal model for biomedical research, primarily due to its genetic tractability and ease of maintenance. These features make this species a versatile tool for pre-clinical drug discovery and toxicological investigations. Here, we present a review regarding the role of different excitatory and inhibitory neurotransmitter systems in zebrafish, such as dopaminergic, serotoninergic, cholinergic, purinergic, histaminergic, nitrergic, glutamatergic, glycinergic, and GABAergic systems, and emphasizing their features as pharmacological and toxicological targets. The increase in the global knowledge of neurotransmitter systems in zebrafish and the elucidation of their pharmacological and toxicological aspects may lead to new strategies and appropriate research priorities to offer insights for biomedical and environmental research. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. System Studies for the ADTF: Target and Materials Test Station

    International Nuclear Information System (INIS)

    Cappiello, M.; Pitcher, E.; Pasamehmetoglu, K.

    2002-01-01

    To meet the objectives of the Advanced Accelerator Applications (AAA) program, the Accelerator-Driven Test Facility (ADTF) provides a world-class accelerator-driven test facility to: - Provide the capability to assess technology options for the transmutation of spent nuclear fuel and waste through a proof-of-performance. - Provide a user facility that allows testing of advanced nuclear technologies and applications, material science and research, experimental physics, and conventional nuclear engineering science applications. - Provide the capability, through upgrades or additions to the ADTF accelerator, to produce tritium for defense purposes, if required. - Provide the capability, through upgrades or additions, to produce radioisotopes for medical and commercial purposes. These missions are diverse and demand a facility with significant flexibility. In order to meet them, it is envisioned that we construct two target stations: the Target and Materials Test (TMT) station and the Subcritical Multiplier (SCM) test station. The two test stations share common hot-cell facilities for post-irradiation examination. It is expected the TMT will come online first, closely followed by the SCM. The TMT will provide the capability to: - Irradiate small samples of proposed ATW (accelerator-driven transmutation of waste) fuels and materials at prototypic flux, temperature, and coolant conditions (requires intense source of neutrons). - Perform transient testing. - Test liquid (lead-bismuth) and solid spallation targets with water, sodium, or helium coolant. - Test generation-IV fuels for advance nuclear systems (requires high-intensity thermal flux). - Irradiate fission product transmutation targets. - Test advanced fuel and coolant combinations, including helium, water, sodium, and lead-bismuth. - Produce isotopes for commercial and medical applications. - Perform neutron physics experiments. The SCM will provide the capability to: - Irradiate large samples of proposed ATW

  15. Evaluating system reliability and targeted hardening strategies of power distribution systems subjected to hurricanes

    International Nuclear Information System (INIS)

    Salman, Abdullahi M.; Li, Yue; Stewart, Mark G.

    2015-01-01

    Over the years, power distribution systems have been vulnerable to extensive damage from hurricanes which can cause power outage resulting in millions of dollars of economic losses and restoration costs. Most of the outage is as a result of failure of distribution support structures. Over the years, various methods of strengthening distribution systems have been proposed and studied. Some of these methods, such as undergrounding of the system, have been shown to be unjustified from an economic point of view. A potential cost-effective strategy is targeted hardening of the system. This, however, requires a method of determining critical parts of a system that when strengthened, will have greater impact on reliability. This paper presents a framework for studying the effectiveness of targeted hardening strategies on power distribution systems subjected to hurricanes. The framework includes a methodology for evaluating system reliability that relates failure of poles and power delivery, determination of critical parts of a system, hurricane hazard analysis, and consideration of decay of distribution poles. The framework also incorporates cost analysis that considers economic losses due to power outage. A notional power distribution system is used to demonstrate the framework by evaluating and comparing the effectiveness of three hardening measures. - Highlight: • Risk assessment of power distribution systems subjected to hurricanes is carried out. • Framework for studying effectiveness of targeted hardening strategies is presented. • A system reliability method is proposed. • Targeted hardening is cost effective for existing systems. • Economic losses due to power outage should be considered for cost analysis.

  16. A Study on Control System Design Based on ARM Sea Target Search System

    Directory of Open Access Journals (Sweden)

    Lin Xinwei

    2015-01-01

    Full Text Available The infrared detector is used for sea target search, which can assist humans in searching suspicious objects at night and under poor visibility conditions, and improving search efficiency. This paper applies for interrupt and stack technology to solve problems of data losses that may be caused by one-to-many multi-byte protocol communication. Meanwhile, this paper implements hardware and software design of the system based on industrial-grade ARM control chip and uC / OS-II embedded operating system. The control system in the sea target search system is an information exchange and control center of the whole system, which solves the problem of controlling over the shooting angle of the infrared detector in the process of target search. After testing, the control system operates stably and reliably, and realizes rotation and control functions of the pan/tilt platform during automatic search, manual search and track.

  17. Update in Systemic and Targeted Therapies in Gastrointestinal Oncology

    Directory of Open Access Journals (Sweden)

    Nelson S. Yee

    2018-03-01

    Full Text Available Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented. The use of peri-operative chemotherapy comprised of 5-fluorouracil or capecitabine, leucovorin, oxaliplatin, and docetaxel (FLOT, and immunotherapy including pembrolizumab, nivolumab, and ipilimumab in gastroesophageal carcinoma are discussed. Data from clinical trials that investigated the targeted therapeutics including nivolumab, ramucirumab, lenvatinib, and BLU-554 are reported. The role of adjuvant capecitabine in resected biliary tract carcinoma (BTC and nab-paclitaxel in combination with gemcitabine and cisplatin in advanced BTC are presented. In colorectal carcinoma, the efficacy of nivolumab, adjuvant FOLFOX or CAPOX, irinotecan/cetuximab/vemurafenib, and trifluridine/tipiracil/bevacizumab, is examined. In summary, some of the above systemic therapies have become or are expected to become new standard of care, while the others demonstrate the potential of becoming new treatment options.

  18. Alkylation damage by lipid electrophiles targets functional protein systems.

    Science.gov (United States)

    Codreanu, Simona G; Ullery, Jody C; Zhu, Jing; Tallman, Keri A; Beavers, William N; Porter, Ned A; Marnett, Lawrence J; Zhang, Bing; Liebler, Daniel C

    2014-03-01

    Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells treated with lipid electrophile probes. Protein target profiles revealed three damage susceptibility classes, as well as proteins that were highly resistant to alkylation. Damage occurred selectively across functional protein interaction networks, with the most highly alkylation-susceptible proteins mapping to networks involved in cytoskeletal regulation. Proteins with lower damage susceptibility mapped to networks involved in protein synthesis and turnover and were alkylated only at electrophile concentrations that caused significant toxicity. Hierarchical susceptibility of proteome systems to alkylation may allow cells to survive sublethal damage while protecting critical cell functions.

  19. Alkylation Damage by Lipid Electrophiles Targets Functional Protein Systems*

    Science.gov (United States)

    Codreanu, Simona G.; Ullery, Jody C.; Zhu, Jing; Tallman, Keri A.; Beavers, William N.; Porter, Ned A.; Marnett, Lawrence J.; Zhang, Bing; Liebler, Daniel C.

    2014-01-01

    Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells treated with lipid electrophile probes. Protein target profiles revealed three damage susceptibility classes, as well as proteins that were highly resistant to alkylation. Damage occurred selectively across functional protein interaction networks, with the most highly alkylation-susceptible proteins mapping to networks involved in cytoskeletal regulation. Proteins with lower damage susceptibility mapped to networks involved in protein synthesis and turnover and were alkylated only at electrophile concentrations that caused significant toxicity. Hierarchical susceptibility of proteome systems to alkylation may allow cells to survive sublethal damage while protecting critical cell functions. PMID:24429493

  20. Standard-target calibration of an acoustic backscatter system

    Science.gov (United States)

    Foote, Kenneth G.; Martini, Marinna A.

    2010-01-01

    The standard-target method used to calibrate scientific echo sounders and other scientific sonars by a single, solid elastic sphere is being adapted to acoustic backscatter (ABS) systems. Its first application, to the AQUAscat 1000, is described. The on-axis sensitivity and directional properties of transducer beams at three operating frequencies, nominally 1, 2.5, and 4 MHz, have been determined using a 10-mm-diameter sphere of tungsten carbide with 6% cobalt binder. Preliminary results are reported for the 1-MHz transducer. Their application to measurements of suspended sediment made in situ with the same device is described. This will enable the data to be expressed directly in physical units of volume backscattering.

  1. Targeting Renin–Angiotensin System Against Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Abadi Kahsu Gebre

    2018-04-01

    Full Text Available Renin Angiotensin System (RAS is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer’s disease (AD, and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD. Angiotensin II (AngII via AT1 receptor is reported to increase brain Aβ level via different mechanisms including increasing amyloid precursor protein (APP mRNA, β-secretase activity, and presenilin expression. Similarly, it was associated with tau phosphorylation, and reactive oxygen species generation. However, these effects are counterbalanced by Ang II mediated AT2 signaling. The protective effect observed with angiotensin receptor blockers (ARBs and angiotensin converting enzyme inhibitors (ACEIs could be as the result of inhibition of Ang II signaling. ARBs also offer additional benefit by shifting the effect of Ang II toward AT2 receptor. To conclude, targeting RAS in the brain may benefit patients with AD though it still requires further in depth understanding.

  2. System dynamic analyses on the JKJ mercury target and cold moderator systems

    International Nuclear Information System (INIS)

    Takahashi, Toshio; Kaminaga, Masanori; Kinoshita, Hidetaka; Aso, Tomokazu; Haga, Katsuhiro; Hino, Ryutaro

    2001-01-01

    The temperature responses of major points in a mercury target cooling system and in a cold moderator system of JKJ (JAERI/KEK Joint Project) were simulated by the analytical code MATLAB (SIMULINK). As a result, it was made clear that non-control of mercury temperature is the best way to control the mercury target cooling system. If the mercury temperature of the system is controlled by the PID control system using an outlet temperature of heat exchanger, the PID control system shows the characteristics of an on-off control system, and the temperature cannot be controlled. Analytical results also showed that mercury temperature remained below the boiling point of 356degC under 0.1 MPa during a transient at one cooling pump trip. Analytical results for the cold moderator system showed that the outlet temperature of cold moderator vessels could be kept within a temperature range of 1 k during steady-state conditions. (author)

  3. The sup(40,44,48)Ca(3He, 3He) and (3He, 4He) reactions at 50 MeV

    International Nuclear Information System (INIS)

    Griffiths, R.J.; Duggan, F.; Clarke, N.M.

    1981-01-01

    Measurements have been made of the ( 3 He, 3 He) and ( 3 He, 4 He) reactions on the isotopes of calcium 40 Ca, 44 Ca and 48 Ca at an energy of 50.4 MeV. The results have been analysed with conventional optical potentials and DWBA. The adequacy of the former and inadequacy of the latter for reactions with composite particles is discussed. (author)

  4. National Ignition Facility Cryogenic Target Systems Interim Management Plan

    International Nuclear Information System (INIS)

    Warner, B

    2002-01-01

    Restricted availability of funding has had an adverse impact, unforeseen at the time of the original decision to projectize the National Ignition Facility (NIF) Cryogenic Target Handling Systems (NCTS) Program, on the planning and initiation of these efforts. The purpose of this document is to provide an interim project management plan describing the organizational structure and management processes currently in place for NCTS. Preparation of a Program Execution Plan (PEP) for NCTS has been initiated, and a current draft is provided as Attachment 1 to this document. The National Ignition Facility is a multi-megajoule laser facility being constructed at Lawrence Livermore National Laboratory (LLNL) by the National Nuclear Security Administration (NNSA) in the Department of Energy (DOE). Its primary mission is to support the Stockpile Stewardship Program (SSP) by performing experiments studying weapons physics, including fusion ignition. NIF also supports the missions of weapons effects, inertial fusion energy, and basic science in high-energy-density physics. NIF will be operated by LLNL under contract to the University of California (UC) as a national user facility. NIF is a low-hazard, radiological facility, and its operation will meet all applicable federal, state, and local Environmental Safety and Health (ES and H) requirements. The NCTS Interim Management Plan provides a summary of primary design criteria and functional requirements, current organizational structure, tracking and reporting procedures, and current planning estimates of project scope, cost, and schedule. The NIF Director controls the NIF Cryogenic Target Systems Interim Management Plan. Overall scope content and execution schedules for the High Energy Density Physics Campaign (SSP Campaign 10) are currently undergoing rebaselining and will be brought into alignment with resources expected to be available throughout the NNSA Future Years National Security Plan (FYNSP). The revised schedule for

  5. Development of the HERA-Β-target-control system and study of target operation at the HERA storage ring

    International Nuclear Information System (INIS)

    Issever, S.

    2001-03-01

    The HERA-B experiment investigates the physics of heavy quarks, which are produced in pN reactions of the 920 GeV protons of HERA with the HERA-B internal fixed target. It consists out of eight wires, which surround the proton beam from four sides and is a high luminosity particle source. As being the closest mechanical device to the proton beam, it has to be operated very carefully and thus needs a secure and automatic control system, which additionally must be efficient and reliable to guarantee an efficient HERA-B data taking. The implementation of the target control system and its performance as well as dedicated studies of target-beam physics are presented. These include the measurement of the aperture limitation, usual target operational position, target efficiency, target independent proton loss in HERA and the scrape velocity of the target. The source of rate fluctuations is investigated in detail; among many dependencies environmental noise has a major impact on the rate fluctuations. Further studies include the analysis of beam position fluctuations and its correlation to the rate fluctuations; the rate changes about a factor of 2, if the beam is changing its position by 10 μm. This rate sensitivity is also verified directly by means of step function measurements. Furthermore the step function measurements can be used to study target-beam dynamics on time scales as short as a second. Experiments to reduce the rate sensitivity - the so called beam tail shaping measurements - are presented as well. During target operation a current, which is proportional to the interaction rate, is measured and used to determine the rate of each single wire. It is shown, that the source of this current is delta electron production. Finally the multiwire performance of the target control system is presented. (orig.)

  6. Solid expandable systems put deepwater targets within reach

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Roca, Eduardo [Enventure Global Technology L.L.C., Houston, TX (United States). Latin America; Fristch, Jerry [Enventure Global Technology L.L.C., Houston, TX (United States)

    2008-07-01

    Enabling technologies that take drilling operations to deeper objectives have made a significant impact on the practicality of many projects, especially deep water offshore targets. Increasing vertical depth and lateral reach requires adequate hole size to attain the desired objectives of the well bore. Solid expandable technology can maintain and retain hole size to address both the physical limitations and the economic feasibility of deep water operations. With each and every casing point, the potential for adequate hole size at total depth (TD) decreases. Solid expandable open hole liners and single-diameter systems reduce and eliminate, respectively, the well bore tapering that dictates hole size at TD and subsequent completion size. Successful mitigation of this tapering, whether through the entire well bore or through select zones, enables operators to gain access to previously unreachable reserves. Solid expandable systems have proven to be reliable and effective with over 1,000 installations in a myriad of conditions and environments worldwide. To date, over 115 of those applications have been in deep water environments. The current operating envelope for solid expandable systems include the deepest installation at {approx}28,750 ft (8,763 m) and the longest at 6,867 ft (2,083 m) in water depth over 3,150 ft (960 m). This record-length application consisted of an open hole liner installed and expanded in a single run. This paper will discuss the effectiveness of solid expandable systems in deep water operations and how the technology brings value to offshore projects especially when planned into the initial design. Case histories will be used to further illustrate the features, advantages, and benefits of expandable technology. In addition, this paper will examine the state of the solid expandable technology and its continuing evolution to provide even more drilling solutions. (author)

  7. Aliskiren targets multiple systems to alleviate cancer cachexia.

    Science.gov (United States)

    Wang, Chaoyi; Guo, Dunwei; Wang, Qiang; You, Song; Qiao, Zhongpeng; Liu, Yong; Dai, Hang; Tang, Hua

    2016-11-01

    To examine the effects of aliskiren, a small-molecule renin inhibitor, on cancer cachexia and to explore the underlying mechanisms. A cancer cachexia model was established by subcutaneously injecting C26 mouse colon carcinoma cells into isogenic BALB/c mice. Aliskiren was administered intragastrically [10 mg/kg body weight (BW)] on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection. Mice that received no C26 injection (healthy controls, HC group) or only C26 injection but not aliskiren (cancer, CA group) were used as controls. BW, tumor growth, whole body functions, and survival were monitored daily in half of the mice in each group, whereas serum, tumors, and gastrocnemius muscles were harvested from the other mice after sacrifice on day 20 for further analysis. Aliskiren significantly alleviated multiple cachexia‑associated symptoms, including BW loss, tumor burden, muscle wasting, muscular dysfunction, and shortened survival. On the molecular level, aliskiren antagonized cachexia‑induced activation of the renin‑angiotensin system (RAS), systematic and muscular inflammation, oxidative stress, and autophagy‑lysosome as well as ubiquitin‑proteasome stimulation. In addition, early administration of aliskiren before cachexia development (AP group) resulted in more robust effects in alleviating cachexia or targeting underlying mechanisms than administration after cachexia development (AT group). Aliskiren exhibited potent anti‑cachexia activities. These activities were achieved through the targeting of at least four mechanisms underlying cachexia development: RAS activation, increase in systematic inflammation, upregulation of oxidative stress, and stimulation of autophagy-lysosome pathway (ALP) and ubiquitin-proteasome pathway (UPP).

  8. 6 Ma age of carving Westernmost Grand Canyon: Reconciling geologic data with combined AFT, (U-Th)/He, and 4He/3He thermochronologic data

    Science.gov (United States)

    Winn, Carmen; Karlstrom, Karl E.; Shuster, David L.; Kelley, Shari; Fox, Matthew

    2017-09-01

    Conflicting hypotheses about the timing of carving of the Grand Canyon involve either a 70 Ma (;old;) or conflict with these lines of evidence, but are reconciled in this paper via the integration of three methods of analyses on the same sample: apatite (U-Th)/He ages (AHe), 4He/3He thermochronometry (4He/3He), and apatite fission-track ages and lengths (AFT). HeFTy software was used to generate time-temperature (t-T) paths that predict all new and published 4He/3He, AHe, and AFT data to within assumed uncertainties. These t-T paths show cooling from ∼100 °C to 40-60 °C in the Laramide (70-50 Ma), long-term residence at 40-60 °C in the mid-Tertiary (50-10 Ma), and cooling to near-surface temperatures after 10 Ma, and thus support young incision of the westernmost Grand Canyon. A subset of AHe data, when interpreted alone (i.e. without 4He/3He or AFT data), are better predicted by t-T paths that cool to surface temperatures during the Laramide, consistent with an ;old; Grand Canyon. However, the combined AFT, AHe, and 4He/3He analysis of a key sample from Separation Canyon can only be reconciled by a ;young; Canyon. Additional new AFT (5 samples) and AHe data (3 samples) in several locations along the canyon corridor also support a ;young; Canyon. This inconsistency, which mimics the overall controversy of the age of the Grand Canyon, is reconciled here by optimizing cooling paths so they are most consistent with multiple thermochronometers from the same rocks. To do this, we adjusted model parameters and uncertainties to account for uncertainty in the rate of radiation damage annealing in these apatites during sedimentary burial and the resulting variations in He retentivity. In westernmost Grand Canyon, peak burial conditions (temperature and duration) during the Laramide were likely insufficient to fully anneal radiation damage that accumulated during prolonged, near-surface residence since the Proterozoic. We conclude that application of multiple

  9. Hulthén potential models for α−α and α−He3 elastic scattering

    Indian Academy of Sciences (India)

    2017-02-09

    Feb 9, 2017 ... considered between each pair of particles, is a finite- depth central potential. As the α-particles are tightly bound, the low-lying states of such systems can be determined fairly well through the relative motion of α-particles. The general procedure to understand such a system is to make use of the partial wave ...

  10. Automatic target alignment of the Helios laser system

    International Nuclear Information System (INIS)

    Liberman, I.; Viswanathan, V.K.; Klein, M.; Seery, B.D.

    1980-01-01

    An automatic target-alignment technique for the Helios laser facility is reported and verified experimentally. The desired alignment condition is completely described by an autocollimation test. A computer program examines the autocollimated return pattern from the surrogate target and correctly describes any changes required in mirror orientation to yield optimum targe alignment with either aberrated or misaligned beams. Automated on-line target alignment is thus shown to be feasible

  11. Muon-catalyzed fusion experiment target and detector system. Preliminary design report

    International Nuclear Information System (INIS)

    Jones, S.E.; Watts, K.D.; Caffrey, A.J.; Walter, J.B.

    1982-03-01

    We present detailed plans for the target and particle detector systems for the muon-catalyzed fusion experiment. Requirements imposed on the target vessel by experimental conditions and safety considerations are delineated. Preliminary designs for the target vessel capsule and secondary containment vessel have been developed which meet these requirements. In addition, the particle detection system is outlined, including associated fast electronics and on-line data acquisition. Computer programs developed to study the target and detector system designs are described

  12. Review of ISOL target-ion-source systems

    CERN Document Server

    Kirchner, R

    2003-01-01

    Any review of target-ion-source systems (TISS) is necessarily a variation of the ISOL-theme 'efficient, fast, selective'. In the first part, more than 30 years of TISS development are examined in view of these key characteristics. By looking at the lines of development that were successful, at the lines that were abandoned (partly for good, partly for less good reasons), the lines with the most promising perspectives emerge. The second part deals with on-line chemistry in the TISS and its possibly double benefits: enhanced selectivity or increased separation speed, or both in favourable cases, as the relatively new sulfide chemistry. For the group-IVa-elements germanium and tin, the separation as sulfide-ions does not only suppress strongly the contamination by the neighbouring elements. It also reduces the effusion part of the release by orders of magnitude to the level of the intrinsic delay caused by molecular flow. The homologue chemistry is likely to work for silicon, but not for lead. While selectivity ...

  13. Programmable Ultrasonic Sensing System for Targeted Spraying in Orchards

    Directory of Open Access Journals (Sweden)

    Marko Hočevar

    2012-11-01

    Full Text Available This research demonstrates the basic elements of a prototype automated orchard sprayer which delivers pesticide spray selectively with respect to the characteristics of the targets. The density of an apple tree canopy was detected by PROWAVE 400EP250 ultrasound sensors controlled by a Cypress PSOC CY8C29466 microcontroller. The ultrasound signal was processed with an embedded computer built around a LPC1343 microcontroller and fed in real time to electro-magnetic valves which open/close spraying nozzles in relation to the canopy structure. The analysis focuses on the detection of appropriate thresholds on 15 cm ultrasound bands, which correspond to maximal response to tree density, and this was selected for accurate spraying guidance. Evaluation of the system was performed in an apple orchard by detecting deposits of tartrazine dye (TD on apple leaves. The employment of programmable microcontrollers and electro-magnetic valves decreased the amount of spray delivered by up to 48.15%. In contrast, the reduction of TD was only up to 37.7% at some positions within the tree crown and 65.1% in the gaps between trees. For all these reasons, this concept of precise orchard spraying can contribute to a reduction of costs and environmental pollution, while obtaining similar or even better leaf deposits.

  14. Programmable Ultrasonic Sensing System for Targeted Spraying in Orchards

    Science.gov (United States)

    Stajnko, Denis; Berk, Peter; Lešnik, Mario; Jejčič, Viktor; Lakota, Miran; Štrancar, Andrej; Hočevar, Marko; Rakun, Jurij

    2012-01-01

    This research demonstrates the basic elements of a prototype automated orchard sprayer which delivers pesticide spray selectively with respect to the characteristics of the targets. The density of an apple tree canopy was detected by PROWAVE 400EP250 ultrasound sensors controlled by a Cypress PSOC CY8C29466 microcontroller. The ultrasound signal was processed with an embedded computer built around a LPC1343 microcontroller and fed in real time to electro-magnetic valves which open/close spraying nozzles in relation to the canopy structure. The analysis focuses on the detection of appropriate thresholds on 15 cm ultrasound bands, which correspond to maximal response to tree density, and this was selected for accurate spraying guidance. Evaluation of the system was performed in an apple orchard by detecting deposits of tartrazine dye (TD) on apple leaves. The employment of programmable microcontrollers and electro-magnetic valves decreased the amount of spray delivered by up to 48.15%. In contrast, the reduction of TD was only up to 37.7% at some positions within the tree crown and 65.1% in the gaps between trees. For all these reasons, this concept of precise orchard spraying can contribute to a reduction of costs and environmental pollution, while obtaining similar or even better leaf deposits. PMID:23202220

  15. Magneto-mechanical trapping systems for biological target detection

    International Nuclear Information System (INIS)

    Li, Fuquan; Kodzius, Rimantas; Gooneratne, Chinthaka P.; Foulds, Ian G.; Kosel, Jürgen

    2014-01-01

    We demonstrate a magnetic microsystem capable of detecting nucleic acids via the size difference between bare magnetic beads and bead compounds. The bead compounds are formed through linking nonmagnetic beads and magnetic beads by the target nucleic acids. The system comprises a tunnel magneto-resistive (TMR) sensor, a trapping well, and a bead-concentrator. The TMR sensor detects the stray field of magnetic beads inside the trapping well, while the sensor output depends on the number of beads. The size of the bead compounds is larger than that of bare magnetic beads, and fewer magnetic beads are required to fill the trapping well. The bead-concentrator, in turn, is capable of filling the trap in a controlled fashion and so to shorten the assay time. The bead-concentrator includes conducting loops surrounding the trapping well and a conducting line underneath. The central conducting line serves to attract magnetic beads in the trapping well and provides a magnetic field to magnetize them so to make them detectable by the TMR sensor. This system excels by its simplicity in that the DNA is incubated with magnetic and nonmagnetic beads, and the solution is then applied to the chip and analyzed in a single step. In current experiments, a signal-to-noise ratio of 40.3 dB was obtained for a solution containing 20.8 nM of DNA. The sensitivity and applicability of this method can be controlled by the size or concentration of the nonmagnetic bead, or by the dimension of the trapping well. (author)

  16. Magneto-mechanical trapping systems for biological target detection

    KAUST Repository

    Li, Fuquan

    2014-03-29

    We demonstrate a magnetic microsystem capable of detecting nucleic acids via the size difference between bare magnetic beads and bead compounds. The bead compounds are formed through linking nonmagnetic beads and magnetic beads by the target nucleic acids. The system comprises a tunnel magneto-resistive (TMR) sensor, a trapping well, and a bead-concentrator. The TMR sensor detects the stray field of magnetic beads inside the trapping well, while the sensor output depends on the number of beads. The size of the bead compounds is larger than that of bare magnetic beads, and fewer magnetic beads are required to fill the trapping well. The bead-concentrator, in turn, is capable of filling the trap in a controlled fashion and so to shorten the assay time. The bead-concentrator includes conducting loops surrounding the trapping well and a conducting line underneath. The central conducting line serves to attract magnetic beads in the trapping well and provides a magnetic field to magnetize them so to make them detectable by the TMR sensor. This system excels by its simplicity in that the DNA is incubated with magnetic and nonmagnetic beads, and the solution is then applied to the chip and analyzed in a single step. In current experiments, a signal-to-noise ratio of 40.3 dB was obtained for a solution containing 20.8 nM of DNA. The sensitivity and applicability of this method can be controlled by the size or concentration of the nonmagnetic bead, or by the dimension of the trapping well.

  17. Target tracking system based on preliminary and precise two-stage compound cameras

    Science.gov (United States)

    Shen, Yiyan; Hu, Ruolan; She, Jun; Luo, Yiming; Zhou, Jie

    2018-02-01

    Early detection of goals and high-precision of target tracking is two important performance indicators which need to be balanced in actual target search tracking system. This paper proposed a target tracking system with preliminary and precise two - stage compound. This system using a large field of view to achieve the target search. After the target was searched and confirmed, switch into a small field of view for two field of view target tracking. In this system, an appropriate filed switching strategy is the key to achieve tracking. At the same time, two groups PID parameters are add into the system to reduce tracking error. This combination way with preliminary and precise two-stage compound can extend the scope of the target and improve the target tracking accuracy and this method has practical value.

  18. Gas, Liquid and Molten Targets at Cyclotron Beams: Target Systems and Related Nuclear Database

    Energy Technology Data Exchange (ETDEWEB)

    Ditrói, F.; Tárkányi, F.; Takács, S. [Institute of Nuclear Research of the Hungarian Academy of Sciences (ATOMKI), Debrecen (Hungary)

    2009-07-01

    In a systematic study our group worked on measurement of activation data of charged particle induced nuclear reaction possible involved in the production of radioisotopes for medical use. We have investigated the cross section and yield data of proton, deuteron helium-3 and alpha particle induced reactions on target materials for isotope productions relevant for medical applications as well as nuclear reactions on different structural material applied in construction of different target units. The acquired information are used or in the future can be used to determine the type of the construction materials optimal for building a certain target unit to be able to produce high specific activity and high quality radioactive isotope. In this work we have investigated different materials in activation point of view. Also several materials and reactions were studied for monitoring purposes. Use of thin metallic foils is a simple method to determine the parameters of the charged particle beams applied for isotope production. Using this method one can determine the energy and intensity of the bombarding beam and in certain cases the distribution or the profile of the bombarding beam. (author)

  19. Preparation of uranium electrodeposited target in aqueous system

    International Nuclear Information System (INIS)

    Chen Qiping; Li Yougen; Zhong Wenbin

    2006-03-01

    The main factors affecting uranium electrodeposition were tested and discussed. In the primary experiment about preparation of uranium isotopic target by electrodeposition, a stainless steel disk has been chosen as the target material, the electrolytic bath is comprised of UO 2 (NO 3 ) 2 and (NH 4 ) 2 C 2 O 4 , which has been adjusted to a pH of 2-3. Composition of the lost electrolytic bath was analysed by spectrophotometer. The thickness of resulting film is about 8-10 mg/cm 2 , the target having a thin, continuous, uniform layer of uranium, and its electrodeposited rate is more than 80%. (authors)

  20. Optical system for Argus 355-nm 90-mm aperture target-illumination experiments

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, B.C.; Boyd, R.; Hermes, G.; Hildum, J.S.; Linford, G.; Martin, W.E.

    1982-02-01

    The requirements of laser alignment, crystal tuning, target alignment, and laser beam diagnosis are provided by this optical system. Initial setup and preshot alignment techniques are discussed. Layout and operation are contrasted with the 532 nm target experiments.

  1. Target Probability Modulates Neuronal Activity in the Primate Saccadic System

    National Research Council Canada - National Science Library

    Basso, M

    2001-01-01

    The brain has a limited capacity to process information, so perceptual discriminations made when viewing natural visual scenes require that individual stimuli be singled out as targets for further analysis...

  2. An active target for the accelerator-based transmutation system

    Energy Technology Data Exchange (ETDEWEB)

    Grebyonkin, K.F. [Institute of Technical Physics, Chelyabinsk (Russian Federation)

    1995-10-01

    Consideration is given to the possibility of radical reduction in power requirements to the proton accelerator of the electronuclear reactor due to neutron multiplication both in the blanket and the target of an active material. The target is supposed to have the fast-neutron spectrum, and the blanket-the thermal one. The blanket and the target are separated by the thermal neutrons absorber, which is responsible for the neutron decoupling of the active target and blanket. Also made are preliminary estimations which illustrate that the realization of the idea under consideration can lead to significant reduction in power requirements to the proton beam and, hence considerably improve economic characteristics of the electronuclear reactor.

  3. Preparation of uranium electrodeposited target in aqueous system

    Energy Technology Data Exchange (ETDEWEB)

    Qiping, Chen; Yougen, Li; Wenbin, Zhong [China Academy of Engineering Physics, Mianyang (China). Inst. of Nuclear Physics and Chemistry

    2006-03-15

    The main factors affecting uranium electrodeposition were tested and discussed. In the primary experiment about preparation of uranium isotopic target by electrodeposition, a stainless steel disk has been chosen as the target material, the electrolytic bath is comprised of UO{sub 2}(NO{sub 3}){sub 2} and (NH{sub 4}){sub 2}C{sub 2}O{sub 4}, which has been adjusted to a pH of 2-3. Composition of the lost electrolytic bath was analysed by spectrophotometer. The thickness of resulting film is about 8-10 mg/cm{sup 2}, the target having a thin, continuous, uniform layer of uranium, and its electrodeposited rate is more than 80%. (authors)

  4. Towards a comprehensive system of methodological considerations for cities' climate targets

    International Nuclear Information System (INIS)

    Kramers, Anna; Wangel, Josefin; Johansson, Stefan; Höjer, Mattias; Finnveden, Göran; Brandt, Nils

    2013-01-01

    Climate targets for cities abound. However, what these targets really imply is dependent on a number of decisions regarding system boundaries and methods of calculation. In order to understand and compare cities' climate targets, there is a need for a generic and comprehensive framework of key methodological considerations. This paper identifies eight key methodological considerations for the different choices that can be made when setting targets for GHG emissions in a city and arranges them in four categories: temporal scope of target, object for target setting, unit of target, and range of target. To explore how target setting is carried out in practice, the climate targets of eight European cities were analysed. The results showed that these targets cover only a limited part of what could be included. Moreover, the cities showed quite limited awareness of what is, or could be, include in the targets. This makes comparison and benchmarking between cities difficult. - Highlights: • Cities' climate targets are almost impossible to compare and benchmark. • There is a need for consistent protocols and frameworks supporting target setting. • A framework with key methodological considerations for cities' climate targets is identified. • The framework is used to explore the climate targets for eight European cities. • The difference between production- and consumption based accounting is illustrated in a new way

  5. Experimental study of hydrodynamics of target system construction with liquid metallic coolant on water models

    International Nuclear Information System (INIS)

    Beznosov, A.; Davidov, D.; Khokhlov, D.

    2001-01-01

    This paper is about experimental study of hydrodynamics of target system construction with a spherical beam window (membrane). The visualization of current and current velocity fields in energy release area was considered. The findings are used to optimize the geometrical characteristics of target system. Also report contains the information about functioning accelerator-driven system, description it principle circuit and description of basic requirements what the target design should satisfy. (authors)

  6. Nuclear and radiation safety assurance federal target programme management system

    International Nuclear Information System (INIS)

    Kryukov, O.V.; Vasil'ev, V.A.; Nikishin, D.A.; Linge, I.I.; Obodinskij, A.N.

    2012-01-01

    The Federal Program Nuclear and Radiation Safety Assurance for 2008-2015 is presented. Specifics of Federal target program management as well as changes to program management are discussed. Data on evaluation of management effectiveness is given. Further efforts to resolve the nuclear legacy problem in Russia are also presented [ru

  7. Therapeutic targets of renin-angiotensin system in ocular disorders

    Directory of Open Access Journals (Sweden)

    Rajesh Choudhary

    2017-03-01

    Conclusions: The RAS components are present in the extrarenal tissues including ocular tissue and have an imperative role in the ocular pathophysiology. The clinical studies are needed to show the role of therapeutic modalities targeting RAS in the treatment of different ocular disorders.

  8. Drug targeting systems for inflammatory disease: one for all, all for one

    NARCIS (Netherlands)

    Crielaard, B.J.; Lammers, Twan Gerardus Gertudis Maria; Schiffelers, R.M.; Storm, Gerrit

    2012-01-01

    Abstract In various systemic disorders, structural changes in the microenvironment of diseased tissues enable both passive and active targeting of therapeutic agents to these tissues. This has led to a number of targeting approaches that enhance the accumulation of drugs in the target tissues,

  9. EXPERIMENTAL TARGET INJECTION AND TRACKING SYSTEM CONSTRUCTION AND SINGLE SHOT TESTING

    International Nuclear Information System (INIS)

    PETZOLDT, R.W.; ALEXANDER, N.B.; DRAKE, T.J.; GOODIN, D.T; JONESTRACK, K; VERMILLION, B.A

    2003-01-01

    Targets must be injected into an IFE power plant at a rate of approximately 5 to 10 Hz. Targets must be tracked very accurately to allow driver beams to be aligned with defined points on the targets with accuracy ± 150 (micro)m for indirect drive and ± 20 (micro)m for direct drive. An experimental target injection and tracking system has been constructed at General Atomics. The injector system will be used as a tool for testing the survivability of various target designs and provide feedback to the target designers. Helium gas propels the targets down an 8 m gun barrel up to 400 m/s. Direct-drive targets are protected in the barrel by sabots that are spring loaded to separate into two halves after acceleration. A sabot deflector directs the sabot halves away from the target injection path. Targets will be optically tracked with laser beams and line-scan cameras. Target position and arrival time will be predicted in real time based on early target position measurements. The system installation will be described. System testing to overcome excessive projectile wear and debris in the gun barrel is presented

  10. Automatic system of production, transfer and processing of coin targets for the production of metallic radioisotopes

    Science.gov (United States)

    Pellicioli, M.; Ouadi, A.; Marchand, P.; Foehrenbacher, T.; Schuler, J.; Dick-Schuler, N.; Brasse, D.

    2017-05-01

    The work presented in this paper gathers three main technical developments aiming at 1) optimizing nuclide production by the mean of solid targets 2) automatically transferring coin targets from vault to hotcell without human intervention 3) processing target dilution and purification in hotcell automatically. This system has been installed on a ACSI TR24 cyclotron in Strasbourg France.

  11. Development of the jet-target system of the MAGIX experiment

    Energy Technology Data Exchange (ETDEWEB)

    Stephan, Aulenbacher [Institut fuer Kernphysik, JGU, Mainz (Germany); Collaboration: Magix/MESA-Collaboration

    2016-07-01

    Since the new accelerator MESA which will be built up in Mainz in the next years operates at low Energies (100 MeV), but at high beam currents (1 mA), a thin windowless target is required. Therefore the MAGIX collaboration is developing a Jet-Target. This target blasts a Gas-Jet perpendicular to the beam through the scattering chamber of MAGIX. This talk is about the development of this Target System.

  12. Conceptual design of the handling and storage system for spent target vessel

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Junichi; Sasaki, Shinobu; Kaminaga, Masanori; Hino, Ryutaro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2001-03-01

    A conceptual design of a handling and storage system for spent target vessels has been carried out, in order to establish spent target technology for the neutron scattering facility. The spent target vessels must be treated remotely with high reliability and safety, since they are highly activated and contain the poisonous mercury. The system is composed of a target exchange trolley to exchange the target vessel, remote handling equipment such as manipulators, airtight casks for the spent target vessel, storage pits and so on. This report presents the results of conceptual design study on a basic plan, a handling procedure, main devices and their arrangement of a handling and storage system for the spent target vessels. (author)

  13. A Target Advertisement System Based on TV Viewer's Profile Reasoning

    Science.gov (United States)

    Lim, Jeongyeon; Kim, Munjo; Lee, Bumshik; Kim, Munchurl; Lee, Heekyung; Lee, Han-Kyu

    With the rapidly growing Internet, the Internet broadcasting and web casting service have been one of the well-known services. Specially, it is expected that the IPTV service will be one of the principal services in the broadband network [2]. However, the current broadcasting environment is served for the general public and requires the passive attitude to consume the TV programs. For the advanced broadcasting environments, various research of the personalized broadcasting is needed. For example, the current unidirectional advertisement provides to the TV viewers the advertisement contents, depending on the popularity of TV programs, the viewing rates, the age groups of TV viewers, and the time bands of the TV programs being broadcast. It is not an efficient way to provide the useful information to the TV viewers from customization perspective. If a TV viewer does not need particular advertisement contents, then information may be wasteful to the TV viewer. Therefore, it is expected that the target advertisement service will be one of the important services in the personalized broadcasting environments. The current research in the area of the target advertisement classifies the TV viewers into clustered groups who have similar preference. The digital TV collaborative filtering estimates the user's favourite advertisement contents by using the usage history [1, 4, 5]. In these studies, the TV viewers are required to provide their profile information such as the gender, job, and ages to the service providers via a PC or Set-Top Box (STB) which is connected to digital TV. Based on explicit information, the advertisement contents are provided to the TV viewers in a customized way with tailored advertisement contents. However, the TV viewers may dislike exposing to the service providers their private information because of the misuse of it. In this case, it is difficult to provide appropriate target advertisement service.

  14. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease.

    Science.gov (United States)

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.

  15. Search for Solar Axions by the CERN Axion Solar Telescope with He3 Buffer Gas: Closing the Hot Dark Matter Gap

    Science.gov (United States)

    Arik, M.; Aune, S.; Barth, K.; Belov, A.; Borghi, S.; Bräuninger, H.; Cantatore, G.; Carmona, J. M.; Cetin, S. A.; Collar, J. I.; Da Riva, E.; Dafni, T.; Davenport, M.; Eleftheriadis, C.; Elias, N.; Fanourakis, G.; Ferrer-Ribas, E.; Friedrich, P.; Galán, J.; García, J. A.; Gardikiotis, A.; Garza, J. G.; Gazis, E. N.; Geralis, T.; Georgiopoulou, E.; Giomataris, I.; Gninenko, S.; Gómez, H.; Gómez Marzoa, M.; Gruber, E.; Guthörl, T.; Hartmann, R.; Hauf, S.; Haug, F.; Hasinoff, M. D.; Hoffmann, D. H. H.; Iguaz, F. J.; Irastorza, I. G.; Jacoby, J.; Jakovčić, K.; Karuza, M.; Königsmann, K.; Kotthaus, R.; Krčmar, M.; Kuster, M.; Lakić, B.; Lang, P. M.; Laurent, J. M.; Liolios, A.; Ljubičić, A.; Luzón, G.; Neff, S.; Niinikoski, T.; Nordt, A.; Papaevangelou, T.; Pivovaroff, M. J.; Raffelt, G.; Riege, H.; Rodríguez, A.; Rosu, M.; Ruz, J.; Savvidis, I.; Shilon, I.; Silva, P. S.; Solanki, S. K.; Stewart, L.; Tomás, A.; Tsagri, M.; van Bibber, K.; Vafeiadis, T.; Villar, J.; Vogel, J. K.; Yildiz, S. C.; Zioutas, K.; CAST Collaboration

    2014-03-01

    The CERN Axion Solar Telescope has finished its search for solar axions with He3 buffer gas, covering the search range 0.64 eV≲ma≲1.17 eV. This closes the gap to the cosmological hot dark matter limit and actually overlaps with it. From the absence of excess x rays when the magnet was pointing to the Sun we set a typical upper limit on the axion-photon coupling of gaγ≲3.3×10-10 GeV-1 at 95% C.L., with the exact value depending on the pressure setting. Future direct solar axion searches will focus on increasing the sensitivity to smaller values of gaγ, for example by the currently discussed next generation helioscope International AXion Observatory.

  16. The LANSCE (Los Alamos Neutron Scattering Center) target data collection system

    International Nuclear Information System (INIS)

    Kernodle, A.K.

    1989-01-01

    The Los Alamos Neutron Scattering Center (LANSCE) Target Data Collection System is the result of an effort to provide a base of information from which to draw conclusions on the performance and operational condition of the overall LANSCE target system. During the conceptualization of the system, several goals were defined. A survey was made of both custom-made and off-the-shelf hardware and software that were capable of meeting these goals. The first stage of the system was successfully implemented for the LANSCE run cycle 52. From the operational experience gained thus far, it appears that the LANSCE Target Data Collection System will meet all of the previously defined requirements

  17. New software of the control and data acquisition system for the Nuclotron internal target station

    International Nuclear Information System (INIS)

    Isupov, A.Yu.

    2012-01-01

    The control and data acquisition system for the Internal Target Station (ITS) of the Nuclotron (LHEP, JINR) is implemented. The new software is based on the ngdp framework under the Unix-like operating system FreeBSD to allow easy network distribution of the on-line data collected from ITS, as well as the internal target remote control

  18. Real-Time Target Motion Animation for Missile Warning System Testing

    Science.gov (United States)

    2006-04-01

    T. Perkins, R. Sundberg, J. Cordell, Z. Tun , and M. Owen, Real-time Target Motion Animation for Missile Warning System Testing, Proc. SPIE Vol 6208...Z39-18 Real-time target motion animation for missile warning system testing Timothy Perkins*a, Robert Sundberga, John Cordellb, Zaw Tunb, Mark

  19. Upgrade to the Cryogenic Hydrogen Gas Target Monitoring System

    Science.gov (United States)

    Slater, Michael; Tribble, Robert

    2013-10-01

    The cryogenic hydrogen gas target at Texas A&M is a vital component for creating a secondary radioactive beam that is then used in experiments in the Momentum Achromat Recoil Spectrometer (MARS). A stable beam from the K500 superconducting cyclotron enters the gas cell and some incident particles are transmuted by a nuclear reaction into a radioactive beam, which are separated from the primary beam and used in MARS experiments. The pressure in the target chamber is monitored so that a predictable isotope production rate can be assured. A ``black box'' received the analog pressure data and sent RS232 serial data through an outdated serial connection to an outdated Visual Basic 6 (VB6) program, which plotted the chamber pressure continuously. The black box has been upgraded to an Arduino UNO microcontroller [Atmel Inc.], which can receive the pressure data and output via USB to a computer. It has been programmed to also accept temperature data for future upgrade. A new computer program, with updated capabilities, has been written in Python. The software can send email alerts, create audible alarms through the Arduino, and plot pressure and temperature. The program has been designed to better fit the needs of the users. Funded by DOE and NSF-REU Program.

  20. Spallation Neutron Source Second Target Station Integrated Systems Update

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-04-01

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

  1. Target experimental area and systems of the Us national ignition facility

    International Nuclear Information System (INIS)

    Tobin, M.; Van Wonterghem, B.; MacGowan, B.J.; Hibbard, W.; Kalantar, D.; Lee, F.D.; Pittenger, L.; Wong, K.

    2000-01-01

    One of the major goals of the US National Ignition Facility is the demonstration of laser driven fusion ignition and burn of targets by inertial confinement and provide capability for a wide variety of high energy density physics experiments. The NIF target area houses the optical systems required to focus the 192 beamlets to a target precisely positioned at the center of the 10 meter diameter, 10-cm thick aluminum target chamber. The chamber serves as mounting surface for the 48 final optics assemblies, the target alignment and positioning equipment, and the target diagnostics. The internal surfaces of the chamber are protected by louvered steel beam dumps. The target area also provides the necessary shielding against target emission and environmental protection equipment. Despite its complexity, the design provides the flexibility to accommodate the needs of the various NIF user groups, such as direct and indirect drive irradiation geometries, modular final optics design, capability to handle cryogenic targets, and easily re-configurable diagnostic instruments. Efficient target area operations are ensured by using line-replaceable designs for systems requiring frequent inspection, maintenance and reconfiguration, such as the final optics, debris shields, phase plates and the diagnostic instruments. A precision diagnostic instrument manipulator (DIMS) allows fast removal and precise repositioning of diagnostic instruments. In addition we will describe several activities to enhance the target chamber availability, such as the target debris mitigation, the use of standard experimental configurations and the development of smart shot operations planning tools. (authors)

  2. Target experimental area and systems of the U.S. National Ignition Facility

    International Nuclear Information System (INIS)

    Tobin, M; Van Wonterghem, B; MacGowan, B J; Hibbard, W; Kalantar, D; Lee, F D; Pittenger, L; Wong, K

    1999-01-01

    One of the major goals of the US National Ignition Facility is the demonstration of laser driven fusion ignition and burn of targets by inertial confinement and provide capability for a wide variety of high energy density physics experiments. The NIF target area houses the optical systems required to focus the 192 beamlets to a target precisely positioned at the center of the 10 meter diameter, 10-cm thick aluminum target chamber. The chamber serves as mounting surface for the 48 final optics assemblies, the target alignment and positioning equipment, and the target diagnostics. The internal surfaces of the chamber are protected by louvered steel beam dumps. The target area also provides the necessary shielding against target emission and environmental protection equipment. Despite its complexity, the design provides the flexibility to accommodate the needs of the various NIF user groups, such as direct and indirect drive irradiation geometries, modular final optics design, capability to handle cryogenic targets, and easily re-configurable diagnostic instruments. Efficient target area operations are ensured by using line-replaceable designs for systems requiring frequent inspection, maintenance and reconfiguration, such as the final optics, debris shields, phase plates and the diagnostic instruments. A precision diagnostic instrument manipulator (DIMS) allows fast removal and precise repositioning of diagnostic instruments. In addition the authors describe several activities to enhance the target chamber availability, such as the target debris mitigation, the use of standard experimental configurations and the development of smart shot operations planning tools

  3. The peripheral GABAergic system as a target in endocrine disorders

    NARCIS (Netherlands)

    Gladkevich, A; Korf, J; Hakobyan, VP; Melkonyan, KV

    2006-01-01

    In addition to its well-recognized function as a cerebral inhibitory transmitter, less well established is the role of GABA in peripheral nervous and endocrine systems. We Summarize current evidence that GABA serves as a neurotransmitter or neuromodulator in the autonomic nervous system and as a

  4. Information Systems curriculum: the moving target phenomenon of ...

    African Journals Online (AJOL)

    This article determines the scope and nature of Information Systems training at Technikons in South Africa. Due to rapid changes in technology, knowledge regarding technology becomes obsolete rapidly. Therefore Information Systems learners should have the means and skills to keep abreast of advances in the ...

  5. Rotating target wheel system for super-heavy element production at ATLAS

    CERN Document Server

    Greene, J P; Falout, J; Janssens, R V F

    2004-01-01

    A new scattering chamber housing a large diameter rotating target wheel has been designed and constructed in front of the Fragment Mass Analyzer (FMA) for the production of very heavy nuclei (Z greater than 100) using beams from the Argonne Tandem Linear Accelerator System (ATLAS). In addition to the target and drive system, the chamber is extensively instrumented in order to monitor target performance and deterioration. Capabilities also exist to install rotating entrance and exit windows for gas cooling of the target within the scattering chamber. The design and initial tests are described.

  6. Nanoparticles laden in situ gelling system for ocular drug targeting

    Directory of Open Access Journals (Sweden)

    Divya Kumar

    2013-01-01

    Full Text Available Designing an ophthalmic drug delivery system is one of the most difficult challenges for the researchers. The anatomy and physiology of eye create barriers like blinking which leads to the poor retention time and penetration of drug moiety. Some conventional ocular drug delivery systems show shortcomings such as enhanced pre-corneal elimination, high variability in efficiency, and blurred vision. To overcome these problems, several novel drug delivery systems such as liposomes, nanoparticles, hydrogels, and in situ gels have been developed. In situ-forming hydrogels are liquid upon instillation and undergo phase transition in the ocular cul-de-sac to form viscoelastic gel and this provides a response to environmental changes. In the past few years, an impressive number of novel temperature, pH, and ion-induced in situ-forming systems have been reported for sustain ophthalmic drug delivery. Each system has its own advantages and drawbacks. Thus, a combination of two drug delivery systems, i.e., nanoparticles and in situ gel, has been developed which is known as nanoparticle laden in situ gel. This review describes every aspects of this novel formulation, which present the readers an exhaustive detail and might contribute to research and development.

  7. Structural systems pharmacology: a new frontier in discovering novel drug targets.

    Science.gov (United States)

    Tan, Hepan; Ge, Xiaoxia; Xie, Lei

    2013-08-01

    The modern target-based drug discovery process, characterized by the one-drug-one-gene paradigm, has been of limited success. In contrast, phenotype-based screening produces thousands of active compounds but gives no hint as to what their molecular targets are or which ones merit further research. This presents a question: What is a suitable target for an efficient and safe drug? In this paper, we argue that target selection should take into account the proteome-wide energetic and kinetic landscape of drug-target interactions, as well as their cellular and organismal consequences. We propose a new paradigm of structural systems pharmacology to deconvolute the molecular targets of successful drugs as well as to identify druggable targets and their drug-like binders. Here we face two major challenges in structural systems pharmacology: How do we characterize and analyze the structural and energetic origins of drug-target interactions on a proteome scale? How do we correlate the dynamic molecular interactions to their in vivo activity? We will review recent advances in developing new computational tools for biophysics, bioinformatics, chemoinformatics, and systems biology related to the identification of genome-wide target profiles. We believe that the integration of these tools will realize structural systems pharmacology, enabling us to both efficiently develop effective therapeutics for complex diseases and combat drug resistance.

  8. Targeting DNA repair systems in antitubercular drug development.

    Science.gov (United States)

    Minias, Alina; Brzostek, Anna; Dziadek, Jaroslaw

    2018-01-28

    Infections with Mycobacterium tuberculosis, the causative agent of tuberculosis, are difficult to treat using currently available chemotherapeutics. Clinicians agree on the urgent need for novel drugs to treat tuberculosis. In this mini review, we summarize data that prompts the consideration of DNA repair-associated proteins as targets for the development of new antitubercular compounds. We discuss data, including gene expression data, that highlight the importance of DNA repair genes during the pathogenic cycle as well as after exposure to antimicrobials currently in use. Specifically, we report experiments on determining the essentiality of DNA repair-related genes. We report the availability of protein crystal structures and summarize discovered protein inhibitors. Further, we describe phenotypes of available gene mutants of M. tuberculosis and model organisms Mycobacterium bovis and Mycobacterium smegmatis. We summarize experiments regarding the role of DNA repair-related proteins in pathogenesis and virulence performed both in vitro and in vivo during the infection of macrophages and animals. We detail the role of DNA repair genes in acquiring mutations, which influence the rate of drug resistance acquisition. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Plasma properties of RF magnetron sputtering system using Zn target

    Energy Technology Data Exchange (ETDEWEB)

    Nafarizal, N.; Andreas Albert, A. R.; Sharifah Amirah, A. S.; Salwa, O.; Riyaz Ahmad, M. A. [Microelectronic and Nanotechnology - Shamsuddin Research Centre (MiNT-SRC), Faculty of Electrical and Electronic Engineering, Universiti Tun Hussein Onn Malaysia 86400 Parit Raja, Batu Pahat, Johor (Malaysia)

    2012-06-29

    In the present work, we investigate the fundamental properties of magnetron sputtering plasma using Zn target and its deposited Zn thin film. The magnetron sputtering plasma was produced using radio frequency (RF) power supply and Argon (Ar) as ambient gas. A Langmuir probe was used to collect the current from the plasma and from the current intensity, we calculate the electron density and electron temperature. The properties of Zn sputtering plasma at various discharge conditions were studied. At the RF power ranging from 20 to 100 W and gas pressure 5 mTorr, we found that the electron temperature was almost unchanged between 2-2.5 eV. On the other hand, the electron temperature increased drastically from 6 Multiplication-Sign 10{sup 9} to 1 Multiplication-Sign 10{sup 10}cm{sup -3} when the discharge gas pressure increased from 5 to 10 mTorr. The electron microscope images show that the grain size of Zn thin film increase when the discharge power is increased. This may be due to the enhancement of plasma density and sputtered Zn density.

  10. Directions for reactor target design based on the US heavy ion fusion systems assessment

    International Nuclear Information System (INIS)

    Wilson, D.C.; Dudziak, D.; Magelssen, G.; Zuckerman, D.; Dreimeyer, D.

    1986-01-01

    We studied areas of major uncertainty in target design using the cost of electricity as our figure of merit. Net electric power from the plant was fixed at 1000 MW to eliminate large effects due to economies of scale. The system is relatively insensitive to target gain. Factors of three changes in gain cause only 8 to 12% changes in electricity cost. An increase in the peak power needed to drive targets poses only a small cost risk, but requires many more beamlets be transported to the target. A shortening of the required ion range causes both cost and beamlet difficulties. A factor of 4 decrease in the required range at a fixed driver energy increases electricity cost by 44% and raises the number of beamlets to 240. Finally, the heavy ion fusion system can accommodate large increases in target costs. To address the major uncertainties, target design should concentrate on the understanding requirements for ion range and peak driver power

  11. The immune system as a target for antibiotics

    NARCIS (Netherlands)

    Grondel, J.L.

    1986-01-01

    Studies on antibiotics, oxytetracycline (OxyTC) in particular, are presented in this thesis with respect to the influence of these drugs on the immune system of carp and chickens. Special attention was paid to the pharmacokinetic behaviour of

  12. Targeted nanodrug delivery systems for the treatment of Tuberculosis

    CSIR Research Space (South Africa)

    Lemmer, Yolandy

    2010-06-01

    Full Text Available patient treatment compliance and drug resistance pose a great challenge to TB treatment programs worldwide. To improve the current inadequate therapeutic management of TB, a polymeric anti-TB nanodrug delivery system for anti-TB drugs was developed...

  13. A proton microbeam deflection system to scan target surfaces

    International Nuclear Information System (INIS)

    Heck, D.

    1978-12-01

    A system to deflect the proton beam within the Karlsruhe microbeam setup is described. The deflection is achieved whithin a transverse electrical field generated between parallel electrodes. Their tension is controlled by a pattern generator, thus enabling areal and line scans with a variable number of scan points at variable scan speed. The application is demonstrated at two different examples. (orig.) [de

  14. Targeting the humoral immune system of patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Teng, Yoe Kie Onno

    2008-01-01

    The aim of this thesis was to unravel the role of the humoral immune system in rheumatoid arthritis patients by employing new immunosuppressive strategies, i.e. specific B-cell depletion with Rituximab and non-specific lymfoablative treatment with high dose chemotherapy and hematopoeietic stem cell

  15. A Customer Relationship Management System to Target Customers at Cisco

    OpenAIRE

    Rahul Bhaskar

    2004-01-01

    This case describes the implementation of an Internet empowered Customer Relationship Management (CRM) at Cisco Systems Inc. After describing the organizational background of Cisco, the case takes the student into the issues that the executives faced after the market crash in 2001. John Chambers, Cisco CEO, and his team decided to strengthen Cisco’s relationship with the customers so that the company could emerge stronger when the markets recovered. Questions are raised as to the implementa...

  16. Sirtuins in the Cardiovascular System: Potential Targets in Pediatric Cardiology.

    Science.gov (United States)

    Ianni, Alessandro; Yuan, Xuejun; Bober, Eva; Braun, Thomas

    2018-06-01

    Cardiovascular diseases represent a major cause of death and morbidity. Cardiac and vascular pathologies develop predominantly in the aged population in part due to lifelong exposure to numerous risk factors but are also found in children and during adolescence. In comparison to adults, much has to be learned about the molecular pathways driving cardiovascular diseases in the pediatric population. Sirtuins are highly conserved enzymes that play pivotal roles in ensuring cardiac homeostasis under physiological and stress conditions. In this review, we discuss novel findings about the biological functions of these molecules in the cardiovascular system and their possible involvement in pediatric cardiovascular diseases.

  17. Solute carrier transporters: potential targets for digestive system neoplasms

    OpenAIRE

    Xie, Jing; Zhu, Xiao Yan; Liu, Lu Ming; Meng, Zhi Qiang

    2018-01-01

    Jing Xie,1,2 Xiao Yan Zhu,1,2 Lu Ming Liu,1,2 Zhi Qiang Meng1,2 1Department of Integrative Oncology, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China Abstract: Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues o...

  18. Professional soldier assessment of a rifle-mounted target hand-off system

    NARCIS (Netherlands)

    Levesque, J.; Banko, K.; Binsch, O.

    2015-01-01

    The miniaturization of digital image acquisition and processing hardware, positional sensors, and batteries has enabled the creation of assisted targeting systems light enough to be integrated onto small firearms to increase the probability of soldiers detecting and hitting targets. As well, the

  19. The endocannabinoid system: a new pharmacological target for obesity treatment?

    Science.gov (United States)

    Hu, Jia; Zhu, Chao; Huang, Mao

    2009-06-01

    Being a great threaten for human health, obesity has become a pandemic chronic disease. There have been several therapeutic treatments for this social health issue, including diet and exercise therapy, medication and surgery, among which the diet is still the most common way. However, none of these therapeutic measures available is ideal, making it necessary to find an effective medical treatment. The endocannabinoid system, which is well known for its contributions in certain mental processes such as relaxation, amelioration of pain and anxiety, and sedation initiation, has been recently reported to play an essential role in regulating appetite and metabolism to maintain energy balance, leading to the belief that endocannabinoid system is closely related to obesity. This new discovery deepens our understanding of obesity, and provides us with a new direction for clinical obesity treatment. Rimonabant is an antagonist for CB1, and has entered the market in some countries. However, although effective as an anti-obesity drug, rimonabant also causes obviously adverse side-effects, thus is being doubted and denied for medical usage.

  20. Conceptual design report for the University of Rochester cryogenic target delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Fagaly, R.L.; Alexander, N.B.; Bourque, R.F.; Dahms, C.F.; Lindgren, J.R.; Miller, W.J. (General Atomics, San Diego, CA (United States)); Bittner, D.N.; Hendricks, C.D. (W.J. Schafer Associates, Livermore, CA (United States))

    1993-05-01

    The upgrade of the Omega laser at the University of Rochester's Laboratory for Laser Energetics (UR/LLE) will result in a need for large targets filled with D[sub 2] or Dt and maintained at cryogenic temperatures. This mandates a cryogenic target delivery system capable of filling, layering, characterizing and delivering cryogenic targets to the Omega Upgrade target chamber. The program goal is to design, construct, and test the entire target delivery system by June 1996. When completed (including an operational demonstration), the system will be shipped to Rochester for reassembly and commissioning in time for the Omega Upgrade cryogenic campaign, scheduled to start in 1998. General Atomics has been assigned the task of developing the conceptual design for the cryogenic target delivery system. Design and fabrication activities will be closely coordinated with the University of Rochester, Lawrence Livermore National laboratory (LLNL) and Los Alamos National Laboratory (LANL), drawing upon their knowledge base in fuel layering and cryogenic characterization. The development of a target delivery system for Omega could also benefit experiments at Lawrence Livermore National Laboratory and the other ICF Laboratories in that the same technologies could be applied to NOVA, the National Ignition Facility or the future Laboratory Microfusion Facility.

  1. Conceptual design report for the University of Rochester cryogenic target delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Fagaly, R.L.; Alexander, N.B.; Bourque, R.F.; Dahms, C.F.; Lindgren, J.R.; Miller, W.J. [General Atomics, San Diego, CA (United States); Bittner, D.N.; Hendricks, C.D. [W.J. Schafer Associates, Livermore, CA (US)

    1993-05-01

    The upgrade of the Omega laser at the University of Rochester`s Laboratory for Laser Energetics (UR/LLE) will result in a need for large targets filled with D{sub 2} or Dt and maintained at cryogenic temperatures. This mandates a cryogenic target delivery system capable of filling, layering, characterizing and delivering cryogenic targets to the Omega Upgrade target chamber. The program goal is to design, construct, and test the entire target delivery system by June 1996. When completed (including an operational demonstration), the system will be shipped to Rochester for reassembly and commissioning in time for the Omega Upgrade cryogenic campaign, scheduled to start in 1998. General Atomics has been assigned the task of developing the conceptual design for the cryogenic target delivery system. Design and fabrication activities will be closely coordinated with the University of Rochester, Lawrence Livermore National laboratory (LLNL) and Los Alamos National Laboratory (LANL), drawing upon their knowledge base in fuel layering and cryogenic characterization. The development of a target delivery system for Omega could also benefit experiments at Lawrence Livermore National Laboratory and the other ICF Laboratories in that the same technologies could be applied to NOVA, the National Ignition Facility or the future Laboratory Microfusion Facility.

  2. Conceptual design report for the University of Rochester cryogenic target delivery system

    International Nuclear Information System (INIS)

    Fagaly, R.L.; Alexander, N.B.; Bourque, R.F.; Dahms, C.F.; Lindgren, J.R.; Miller, W.J.; Bittner, D.N.; Hendricks, C.D.

    1993-05-01

    The upgrade of the Omega laser at the University of Rochester's Laboratory for Laser Energetics (UR/LLE) will result in a need for large targets filled with D 2 or Dt and maintained at cryogenic temperatures. This mandates a cryogenic target delivery system capable of filling, layering, characterizing and delivering cryogenic targets to the Omega Upgrade target chamber. The program goal is to design, construct, and test the entire target delivery system by June 1996. When completed (including an operational demonstration), the system will be shipped to Rochester for reassembly and commissioning in time for the Omega Upgrade cryogenic campaign, scheduled to start in 1998. General Atomics has been assigned the task of developing the conceptual design for the cryogenic target delivery system. Design and fabrication activities will be closely coordinated with the University of Rochester, Lawrence Livermore National laboratory (LLNL) and Los Alamos National Laboratory (LANL), drawing upon their knowledge base in fuel layering and cryogenic characterization. The development of a target delivery system for Omega could also benefit experiments at Lawrence Livermore National Laboratory and the other ICF Laboratories in that the same technologies could be applied to NOVA, the National Ignition Facility or the future Laboratory Microfusion Facility

  3. Coping with Atmospheric Turbulence in the Selection of Laser Hardening Technology for FCS Targeting Systems

    National Research Council Canada - National Science Library

    Pritchett, Timothy M

    2004-01-01

    ... by frequency-agile battlefield lasers at both long and short range. Evidently, the selection of sensor protection technologies for incorporation into the final targeting system will be based on their optical limiting performance under field conditions...

  4. Performance of target detection algorithm in compressive sensing miniature ultraspectral imaging compressed sensing system

    Science.gov (United States)

    Gedalin, Daniel; Oiknine, Yaniv; August, Isaac; Blumberg, Dan G.; Rotman, Stanley R.; Stern, Adrian

    2017-04-01

    Compressive sensing theory was proposed to deal with the high quantity of measurements demanded by traditional hyperspectral systems. Recently, a compressive spectral imaging technique dubbed compressive sensing miniature ultraspectral imaging (CS-MUSI) was presented. This system uses a voltage controlled liquid crystal device to create multiplexed hyperspectral cubes. We evaluate the utility of the data captured using the CS-MUSI system for the task of target detection. Specifically, we compare the performance of the matched filter target detection algorithm in traditional hyperspectral systems and in CS-MUSI multiplexed hyperspectral cubes. We found that the target detection algorithm performs similarly in both cases, despite the fact that the CS-MUSI data is up to an order of magnitude less than that in conventional hyperspectral cubes. Moreover, the target detection is approximately an order of magnitude faster in CS-MUSI data.

  5. Development of Cursor-on-Target Control for Semi-Autonomous Unmanned Aircraft Systems

    National Research Council Canada - National Science Library

    Crouse, Joshua D

    2007-01-01

    .... The goal of this research is to develop a preliminary Cursor-on-Target control system to enable the operator to guide the unmanned aircraft with minimal workload during high task phases of flight...

  6. Double-shell target designs for the Los Alamos Scientific Laboratory eight-beam laser system

    International Nuclear Information System (INIS)

    Kindel, J.M.; Stroscio, M.A.

    1978-03-01

    We investigate two double-pusher laser fusion targets, one that incorporates an outer exploding pusher shell and another that uses velocity multiplication. Specific designs are presented for the Los Alamos Scientific Laboratory Eight-Beam Laser System

  7. Mechanical design and development of a high power target system for the SLC Positron Source

    International Nuclear Information System (INIS)

    Reuter, E.; Mansour, D.; Porter, T.; Sax, W.; Szumillo, A.

    1991-12-01

    In order to bring the SLC Positron Source luminosity up to design specifications, the previous (stationary) positron target had to be replaced with a version which could reliably dissipate the higher power levels and cyclic pulsed thermal stresses of the high intensity 33GeV electron beam. In addition to this basic requirement, the new target system had to meet SLAC's specifications for Ultra High Vacuum, be remotely controllable, ''radiation hard,'' and designed in such a way that it could be removed and replaced quickly and easily with minimum personnel exposure to radiation. It was also desirable to integrate the target and collection components into a compact, easily manufacturable, and easily maintainable module. This paper briefly summarize the mechanical design and development of the new modular target system, its associated controls and software, alignment, and the quick removal system. Operational experience gained with the new system over the first running cycle is also summarized

  8. Cryogenic-laser-fusion target implosion studies performed with the OMEGA uv-laser system

    International Nuclear Information System (INIS)

    Marshall, F.J.; Letzring, S.A.; Verdon, C.P.; Skupsky, S.; Keck, R.L.; Knauer, J.P.; Kremens, R.L.; Bradley, D.K.; Kessler, T.; Delettrez, J.; and others.

    1989-01-01

    A series of direct-drive laser-fusion implosion experiments was performed on cryogenically cooled, DT-filled glass microballoons with the OMEGA 24-beam uv (351-nm) laser system. The targets consisted of glass microballoons having radii of 100 to 150 μm, wall thicknesses of 3 to 7 μm, filled with DT gas at pressures of 75 to 100 atm. The targets were cooled to below the freezing point of DT, in situ, by a cryogenic target system. The targets were irradiated by approximately 1 to 1.2 kJ of uv light in 650-ps Gaussian pulses. The on-target irradiation uniformity was enhanced for these experiments by the use of distributed phase plates, which brought the estimated irradiation nonuniformities to ∼12% (σ rms ). Target performance was diagnosed by an array of x-ray, plasma, and nuclear instruments. The measured target performance showed ∼70% absorption, thermonuclear yields of 10 6 to 10 8 neutrons, and final fuel areal densities of 20 to 40 mg/cm 2 for the optimum targets examined in these experiments. Fuel densities at the time of thermonuclear neutron production, inferred from direct measurements of the fuel areal density, were in the range of 20 to 50 g/cm 3 (100 to 200 times the density of liquid DT) for the optimum targets

  9. Experimental study of liquid-metal target designs of accelerating-controlled systems

    International Nuclear Information System (INIS)

    Iarmonov, Mikhail; Makhov, Kirill; Novozhilova, Olga; Meluzov, A.G.; Beznosov, A.V.

    2011-01-01

    Models of a liquid-metal target of an accelerator-controlled system have been experimentally studied at the Nizhny Novgorod State Technical University to develop an optimal design of the flow part of the target. The main explored variants of liquid-metal targets are: Design with a diaphragm (firm-and-impervious plug) mounted on the pipe tap of particle transport from the accelerator cavity to the working cavity of the liquid-metal target. Design without a diaphragm on the pipe tab of particle transport from the accelerator. The study was carried out in a high-temperature liquid-metal test bench under the conditions close to full-scale ones: the temperature of the eutectic lead-bismuth alloy was 260degC - 400degC, the coolant mass flow was 5-80 t/h, and the rarefaction in the gas cavity was 10 5 Pa, the coefficient of geometric similarity equal to 1. The experimental studies of hydrodynamic characteristics of flow parts in the designs of targets under full-scale conditions indicated high efficiency of a target in triggering, operating, and deactivating modes. Research and technology instructions for designs of the flow part of the liquid-metal target, the target design as a whole, and the target circuit of accelerator-controlled systems were formulated as a result of the studies. (author)

  10. Transmutation of 126Sn in spallation targets of accelerator-driven systems

    International Nuclear Information System (INIS)

    Han, Chi Young; Saito, Masaki; Sagara, Hiroshi

    2009-01-01

    The practical feasibility of 126 Sn transmutation in spallation targets of accelerator-driven systems was evaluated from the viewpoints of accumulation of radioactive spallation products and neutron production as well as transmutation amount of 126 Sn. A cylindrical liquid 126 Sn target whose length depends on proton beam energy was described, based on a Pb-Bi target design of accelerator-driven system being developed in JAEA. A proton beam of 1.5 GeV-20 mA was estimated to give the transmutation rate of 126 Sn 6.4 kg/yr, which corresponds to the amount of 126 Sn annually discharged in 27 LWRs of 1 GWt and 33 GWd/THM. The equilibrium radioactivity of spallation products would reach 9% of that of 126 Sn transmuted in the spallation target, and the equilibrium toxicity would be just 3%. Some parametric analyses showed that the effective half-life of 126 Sn could be reduced through a proper reduction of the target size. The 126 Sn target was calculated to produce 40 neutrons per proton of 1.5 GeV and give a neutron spectrum very similar to that of the reference Pb-Bi target. As a result, the transmutation of 126 Sn in the spallation target has a high feasibility in terms of better transmutation performance and comparable target performance. (author)

  11. Penalty dynamic programming algorithm for dim targets detection in sensor systems.

    Science.gov (United States)

    Huang, Dayu; Xue, Anke; Guo, Yunfei

    2012-01-01

    In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD) called penalty DP-TBD (PDP-TBD) is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations.

  12. Integrated Solution of a Back Office System for Serious Games Targeted at Physiotherapy

    Directory of Open Access Journals (Sweden)

    Tiago Martins

    2016-01-01

    Full Text Available Serious games targeted at physiotherapy can be a solution to help the physical therapy professionals. However, the entire game management, in its various aspects, is under the professional’s responsibility. One way to reduce the professional management work will be to integrate a Back Office system in the game. Following this trend, the purpose of this paper is to present a modular Back Office system for centralized management of one or more games targeted at physical therapy.

  13. Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei.

    Science.gov (United States)

    Zimmermann, Stefanie; Oufir, Mouhssin; Leroux, Alejandro; Krauth-Siegel, R Luise; Becker, Katja; Kaiser, Marcel; Brun, Reto; Hamburger, Matthias; Adams, Michael

    2013-11-15

    In mice cynaropicrin (CYN) potently inhibits the proliferation of Trypanosoma brucei-the causative agent of Human African Trypanosomiasis-by a so far unknown mechanism. We hypothesized that CYNs α,β-unsaturated methylene moieties act as Michael acceptors for glutathione (GSH) and trypanothione (T(SH)2), the main low molecular mass thiols essential for unique redox metabolism of these parasites. The analysis of this putative mechanism and the effects of CYN on enzymes of the T(SH)2 redox metabolism including trypanothione reductase, trypanothione synthetase, glutathione-S-transferase, and ornithine decarboxylase are shown. A two step extraction protocol with subsequent UPLC-MS/MS analysis was established to quantify intra-cellular CYN, T(SH)2, GSH, as well as GS-CYN and T(S-CYN)2 adducts in intact T. b. rhodesiense cells. Within minutes of exposure to CYN, the cellular GSH and T(SH)2 pools were entirely depleted, and the parasites entered an apoptotic stage and died. CYN also showed inhibition of the ornithine decarboxylase similar to the positive control eflornithine. Significant interactions with the other enzymes involved in the T(SH)2 redox metabolism were not observed. Alongside many other biological activities sesquiterpene lactones including CYN have shown antitrypanosomal effects, which have been postulated to be linked to formation of Michael adducts with cellular nucleophiles. Here the interaction of CYN with biological thiols in a cellular system in general, and with trypanosomal T(SH)2 redox metabolism in particular, thus offering a molecular explanation for the antitrypanosomal activity is demonstrated. At the same time, the study provides a novel extraction and analysis protocol for components of the trypanosomal thiol metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. An analytical approach of thermodynamic behavior in a gas target system on a medical cyclotron.

    Science.gov (United States)

    Jahangiri, Pouyan; Zacchia, Nicholas A; Buckley, Ken; Bénard, François; Schaffer, Paul; Martinez, D Mark; Hoehr, Cornelia

    2016-01-01

    An analytical model has been developed to study the thermo-mechanical behavior of gas targets used to produce medical isotopes, assuming that the system reaches steady-state. It is based on an integral analysis of the mass and energy balance of the gas-target system, the ideal gas law, and the deformation of the foil. The heat transfer coefficients for different target bodies and gases have been calculated. Excellent agreement is observed between experiments performed at TRIUMF's 13 MeV cyclotron and the model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Elucidating antimalarial drug targets/mode-of-action by application of system biology technologies

    CSIR Research Space (South Africa)

    Becker, J

    2008-11-01

    Full Text Available targets/mode-of-action by application of systems biology technologies J BECKER, L MTWISHA, B CRAMPTON AND D MANCAMA CSIR Biosciences, PO Box 395, Pretoria, 0001, South Africa Email: JBecker@csir.co.za – www.csir.co.za INTRODUCTION Malaria is one... The objective of this study was to use systems biology tools to unravel the drug target/mode-of-action (MoA) of an antimalarial drug (cyclohexylamine) with a known drug target/MoA, by analysing differential expression profiles of drug treated vs untreated...

  16. System design and as-built MCNP model comparison for the Lujan Center target moderator reflector system

    International Nuclear Information System (INIS)

    Muhrer, G.; Ferguson, P.D.; Russell, G.J.; Pitcher, E.J.

    2000-01-01

    During the design of the Manuel Lujan, Jr., Neutron Scattering Center target, a simplified Monte Carlo model was used to estimate target system performance and to aid engineers as decisions were made regarding the construction of the target system. Although the simplified model ideally would perfectly reflect the as-built system performance, assumptions were made in the model during the design process that may result in deviations between the model predictions and the as-built system performance. Now that the Lujan Center target system has been completed, a more detailed, as-built, model of the target system has been completed. The purpose of this work is to investigate differences between the predicted target system performance of the simplified model and the as-built model from the standpoint of time-averaged moderator brightness. Calculated discrepancies between the two models have been isolated to a few key issues. Figure 1 shows MCNP geometric plots of the simplified and as-built models. Major differences between these two models include details in the moderator designs (plena) and piping, full versus partial moderator canisters (only in the direction of the extracted neutron beam for the simplified model), and reflector details including cooling pipes and engineering tolerance gaps. In addition, Fig. 1 demonstrates that the detailed model includes shielding and additional material beyond that which was modeled by the original simplified model

  17. Design and implement of infrared small target real-time detection system based on pipeline technology

    Science.gov (United States)

    Sun, Lihui; Wang, Yongzhong; He, Yongqiang

    2007-01-01

    The detection for motive small target in infrared image sequence has become a hot topic nowadays. Background suppress algorithm based on minim gradient median filter and temporal recursion target detection algorithm are introduced. On the basis of contents previously mentioned, a four stages pipeline structure infrared small target detection process system, which aims at characters of algorithm complexity, large amounts of data to process, high frame frequency and exigent real-time character in this kind of application, is designed and implemented. The logical structure of the system was introduced and the function and signals flows are programmed. The system is composed of two FPGA chips and two DSP chips of TI. According to the function of each part, the system is divided into image preprocess stage, target detection stage, track relation stage and image output stage. The experiment of running algorithms on the system presented in this paper proved that the system could meet acquisition and process of 50Hz 240x320 digital image and the system could real time detect small target with a signal-noise ratio more than 3 reliably. The system achieves the characters of large amount of memory, high real-time processing, excellent extension and favorable interactive interface.

  18. System for automatic x-ray-image analysis, measurement, and sorting of laser fusion targets

    International Nuclear Information System (INIS)

    Singleton, R.M.; Perkins, D.E.; Willenborg, D.L.

    1980-01-01

    This paper describes the Automatic X-Ray Image Analysis and Sorting (AXIAS) system which is designed to analyze and measure x-ray images of opaque hollow microspheres used as laser fusion targets. The x-ray images are first recorded on a high resolution film plate. The AXIAS system then digitizes and processes the images to accurately measure the target parameters and defects. The primary goals of the AXIAS system are: to provide extremely accurate and rapid measurements, to engineer a practical system for a routine production environment and to furnish the capability of automatically measuring an array of images for sorting and selection

  19. Repetitive laser fusion experiment and operation using a target injection system

    International Nuclear Information System (INIS)

    Nishimura, Yasuhiko; Komeda, Osamu; Mori, Yoshitaka

    2017-01-01

    Since 2008, a collaborative research project on laser fusion development based on a high-speed ignition method using repetitive laser has been carried out with several collaborative research institutes. This paper reports the current state of operation of high repetition laser fusion experiments, such as target introduction and control based on a target injection system that allows free falling under 1 Hz, using a high repetition laser driver that has been under research and development, as well as the measurement of targets that freely fall. The HAMA laser driver that enabled high repetition fusion experiments is a titanium sapphire laser using a diode-pumped solid-state laser KURE-I of green light output as a driver pump light source. In order to carry out high repetition laser fusion experiments, the target injection device allows free falling of deuterated polystyrene solid sphere targets of 1 mm in diameter under 1 Hz. The authors integrated the developed laser and injection system, and succeeded first in the world in making the nuclear fusion reaction continuously by hitting the target to be injected with laser, which is essential technology for future laser nuclear fusion reactor. In order to realize repetition laser fusion experiments, stable laser, target synchronization control, and target position measurement technologies are indispensable. (A.O.)

  20. Elemental Technologies for Lead-Bismuth Spallation Target System in J-PARC

    International Nuclear Information System (INIS)

    Obayashi, H.; Yamaguchi, K.; Saito, S.; Sugawara, T.; Takei, H.; Sasa, T.

    2015-01-01

    Japan Atomic Energy Agency (JAEA) has been researching and developing an Accelerator-Driven System (ADS) as a dedicated system for the transmutation of long-lived radioactive nuclides. The ADS proposed by JAEA uses the lead-bismuth eutectic (LBE) alloy as a spallation target material and a coolant. In the various R and D for ADS, construction of the Transmutation Experimental Facility (TEF) is planned under the framework of the J-PARC project as a preceding step before the construction of demonstrative ADS. In this R and D, TEF is considered for the experimental investigation of the feasibility of the beam window, the structural materials, and to investigate the operation properties of the target system by using 400 MeV-250 kW proton beam. This target system is consisted of various elements and must be able to operate without troubles during an operation period of TEF facility. Furthermore, in the maintenance period after the operation, because the inside of a hot cell storing a target is exposed to strong radiations, all elements must be designed as remote control devices. In this study, the present conditions of the design and the result of performance test of each important elements were confirmed in the realisation of the LBE target system, such as the monitoring system of flow rate by using the ultrasonic method, the heater system with the metallic heat insulator joined to a flow channel of LBE, and the operability of remote handing. (authors)

  1. Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Feng Jiang

    2015-10-01

    Full Text Available Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX, are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

  2. The design of a lead-bismuth target system with a dual injection tube

    International Nuclear Information System (INIS)

    Cho, C.H.; Kim, Y.; Song, T.Y.; Park, W.S.

    2005-01-01

    A spallation target system is a key component to be developed for an accelerator driven system (ADS). It is known that a 15 ∼ 25 MW spallation target is required for a practical 1000 MWth ADS. The design of a 20 MW spallation target is very challenging because more than 60% of the beam power is deposited as heat in a small volume of the target system. In the present work, a numerical design study was performed to obtain the optimal design parameters for a 20 MW spallation target for a 1000 MW ADS. A dual injection tube was proposed for the reduction of the LBE flow rate at the target channel. The results of the present study show that a 30 cm wide proton beam with a uniform beam distribution should be adopted for the spallation target of a 20 MW power. When the dual LBE injection tube is employed, the LBE flow rate could be reduced by a factor of 4 without reducing the maximum allowable beam current. (authors)

  3. High-Speed Target Identification System Based on the Plume’s Spectral Distribution

    Directory of Open Access Journals (Sweden)

    Wenjie Lang

    2015-01-01

    Full Text Available In order to recognize the target of high speed quickly and accurately, an identification system was designed based on analysis of the distribution characteristics of the plume spectrum. In the system, the target was aligned with visible light tracking module, and the spectral analysis of the target’s plume radiation was achieved by interference module. The distinguishing factor recognition algorithm was designed on basis of ratio of multifeature band peaks and valley mean values. Effective recognition of the high speed moving target could be achieved after partition of the active region and the influence of target motion on spectral acquisition was analyzed. In the experiment the small rocket combustion was used as the target. The spectral detection experiment was conducted at different speeds 2.0 km away from the detection system. Experimental results showed that spectral distribution had significant spectral offset in the same sampling period for the target with different speeds, but the spectral distribution was basically consistent. Through calculation of the inclusion relationship between distinguishing factor and distinction interval of the peak value and the valley value at the corresponding wave-bands, effective identification of target could be achieved.

  4. Nanobody-Based Delivery Systems for Diagnosis and Targeted Tumor Therapy

    Directory of Open Access Journals (Sweden)

    Yaozhong Hu

    2017-11-01

    Full Text Available The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma’s, monoclonal antibodies (mAbs have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue. By serendipity, a new kind of functional homodimeric antibody format was discovered in camelidae, known as heavy-chain antibodies (HCAbs. The cloning of the variable domain of HCAbs produces an attractive minimal-sized alternative for mAbs, referred to as VHH or nanobodies (Nbs. Apart from their dimensions in the single digit nanometer range, the unique characteristics of Nbs combine a high stability and solubility, low immunogenicity and excellent affinity and specificity against all possible targets including tumor markers. This stimulated the development of tumor-targeted therapeutic strategies. Some autonomous Nbs have been shown to act as antagonistic drugs, but more importantly, the targeting capacity of Nbs has been exploited to create drug delivery systems. Obviously, Nb-based targeted cancer therapy is mainly focused toward extracellular tumor markers, since the membrane barrier prevents antibodies to reach the most promising intracellular tumor markers. Potential strategies, such as lentiviral vectors and bacterial type 3 secretion system, are proposed to deliver target-specific Nbs into tumor cells and to block tumor markers intracellularly. Simultaneously, Nbs have also been employed for in vivo molecular imaging to diagnose diseased tissues and to monitor the treatment effects. Here, we review the state of the art and focus on recent developments with Nbs as

  5. Isovector excitations in 100Nb and their decays by neutron emission studied via the Mo100(t,He3+n reaction at 115 MeV/u

    Directory of Open Access Journals (Sweden)

    K. Miki

    2017-06-01

    Full Text Available Spin–isospin excitations in Nb100 were studied via the Mo100(t,He3 charge-exchange reaction at 115 MeV/u with the goal to constrain theoretical models used to describe the isovector spin response of nuclei. The experiment was performed with a secondary beam of tritons, and 3He particles were analyzed in the S800 magnetic spectrometer. Decay by neutron emission from excited states in Nb100 was observed by using plastic and liquid scintillator arrays. Differential cross sections were analyzed and monopole excitations were revealed by using a multipole decomposition analysis. The Gamow–Teller transition strength observed at low excitation energies, which is important for estimating the electron-capture rate in astrophysical scenarios, was strongly fragmented and reduced compared to single-particle and spherical mean-field models. The consideration of deformation in the theoretical estimates was found to be important to better describe the fragmentation and strengths. A strong excitation of the isovector spin giant monopole resonance was observed, and well reproduced by the mean-field models. Its presence makes the extraction of Gamow–Teller strengths at high excitation energies difficult. The branches for statistical and direct decay by neutron emission were identified in the spectra. The upper limit for the branching ratio by direct decay (integrated over all observed excitations was determined to be 20±6%. Even though the statistical uncertainties in the neutron-coincident data were too large to perform detailed studies of the decay by neutron emission from individual states and resonances, the experiment demonstrates the feasibility of the method.

  6. Reconciling Conflicting Geologic and Thermochronologic Interpretations Via Multiple Apatite Thermochronometers (AHe, AFT, and 4He/3He): 6 Ma Incision of the Westernmost Grand Canyon

    Science.gov (United States)

    Winn, C.; Karlstrom, K. E.; Shuster, D. L.; Kelley, S.; Fox, M.

    2017-12-01

    The application of low-temperature apatite thermochronology to the incision history of the Grand Canyon has led to conflicting hypotheses of either a 70 Ma ("old") or conflict with these lines of evidence and indicate a much older ( 70 Ma) westernmost Grand Canyon. We reconcile this conflict by applying apatite (U-Th)/He ages (AHe), 4He/3He thermochronometry, and apatite fission track ages and lengths (AFT) to the same sample at a key location. Using HeFTy, t-T paths that predict these data show cooling from ˜100 °C to 40-60 °C at 70-50 Ma, long-term residence at 40-60 °C from 50-10 Ma, and cooling to surface temperatures after 10 Ma, indicating young incision. New AFT (5) and AHe (3) datasets are also presented here. When datasets are examined separately, AHe data show t-T paths that cool to surface temperatures during the Laramide, consistent with an "old" Canyon. When multiple methods are applied, t-T paths instead show young incision. This inconsistency demonstrates the age of the Grand Canyon controversy. Here we reconcile the difference in t-T paths by adjusting model parameters to account for uncertainty in the rate of radiation damage annealing in apatite during burial heating and the resulting variations in He retentivity. In this area, peak burial conditions during the Laramide were likely insufficient to fully anneal radiation damage that accumulated during prolonged near-surface residence prior to burial. We conclude that application of multiple thermochronometers from common rocks reconciles conflicting thermochronologic interpretations and these data are best explained by a "young" westernmost Grand Canyon.

  7. Enhancement of the efficiency of magnetic targeting for drug delivery: Development and evaluation of magnet system

    International Nuclear Information System (INIS)

    Cao Quanliang; Han Xiaotao; Li Liang

    2011-01-01

    Deep magnetic capture and clinical application are the current trends for magnetic targeted drug delivery system. More promising and possible strategies are needed to overcome the current limitations and further improve the magnetic targeting technique. Recent advances in the development of targeting magnet system show promise in progressing this technology from the laboratory to the clinic. Starting from well-known basic concepts, current limitations of magnetic targeted drug delivery system are analyzed. Meanwhile, the design concepts and evaluations of some effective improvements in magnet system are discussed and reviewed with reference to (i) reasonable design of magnet system; (ii) control modes of magnet system used to generate dynamical magnetic fields; and (iii) magnetic field driving types. - Research Highlights: → The current limitations of MTDDS for deep capture and clinical application are analyzed. → The development of magnet system shows promise in progressing MTDDS to clinical application. → The design concepts and evaluations of improvements in magnet system are reviewed and discussed. → The key to improve magnet system lies in controllable magnets and different excitations.

  8. Spallation Neutron Source Accelerator Facility Target Safety and Non-safety Control Systems

    International Nuclear Information System (INIS)

    Battle, Ronald E.; DeVan, B.; Munro, John K. Jr.

    2006-01-01

    The Spallation Neutron Source (SNS) is a proton accelerator facility that generates neutrons for scientific researchers by spallation of neutrons from a mercury target. The SNS became operational on April 28, 2006, with first beam on target at approximately 200 W. The SNS accelerator, target, and conventional facilities controls are integrated by standardized hardware and software throughout the facility and were designed and fabricated to SNS conventions to ensure compatibility of systems with Experimental Physics Integrated Control System (EPICS). ControlLogix Programmable Logic Controllers (PLCs) interface to instruments and actuators, and EPICS performs the high-level integration of the PLCs such that all operator control can be accomplished from the Central Control room using EPICS graphical screens that pass process variables to and from the PLCs. Three active safety systems were designed to industry standards ISA S84.01 and IEEE 603 to meet the desired reliability for these safety systems. The safety systems protect facility workers and the environment from mercury vapor, mercury radiation, and proton beam radiation. The facility operators operated many of the systems prior to beam on target and developed the operating procedures. The safety and non-safety control systems were tested extensively prior to beam on target. This testing was crucial to identify wiring and software errors and failed components, the result of which was few problems during operation with beam on target. The SNS has continued beam on target since April to increase beam power, check out the scientific instruments, and continue testing the operation of facility subsystems

  9. Cannonball target experiment with the GEKKO laser system at ILE Osaka

    International Nuclear Information System (INIS)

    Yamanaka, C.; Azechi, H.; Fujiwara, E.

    1985-01-01

    The GEKKO series glass laser systems are now in operation for the Cannonball target experiments. GEKKO XII is a twelve-beam 30 kJ, 50 TW laser provided with two target chambers. Three types of GEKKO lasers cover the UV, blue, green and red frequency ranges. The Cannonball target displays an excellent performance in implosion. Two kinds of Cannonball target are proposed: the plasma Cannonball and the radiation Cannonball. The neutron yield is 4x10 10 , and the DT fuel density attains 10 g.cm -3 . Laser-to-X-ray conversion has been investigated. Cryogenic target implosion has been performed by using a tailored laser pulse to produce the flush at the core. Various kinds of new diagnostics are being developed. (author)

  10. NIF pointing and centering systems and target alignment using a 351 nm laser source

    International Nuclear Information System (INIS)

    Boege, S.J.; Bliss, E.S.; Chocol, C.J.; Holdener, F.R.; Miller, J.L.; Toeppen, J.S.; Vann, C.S.; Zacharias, R.A.

    1996-10-01

    The operational requirements of the National Ignition Facility (NIF) place tight constraints upon its alignment system. In general, the alignment system must establish and maintain the correct relationships between beam position, beam angle, laser component clear apertures, and the target. At the target, this includes adjustment of beam focus to obtain the correct spot size. This must be accomplished for all beamlines in a time consistent with planned shot rates and yet, in the front end and main laser, beam control functions cannot be initiated until the amplifiers have sufficiently cooled so as to minimize dynamic thermal distortions during and after alignment and wavefront optimization. The scope of the task dictates an automated system that implements parallel processes. We describe reticle choices and other alignment references, insertion of alignment beams, principles of operation of the Chamber Center Reference System 2048 and Target Alignment Sensor, and the anticipated alignment sequence that will occur between shots

  11. An underwater ranging system based on photoacoustic effect occurring on target surface

    Science.gov (United States)

    Ni, Kai; Hu, Kai; Li, Xinghui; Wang, Lidai; Zhou, Qian; Wang, Xiaohao

    2016-11-01

    In this paper, an underwater ranging system based on photoacoustic effect occurring on target surface is proposed. In this proposal, laser pulse generated by blue-green laser is directly incident on target surface, where the photoacoustic effect occurs and a sound source is formed. And then the sound wave which is also called photoacoustic signal is received by the ultrasonic receiver after passing through water. According to the time delay between transmitting laser and receiving photoacoustic signal, and sound velocity in water, the distance between the target and the ultrasonic receiver can be calculated. Differing from underwater range finding by only laser, this approach can avoid backscattering of laser beam, so easier to implement. Experimental system according to this principle has been constructed to verify the feasibility of this technology. The experimental results showed that a ranging accuracy of 1 mm can be effectively achieved when the target is close to the ultrasonic receiver.

  12. Analysis of the Neutron Generator and Target for the LSDTS System

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chang Je; Lee, Yong Deok; Song, Jae Hoon; Song, Kee Chan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-11-15

    A preliminary analysis was performed based on the literatures and the patents for the neutron generators and targets for the lead slowing down time spectrometer (LSDTS) system. It was found that local neutron generator did not exhibit enough neutron intensity such as 1E+12 n/s, which is a minimum requirement for the LSDTS system to overcome curium backgrounds. However, a neutron generator implemented with an electron accelerator may provide a higher intensity around 1E+13 n/s and it is required to investigate further including a detail analysis. In addition to the neutron generator, a study on target was performed with the Monte Carlo simulation. In the study, an optimal design of target was suggested to provide a high neutron yield and a better thermal resistance. The suggested target consists several cylindrical plates with a certain cooling gap, which have increasing thickness and increasing radius.

  13. [The research on a pocket microcontroller system for target controlled infusion].

    Science.gov (United States)

    Cheng, Yu-Ke; Zhang, Xin-An; Zhang, Yan-Wu; Wu, Qun-Ling; Dou, Jian-Hong; Wang, Rou-Shong

    2005-05-01

    This paper present a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extended function and easy operation. It has been now used in the clinical anesthesia.

  14. ORAL COLON TARGETED DRUG DELIVERY SYSTEM: A REVIEW ON CURRENT AND NOVEL PERSPECTIVES

    OpenAIRE

    Asija Rajesh; Chaudhari Bharat; Asija Sangeeta

    2012-01-01

    Small intestine is mostly the site for drug absorption but in some cases the drug needs to be targeted to colon due to some factors like local colonic disease, degradation related conditions, delayed release of drugs, systemic delivery of protein and peptide drugs etc. Colon targeted drug delivery is important and relatively new concept for the absorption of drugs because it offers almost neutral pH and long residence time, thereby increasing the drug absorption. Colon has proved to be a site...

  15. CFD Study of the Active Part of the HYPER LBE Spallation Target System

    International Nuclear Information System (INIS)

    Cho, Chung-ho; Tak, Nam-il; Lee, Yong-bum; Choi, Jae-Hyuk

    2007-01-01

    In an accelerator driven system (ADS), a high-energy proton beam impinges on a heavy metal target to produce spallation neutrons that are multiplied in a subcritical blanket. Therefore, the spallation target is one of the most important units of an ADS. A beam power of 15-25 MW is required for an operation of the HYPER system. But, the design of a 20 MW spallation target is very challenging because more than 60% of a beam power is deposited as heat in a small volume of a target system. LBE is preferred as the target material due to its high neutron production rate, effective heat removal, low melting point and vapor pressure, low neutron absorption and good radiation damage properties. In addition, it can be used simultaneously as a reactor coolant. Single hemi-spherical beam window is considered for the HYPER target. The beam window is a thin physical barrier to separate the vacuum space from the LBE. It is exposed to high thermal and irradiation loads, which affect its life time. The integrity of the beam window is crucial for a safe operation of the HYPER, for preventing the penetration of the radioactive spallation products into the accelerator island. Therefore, a sufficient cooling capability of the beam window is one of the key issues of the target design. In the previous study, a series of parametric thermal and mechanical studies were made for the optimization of the HYPER target. The optimized target has a 0.2 cm thick beam window with a diameter of 35 cm. Also, a 30 cm wide proton beam with a uniform beam distribution should be adopted for the spallation target of the HYPER. A dual injection tube is adopted to economize the LBE flow in the primary system. This paper presents the numerical studies on the optimized spallation target system. Several advanced turbulence models with different grid structures are investigated by using a commercial computational fluid dynamics (CFD) code CFX 5.7.1

  16. Very high stability systems: LMJ target alignment system and MTG imager test setup

    Science.gov (United States)

    Compain, Eric; Maquet, Philippe; Kunc, Thierry; Marque, Julien; Lauer-Solelhac, Maxime; Delage, Laurent; Lanternier, Catherine

    2015-09-01

    Most of space instruments and research facilities require test equipment with demanding opto-mechanical stability. In some specific cases, when the stability performance directly drives the final performance of the scientific mission and when feasibility is questionable, specific methods must be implemented for the associated technical risk management. In present paper, we will present our heritage in terms of methodology, design, test and the associated results for two specific systems : the SOPAC-POS and the MOTA, generating new references for future developments. From a performance point of view, we will emphasis on following key parameters : design symmetry, thermal load management, and material and structural choices. From a method point of view the difficulties arise first during design, from the strong coupling between the thermal, mechanical and optical performance models, and then during testing, from the difficulty of conceiving test setup having appropriate performance level. We will present how these limitations have been overcome. SOPAC-POS is the target alignment system of the LMJ, Laser Mega Joule, the French inertial confinement fusion research center. Its stability has been demonstrated by tests in 2014 after 10 years of research and development activities, achieving 1μm stability @ 6m during one hour periods. MOTA is an Optical Ground Support Equipment aiming at qualifying by tests the Flexible Combined Imager (FCI). FCI is an instrument for the meteorological satellite MTG-I, a program of and funded by the European Space Agency and under prime contractorship of Thales Alenia Space. Optimized design will allow to get better than 0.2 μrad stability for one hour periods, as required for MTF measurement.

  17. The application of carbon nanotubes in target drug delivery systems for cancer therapies

    Science.gov (United States)

    Zhang, Wuxu; Zhang, Zhenzhong; Zhang, Yingge

    2011-10-01

    Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.

  18. Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery Systems

    Science.gov (United States)

    Kydd, Janel; Jadia, Rahul; Velpurisiva, Praveena; Gad, Aniket; Paliwal, Shailee; Rai, Prakash

    2017-01-01

    Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment—due to the hostile tumor microenvironment—that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration. Nanomedicine can provide a more effective approach to targeting cancer by focusing on the vascular, tissue, and cellular characteristics that are unique to solid tumors. Targeted methods of treatment using nanoparticles can decrease the likelihood of resistant clonal populations of cancerous cells. Dual encapsulation of chemotherapeutic drug allows simultaneous targeting of more than one characteristic of the tumor. Several first-generation, non-targeted nanomedicines have received clinical approval starting with Doxil® in 1995. However, more than two decades later, second-generation or targeted nanomedicines have yet to be approved for treatment despite promising results in pre-clinical studies. This review highlights recent studies using targeted nanoparticles for cancer treatment focusing on approaches that target either the tumor vasculature (referred to as ‘vascular targeting’), the tumor microenvironment (‘tissue targeting’) or the individual cancer cells (‘cellular targeting’). Recent studies combining these different targeting methods are also discussed in this review. Finally, this review summarizes some of the reasons for the lack of clinical success in the field of targeted nanomedicines. PMID:29036899

  19. Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Janel Kydd

    2017-10-01

    Full Text Available Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment—due to the hostile tumor microenvironment—that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration. Nanomedicine can provide a more effective approach to targeting cancer by focusing on the vascular, tissue, and cellular characteristics that are unique to solid tumors. Targeted methods of treatment using nanoparticles can decrease the likelihood of resistant clonal populations of cancerous cells. Dual encapsulation of chemotherapeutic drug allows simultaneous targeting of more than one characteristic of the tumor. Several first-generation, non-targeted nanomedicines have received clinical approval starting with Doxil® in 1995. However, more than two decades later, second-generation or targeted nanomedicines have yet to be approved for treatment despite promising results in pre-clinical studies. This review highlights recent studies using targeted nanoparticles for cancer treatment focusing on approaches that target either the tumor vasculature (referred to as ‘vascular targeting’, the tumor microenvironment (‘tissue targeting’ or the individual cancer cells (‘cellular targeting’. Recent studies combining these different targeting methods are also discussed in this review. Finally, this review summarizes some of the reasons for the lack of clinical success in the field of targeted nanomedicines.

  20. Passive Target Tracking in Non-cooperative Radar System Based on Particle Filtering

    Institute of Scientific and Technical Information of China (English)

    LI Shuo; TAO Ran

    2006-01-01

    We propose a target tracking method based on particle filtering(PF) to solve the nonlinear non-Gaussian target-tracking problem in the bistatic radar systems using external radiation sources. Traditional nonlinear state estimation method is extended Kalman filtering (EKF), which is to do the first level Taylor series extension. It will cause an inaccuracy or even a scatter estimation result on condition that there is either a highly nonlinear target or a large noise square-error. Besides, Kalman filtering is the optimal resolution under a Gaussian noise assumption, and is not suitable to the non-Gaussian condition. PF is a sort of statistic filtering based on Monte Carlo simulation that is using some random samples (particles) to simulate the posterior probability density of system random variables. This method can be used in any nonlinear random system. It can be concluded through simulation that PF can achieve higher accuracy than the traditional EKF.

  1. Targeted mutagenesis in Zea mays using TALENs and the CRISPR/Cas system.

    Science.gov (United States)

    Liang, Zhen; Zhang, Kang; Chen, Kunling; Gao, Caixia

    2014-02-20

    Transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems have emerged as powerful tools for genome editing in a variety of species. Here, we report, for the first time, targeted mutagenesis in Zea mays using TALENs and the CRISPR/Cas system. We designed five TALENs targeting 4 genes, namely ZmPDS, ZmIPK1A, ZmIPK, ZmMRP4, and obtained targeting efficiencies of up to 23.1% in protoplasts, and about 13.3% to 39.1% of the transgenic plants were somatic mutations. Also, we constructed two gRNAs targeting the ZmIPK gene in maize protoplasts, at frequencies of 16.4% and 19.1%, respectively. In addition, the CRISPR/Cas system induced targeted mutations in Z. mays protoplasts with efficiencies (13.1%) similar to those obtained with TALENs (9.1%). Our results show that both TALENs and the CRISPR/Cas system can be used for genome modification in maize. Copyright © 2013. Published by Elsevier Ltd.

  2. An Analytic Model for the Success Rate of a Robotic Actuator System in Hitting Random Targets.

    Science.gov (United States)

    Bradley, Stuart

    2015-11-20

    Autonomous robotic systems are increasingly being used in a wide range of applications such as precision agriculture, medicine, and the military. These systems have common features which often includes an action by an "actuator" interacting with a target. While simulations and measurements exist for the success rate of hitting targets by some systems, there is a dearth of analytic models which can give insight into, and guidance on optimization, of new robotic systems. The present paper develops a simple model for estimation of the success rate for hitting random targets from a moving platform. The model has two main dimensionless parameters: the ratio of actuator spacing to target diameter; and the ratio of platform distance moved (between actuator "firings") to the target diameter. It is found that regions of parameter space having specified high success are described by simple equations, providing guidance on design. The role of a "cost function" is introduced which, when minimized, provides optimization of design, operating, and risk mitigation costs.

  3. Cetuximab-conjugated nanodiamonds drug delivery system for enhanced targeting therapy and 3D Raman imaging.

    Science.gov (United States)

    Li, Dandan; Chen, Xin; Wang, Hong; Liu, Jie; Zheng, Meiling; Fu, Yang; Yu, Yuan; Zhi, Jinfang

    2017-12-01

    In this study, a multicomponent nanodiamonds (NDs)-based targeting drug delivery system, cetuximab-NDs-cisplatin bioconjugate, combining both specific targeting and enhanced therapeutic efficacy capabilities, is developed and characterized. The specific targeting ability of cetuximab-NDs-cisplatin system on human liver hepatocellular carcinoma (HepG2) cells is evaluated through epidermal growth factor receptor (EGFR) blocking experiments, since EGFR is over-expressed on HepG2 cell membrane. Besides, cytotoxic evaluation confirms that cetuximab-NDs-cisplatin system could significantly inhibit the growth of HepG2 cells, and the therapeutic activity of this system is proven to be better than that of both nonspecific NDs-cisplatin conjugate and specific EGF-NDs-cisplatin conjugate. Furthermore, a 3-dimensional (3D) Raman imaging technique is utilized to visualize the targeting efficacy and enhanced internalization of cetuximab-NDs-cisplatin system in HepG2 cells, using the NDs existing in the bioconjugate as Raman probes, based on the characteristic Raman signal of NDs at 1332 cm -1 . These advantageous properties of cetuximab-NDs-cisplatin system propose a prospective imaging and treatment tool for further diagnostic and therapeutic purposes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Ground target geolocation based on digital elevation model for airborne wide-area reconnaissance system

    Science.gov (United States)

    Qiao, Chuan; Ding, Yalin; Xu, Yongsen; Xiu, Jihong

    2018-01-01

    To obtain the geographical position of the ground target accurately, a geolocation algorithm based on the digital elevation model (DEM) is developed for an airborne wide-area reconnaissance system. According to the platform position and attitude information measured by the airborne position and orientation system and the gimbal angles information from the encoder, the line-of-sight pointing vector in the Earth-centered Earth-fixed coordinate frame is solved by the homogeneous coordinate transformation. The target longitude and latitude can be solved with the elliptical Earth model and the global DEM. The influences of the systematic error and measurement error on ground target geolocation calculation accuracy are analyzed by the Monte Carlo method. The simulation results show that this algorithm can improve the geolocation accuracy of ground target in rough terrain area obviously. The geolocation accuracy of moving ground target can be improved by moving average filtering (MAF). The validity of the geolocation algorithm is verified by the flight test in which the plane flies at a geodetic height of 15,000 m and the outer gimbal angle is <47°. The geolocation root mean square error of the target trajectory is <45 and <7 m after MAF.

  5. Performance Measurement and Target-Setting in California's Safety Net Health Systems.

    Science.gov (United States)

    Hemmat, Shirin; Schillinger, Dean; Lyles, Courtney; Ackerman, Sara; Gourley, Gato; Vittinghoff, Eric; Handley, Margaret; Sarkar, Urmimala

    Health policies encourage implementing quality measurement with performance targets. The 2010-2015 California Medicaid waiver mandated quality measurement and reporting. In 2013, California safety net hospitals participating in the waiver set a voluntary performance target (the 90th percentile for Medicare preferred provider organization plans) for mammography screening and cholesterol control in diabetes. They did not reach the target, and the difference-in-differences analysis suggested that there was no difference for mammography ( P = .39) and low-density lipoprotein control ( P = .11) performance compared to measures for which no statewide quality improvement initiative existed. California's Medicaid waiver was associated with improved performance on a number of metrics, but this performance was not attributable to target setting on specific health conditions. Performance may have improved because of secular trends or systems improvements related to waiver funding. Relying on condition-specific targets to measure performance may underestimate improvements and disadvantage certain health systems. Achieving ambitious targets likely requires sustained fiscal, management, and workforce investments.

  6. Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Han-Chung Wu

    2010-01-01

    Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

  7. Therapeutic Innovations for Targeting Childhood Neuroblastoma: Implications of the Neurokinin-1 Receptor System.

    Science.gov (United States)

    Berger, Michael; VON Schweinitz, Dietrich

    2017-11-01

    Neuroblastoma is the most common solid extracranial malignant tumor in children. Despite recent advances in the treatment of this heterogenous tumor with surgery and chemotherapy, the prognosis in advanced stages remains poor. Interestingly, neuroblastoma is one of the few solid tumors, to date, in which an effect for targeted immunotherapy has been proven in controlled clinical trials, giving hope for further advances in the treatment of this and other tumors by targeted therapy. A large array of novel therapeutic options for targeted therapy of neuroblastoma is on the horizon. To this repεrtoirε, the neurokinin-1 receptor (NK1R) system was recently added. The present article explores the most recent developments in targeting neuroblastoma cells via the NK1R and how this new knowledge could be helpful to create new anticancer therapies agains neuroblastoma and other cancers. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. Development of a nickel plated aluminum krypton-81m target system.

    Science.gov (United States)

    Alrumayan, F; Okarvi, S M; Nagatsu, K; Yanbawi, S; Aljammaz, I

    2017-03-01

    A fully automated system was developed to produce rubidium-81 ( 81 Rb), based on the nat Kr (p, n) 81 Rb reaction. The energy incident on the target was 26MeV. Only 6MeV was stopped inside the gas and the remainder was stopped by a specially designed flange. The target body was characterized by its conical shape and its inner walls were chemically plated with 100±10µm of nickel (Ni). Ni is advantageous as a fairly good conductor of heat whose surface can resist solutions. Additionally, the Ni plated target allowed potassium chloride to dissolve 81 Rb, with no further effect on the target body. The system produced 81 Rb with a production yield of approximately 4.5mCi/µAh, which is close to the calculated expected yield of 5.3mCi/µAh. The system is able to deliver reliable and reproducible radioactivity for patients and can be operated up to 1500µAh before preventive maintenance is due. Key steps in designing the 81 Rb target for selected energy ranges are reported here. Copyright © 2016. Published by Elsevier Ltd.

  9. An integrated CRISPR Bombyx mori genome editing system with improved efficiency and expanded target sites.

    Science.gov (United States)

    Ma, Sanyuan; Liu, Yue; Liu, Yuanyuan; Chang, Jiasong; Zhang, Tong; Wang, Xiaogang; Shi, Run; Lu, Wei; Xia, Xiaojuan; Zhao, Ping; Xia, Qingyou

    2017-04-01

    Genome editing enabled unprecedented new opportunities for targeted genomic engineering of a wide variety of organisms ranging from microbes, plants, animals and even human embryos. The serial establishing and rapid applications of genome editing tools significantly accelerated Bombyx mori (B. mori) research during the past years. However, the only CRISPR system in B. mori was the commonly used SpCas9, which only recognize target sites containing NGG PAM sequence. In the present study, we first improve the efficiency of our previous established SpCas9 system by 3.5 folds. The improved high efficiency was also observed at several loci in both BmNs cells and B. mori embryos. Then to expand the target sites, we showed that two newly discovered CRISPR system, SaCas9 and AsCpf1, could also induce highly efficient site-specific genome editing in BmNs cells, and constructed an integrated CRISPR system. Genome-wide analysis of targetable sites was further conducted and showed that the integrated system cover 69,144,399 sites in B. mori genome, and one site could be found in every 6.5 bp. The efficiency and resolution of this CRISPR platform will probably accelerate both fundamental researches and applicable studies in B. mori, and perhaps other insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. The Effusive-Flow Properties of Target/Vapor-Transport Systems for Radioactive Ion Beam Applications

    CERN Document Server

    Kawai, Yoko; Liu, Yuan

    2005-01-01

    Radioactive atoms produced by the ISOL technique must diffuse from a target, effusively flow to an ion source, be ionized, be extracted, and be accelerated to research energies in a time commensurate with the lifetime of the species of interest. We have developed a fast valve system (closing time ~100 us) that can be used to accurately measure the effusion times of chemically active or inactive species through arbitrary geometry and size vapor transport systems with and without target material in the reservoir. The effusive flow times are characteristic of the system and thus serve as figures of merit for assessing the quality of a given vapor transport system as well as for assessing the permeability properties of a given target design. This article presents effusive flow data for noble gases flowing through a target reservoir and ion source system routinely used to generate radioactive species at the HRIBF with and without disks of 6 times and 10 times compressed Reticulated Vitreous Carbon Foam (RVCF) with...

  11. Radiological Protection and Nuclear Engineering Studies in Multi-MW Target Systems

    Science.gov (United States)

    Luis, Raul Fernandes

    Several innovative projects involving nuclear technology have emerged around the world in recent years, for applications such as spallation neutron sources, accelerator-driven systems for the transmutation of nuclear waste and radioactive ion beam (RIB) production. While the available neutron Wuxes from nuclear reactors did not increase substantially in intensity over the past three decades, the intensities of neutron sources produced in spallation targets have increased steadily, and should continue to do so during the 21st century. Innovative projects like ESS, MYRRHA and EURISOL lie at the forefront of the ongoing pursuit for increasingly bright neutron sources; driven by proton beams with energies up to 2 GeV and intensities up to several mA, the construction of their proposed facilities involves complex Nuclear Technology and Radiological Protection design studies executed by multidisciplinary teams of scientists and engineers from diUerent branches of Science. The intense neutron Wuxes foreseen for those facilities can be used in several scientiVc research Velds, such as Nuclear Physics and Astrophysics, Medicine and Materials Science. In this work, the target systems of two facilitites for the production of RIBs using the Isotope Separation On-Line (ISOL) method were studied in detail: ISOLDE, operating at CERN since 1967, and EURISOL, the next-generation ISOL facility to be built in Europe. For the EURISOL multi-MW target station, a detailed study of Radiological Protection was carried out using the Monte Carlo code FLUKA. Simulations were done to assess neutron Wuences, Vssion rates, ambient dose equivalent rates during operation and after shutdown and the production of radioactive nuclei in the targets and surrounding materials. DiUerent materials were discussed for diUerent components of the target system, aiming at improving its neutronics performance while keeping the residual activities resulting from material activation as low as possible. The second

  12. Targeted Mutagenesis in Rice Using TALENs and the CRISPR/Cas9 System.

    Science.gov (United States)

    Endo, Masaki; Nishizawa-Yokoi, Ayako; Toki, Seiichi

    2016-01-01

    Sequence-specific nucleases (SSNs), such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) system, are powerful tools for understanding gene function and for developing novel traits in plants. In plant species for which transformation and regeneration systems using protoplasts are not yet established, direct delivery to nuclei of SSNs either in the form of RNA or protein is difficult. Thus, Agrobacterium-mediated transformation of SSN expression constructs in cultured cells is a practical means of delivering targeted mutagenesis in some plant species including rice. Because targeted mutagenesis occurs stochastically in transgenic cells and SSN-mediated targeted mutagenesis often leads to no selectable phenotype, identification of highly mutated cell lines is a critical step in obtaining regenerated plants with desired mutations.

  13. Systems biology-embedded target validation: improving efficacy in drug discovery.

    Science.gov (United States)

    Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter

    2014-01-01

    The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment. © 2013 Wiley Periodicals, Inc.

  14. Modelling the impacts of challenging 2050 European climate mitigation targets on Ireland’s energy system

    International Nuclear Information System (INIS)

    Chiodi, Alessandro; Gargiulo, Maurizio; Rogan, Fionn; Deane, J.P.; Lavigne, Denis; Rout, Ullash K.; Ó Gallachóir, Brian P.

    2013-01-01

    The Copenhagen Accord established political consensus on the 2 °C limit (in global temperature increase) and for deep cuts in greenhouse gas (GHG) emissions levels to achieve this goal. The European Union has set ambitious GHG targets for the year 2050 (80–95% below 1990 levels), with each Member State developing strategies to contribute to these targets. This paper focuses on mitigation targets for one Member State, Ireland, an interesting case study due to the growth in GHG emissions (24% increase between 1990 and 2005) and the high share of emissions from agriculture (30% of total GHG emissions). We use the Irish TIMES energy systems modelling tool to build a number of scenarios delivering an 80% emissions reduction target by 2050, including accounting for the limited options for agriculture GHG abatement by increasing the emissions reduction target for the energy system. We then compare the scenario results in terms of changes in energy technology, the role of energy efficiency and renewable energy. We also quantify the economic impacts of the mitigation scenarios in terms of marginal CO 2 abatement costs and energy system costs. The paper also sheds light on the impacts of short term targets and policies on long term mitigation pathways. - Highlights: ► We developed a techno-economic energy model of Ireland to the year 2050. ► Reductions between 80% and 95% of GHG emissions can be technically achieved. ► A 50% emissions cut in agriculture requires a 95% reductions from the energy system. ► Extending current policies implies greater electrification and efficiency measures. ► The additional cost to achieve mitigation remain less than 2% of GDP levels in 2050.

  15. Reimbursement of targeted cancer therapies within three different European health care systems

    NARCIS (Netherlands)

    Mihajlovic, Jovan; Dolk, C.; Postma, Maarten

    2014-01-01

    Objectives: To identify differences in the recommendations for targeted cancer therapies (TCT) in three distinctive European health care systems: Serbian, Scottish and Dutch, and to examine the role of cost effectiveness analyses (CEA) in such recommendations. Methods: A list of currently approved

  16. [Study on liver targeted drug delivery system of the effective anticancer component from Bolbstemma paniculatum].

    Science.gov (United States)

    Sun, Yi-Yi; Ll, Tong-Hui; Tang, Chen-Kang; Zhu, Zi-Ping; Chi, Qun; Hou, Shi-Xiang

    2005-06-01

    To study the liver targeted drug delivery system of TBMS--the effective anticancer component from Bolbstemma paniculatum, and to discuss the system's function of decreasing toxicity. BCA was used as carrier material. The preparation through overall feedback dynamic techniques. The properties of preparation and toxicology were also technology of nanoparticles was optimized studied. Thenanoparticles' targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system. D50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t 1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much lower than injection. The TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.

  17. 77 FR 30433 - Privacy Act of 1974: Implementation of Exemptions; Automated Targeting System

    Science.gov (United States)

    2012-05-23

    ... Border Protection, Mint Annex, 799 Ninth Street NW., Washington, DC 20229. For privacy issues please... Secretary 6 CFR Part 5 [Docket No. DHS-2012-0020] Privacy Act of 1974: Implementation of Exemptions; Automated Targeting System AGENCY: Privacy Office, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The...

  18. Flood risk and economically optimal safety targets for coastal flood defense systems

    NARCIS (Netherlands)

    Dupuits, E.J.C.; Schweckendiek, T.

    2015-01-01

    A front defense can improve the reliability of a rear defense in a coastal flood defense system. The influence of this interdependency on the accompanying economically optimal safety targets of both front and rear defense is investigated. The results preliminary suggest that the optimal safety level

  19. Simulation of beam pointing stability on targeting plane of high power excimer laser system

    International Nuclear Information System (INIS)

    Wang Dahui; Zhao Xueqing; Zhang Yongsheng; Zheng Guoxin; Hu Yun; Zhao Jun

    2011-01-01

    Based on characteristics of image-relaying structure in high power excimer MOPA laser system, simulation and analysis software of targeting beam's barycenter stability was designed by using LABVIEW and MATLAB. Simulation was made to measured results of every optical component in laboratory environment. Simulation and validation of budget values for optical components was and optimization of error budget of system was accomplished via post-allocation for several times. It is shown that targeting beam's barycenter stability in the condition of current laboratory environment can't satisfy needs and index of high demand optical components can be allotted to 1.7 μrad when index of low demand optical components have some stability margin. These results can provide a guide to construction of system and design and machining of optical components and optimization of system. Optical components of laboratory on work can satisfy optimized distributed index, which reduce the demand of structure to some extent. (authors)

  20. Design of a control system for HIRFL-CSRe internal target facility in Lanzhou

    International Nuclear Information System (INIS)

    Wang Yanyu; Liu Wufeng; Shao Caojie; Lin Feiyu; Zhang Jianchuan; Xiao Wenjun

    2010-01-01

    It is described in this paper the design of the control system for HIRFL-CSRe internal target facility, in which there are many different kinds of units need to be monitored and controlled. The control system is composed of several subsystems which are designed to control the gas-jet temperature, chamber vacuum, valves and molecular pumps. A human-computer interaction interface is also realized to do the data acquisition, data processing and display. The whole system has been working stably and safely, it fully meets the requirements of physical experiments in the internal target facility. In January of 2010, the first physics experiment of the radioactive electron capture was finished successfully with the aids of this control system. (authors)

  1. [Advances of tumor targeting peptides drug delivery system with pH-sensitive activities].

    Science.gov (United States)

    Ma, Yin-yun; Li, Li; Huang, Hai-feng; Gou, San-hu; Ni, Jing-man

    2016-05-01

    The pH-sensitive peptides drug delivery systems, which target to acidic extracellular environment of tumor tissue, have many advantages in drug delivery. They exhibit a high specificity to tumor and low cytotoxicity, which significantly increase the efficacy of traditional anti-cancer drugs. In recent years the systems have received a great attention. The pH-sensitive peptides drug delivery systems can be divided into five types according to the difference in pH-responsive mechanism,type of peptides and carrier materials. This paper summarizes the recent progresses in the field with a focus on the five types of pH-sensitive peptides in drug delivery systems. This may provide a guideline to design and application of tumor targeting drugs.

  2. Penalty Dynamic Programming Algorithm for Dim Targets Detection in Sensor Systems

    Directory of Open Access Journals (Sweden)

    Yunfei Guo

    2012-04-01

    Full Text Available In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD called penalty DP-TBD (PDP-TBD is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations.

  3. Targeted gene deletion of miRNAs in mice by TALEN system.

    Science.gov (United States)

    Takada, Shuji; Sato, Tempei; Ito, Yoshiaki; Yamashita, Satoshi; Kato, Tomoko; Kawasumi, Miyuri; Kanai-Azuma, Masami; Igarashi, Arisa; Kato, Tomomi; Tamano, Moe; Asahara, Hiroshi

    2013-01-01

    Mice are among the most valuable model animal species with an enormous amount of heritage in genetic modification studies. However, targeting genes in mice is sometimes difficult, especially for small genes, such as microRNAs (miRNAs) and targeting genes in repeat sequences. Here we optimized the application of TALEN system for mice and successfully obtained gene targeting technique in mice for intergenic region and series of microRNAs. Microinjection of synthesized RNA of TALEN targeting each gene in one cell stage of embryo was carried out and injected oocytes were transferred into pseudopregnant ICR female mice, producing a high success rate of the targeted deletion of miRNA genes. In our condition, TALEN RNA without poly(A) tail worked better than that of with poly(A) tail. This mutated allele in miRNA was transmitted to the next generation, suggesting the successful germ line transmission of this targeting method. Consistent with our notion of miRNAs maturation mechanism, in homozygous mutant mice of miR-10a, the non- mutated strand of miRNAs expression was completely diminished. This method will lead us to expand and accelerate our genetic research using mice in a high throughput way.

  4. Targeted gene deletion of miRNAs in mice by TALEN system.

    Directory of Open Access Journals (Sweden)

    Shuji Takada

    Full Text Available Mice are among the most valuable model animal species with an enormous amount of heritage in genetic modification studies. However, targeting genes in mice is sometimes difficult, especially for small genes, such as microRNAs (miRNAs and targeting genes in repeat sequences. Here we optimized the application of TALEN system for mice and successfully obtained gene targeting technique in mice for intergenic region and series of microRNAs. Microinjection of synthesized RNA of TALEN targeting each gene in one cell stage of embryo was carried out and injected oocytes were transferred into pseudopregnant ICR female mice, producing a high success rate of the targeted deletion of miRNA genes. In our condition, TALEN RNA without poly(A tail worked better than that of with poly(A tail. This mutated allele in miRNA was transmitted to the next generation, suggesting the successful germ line transmission of this targeting method. Consistent with our notion of miRNAs maturation mechanism, in homozygous mutant mice of miR-10a, the non- mutated strand of miRNAs expression was completely diminished. This method will lead us to expand and accelerate our genetic research using mice in a high throughput way.

  5. A PCA3 gene-based transcriptional amplification system targeting primary prostate cancer

    OpenAIRE

    Neveu, Bertrand; Jain, Pallavi; T?tu, Bernard; Wu, Lily; Fradet, Yves; Pouliot, Fr?d?ric

    2015-01-01

    Targeting specifically primary prostate cancer (PCa) cells for immune therapy, gene therapy or molecular imaging is of high importance. The PCA3 long non-coding RNA is a unique PCa biomarker and oncogene that has been widely studied. This gene has been mainly exploited as an accurate diagnostic urine biomarker for PCa detection. In this study, the PCA3 promoter was introduced into a new transcriptional amplification system named the 3-Step Transcriptional Amplification System (PCA3-3STA) and ...

  6. Enhancing Targeted Genomic DNA Editing in Chicken Cells Using the CRISPR/Cas9 System

    Science.gov (United States)

    Wang, Ling; Yang, Likai; Guo, Yijie; Du, Weili; Yin, Yajun; Zhang, Tao; Lu, Hongzhao

    2017-01-01

    The CRISPR/Cas9 system has enabled highly efficient genome targeted editing for various organisms. However, few studies have focused on CRISPR/Cas9 nuclease-mediated chicken genome editing compared with mammalian genomes. The current study combined CRISPR with yeast Rad52 (yRad52) to enhance targeted genomic DNA editing in chicken DF-1 cells. The efficiency of CRISPR/Cas9 nuclease-induced targeted mutations in the chicken genome was increased to 41.9% via the enrichment of the dual-reporter surrogate system. In addition, the combined effect of CRISPR nuclease and yRad52 dramatically increased the efficiency of the targeted substitution in the myostatin gene using 50-mer oligodeoxynucleotides (ssODN) as the donor DNA, resulting in a 36.7% editing efficiency after puromycin selection. Furthermore, based on the effect of yRad52, the frequency of exogenous gene integration in the chicken genome was more than 3-fold higher than that without yRad52. Collectively, these results suggest that ssODN is an ideal donor DNA for targeted substitution and that CRISPR/Cas9 combined with yRad52 significantly enhances chicken genome editing. These findings could be extensively applied in other organisms. PMID:28068387

  7. Drugs and drug delivery systems targeting amyloid-β in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Morgan Robinson

    2015-07-01

    Full Text Available Alzheimer's disease (AD is a devastating neurodegenerative disorder with no cure and limited treatment solutions that are unable to target any of the suspected causes. Increasing evidence suggests that one of the causes of neurodegeneration is the overproduction of amyloid beta (Aβ and the inability of Aβ peptides to be cleared from the brain, resulting in self-aggregation to form toxic oligomers, fibrils and plaques. One of the potential treatment options is to target Aβ and prevent self-aggregation to allow for a natural clearing of the brain. In this paper, we review the drugs and drug delivery systems that target Aβ in relation to Alzheimer's disease. Many attempts have been made to use anti-Aβ targeting molecules capable of targeting Aβ (with much success in vitro and in vivo animal models, but the major obstacle to this technique is the challenge posed by the blood brain barrier (BBB. This highly selective barrier protects the brain from toxic molecules and pathogens and prevents the delivery of most drugs. Therefore novel Aβ aggregation inhibitor drugs will require well thought-out drug delivery systems to deliver sufficient concentrations to the brain.

  8. Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy

    International Nuclear Information System (INIS)

    Sun Yun; Chen Zhilong; Yang Xiaoxia; Huang Peng; Zhou Xinping; Du Xiaoxia

    2009-01-01

    Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0-100 μM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.

  9. Location detection and tracking of moving targets by a 2D IR-UWB radar system.

    Science.gov (United States)

    Nguyen, Van-Han; Pyun, Jae-Young

    2015-03-19

    In indoor environments, the Global Positioning System (GPS) and long-range tracking radar systems are not optimal, because of signal propagation limitations in the indoor environment. In recent years, the use of ultra-wide band (UWB) technology has become a possible solution for object detection, localization and tracking in indoor environments, because of its high range resolution, compact size and low cost. This paper presents improved target detection and tracking techniques for moving objects with impulse-radio UWB (IR-UWB) radar in a short-range indoor area. This is achieved through signal-processing steps, such as clutter reduction, target detection, target localization and tracking. In this paper, we introduce a new combination consisting of our proposed signal-processing procedures. In the clutter-reduction step, a filtering method that uses a Kalman filter (KF) is proposed. Then, in the target detection step, a modification of the conventional CLEAN algorithm which is used to estimate the impulse response from observation region is applied for the advanced elimination of false alarms. Then, the output is fed into the target localization and tracking step, in which the target location and trajectory are determined and tracked by using unscented KF in two-dimensional coordinates. In each step, the proposed methods are compared to conventional methods to demonstrate the differences in performance. The experiments are carried out using actual IR-UWB radar under different scenarios. The results verify that the proposed methods can improve the probability and efficiency of target detection and tracking.

  10. Location Detection and Tracking of Moving Targets by a 2D IR-UWB Radar System

    Directory of Open Access Journals (Sweden)

    Van-Han Nguyen

    2015-03-01

    Full Text Available In indoor environments, the Global Positioning System (GPS and long-range tracking radar systems are not optimal, because of signal propagation limitations in the indoor environment. In recent years, the use of ultra-wide band (UWB technology has become a possible solution for object detection, localization and tracking in indoor environments, because of its high range resolution, compact size and low cost. This paper presents improved target detection and tracking techniques for moving objects with impulse-radio UWB (IR-UWB radar in a short-range indoor area. This is achieved through signal-processing steps, such as clutter reduction, target detection, target localization and tracking. In this paper, we introduce a new combination consisting of our proposed signal-processing procedures. In the clutter-reduction step, a filtering method that uses a Kalman filter (KF is proposed. Then, in the target detection step, a modification of the conventional CLEAN algorithm which is used to estimate the impulse response from observation region is applied for the advanced elimination of false alarms. Then, the output is fed into the target localization and tracking step, in which the target location and trajectory are determined and tracked by using unscented KF in two-dimensional coordinates. In each step, the proposed methods are compared to conventional methods to demonstrate the differences in performance. The experiments are carried out using actual IR-UWB radar under different scenarios. The results verify that the proposed methods can improve the probability and efficiency of target detection and tracking.

  11. Interacting with target tracking algorithms in a gaze-enhanced motion video analysis system

    Science.gov (United States)

    Hild, Jutta; Krüger, Wolfgang; Heinze, Norbert; Peinsipp-Byma, Elisabeth; Beyerer, Jürgen

    2016-05-01

    Motion video analysis is a challenging task, particularly if real-time analysis is required. It is therefore an important issue how to provide suitable assistance for the human operator. Given that the use of customized video analysis systems is more and more established, one supporting measure is to provide system functions which perform subtasks of the analysis. Recent progress in the development of automated image exploitation algorithms allow, e.g., real-time moving target tracking. Another supporting measure is to provide a user interface which strives to reduce the perceptual, cognitive and motor load of the human operator for example by incorporating the operator's visual focus of attention. A gaze-enhanced user interface is able to help here. This work extends prior work on automated target recognition, segmentation, and tracking algorithms as well as about the benefits of a gaze-enhanced user interface for interaction with moving targets. We also propose a prototypical system design aiming to combine both the qualities of the human observer's perception and the automated algorithms in order to improve the overall performance of a real-time video analysis system. In this contribution, we address two novel issues analyzing gaze-based interaction with target tracking algorithms. The first issue extends the gaze-based triggering of a target tracking process, e.g., investigating how to best relaunch in the case of track loss. The second issue addresses the initialization of tracking algorithms without motion segmentation where the operator has to provide the system with the object's image region in order to start the tracking algorithm.

  12. Systems biology approaches and tools for analysis of interactomes and multi-target drugs.

    Science.gov (United States)

    Schrattenholz, André; Groebe, Karlfried; Soskic, Vukic

    2010-01-01

    Systems biology is essentially a proteomic and epigenetic exercise because the relatively condensed information of genomes unfolds on the level of proteins. The flexibility of cellular architectures is not only mediated by a dazzling number of proteinaceous species but moreover by the kinetics of their molecular changes: The time scales of posttranslational modifications range from milliseconds to years. The genetic framework of an organism only provides the blue print of protein embodiments which are constantly shaped by external input. Indeed, posttranslational modifications of proteins represent the scope and velocity of these inputs and fulfil the requirements of integration of external spatiotemporal signal transduction inside an organism. The optimization of biochemical networks for this type of information processing and storage results in chemically extremely fine tuned molecular entities. The huge dynamic range of concentrations, the chemical diversity and the necessity of synchronisation of complex protein expression patterns pose the major challenge of systemic analysis of biological models. One further message is that many of the key reactions in living systems are essentially based on interactions of moderate affinities and moderate selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. In complex disorders such as cancer or neurodegenerative diseases, which initially appear to be rooted in relatively subtle dysfunctions of multimodal physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which has been dominating the pharmaceutical industry for a long time, increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade, and the treatment of "complex

  13. Muon catalyzed fusion at very low temperature: A new target system

    International Nuclear Information System (INIS)

    Mulhauser, F.; Beveridge, J.L.; Marshall, G.M.

    1994-10-01

    Muon catalyzed fusion (μCF) processes are usually studied in gases or liquids. A new target system allows experiments on muonic hydrogen isotopes in solid hydrogen layers at 3K, where processes of the μCF cycle can be separated and the energy dependence of reactions can be measured. Muonic tritium atomic beams with energy of the order of 1 eV have been produced via transfer and emission from solid hydrogen target containing small tritium concentrations. The μt energy distribution overlaps the predicted muonic molecular (dμt) formation resonances. Preliminary time of flight results are shown. (author). 9 refs., 5 figs

  14. Ovarian cancer and the immune system - The role of targeted therapies.

    Science.gov (United States)

    Turner, Taylor B; Buchsbaum, Donald J; Straughn, J Michael; Randall, Troy D; Arend, Rebecca C

    2016-08-01

    The majority of patients with epithelial ovarian cancer are diagnosed with advanced disease. While many of these patients will respond initially to chemotherapy, the majority will relapse and die of their disease. Targeted therapies that block or activate specific intracellular signaling pathways have been disappointing. In the past 15years, the role of the immune system in ovarian cancer has been investigated. Patients with a more robust immune response, as documented by the presence of lymphocytes infiltrating within their tumor, have increased survival and better response to chemotherapy. In addition, a strong immunosuppressive environment often accompanies ovarian cancer. Recent research has identified potential therapies that leverage the immune system to identify and destroy tumor cells that previously evaded immunosurveillance mechanisms. In this review, we discuss the role of the immune system in ovarian cancer and focus on specific pathways and molecules that show a potential for targeted therapy. We also review the ongoing clinical trials using targeted immunotherapy in ovarian cancer. The role of targeted immunotherapy in patients with ovarian cancer represents a field of growing research and clinical importance. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.

    Directory of Open Access Journals (Sweden)

    Julia K Bialek

    Full Text Available CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs, act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR, for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

  16. Los Alamos pulsed spallation neutron source target systems - present and future

    International Nuclear Information System (INIS)

    Russell, G.J.; Daemen, L.L.; Pitcher, E.J.; Brun, T.O.; Hjelm, R.P. Jr.

    1993-01-01

    For the past 16 yr, spallation target-system designers have devoted much time and effort to the design and optimization of pulsed spallation neutron sources. Many concepts have been proposed, but, in practice, only one has been implemented horizontal beam insertion with moderators in wing geometry i.e., until we introduced the innovative split-target/flux-trap-moderator design with a composite reflector shield at the Manuel Lujan, Jr., Neutron Scattering Center (LANSCE). The LANSCE target system design is now considered a classic by spallation target system designers worldwide. LANSCE, a state-of-the-art pulsed spallation neutron source for materials science and nuclear physics research, uses 800-MeV protons from the Clinton P. Anderson Meson Physics Facility. These protons are fed into the proton storage ring to be compressed to 250-ns pulses before being delivered to LANSCE at 20 Hz. LANSCE produces the highest peak neutron flux of any pulsed spallation neutron source in the world

  17. Current status of the 124Xe target system development for the high purity 123I production in KCCH

    International Nuclear Information System (INIS)

    Chun, Kwon Soo

    2002-01-01

    This report describes the 124 Xe gaseous target system employed for 123 I production at the Korea Cancer Center Hospital. Currently the control system is manual and will be computerized after the system parameters have been established

  18. Crosstalk between bone niche and immune system: osteoimmunology signaling as a potential target for cancer treatment.

    Science.gov (United States)

    Criscitiello, Carmen; Viale, Giulia; Gelao, Lucia; Esposito, Angela; De Laurentiis, Michele; De Placido, Sabino; Santangelo, Michele; Goldhirsch, Aron; Curigliano, Giuseppe

    2015-02-01

    There is a well recognized link between the bone and the immune system and in recent years there has been a major effort to elucidate the multiple functions of the molecules expressed in both bone and immune cells. Several molecules that were initially identified and studied in the immune system have been shown to have essential functions also in the bone. An interdisciplinary field embracing immune and bone biology has been brought together and called "osteoimmunology". The co-regulation of the skeletal and immune systems strikingly exemplifies the extreme complexity of such an interaction. Their interdependency must be considered in designing therapeutic approaches for either of the two systems. In other words, it is necessary to think of the osteoimmune system as a complex physiological unit. Denosumab was originally introduced to specifically target bone resorption, but it is now under evaluation for its effect on the long term immune response. Similarly, our current and still growing knowledge of the intimate link between the immune system and bone will be beneficial for the safety of drugs targeting either of these integrated systems. Given the large number of molecules exerting functions on both the skeletal and immune systems, osteoimmunological understanding is becoming increasingly important. Both bone and immune systems are frequently disrupted in cancer; and they may be crucial in regulating tumor growth and progression. Some therapies - such as bisphosphonates and receptor activator of NF-κB ligand (RANKL) targeted drugs - that aim at reducing pathologic osteolysis in cancer may interact with the immune system, thus providing potential favorable effects on survival. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Type I-E CRISPR-Cas Systems Discriminate Target from Non-Target DNA through Base Pairing-Independent PAM Recognition

    Science.gov (United States)

    Datsenko, Kirill A.; Jackson, Ryan N.; Wiedenheft, Blake; Severinov, Konstantin; Brouns, Stan J. J.

    2013-01-01

    Discriminating self and non-self is a universal requirement of immune systems. Adaptive immune systems in prokaryotes are centered around repetitive loci called CRISPRs (clustered regularly interspaced short palindromic repeat), into which invader DNA fragments are incorporated. CRISPR transcripts are processed into small RNAs that guide CRISPR-associated (Cas) proteins to invading nucleic acids by complementary base pairing. However, to avoid autoimmunity it is essential that these RNA-guides exclusively target invading DNA and not complementary DNA sequences (i.e., self-sequences) located in the host's own CRISPR locus. Previous work on the Type III-A CRISPR system from Staphylococcus epidermidis has demonstrated that a portion of the CRISPR RNA-guide sequence is involved in self versus non-self discrimination. This self-avoidance mechanism relies on sensing base pairing between the RNA-guide and sequences flanking the target DNA. To determine if the RNA-guide participates in self versus non-self discrimination in the Type I-E system from Escherichia coli we altered base pairing potential between the RNA-guide and the flanks of DNA targets. Here we demonstrate that Type I-E systems discriminate self from non-self through a base pairing-independent mechanism that strictly relies on the recognition of four unchangeable PAM sequences. In addition, this work reveals that the first base pair between the guide RNA and the PAM nucleotide immediately flanking the target sequence can be disrupted without affecting the interference phenotype. Remarkably, this indicates that base pairing at this position is not involved in foreign DNA recognition. Results in this paper reveal that the Type I-E mechanism of avoiding self sequences and preventing autoimmunity is fundamentally different from that employed by Type III-A systems. We propose the exclusive targeting of PAM-flanked sequences to be termed a target versus non-target discrimination mechanism. PMID:24039596

  20. Colon-targeted oral drug delivery systems: design trends and approaches.

    Science.gov (United States)

    Amidon, Seth; Brown, Jack E; Dave, Vivek S

    2015-08-01

    Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

  1. Quality Assurance of Ultrasound Imaging Systems for Target Localization and Online Setup Corrections

    International Nuclear Information System (INIS)

    Tome, Wolfgang A.; Orton, Nigel P.

    2008-01-01

    We describe quality assurance paradigms for ultrasound imaging systems for target localization (UISTL). To determine the absolute localization accuracy of a UISTL, an absolute coordinate system can be established in the treatment room and spherical targets at various depths can be localized. To test the ability of such a system to determine the magnitude of internal organ motion, a phantom that mimics the human male pelvic anatomy can be used to simulate different organ motion ranges. To assess the interuser variability of ultrasound (US) guidance, different experienced users can independently determine the daily organ shifts for the same patients for a number of consecutive fractions. The average accuracy for a UISTL for the localization of spherical targets at various depths has been found to be 0.57 ± 0.47 mm in each spatial dimension for various focal depths. For the phantom organ motion test it was found that the true organ motion could be determined to within 1.0 mm along each axis. The variability between different experienced users who localized the same 5 patients for five consecutive fractions was small in comparison to the indicated shifts. In addition to the quality assurance tests that address the ability of a UISTL to accurately localize a target, a thorough quality assurance program should also incorporate the following two aspects to ensure consistent and accurate localization in daily clinical use: (1) adequate training and performance monitoring of users of the US target localization system, and (2) prescreening of patients who may not be good candidates for US localization

  2. Comprehensive target populations for current active safety systems using national crash databases.

    Science.gov (United States)

    Kusano, Kristofer D; Gabler, Hampton C

    2014-01-01

    The objective of active safety systems is to prevent or mitigate collisions. A critical component in the design of active safety systems is the identification of the target population for a proposed system. The target population for an active safety system is that set of crashes that a proposed system could prevent or mitigate. Target crashes have scenarios in which the sensors and algorithms would likely activate. For example, the rear-end crash scenario, where the front of one vehicle contacts another vehicle traveling in the same direction and in the same lane as the striking vehicle, is one scenario for which forward collision warning (FCW) would be most effective in mitigating or preventing. This article presents a novel set of precrash scenarios based on coded variables from NHTSA's nationally representative crash databases in the United States. Using 4 databases (National Automotive Sampling System-General Estimates System [NASS-GES], NASS Crashworthiness Data System [NASS-CDS], Fatality Analysis Reporting System [FARS], and National Motor Vehicle Crash Causation Survey [NMVCCS]) the scenarios developed in this study can be used to quantify the number of police-reported crashes, seriously injured occupants, and fatalities that are applicable to proposed active safety systems. In this article, we use the precrash scenarios to identify the target populations for FCW, pedestrian crash avoidance systems (PCAS), lane departure warning (LDW), and vehicle-to-vehicle (V2V) or vehicle-to-infrastructure (V2I) systems. Crash scenarios were derived using precrash variables (critical event, accident type, precrash movement) present in all 4 data sources. This study found that these active safety systems could potentially mitigate approximately 1 in 5 of all severity and serious injury crashes in the United States and 26 percent of fatal crashes. Annually, this corresponds to 1.2 million all severity, 14,353 serious injury (MAIS 3+), and 7412 fatal crashes. In addition

  3. Safety concept for spallation target system. JAERI/KEK joint project

    International Nuclear Information System (INIS)

    Kobayashi, K.; Kaminaga, M.; Haga, K.; Kinoshita, H.; Hino, R.

    2001-01-01

    A MW-class mercury target of the spallation target generates much larger amounts of radioactive nuclides than existing spallation neutron sources. To estimate the maximum level of public exposure under the guillotine break of mercury pipelines that is one of the major accidents of the target system, the hazard analyses were carried out by using a transportation model which considers heat transmission of mercury decay heat, diffusion of evaporated radioactive nuclides, etc. In the analyses, mercury, iodine, bromine and noble gas were selected as the effective source term because of their high vapor pressures and activation levels. From the preliminary analytical results obtained under the conservative conditions of 2 m/s of the air velocity around the mercury leakage area, the maximum level of the public exposure was approximately 5.8 x 10 -3 mSv. This level is negligible in comparison with 1 mSV one-year natural radiation exposure. (author)

  4. A dual-reservoir remote loading water target system for 18F and 13N production with direct in-target liquid level sensing

    International Nuclear Information System (INIS)

    Ferrieri, R.A.; Alexoff, D.L.; Schlyer, D.J.; Wolf, A.P.

    1991-01-01

    This report describes our universal water target loading system that serves both [ 18 F] and [ 13 N] production targets, and a radionuclide delivery system that is specific for [ 18 F] fluoride. The system was designed and fabricated around the operation of a single pneumatic syringe dispenser that accesses one of two reservoirs filled with [ 18 O] enriched water for [ 18 F] fluoride production from the 18 O(p,n) 18 F reaction and natural abundance water for [ 13 N] nitrate/nitrite production from the 16 O(p,α) 13 N reaction and loads one of two targets depending on the radionuclide desired. The system offers several novel features for reliable radionuclide production. First, there exists an in-target probe for direct liquid level sensing using the conductivity response of water. In addition, transfer of [ 18 F] fluoride to the Hot Lab is completely decoupled from the irradiated water through the actions of a resin/recovery system which is located in the cyclotron vault, thus maintaining transfer line integrity. This feature also provides a mechanism for vault-containment of long-lived contaminants generated through target activation and leaching into the water

  5. Production of Y-86 and other radiometals for research purposes using a solution target system

    International Nuclear Information System (INIS)

    Oehlke, Elisabeth; Hoehr, Cornelia; Hou, Xinchi; Hanemaayer, Victoire; Zeisler, Stefan; Adam, Michael J.; Ruth, Thomas J.; Celler, Anna; Buckley, Ken; Benard, Francois; Schaffer, Paul

    2015-01-01

    Introduction: Diagnostic radiometals are typically obtained from cyclotrons by irradiating solid targets or from radioisotope generators. These methods have the advantage of high production yields, but require additional solid target handling infrastructure that is not readily available to many cyclotron facilities. Herein, we provide an overview of our results regarding the production of various positron-emitting radiometals using a liquid target system installed on a 13 MeV cyclotron at TRIUMF. Details about the production, purification and quality control of 89 Zr, 68 Ga and for the first time 86 Y are discussed. Methods: Aqueous solutions containing 1.35–1.65 g/mL of natural-abundance zinc nitrate, yttrium nitrate, and strontium nitrate were irradiated on a 13 MeV cyclotron using a standard liquid target. Different target body and foil materials were investigated for corrosion. Production yields were calculated using theoretical cross-sections from the EMPIRE code and compared with experimental results. The radioisotopes were extracted from irradiated target material using solid phase extraction methods adapted from previously reported methods, and used for radiolabelling experiments. Results: We demonstrated production quantities that are sufficient for chemical and biological studies for three separate radiometals, 89 Zr (A sat = 360 MBq/μA and yield = 3.17 MBq/μA), 86 Y (A sat = 31 MBq/μA and yield = 1.44 MBq/μA), and 68 Ga (A sat = 141 MBq/μA and yield = 64 MBq/μA) from one hour long irradiations on a typical medical cyclotron. 68 Ga yields were sufficient for potential clinical applications. In order to avoid corrosion of the target body and target foil, nitrate solutions were chosen as well as niobium as target-body material. An automatic loading system enabled up to three production runs per day. The separation efficiency ranged from 82 to 99%. Subsequently, 68 Ga and 86 Y were successfully used to radiolabel DOTA-based chelators while

  6. Strategies for systemic radiotherapy of micrometastases using antibody-targeted 131I.

    Science.gov (United States)

    Wheldon, T E; O'Donoghue, J A; Hilditch, T E; Barrett, A

    1988-02-01

    A simple analysis is developed to evaluate the likely effectiveness of treatment of micrometastases by antibody-targeted 131I. Account is taken of the low levels of tumour uptake of antibody-conjugated 131I presently achievable and of the "energy wastage" in targeting microscopic tumours with a radionuclide whose disintegration energy is widely dissipated. The analysis shows that only modest doses can be delivered to micrometastases when total body dose is restricted to levels which allow recovery of bone marrow. Much higher doses could be delivered to micrometastases when bone marrow rescue is used. A rationale is presented for targeted systemic radiotherapy used in combination with external beam total body irradiation (TBI) and bone marrow rescue. This has some practical advantages. The effect of the targeted component is to impose a biological non-uniformity on the total body dose distribution with regions of high tumour cell density receiving higher doses. Where targeting results in high doses to particular normal organs (e.g. liver, kidney) the total dose to these organs could be kept within tolerable limits by appropriate shielding of the external beam radiation component of the treatment. Greater levels of tumour cell kill should be achievable by the combination regime without any increase in normal tissue damage over that inflicted by conventional TBI. The predicted superiority of the combination regime is especially marked for tumours just below the threshold for detectability (e.g. approximately 1 mm-1 cm diameter). This approach has the advantage that targeted radiotherapy provides only a proportion of the total body dose, most of which is given by a familiar technique. The proportion of dose given by the targeted component could be increased as experience is gained. The predicted superiority of the combination strategy should be experimentally testable using laboratory animals. Clinical applications should be cautiously approached, with due regard to

  7. Accuracy of position measurement method using Arago spot for inertial fusion energy target tracking system

    International Nuclear Information System (INIS)

    Saruta, Koichi; Tsuji, Ryusuke

    2007-01-01

    The accuracy of a position measurement method using the Arago spot is reported for an inertial fusion energy (IFE) target tracking system, where the position of the target is determined by the position of the Arago spot, which is a bright spot appearing in the central portion of the diffraction pattern of a spherical obstacle. We use a He-Ne laser as the light source and a charge-coupled device (CCD) camera with a microscope objective lens to magnify and record the diffraction pattern of a spherical target. We examine two different algorithms to determine the center of the Arago spot in order to compare the measurement performances. The experimental results show that the position of a 5-mm-diameter target can be obtained with a measurement resolution of 1 μm and an rms measurement error of less than 0.2μm for both algorithms when the distance between the target and the microscope objective lens is 5 cm. (author)

  8. Development of target ion source systems for radioactive beams at GANIL

    Energy Technology Data Exchange (ETDEWEB)

    Bajeat, O., E-mail: bajeat@ganil.fr [GANIL, BP 55027, 14076 CAEN Cedex 05 (France); Delahaye, P. [GANIL, BP 55027, 14076 CAEN Cedex 05 (France); Couratin, C. [GANIL, BP 55027, 14076 CAEN Cedex 05 (France); LPC Caen, 6 bd Maréchal Juin, 14050 CAEN Cedex (France); Dubois, M.; Franberg-Delahaye, H.; Henares, J.L.; Huguet, Y.; Jardin, P.; Lecesne, N.; Lecomte, P.; Leroy, R.; Maunoury, L.; Osmond, B.; Sjodin, M. [GANIL, BP 55027, 14076 CAEN Cedex 05 (France)

    2013-12-15

    Highlights: • For Spiral 1, a febiad ion source has been connected to a graphite target. • For Spiral 2, an oven made with a carbon resistor is under development. • We made some measurement of effusion in the Spiral 2 target. • A laser ion source is under construction. -- Abstract: The GANIL facility (Caen, France) is dedicated to the acceleration of heavy ion beams including radioactive beams produced by the Isotope Separation On-Line (ISOL) method at the SPIRAL1 facility. To extend the range of radioactive ion beams available at GANIL, using the ISOL method two projects are underway: SPIRAL1 upgrade and the construction of SPIRAL2. For SPIRAL1, a new target ion source system (TISS) using the VADIS FEBIAD ion source coupled to the SPIRAL1 carbon target will be tested on-line by the end of 2013 and installed in the cave of SPIRAL1 for operation in 2015. The SPIRAL2 project is under construction and is being design for using different production methods as fission, fusion or spallation reactions to cover a large area of the chart of nuclei. It will produce among others neutron rich beams obtained by the fission of uranium induced by fast neutrons. The production target made from uranium carbide and heated at 2000 °C will be associated with several types of ion sources. Developments currently in progress at GANIL for each of these projects are presented.

  9. Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

    Science.gov (United States)

    Distler, Oliver; Cozzio, Antonio

    2016-01-01

    Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

  10. Exploiting off-targeting in guide-RNAs for CRISPR systems for simultaneous editing of multiple genes

    DEFF Research Database (Denmark)

    Ferreira, Raphael; Gatto, Francesco; Nielsen, Jens

    2017-01-01

    Bioinformatics tools to design guide-RNAs (gRNAs) in Clustered Regularly Interspaced Short Palindromic Repeats systems mostly focused on minimizing off-targeting to enhance efficacy of genome editing. However, there are circumstances in which off-targeting might be desirable to target multiple ge...

  11. Real-Time Implementation of an Asynchronous Vision-Based Target Tracking System for an Unmanned Aerial Vehicle

    Science.gov (United States)

    2007-06-01

    Chin Khoon Quek. “Vision Based Control and Target Range Estimation for Small Unmanned Aerial Vehicle.” Master’s Thesis, Naval Postgraduate School...December 2005. [6] Kwee Chye Yap. “Incorporating Target Mensuration System for Target Motion Estimation Along a Road Using Asynchronous Filter

  12. Lactoferrin bioconjugated solid lipid nanoparticles: a new drug delivery system for potential brain targeting.

    Science.gov (United States)

    Singh, Indu; Swami, Rajan; Pooja, Deep; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

    2016-01-01

    Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf) conjugated SLN system is first time attempted for effective brain targeting in this study. Preparation of Lf-modified docetaxel (DTX)-loaded SLN for proficient delivery of DTX to brain. DTX-loaded SLN were prepared using emulsification and solvent evaporation method and conjugation of Lf on SLN surface (C-SLN) was attained through carbodiimide chemistry. These lipidic nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro release studies. Colloidal stability study was performed in biologically simulated environment (normal saline and serum). These lipidic nanoparticles were further evaluated for its targeting mechanism for uptake in brain tumour cells and brain via receptor saturation studies and distribution studies in brain, respectively. Particle size of lipidic nanoparticles was found to be optimum. Surface morphology (zeta potential, AFM) and surface chemistry (FTIR) confirmed conjugation of Lf on SLN surface. Cytotoxicity studies revealed augmented apoptotic activity of C-SLN than SLN and DTX. Enhanced cytotoxicity was demonstrated by receptor saturation and uptake studies. Brain concentration of DTX was elevated significantly with C-SLN than marketed formulation. It is evident from the cytotoxicity, uptake that SLN has potential to deliver drug to brain than marketed formulation but conjugating Lf on SLN surface (C-SLN) further increased the targeting potential for brain tumour. Moreover, brain distribution studies corroborated the use of C-SLN as a viable vehicle to target drug to brain. Hence, C-SLN was demonstrated to be a promising DTX delivery system to brain as it possessed remarkable biocompatibility, stability and efficacy than

  13. Design of the fill/transfer station cryostat for the OMEGA cryogenic target system

    International Nuclear Information System (INIS)

    Gibson, C.R.; Charmin, C.M.; Del Bene, J.V.; Hoffmann, E.H.; Besenbruch, G.E.; Anteby, I.

    1997-09-01

    General Atomics is designing, testing and fabricating a system for supplying cryogenic targets for the University of Rochester's OMEGA laser system. A prototype system has demonstrated the filling of 1 mm diameter, 3 microm wall plastic spheres to 111 MPa (1,100 atm) with deuterium and then cooling to 18 K to condense the fuel. The production design must be capable of routinely filling and cooling targets with a 50/50 mix of deuterium and tritium and transferring them to a device which places the targets into the focus of 60 laser beams. This paper discusses the design and analysis of the production Fill/Transfer Station cryostat. The cryostat has two major components, a fixed base and a removable dome. The joint between the base and the dome is similar to a bayonet fitting and is sealed by a room temperature elastomeric o-ring. Since the cryostat must be housed in a glovebox, its design is driven strongly by maintenance requirements. To reach the equipment inside the cryostat, the dome is simply unbolted and lifted. The inside of the cryostat is maintained at 16 K by a closed loop helium flow system. Gaseous helium at about 1.4 MPa (200 psi) flows through tubes which are brazed to the inner walls. Cooling is provided by several cryocoolers which are located external to the cryostat. Liquid nitrogen is used as a heat intercept and to precool the helium gas

  14. PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma.

    Science.gov (United States)

    Jiang, Yan; Lv, Lingyan; Shi, Huihui; Hua, Yabing; Lv, Wei; Wang, Xiuzhen; Xin, Hongliang; Xu, Qunwei

    2016-11-01

    Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor α2 (IL-13Rα2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p<0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Quantitative performance targets by using balanced scorecard system: application to waste management and public administration.

    Science.gov (United States)

    Mendes, Paula; Nunes, Luis Miguel; Teixeira, Margarida Ribau

    2014-09-01

    This article demonstrates how decision-makers can be guided in the process of defining performance target values in the balanced scorecard system. We apply a method based on sensitivity analysis with Monte Carlo simulation to the municipal solid waste management system in Loulé Municipality (Portugal). The method includes two steps: sensitivity analysis of performance indicators to identify those performance indicators with the highest impact on the balanced scorecard model outcomes; and sensitivity analysis of the target values for the previously identified performance indicators. Sensitivity analysis shows that four strategic objectives (IPP1: Comply with the national waste strategy; IPP4: Reduce nonrenewable resources and greenhouse gases; IPP5: Optimize the life-cycle of waste; and FP1: Meet and optimize the budget) alone contribute 99.7% of the variability in overall balanced scorecard value. Thus, these strategic objectives had a much stronger impact on the estimated balanced scorecard outcome than did others, with the IPP1 and the IPP4 accounting for over 55% and 22% of the variance in overall balanced scorecard value, respectively. The remaining performance indicators contribute only marginally. In addition, a change in the value of a single indicator's target value made the overall balanced scorecard value change by as much as 18%. This may lead to involuntarily biased decisions by organizations regarding performance target-setting, if not prevented with the help of methods such as that proposed and applied in this study. © The Author(s) 2014.

  16. TargetVue: Visual Analysis of Anomalous User Behaviors in Online Communication Systems.

    Science.gov (United States)

    Cao, Nan; Shi, Conglei; Lin, Sabrina; Lu, Jie; Lin, Yu-Ru; Lin, Ching-Yung

    2016-01-01

    Users with anomalous behaviors in online communication systems (e.g. email and social medial platforms) are potential threats to society. Automated anomaly detection based on advanced machine learning techniques has been developed to combat this issue; challenges remain, though, due to the difficulty of obtaining proper ground truth for model training and evaluation. Therefore, substantial human judgment on the automated analysis results is often required to better adjust the performance of anomaly detection. Unfortunately, techniques that allow users to understand the analysis results more efficiently, to make a confident judgment about anomalies, and to explore data in their context, are still lacking. In this paper, we propose a novel visual analysis system, TargetVue, which detects anomalous users via an unsupervised learning model and visualizes the behaviors of suspicious users in behavior-rich context through novel visualization designs and multiple coordinated contextual views. Particularly, TargetVue incorporates three new ego-centric glyphs to visually summarize a user's behaviors which effectively present the user's communication activities, features, and social interactions. An efficient layout method is proposed to place these glyphs on a triangle grid, which captures similarities among users and facilitates comparisons of behaviors of different users. We demonstrate the power of TargetVue through its application in a social bot detection challenge using Twitter data, a case study based on email records, and an interview with expert users. Our evaluation shows that TargetVue is beneficial to the detection of users with anomalous communication behaviors.

  17. Targeting choroid plexus epithelia and ventricular ependyma for drug delivery to the central nervous system

    Directory of Open Access Journals (Sweden)

    Stopa Edward G

    2011-01-01

    Full Text Available Abstract Background Because the choroid plexus (CP is uniquely suited to control the composition of cerebrospinal fluid (CSF, there may be therapeutic benefits to increasing the levels of biologically active proteins in CSF to modulate central nervous system (CNS functions. To this end, we sought to identify peptides capable of ligand-mediated targeting to CP epithelial cells reasoning that they could be exploited to deliver drugs, biotherapeutics and genes to the CNS. Methods A peptide library displayed on M13 bacteriophage was screened for ligands capable of internalizing into CP epithelial cells by incubating phage with CP explants for 2 hours at 37C and recovering particles with targeting capacity. Results Three peptides, identified after four rounds of screening, were analyzed for specific and dose dependant binding and internalization. Binding was deemed specific because internalization was prevented by co-incubation with cognate synthetic peptides. Furthermore, after i.c.v. injection into rat brains, each peptide was found to target phage to epithelial cells in CP and to ependyma lining the ventricles. Conclusion These data demonstrate that ligand-mediated targeting can be used as a strategy for drug delivery to the central nervous system and opens the possibility of using the choroid plexus as a portal of entry into the brain.

  18. Toward improved target conformity for two spot scanning proton therapy delivery systems using dynamic collimation

    Science.gov (United States)

    Moignier, Alexandra; Gelover, Edgar; Smith, Blake R.; Wang, Dongxu; Flynn, Ryan T.; Kirk, Maura L.; Lin, Liyong; Solberg, Timothy D.; Lin, Alexander; Hyer, Daniel E.

    2016-01-01

    Purpose: To quantify improvement in target conformity in brain and head and neck tumor treatments resulting from the use of a dynamic collimation system (DCS) with two spot scanning proton therapy delivery systems (universal nozzle, UN, and dedicated nozzle, DN) with median spot sizes of 5.2 and 3.2 mm over a range of energies from 100 to 230 MeV. Methods: Uncollimated and collimated plans were calculated with both UN and DN beam models implemented within our in-house treatment planning system for five brain and ten head and neck datasets in patients previously treated with spot scanning proton therapy. The prescription dose and beam angles from the clinical plans were used for both the UN and DN plans. The average reduction of the mean dose to the 10-mm ring surrounding the target between the uncollimated and collimated plans was calculated for the UN and the DN. Target conformity was analyzed using the mean dose to 1-mm thickness rings surrounding the target at increasing distances ranging from 1 to 10 mm. Results: The average reductions of the 10-mm ring mean dose for the UN and DN plans were 13.7% (95% CI: 11.6%–15.7%; p < 0.0001) and 11.5% (95% CI: 9.5%–13.5%; p < 0.0001) across all brain cases and 7.1% (95% CI: 4.4%–9.8%; p < 0.001) and 6.3% (95% CI: 3.7%–9.0%; p < 0.001), respectively, across all head and neck cases. The collimated UN plans were either more conformal (all brain cases and 60% of the head and neck cases) than or equivalent (40% of the head and neck cases) to the uncollimated DN plans. The collimated DN plans offered the highest conformity. Conclusions: The DCS added either to the UN or DN improved the target conformity. The DCS may be of particular interest for sites with UN systems looking for a more economical solution than upgrading the nozzle to improve the target conformity of their spot scanning proton therapy system. PMID:26936726

  19. Programmable removal of bacterial strains by use of genome-targeting CRISPR-Cas systems.

    Science.gov (United States)

    Gomaa, Ahmed A; Klumpe, Heidi E; Luo, Michelle L; Selle, Kurt; Barrangou, Rodolphe; Beisel, Chase L

    2014-01-28

    CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems in bacteria and archaea employ CRISPR RNAs to specifically recognize the complementary DNA of foreign invaders, leading to sequence-specific cleavage or degradation of the target DNA. Recent work has shown that the accidental or intentional targeting of the bacterial genome is cytotoxic and can lead to cell death. Here, we have demonstrated that genome targeting with CRISPR-Cas systems can be employed for the sequence-specific and titratable removal of individual bacterial strains and species. Using the type I-E CRISPR-Cas system in Escherichia coli as a model, we found that this effect could be elicited using native or imported systems and was similarly potent regardless of the genomic location, strand, or transcriptional activity of the target sequence. Furthermore, the specificity of targeting with CRISPR RNAs could readily distinguish between even highly similar strains in pure or mixed cultures. Finally, varying the collection of delivered CRISPR RNAs could quantitatively control the relative number of individual strains within a mixed culture. Critically, the observed selectivity and programmability of bacterial removal would be virtually impossible with traditional antibiotics, bacteriophages, selectable markers, or tailored growth conditions. Once delivery challenges are addressed, we envision that this approach could offer a novel means to quantitatively control the composition of environmental and industrial microbial consortia and may open new avenues for the development of "smart" antibiotics that circumvent multidrug resistance and differentiate between pathogenic and beneficial microorganisms. Controlling the composition of microbial populations is a critical aspect in medicine, biotechnology, and environmental cycles. While different antimicrobial strategies, such as antibiotics, antimicrobial peptides, and lytic bacteriophages, offer partial solutions

  20. Dynamic target high pressure control of a VRF system for heating energy savings

    International Nuclear Information System (INIS)

    Yun, Geun Young; Lee, Je Hyeon; Kim, Inhan

    2017-01-01

    Highlights: • We developed the dynamic target high pressure control of a VRF system. • We created the VRF control model using the EnergyPlus runtime language. • Multicalorimeter experimental results indicate that the energy efficiency improved by 21%. • EnergyPlus simulations demonstrate that the annual heating energy consumption was lowered by 22%. - Abstract: Variable refrigerant flow (VRF) systems are widely used because of their ability to provide individualized comfort control with energy-saving potential. This study develops load responsive high pressure control of a VRF system with the aim of reducing the heating energy consumption of a VRF system under part load conditions. The developed control consists of two parts: one part that determines the level of heating load, and the other that assigns a target high pressure based on the level of heating load. In this way, the compressor speed can be accurately matched to heating load, which improves the energy performance of the VRF system. A series of multicalorimeter experiments revealed that the heating capacity of the VRF system varied by 45% by modulating the target high pressure and that its efficiency was enhanced by 21% by changing the high pressure from 30 kgf/cm"2 to 25 kgf/cm"2. To evaluate the annual heating energy performance of the VRF system with the developed control, a custom computer code was developed to implement the developed control using a programming language called EnergyPlus Runtime Language. Simulation outcomes showed that the annual heating energy consumption of a medium-size office building was reduced by 22% when the developed control was applied.

  1. Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

    Science.gov (United States)

    Palmer, Brian C.; DeLouise, Lisa A.

    2017-01-01

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

  2. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

    Science.gov (United States)

    Palmer, Brian C; DeLouise, Lisa A

    2016-12-15

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  3. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting

    Directory of Open Access Journals (Sweden)

    Brian C. Palmer

    2016-12-01

    Full Text Available Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  4. Repurposing Auranofin, Ebselen, and PX-12 as Antimicrobial Agents Targeting the Thioredoxin System

    Directory of Open Access Journals (Sweden)

    Holly C. May

    2018-03-01

    Full Text Available As microbial resistance to drugs continues to rise at an alarming rate, finding new ways to combat pathogens is an issue of utmost importance. Development of novel and specific antimicrobial drugs is a time-consuming and expensive process. However, the re-purposing of previously tested and/or approved drugs could be a feasible way to circumvent this long and costly process. In this review, we evaluate the U.S. Food and Drug Administration tested drugs auranofin, ebselen, and PX-12 as antimicrobial agents targeting the thioredoxin system. These drugs have been shown to act on bacterial, fungal, protozoan, and helminth pathogens without significant toxicity to the host. We propose that the thioredoxin system could serve as a useful therapeutic target with broad spectrum antimicrobial activity.

  5. Orally active-targeted drug delivery systems for proteins and peptides.

    Science.gov (United States)

    Li, Xiuying; Yu, Miaorong; Fan, Weiwei; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

    2014-09-01

    In the past decade, extensive efforts have been devoted to designing 'active targeted' drug delivery systems (ATDDS) to improve oral absorption of proteins and peptides. Such ATDDS enhance cellular internalization and permeability of proteins and peptides via molecular recognition processes such as ligand-receptor or antigen-antibody interaction, and thus enhance drug absorption. This review focuses on recent advances with orally ATDDS, including ligand-protein conjugates, recombinant ligand-protein fusion proteins and ligand-modified carriers. In addition to traditional intestinal active transport systems of substrates and their corresponding receptors, transporters and carriers, new targets such as intercellular adhesion molecule-1 and β-integrin are also discussed. ATDDS can improve oral absorption of proteins and peptides. However, currently, no clinical studies on ATDDS for proteins and peptides are underway, perhaps due to the complexity and limited knowledge of transport mechanisms. Therefore, more research is warranted to optimize ATDDS efficiency.

  6. Neurosteroid vitamin D system as a nontraditional drug target in neuropsychopharmacology.

    Science.gov (United States)

    Stewart, Adam; Wong, Keith; Cachat, Jonathan; Elegante, Marco; Gilder, Tom; Mohnot, Sopan; Wu, Nadine; Minasyan, Anna; Tuohimaa, Pentti; Kalueff, Allan V

    2010-09-01

    Vitamin D is becoming increasingly recognized as a nontraditional drug target for different brain pathologies. Although widely known for their role in calcium metabolism, vitamin D and its receptor have been linked to several brain disorders, including cognitive decline, epilepsy, affective disorders, and schizophrenia. Here we discuss mounting evidence, and parallel recent clinical and animal behavioral, genetic and pharmacological data to emphasize the emerging role of the neurosteroid vitamin D system in brain function.

  7. VME online system of the Bonn polarized nucleon targets and polarization measurements on NH3

    International Nuclear Information System (INIS)

    Thiel, W.

    1991-02-01

    The measurement of spin observables is the main purpose of the PHOENICS detector at the Bonn Electron Accelerator ELSA. Therefore a new frosen spin target was built allowing any spin orientation by means of two perpendicular holding fields and the use of a polarizing field up to 7 Tesla. With a vertical dilution refrigerator the polarization can be frozen at a temperature of 70 mK. This thesis describe a VME based control and monitor system for the various parts of this target. It mainly consists of a VIP processor together with different kinds of I/O and interface boards. Caused by its modular structure in hard- and software it can be easyly set up to control and monitor different hardware environments. A menu and command oriented user interface running on an ATARI computer allows a comfortable operation. Secondly the new NMR system is described in detail. It is based on the Liferpool module allowing a dispersion user interface running on an ATARI computer allows a comfortable operation. Secondly the new NMR system is described in detail. It is based on the Liverpool module allowing a dispersion free detection and a simple adjustment to different magnetic fields. A similar VME system takes care of all the necessary task for the polarization measurements. Fast optodecoupled analog I/O modules a e used as an interface to the NMR hardware. Finally the first measurements with this target are presented. Using NH 3 as target material and a polarizing field of 3.5 Tesla a proton polarization of +94% and -100% could be achieved. By lowering the magnetic field to 0.35 Tesla a superradiance effect was observed. (orig.)

  8. Remote-controlled flexible pose measurement system and method for a moving target in wind tunnel

    Directory of Open Access Journals (Sweden)

    Wei LIU

    2018-01-01

    Full Text Available The measurement of position and attitude parameters for the isolated target from a high-speed aircraft is a great challenge in the field of wind tunnel simulation technology. This paper proposes a remote-controlled flexible pose measurement system in wind tunnel conditions for the separation of a target from an aircraft. The position and attitude parameters of a moving object are obtained by utilizing a single camera with a focal length and camera orientation that can be changed based on different measurement conditions. Using this proposed system and method, both the flexibility and efficiency of the pose measurement system can be enhanced in wind tunnel conditions to meet the measurement requirements of different objects and experiments, which is also useful for the development of an intelligent position and attitude measurement system. The position and the focal length of the camera also can be controlled remotely during measurements to enlarge both the vertical and horizontal measurement range of this system. Experiments are conducted in the laboratory to measure the position and attitude of moving objects with high flexibility and efficiency, and the measurement precision of the measurement system is also verified through experiments.

  9. Nanomedicine strategies for sustained, controlled, and targeted treatment of cancer stem cells of the digestive system.

    Science.gov (United States)

    Xie, Fang-Yuan; Xu, Wei-Heng; Yin, Chuan; Zhang, Guo-Qing; Zhong, Yan-Qiang; Gao, Jie

    2016-10-15

    Cancer stem cells (CSCs) constitute a small proportion of the cancer cells that have self-renewal capacity and tumor-initiating ability. They have been identified in a variety of tumors, including tumors of the digestive system. CSCs exhibit some unique characteristics, which are responsible for cancer metastasis and recurrence. Consequently, the development of effective therapeutic strategies against CSCs plays a key role in increasing the efficacy of cancer therapy. Several potential approaches to target CSCs of the digestive system have been explored, including targeting CSC surface markers and signaling pathways, inducing the differentiation of CSCs, altering the tumor microenvironment or niche, and inhibiting ATP-driven efflux transporters. However, conventional therapies may not successfully eradicate CSCs owing to various problems, including poor solubility, stability, rapid clearance, poor cellular uptake, and unacceptable cytotoxicity. Nanomedicine strategies, which include drug, gene, targeted, and combinational delivery, could solve these problems and significantly improve the therapeutic index. This review briefly summarizes the ongoing development of strategies and nanomedicine-based therapies against CSCs of the digestive system.

  10. Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

    Directory of Open Access Journals (Sweden)

    Umberto Tosi

    2017-02-01

    Full Text Available Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

  11. Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

    Science.gov (United States)

    Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

    2017-01-01

    Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

  12. Production of multicharged radioactive ion beams for spiral: studies and realization of the first target-ion source system

    International Nuclear Information System (INIS)

    Maunoury, L.

    1998-01-01

    In the framework of the SPIRAL project, which concerns the production and the acceleration of a multicharged radioactive ions beam, the following part has been studied: production and ionization of the radioactive ions beam. A first target-source (nanogan II), devoted exclusively to the production of multicharged radioactive ions gas type beams, has been studied and tested. The diffusion efficiency has been deduced from the diffusion equations (Fick laws). This efficiency is governed by the following parameters: the temperature, the grains size of the target, the Arrhenius parameters and the radioactive period. Another study concerning the production targets is presented. It deals with the temperature distribution allowing an utilization of more than one month at a temperature of 2400 K. Another development (SPIRAL II) is devoted to the production of high neutron content radioactive atoms created by the uranium fission, from fast neutrons. The neutrons beam is produced by the ''stripping break-up'' of a deutons beam in a converter. (A.L.B.)

  13. Modeling of Target Tracking System for Homing Missiles and Air Defense Systems

    Directory of Open Access Journals (Sweden)

    Yunes Sh. ALQUDSI

    2018-06-01

    Full Text Available One reason of why the guidance and control systems are imperfect is due to the dynamics of both the tracker and the missile, which appears as an error in the alignment with the LOS and delay in the response of the missile to change its orientation. Other reasons are the bias and disturbances as well as the noise about and within the system such as the thermal noise. This paper deals with the tracking system used in the homing guidance and air defense systems. A realistic model for the tracking system model is developed including the receiver servo dynamics and the possible disturbance and noise that may affect the accuracy of the tracking signals measured by the seeker sensor. Modeling the parameters variability and uncertainty is also examined to determine the robustness margin of the tracking system.

  14. Interaction of a 29 MeV 3He particle beam with a Cl4C vapour target

    International Nuclear Information System (INIS)

    Lleo Morilla, A.

    1963-01-01

    The interactions of a 29 MeV 3 H e particles beam on a Cl 4 C vapour target have been studied using the photographic method. differential cross-sections for the Cl( 3 He, 3 He)Cl elastic scattering and 1 2C( 3 He, α) 1 1C pick-up reaction are shown; the corresponding angular distributions in the centre-of-mass system have been compared with the predictions of optical model and A.B.M. theories. (Author) 21 refs

  15. A free Hg jet system for use in a high-power target experiment

    CERN Document Server

    Spampinato, Philip; Gabriel, Tony A; Graves, Van; Haseroth, H; Kirk, Harold G; Lettry, Jacques; McDonald, Kirk T; Rennich, Mark; Simos, Nikolaos; Titus, P; Tsang, Thomas

    2005-01-01

    We describe a mercury jet system that is suitable for insertion into the 15cm diameter bore of a high-field solenoid magnet. The device features a hermetically sealed primary containment volume which is enclosed in a secondary containment system to insure isolation of mercury vapors from the remaining experimental environment. The jet diameter is 1-cm while the jet velocity will be up to 20 m/s. Optical diagnostics is incorporated into the target design to allow observation of the dispersal of the mercury as a result of interaction with a 24 GeV proton beam with up to 20 x 10

  16. Target Tracking of a Linear Time Invariant System under Irregular Sampling

    Directory of Open Access Journals (Sweden)

    Jin Xue-Bo

    2012-11-01

    Full Text Available Due to event-triggered sampling in a system, or maybe with the aim of reducing data storage, tracking many applications will encounter irregular sampling time. By calculating the matrix exponential using an inverse Laplace transform, this paper transforms the irregular sampling tracking problem to the problem of tracking with time-varying parameters of a system. Using the common Kalman filter, the developed method is used to track a target for the simulated trajectory and video tracking. The results of simulation experiments have shown that it can obtain good estimation performance even at a very high irregular rate of measurement sampling time.

  17. The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke.

    Science.gov (United States)

    Winek, Katarzyna; Dirnagl, Ulrich; Meisel, Andreas

    2016-10-01

    Research on commensal microbiota and its contribution to health and disease is a new and very dynamically developing field of biology and medicine. Recent experimental and clinical investigations underscore the importance of gut microbiota in the pathogenesis and course of stroke. Importantly, microbiota may influence the outcome of cerebral ischemia by modulating central nervous system antigen-specific immune responses. In this review we summarize studies linking gut microbiota with physiological function and disorders of the central nervous system. Based on these insights we speculate about targeting the gut microbiome in order to treat stroke.

  18. The GEKKO XII-HIPER (High Intensity Plasma Experimental Research) system relevant to ignition targets

    International Nuclear Information System (INIS)

    Miyanaga, N.; Nakatsuka, M.; Azechi, H.

    2001-01-01

    To test high gain targets surrogated in the planar geometry, we have constructed a new experimental system (HIPER) which provides the high ablation pressure with a uniform irradiance profile. These performances were achieved by bundling twelve beams of the existing GEKKO XII into a F/3 focus cone. The partially coherent light is introduced for the beam smoothing of a green foot pulse consisting of three beams, and the three-directional smoothing by spectral dispersion is utilized for residual nine beams delivering a blue main drive pulse. The detail of design concept and results of initial activation of this system are reported. (author)

  19. Deposition of Al/Cu Multilayer By Double Targets Cylindrical DC Magnetron Sputtering System

    Directory of Open Access Journals (Sweden)

    P. Balashabadi

    2013-12-01

    Full Text Available A cylindrical direct current magnetron sputtering coater with two targets for deposition of multilayer thin films and cermet solar selective surfaces has been constructed. The substrate holder was able to rotate around the target for obtaining the uniform layer and separated multilayer phases. The Al/ Cu multilayer film was deposited on the glass substrate at the following conditions: Working gas = Pure argon, Working pressure = 1 Pa, Cathode current = 8 A and cathode voltage = -600 V .Microstructure of the film was investigated by X-Ray Diffraction and the scanning electron microscopy analyses. The elements profile was determined by glow discharge–optical emission spectroscopy analysis. During deposition, both targets with magnetron configuration were sputtered simultaneously by argon ions. A Plasma column on the targets surface was generated by a 290 G permanent magnet unit. Two DC power supply units with three phases input and maximum output of 12 A/1000V were used to deposit the multilayer thin films. A control phase system was used to adjust output voltage.

  20. Fabrication of a nanocarrier system through self-assembly of plasma protein and its tumor targeting

    International Nuclear Information System (INIS)

    Gong Guangming; Zhi Feng; Wang Kaikai; Tang Xiaolei; Yuan Ahu; Zhao Lili; Ding Dawei; Hu Yiqiao

    2011-01-01

    Human serum albumin (HSA) nanoparticles hold great promise as a nanocarrier system for targeted drug delivery. The objective of this study was to explore the possibility of preparing size controllable albumin nanoparticles using the disulfide bond breaking reagent β-mercaptoethanol (β-ME). The results showed that the protein concentration and temperature had positive effects on the sizes of the albumin nanoparticles, while pH had a negative effect on the rate of nanoparticle formation. The addition of β-ME induced changes in HSA secondary structure and exposed the hydrophobic core of HSA, leading to the formation of nanoparticles. Human serum albumin nanoparticles could be internalized by MCF-7 cells and mainly accumulated in cytoplasm. After injection in tumor bearing mice, the HSA nanoparticles accumulated in tumor tissues, demonstrating the targeting ability of the nanoparticles. Therefore, human serum albumin can be fabricated into nanoparticles by breaking the disulfide bonds and these nanoparticles exhibit high tumor targeting ability. Human serum albumin nanoparticles could be ideal for the targeted delivery of pharmacologically active substances.

  1. Seismic Target Classification Using a Wavelet Packet Manifold in Unattended Ground Sensors Systems

    Directory of Open Access Journals (Sweden)

    Enliang Song

    2013-07-01

    Full Text Available One of the most challenging problems in target classification is the extraction of a robust feature, which can effectively represent a specific type of targets. The use of seismic signals in unattended ground sensor (UGS systems makes this problem more complicated, because the seismic target signal is non-stationary, geology-dependent and with high-dimensional feature space. This paper proposes a new feature extraction algorithm, called wavelet packet manifold (WPM, by addressing the neighborhood preserving embedding (NPE algorithm of manifold learning on the wavelet packet node energy (WPNE of seismic signals. By combining non-stationary information and low-dimensional manifold information, WPM provides a more robust representation for seismic target classification. By using a K nearest neighbors classifier on the WPM signature, the algorithm of wavelet packet manifold classification (WPMC is proposed. Experimental results show that the proposed WPMC can not only reduce feature dimensionality, but also improve the classification accuracy up to 95.03%. Moreover, compared with state-of-the-art methods, WPMC is more suitable for UGS in terms of recognition ratio and computational complexity.

  2. Intracellular Protein Delivery System Using a Target-Specific Repebody and Translocation Domain of Bacterial Exotoxin.

    Science.gov (United States)

    Kim, Hee-Yeon; Kang, Jung Ae; Ryou, Jeong-Hyun; Lee, Gyeong Hee; Choi, Dae Seong; Lee, Dong Eun; Kim, Hak-Sung

    2017-11-17

    With the high efficacy of protein-based therapeutics and plenty of intracellular drug targets, cytosolic protein delivery in a cell-specific manner has attracted considerable attention in the field of precision medicine. Herein, we present an intracellular protein delivery system based on a target-specific repebody and the translocation domain of Pseudomonas aeruginosa exotoxin A. The delivery platform was constructed by genetically fusing an EGFR-specific repebody as a targeting moiety to the translocation domain, while a protein cargo was fused to the C-terminal end of the delivery platform. The delivery platform was revealed to efficiently translocate a protein cargo to the cytosol in a target-specific manner. We demonstrate the utility and potential of the delivery platform by showing a remarkable tumor regression with negligible toxicity in a xenograft mice model when gelonin was used as the cytotoxic protein cargo. The present platform can find wide applications to the cell-selective cytosolic delivery of diverse proteins in many areas.

  3. A SYSTEM APPROACH TO ORGANISING PROTECTION FROM TARGETED INFORMATION IN SOCIAL NETWORKS

    Directory of Open Access Journals (Sweden)

    Marina V. Tumbinskaya

    2017-01-01

    Full Text Available Abstract. Objectives The aim of the study is to formalise a generalised algorithm for the distribution of targeted information in social networks, serving as the basis for a methodology for increasing personal information security. Method The research is based on the methodology of protection from unwanted information distributed across social network systems. Results The article presents the formalisation of an algorithm for the distribution of targeted information across social networks: input and output parameters are defined and the algorithm’s internal conditions are described, consisting of parameters for implementing attack scenarios, which variation would allow them to be detailed. A technique for protection from targeted information distributed across social networks is proposed, allowing the level of protection of personal data and information of social networks users to be enhanced, as well as the reliability of information increased. Conclusion The results of the research will help to prevent threats to information security, counteract attacks by intruders who often use methods of competitive intelligence and social engineering through the use of countermeasures. A model for protection against targeted information and implement special software for its integration into online social network social information systems is developed. The system approach will allow external monitoring of events in social networks to be carried out and vulnerabilities identified in the mechanisms of instant messaging, which provide opportunities for attacks by intruders. The results of the research make it possible to apply a network approach to the study of informal communities, which are actively developing today, at a new level. 

  4. Direct renin inhibition — a new way of targeting the renin system

    Directory of Open Access Journals (Sweden)

    Morris J Brown

    2006-06-01

    Full Text Available The renin system plays a key role in the pathology of hypertension and is influenced, both directly and indirectly, by most antihypertensive agents. The system is the target of several established classes of antihypertensive agents including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers. Of currently available drugs, only the beta-blockers suppress renin secretion, but these also reduce heart rate and cardiac output. Calcium channel blockers and diuretics cause a modest activation of the renin system secondary to the fall in renal afferent arteriolar pressure and reduction in filtered sodium load. Aliskiren is the first orally available direct inhibitor that blocks the renin system at its rate limiting step and is shown to reduce angiotensin I and II and plasma renin activity.

  5. Peptide and low molecular weight proteins based kidney targeted drug delivery systems.

    Science.gov (United States)

    Xu, Pengfei; Zhang, Hailiang; Dang, Ruili; Jiang, Pei

    2018-05-30

    Renal disease is a worldwide public health problem, and unfortunately, the therapeutic index of regular drugs is limited. Thus, it is a great need to develop effective treatment strategies. Among the reported strategies, kidney-targeted drug delivery system is a promising method to increase renal efficacy and reduce extra-renal toxicity. In recent years, working as vehicles for targeted drug delivery, low molecular weight proteins (LMWP) and peptide have received immense attention due to their many advantages, such as selective accumulation in kidney, high drug loading capability, control over routes of biodegradation, convenience in modification at the amino terminus, and good biocompatibility. In this review, we describe the current LMWP and peptide carriers for kidney targeted drug delivery systems. In addition, we discuss different linking strategies between carriers and drugs. Furthermore, we briefly outline the current status and attempt to give an outlook on the further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Dissecting molecular interactions involved in recognition of target disulfides by the barley thioredoxin system

    DEFF Research Database (Denmark)

    Björnberg, Olof; Maeda, Kenji; Svensson, Birte

    2012-01-01

    Thioredoxin reduces disulfide bonds, thus regulating activities of target proteins in various biological systems, e.g., inactivation of inhibitors of starch hydrolases and proteases in germinating plant seeds. In the three-dimensional structure of a complex with barley α-amylase/subtilisin inhibi......Thioredoxin reduces disulfide bonds, thus regulating activities of target proteins in various biological systems, e.g., inactivation of inhibitors of starch hydrolases and proteases in germinating plant seeds. In the three-dimensional structure of a complex with barley α...... thioredoxin reductase. HvTrxh2 M88G and M88A adjacent to the invariant cis-proline lost efficiency in both BASI disulfide reduction and recycling by thioredoxin reductase. These effects were further pronounced in M88P lacking a backbone NH group. Remarkably, HvTrxh2 E86R in the same loop displayed overall...... retained catalytic properties, with the exception of a 3-fold increased activity toward BASI. From the 104VGA106 loop, a backbone hydrogen bond donated by A106 appears to be important for target disulfide recognition as A106P lost 90% activity toward BASI but was efficiently recycled by thioredoxin...

  7. Exploiting the CRISPR/Cas9 System for Targeted Genome Mutagenesis in Petunia.

    Science.gov (United States)

    Zhang, Bin; Yang, Xia; Yang, Chunping; Li, Mingyang; Guo, Yulong

    2016-02-03

    Recently, CRISPR/Cas9 technology has emerged as a powerful approach for targeted genome modification in eukaryotic organisms from yeast to human cell lines. Its successful application in several plant species promises enormous potential for basic and applied plant research. However, extensive studies are still needed to assess this system in other important plant species, to broaden its fields of application and to improve methods. Here we showed that the CRISPR/Cas9 system is efficient in petunia (Petunia hybrid), an important ornamental plant and a model for comparative research. When PDS was used as target gene, transgenic shoot lines with albino phenotype accounted for 55.6%-87.5% of the total regenerated T0 Basta-resistant lines. A homozygous deletion close to 1 kb in length can be readily generated and identified in the first generation. A sequential transformation strategy--introducing Cas9 and sgRNA expression cassettes sequentially into petunia--can be used to make targeted mutations with short indels or chromosomal fragment deletions. Our results present a new plant species amenable to CRIPR/Cas9 technology and provide an alternative procedure for its exploitation.

  8. Effective Viscosity of Liquid Helium4 - With Minute He3 Impurity at Temperatures from 0.05K to 2K and at Velocities Spanning the Critical Velocities.

    Science.gov (United States)

    1981-03-01

    cryogenic systems which not only functioned with efficiency , but were a work of art. Mr. Dauwalter ms contribution to these programs has been considerable...excitation voltage e and amplifier gain G, and forex a linear system the DC output voltage e is directly proportional to theo angular displacement de0 e (4.4

  9. Thermal-hydraulic design concept of the solid-target system of spallation neutron source

    International Nuclear Information System (INIS)

    Tanaka, F.; Hibiki, T.; Saito, Y.; Takeda, T.; Mishima, K.

    2001-01-01

    In relation to thermal-hydraulic design of the N-Arena solid-target system of the JHF project, heat transfer experiments were performed to obtain experimental data systematically on heat transfer coefficient and CHF for vertical upward and horizontal flows in a thin rectangular channel simulating a coolant channel of the proposed spallation neutron source. Thermal-hydraulic correlations which can be used for design calculations were proposed based on the obtained data. Finally tentative results of feasibility study on maximum beam power which could be attained with a solid target were presented. The result indicated that the condition for the onset of nucleate boiling is the most significant limiting factor to the maximum beam power. (author)

  10. A new type of liquid-3He target system using small mechanical refrigerators

    International Nuclear Information System (INIS)

    Kato, S.; Kobayashi, K.; Maruyama, K.; Okuno, H.; Konno, O.; Suda, T.; Maki, T.; Asami, H.; Koizumi, T.

    1991-04-01

    A new type of liquid- 3 He target has been developed for photoabsorption experiments at intermediate energies. Using the cooling power of liquid 4 He at reduced vapour pressure, 3 He gas is liquefied into a cylindrical target cell of 180 ml and is maintained at 2.0 K during the experiment. Evaporated 4 He gas is evacuated by a rotary pump and returned into the 4 He bath in the cryostat, where two small mechanical refrigerators with cooling capacities of 3 W at 4.3 K and 10 W at 20 K are operated for the purpose of 4 He recondensation. A maintenance-free operation of more than 1,000 hours has become possible by adopting the 4 He circulation system. (author)

  11. External tandem target system for efficient production of short-lived positron emitting radionuclides

    International Nuclear Information System (INIS)

    Koh, K.; Dwyer, J.; Finn, R.; Sheh, Y.; Sinnreich, J.; Wooten, T.

    1983-01-01

    Recent developments in radiopharmaceutical chemistry allow the incorporation of short-lived, positron-emitting radionuclides into a variety of compounds which when used with a positron emission tomograph provide a means of monitoring physiological disorders by a standard technique. To effectively meet the increased ''in-house'' clinical demands while maintaining a production schedule, a tandem target was designed and has been installed for the simultaneous ''on-line'' preparation of oxygen-15 labelled compounds such as CO 2 15 , H 2 O 15 ; and nitrogen-13 labelled compounds such as 13 NH 3 , 13 N 2 O, and 13 N 2 . The processing time required for the synthesis of the nitrogen-13 products as compared to the essentially instantaneous formation of oxygen-15 labelled compounds has provided the necessary time delay for clinical utilization. The characterisitcs of this external tandem target system as well as the automation for the dual processing are presented

  12. A targeted drug delivery system based on dopamine functionalized nano graphene oxide

    Science.gov (United States)

    Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

    2017-01-01

    The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

  13. Adaptive estimation for control of uncertain nonlinear systems with applications to target tracking

    Science.gov (United States)

    Madyastha, Venkatesh Kattigari

    2005-08-01

    Design of nonlinear observers has received considerable attention since the early development of methods for linear state estimation. The most popular approach is the extended Kalman filter (EKF), that goes through significant degradation in the presence of nonlinearities, particularly if unmodeled dynamics are coupled to the process and the measurement. For uncertain nonlinear systems, adaptive observers have been introduced to estimate the unknown state variables where no priori information about the unknown parameters is available. While establishing global results, these approaches are applicable only to systems transformable to output feedback form. Over the recent years, neural network (NN) based identification and estimation schemes have been proposed that relax the assumptions on the system at the price of sacrificing on the global nature of the results. However, most of the NN based adaptive observer approaches in the literature require knowledge of the full dimension of the system, therefore may not be suitable for systems with unmodeled dynamics. We first propose a novel approach to nonlinear state estimation from the perspective of augmenting a linear time invariant observer with an adaptive element. The class of nonlinear systems treated here are finite but of otherwise unknown dimension. The objective is to improve the performance of the linear observer when applied to a nonlinear system. The approach relies on the ability of the NNs to approximate the unknown dynamics from finite time histories of available measurements. Next we investigate nonlinear state estimation from the perspective of adaptively augmenting an existing time varying observer, such as an EKF. EKFs find their applications mostly in target tracking problems. The proposed approaches are robust to unmodeled dynamics, including unmodeled disturbances. Lastly, we consider the problem of adaptive estimation in the presence of feedback control for a class of uncertain nonlinear systems

  14. Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems

    Science.gov (United States)

    Mullen, Douglas Gurnett

    Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution. Motivated by the problems experienced with the modular design, the actual composition of nanoparticle-ligand distributions were examined using a model dendrimer-ligand system. High Pressure Liquid Chromatography (HPLC) resolved the distribution of components in samples with mean ligand/dendrimer ratios ranging from 0.4 to 13. A peak fitting analysis enabled the quantification of the component distribution. Quantified distributions were found to be significantly more heterogeneous than commonly expected and standard analytical parameters, namely the mean ligand/nanoparticle ratio, failed to adequately represent the component heterogeneity. The distribution of components was also found to be sensitive to particle modifications that preceded the ligand conjugation. With the knowledge gained from this detailed distribution analysis, a new platform design was developed to provide a system with dramatically improved control over the number of components and with improved batch reproducibility. Using semi-preparative HPLC, individual dendrimer-ligand components were isolated. The isolated dendrimer with precise numbers of ligands were characterized by NMR and analytical HPLC. In total, nine different dendrimer-ligand components were obtained with degrees of purity ≥80%. This system has the potential to serve as a platform to which a precise number of functional molecules

  15. CRISPR-DT: designing gRNAs for the CRISPR-Cpf1 system with improved target efficiency and specificity

    OpenAIRE

    Liang, Chun; Zhu, Houxiang

    2018-01-01

    The CRISPR-Cpf1 system has been successfully applied in genome editing. However, target efficiency of the CRISPR-Cpf1 system varies among different gRNA sequences. We reanalyzed the published CRISPR-Cpf1 gRNAs data and found many sequence and structural features related to their target efficiency. Using machine learning technology, a SVM model was created to predict target efficiency for any given gRNAs. We have developed the first web service application, CRISPR-DT (CRISPR DNA Targeting), to...

  16. Developing plan and pre-conceptual design of target system for JAERI`s high intensity neutron source

    Energy Technology Data Exchange (ETDEWEB)

    Hino, Ryutaro; Kaminaga, Masanori; Haga, Katsuhiro; Ishikura, Syuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Nakamura, Fumito; Uchida, Shoji

    1997-11-01

    This paper presents an outline of developing plan of a target system and topics obtained by a pre-conceptual design, which aims to establish a technology base of the target system and to make clear a system concept. In the plan, two types of target - solid and mercury targets - are to be developed for a neutron scattering facility. Information obtained through the development shall be applied to designs of an irradiation and a transmutation facilities. Through the pre-conceptual design, system arrangement, scale etc. were made clear: total weight will be 12000 ton, and 26 beam lines with beam shutters will be equipped for 4 moderators. Engineering problems were also made clear through the design; high flux heat removal, dynamic stress caused by thermal shock and pressure wave, loop technology for the mercury target and a slurry moderator consisting of methane pellets and liquefied hydrogen. We are now constructing new test apparatuses and arranging computer codes for solving these problems. (author)

  17. Measurement of the Spin Structure Function of the Neutron G1(N) from Deep Inelastic Scattering of Polarized Electrons from Polarized Neutrons in He-3

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, J

    2004-01-06

    Polarized electrons of energies 19.42, 22.67, and 25.5 GeV were scattered off a polarized {sup 3}He target at SLAC's End Station A to measure the spin asymmetry of the neutron. From this asymmetry, the spin dependent structure function g{sub 1}{sup n}(x) was determined over a range in x from 0.03 to 0.6 with an average Q{sup 2} of 2 (GeV/C){sup 2}. The value of the integral of g{sub 1}{sup n} over x is {integral}g{sub 1}{sup n}(x)dx = -0.036 {+-} 0.009. The results were interpreted in the frame work of the Quark Parton Model (QPM) and used to test the Ellis-Jaffe and Bjorken sum rules. The value of the integral is 2.6 standard deviations from the Ellis-Jaffe prediction while the Bjorken sum rule was found to be in agreement with this data and proton data from SMC and E-143.

  18. Oral heparin delivery: design and in vivo evaluation of a stomach-targeted mucoadhesive delivery system.

    Science.gov (United States)

    Schmitz, Thierry; Leitner, Verena M; Bernkop-Schnürch, Andreas

    2005-05-01

    Low molecular weight heparin (LMWH) is an agent of choice in the anti-coagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, the therapeutic use is partially limited due to a poor oral bioavailability. It was therefore the aim of this study to design and evaluate a highly efficient stomach-targeted oral delivery system for LMWH. In order to appraise the influence of the molecular weight on the oral bioavailability, mini-tablets comprising 3 kDa (279 IU) and 6 kDa (300 IU) LMWH, respectively, were generated and tested in vivo in rats. The potential of the test formulations based on thiolated polycarbophil, was evaluated in comparison to hydroxyethylcellulose (HEC) as control carrier matrix. The plasma levels of LMWH after oral versus subcutaneous administration were determined in order to calculate the relative bioavailability. With the delivery system containing 3 kDa LMWH (279 IU) a relative bioavailability of 19.1% was achieved, offering a significantly (p thiolated polymers are a promising tool for the non-invasive stomach-targeted systemic delivery of LMWH as model for a hydrophilic macromolecular polysaccharide. Copyright 2005 Wiley-Liss, Inc

  19. Acid-Sensing Ion Channels as Potential Pharmacological Targets in Peripheral and Central Nervous System Diseases.

    Science.gov (United States)

    Radu, Beatrice Mihaela; Banciu, Adela; Banciu, Daniel Dumitru; Radu, Mihai

    2016-01-01

    Acid-sensing ion channels (ASICs) are widely expressed in the body and represent good sensors for detecting protons. The pH drop in the nervous system is equivalent to ischemia and acidosis, and ASICs are very good detectors in discriminating slight changes in acidity. ASICs are important pharmacological targets being involved in a variety of pathophysiological processes affecting both the peripheral nervous system (e.g., peripheral pain, diabetic neuropathy) and the central nervous system (e.g., stroke, epilepsy, migraine, anxiety, fear, depression, neurodegenerative diseases, etc.). This review discusses the role played by ASICs in different pathologies and the pharmacological agents acting on ASICs that might represent promising drugs. As the majority of above-mentioned pathologies involve not only neuronal dysfunctions but also microvascular alterations, in the next future, ASICs may be also considered as potential pharmacological targets at the vasculature level. Perspectives and limitations in the use of ASICs antagonists and modulators as pharmaceutical agents are also discussed. © 2016 Elsevier Inc. All rights reserved.

  20. The control system of the polarized internal target of ANKE at COSY

    Energy Technology Data Exchange (ETDEWEB)

    Kleines, H. [Zentralinstitut fuer Elektronik, Forschungszentrum Juelich, 52425 Juelich (Germany); Sarkadi, J. [Zentralinstitut fuer Elektronik, Forschungszentrum Juelich, 52425 Juelich (Germany); Zwoll, K. [Zentralinstitut fuer Elektronik, Forschungszentrum Juelich, 52425 Juelich (Germany); Engels, R. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Grigoryev, K. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Mikirtychyants, M. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Nekipelov, M. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Rathmann, F. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Seyfarth, H. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany)]. E-mail: h.seyfarth@fz-juelich.de; Kravtsov, P. [St. Petersburg Nuclear Physics Institute, 188350 Gatchina (Russian Federation); Vasilyev, A. [St. Petersburg Nuclear Physics Institute, 188350 Gatchina (Russian Federation)

    2006-05-10

    The polarized internal target for the ANKE experiment at the Cooler Synchrotron COSY of the Forschungszentrum Juelich utilizes a polarized atomic beam source to feed a storage cell with polarized hydrogen or deuterium atoms. The nuclear polarization is measured with a Lamb-shift polarimeter. For common control of the two systems, industrial equipment was selected providing reliable, long-term support and remote control of the target as well as measurement and optimization of its operating parameters. The interlock system has been implemented on the basis of SIEMENS SIMATIC S7-300 family of programmable logic controllers. In order to unify the interfacing to the control computer, all front-end equipment is connected via the PROFIBUS DP fieldbus. The process control software was implemented using the Windows-based WinCC toolkit from SIEMENS. The variety of components, to be controlled, and the logical structure of the control and interlock system are described. Finally, a number of applications derived from the present development to other, new installations are briefly mentioned.

  1. The control system of the polarized internal target of ANKE at COSY

    Science.gov (United States)

    Kleines, H.; Sarkadi, J.; Zwoll, K.; Engels, R.; Grigoryev, K.; Mikirtychyants, M.; Nekipelov, M.; Rathmann, F.; Seyfarth, H.; Kravtsov, P.; Vasilyev, A.

    2006-05-01

    The polarized internal target for the ANKE experiment at the Cooler Synchrotron COSY of the Forschungszentrum Jülich utilizes a polarized atomic beam source to feed a storage cell with polarized hydrogen or deuterium atoms. The nuclear polarization is measured with a Lamb-shift polarimeter. For common control of the two systems, industrial equipment was selected providing reliable, long-term support and remote control of the target as well as measurement and optimization of its operating parameters. The interlock system has been implemented on the basis of SIEMENS SIMATIC S7-300 family of programmable logic controllers. In order to unify the interfacing to the control computer, all front-end equipment is connected via the PROFIBUS DP fieldbus. The process control software was implemented using the Windows-based WinCC toolkit from SIEMENS. The variety of components, to be controlled, and the logical structure of the control and interlock system are described. Finally, a number of applications derived from the present development to other, new installations are briefly mentioned.

  2. Targeted therapy for Hodgkin lymphoma and systemic anaplastic large cell lymphoma: focus on brentuximab vedotin

    Directory of Open Access Journals (Sweden)

    Chen X

    2013-12-01

    Full Text Available Xueyan Chen, Lorinda A Soma, Jonathan R FrommDepartment of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USAAbstract: Despite the relative success of chemotherapy for Hodgkin lymphoma (HL and systemic anaplastic large cell lymphoma (ALCL, novel therapeutic agents are needed for refractory or relapsed patients. Targeted immunotherapy has emerged as a novel treatment option for these patients. Although unconjugated anti-cluster of differentiation (CD30 antibodies showed minimal antitumor activity in early clinical trials, development of antibody–drug conjugates (ADCs appears promising. Brentuximab vedotin is an ADC composed of an anti-CD30 antibody linked to a potent microtubule-disrupting agent monomethyl auristatin E (MMAE. It has the ability to target CD30-positive tumor cells and, once bound to CD30, brentuximab vedotin is internalized and MMAE is released to induce cell cycle arrest and apoptosis. In two phase II trials, objective response was reported in 75% and 86% of patients with refractory or relapsed HL and systemic ALCL, respectively, with an acceptable toxicity profile. Based on these studies, the US Food and Drug Administration (FDA granted accelerated approval of brentuximab vedotin in August 2011 for the treatment of refractory and relapsed HL and ALCL. We review the key characteristics of brentuximab vedotin, clinical data supporting its therapeutic efficacy, and current ongoing trials to explore its utility in other CD30-positive malignancies.Keywords: classical Hodgkin lymphoma, systemic anaplastic large cell lymphoma, CD30, brentuximab vedotin, SGN-35

  3. Neutrophil targeted nano-drug delivery system for chronic obstructive lung diseases.

    Science.gov (United States)

    Vij, Neeraj; Min, Taehong; Bodas, Manish; Gorde, Aakruti; Roy, Indrajit

    2016-11-01

    The success of drug delivery to target airway cell(s) remains a significant challenge due to the limited ability of nanoparticle (NP) systems to circumvent protective airway-defense mechanisms. The size, density, surface and physical-chemical properties of nanoparticles are the key features that determine their ability to navigate across the airway-barrier. We evaluated here the efficacy of a PEGylated immuno-conjugated PLGA-nanoparticle (PINP) to overcome this challenge and selectively deliver drug to specific inflammatory cells (neutrophils). We first characterized the size, shape, surface-properties and neutrophil targeting using dynamic laser scattering, transmission electron microscopy and flow cytometry. Next, we assessed the efficacy of neutrophil-targeted PINPs in transporting through the airway followed by specific binding and release of drug to neutrophils. Finally, our results demonstrate the efficacy of PINP mediated non-steroidal anti-inflammatory drug-(ibuprofen) delivery to neutrophils in murine models of obstructive lung diseases, based on its ability to control neutrophilic-inflammation and resulting lung disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Morphological Effect of Non-targeted Biomolecule-Modified MNPs on Reticuloendothelial System.

    Science.gov (United States)

    Li, Xiao; Hu, Yan; Xiao, Jie; Cheng, Dengfeng; Xiu, Yan; Shi, Hongcheng

    2015-12-01

    Magnetic nanoparticles (MNPs) with special morphology were commonly used as biomaterials, while morphological effects of non-targeted biomolecule-modified MNPs on biological behaviors were still unclear. In this research, spherical and rod-like Fe3O4 in a comparable size were synthesized and then surface-modified by bovine serum albumin (BSA) as a model of non-targeted biomolecule-modified MNPs. Morphological effects were featured by TEM and quantification of in vitro phagocytic uptake, as well as the in vivo quantification of particles in reticuloendothelial system (RES)-related organs of normal Kunming mice. For these non-targeted BSA-modified MNPs, intracellular distributions were the same, but the rod-like MNPs were more likely to be uptake by macrophages; furthermore, the BSA-modified MNPs gathered in RES-related organs soon after intravenous injection, but the rod-like ones were expelled from the lung more quickly and expelled from the spleen more slowly. These preliminary results may be referable if MNPs or other similar biomolecule-modified nanoparticles were used.

  5. Detection of ferromagnetic target based on mobile magnetic gradient tensor system

    Energy Technology Data Exchange (ETDEWEB)

    Gang, Y.I.N., E-mail: gang.gang88@163.com; Yingtang, Zhang; Zhining, Li; Hongbo, Fan; Guoquan, Ren

    2016-03-15

    Attitude change of mobile magnetic gradient tensor system critically affects the precision of gradient measurements, thereby increasing ambiguity in target detection. This paper presents a rotational invariant-based method for locating and identifying ferromagnetic targets. Firstly, unit magnetic moment vector was derived based on the geometrical invariant, such that the intermediate eigenvector of the magnetic gradient tensor is perpendicular to the magnetic moment vector and the source–sensor displacement vector. Secondly, unit source–sensor displacement vector was derived based on the characteristic that the angle between magnetic moment vector and source–sensor displacement is a rotational invariant. By introducing a displacement vector between two measurement points, the magnetic moment vector and the source–sensor displacement vector were theoretically derived. To resolve the problem of measurement noises existing in the realistic detection applications, linear equations were formulated using invariants corresponding to several distinct measurement points and least square solution of magnetic moment vector and source–sensor displacement vector were obtained. Results of simulation and principal verification experiment showed the correctness of the analytical method, along with the practicability of the least square method. - Highlights: • Ferromagnetic target detection method is proposed based on rotational invariants • Intermediate eigenvector is perpendicular to magnetic moment and displacement vector • Angle between magnetic moment and displacement vector is a rotational invariant • Magnetic moment and displacement vector are derived based on invariants of two points.

  6. Multi-target-qubit unconventional geometric phase gate in a multi-cavity system.

    Science.gov (United States)

    Liu, Tong; Cao, Xiao-Zhi; Su, Qi-Ping; Xiong, Shao-Jie; Yang, Chui-Ping

    2016-02-22

    Cavity-based large scale quantum information processing (QIP) may involve multiple cavities and require performing various quantum logic operations on qubits distributed in different cavities. Geometric-phase-based quantum computing has drawn much attention recently, which offers advantages against inaccuracies and local fluctuations. In addition, multiqubit gates are particularly appealing and play important roles in QIP. We here present a simple and efficient scheme for realizing a multi-target-qubit unconventional geometric phase gate in a multi-cavity system. This multiqubit phase gate has a common control qubit but different target qubits distributed in different cavities, which can be achieved using a single-step operation. The gate operation time is independent of the number of qubits and only two levels for each qubit are needed. This multiqubit gate is generic, e.g., by performing single-qubit operations, it can be converted into two types of significant multi-target-qubit phase gates useful in QIP. The proposal is quite general, which can be used to accomplish the same task for a general type of qubits such as atoms, NV centers, quantum dots, and superconducting qubits.

  7. HOW BOXERS DECIDE TO PUNCH A TARGET: EMERGENT BEHAVIOUR IN NONLINEAR DYNAMICAL MOVEMENT SYSTEMS

    Directory of Open Access Journals (Sweden)

    Robert Hristovski

    2006-07-01

    Full Text Available Previous research has shown how dynamical systems theory provides a relevant framework for investigating decision-making behavior in sport. The aim of this study was to adopt concepts and tools from nonlinear dynamics in examining effects of boxer-target distance and perceived punching efficiency on emergent decision-making during a typical practice task in boxing. Results revealed the existence of critical values of scaled distances between boxers and targets for first time appearance and disappearance of a diverse range of boxing actions including jabs, hooks and uppercuts. Reasons for the diversity of actions were twofold: i abrupt (qualitative changes in the number of the possible punches, i.e. motor solutions to the hitting task; and ii, fine modification of the probabilities of selecting specific striking patterns. Boxers were able to exploit the emerging perception of strikeability, leading to a changing diversity of selected actions and a cascade of abrupt changes in the perceptual-motor work space of the task. Perceived efficiency of a punching action by the participants also changed as a function of the scaled distance to a target and was correlated with the probability of occurrence of specific boxing actions. Accordingly, scaled distance-dependent perceived efficiency seems an important perceptual constraint in the training task of punching a heavy bag in boxers

  8. Target area acquisition and control system survivability for the National Ignition Facility

    International Nuclear Information System (INIS)

    Hagans, K.; Stathis, P.; Wiedwald, J.; Campbell, D.

    1994-06-01

    The hardening of instruments to survive NIF target emission environments presents a significant challenge. Neutron flux is predicted to be as much as six orders of magnitude greater than the highest achieved neutron flux on NOVA. Not withstanding the high prompt radiation fields, the specifications for the instruments are demanding; requiring high resolution imaging and sub nanosecond transient measurements. We present an analysis of the sensitivity of the proposed NIF instrumentation design to EMP, X-rays, gamma rays, and neutrons. Major components assessed include fiber optic cable transport, high bandwidth cable and charge coupled detector (CCD) imaging systems

  9. Evaluation of Community-Based Policy, Systems, and Environment Interventions Targeting the Vending Machines.

    Science.gov (United States)

    Garcia, Kristen M; Garney, Whitney R; Primm, Kristin M; McLeroy, Kenneth R

    The American Heart Association conducted policy, systems, and environmental (PSE) focused interventions to increase healthy vending in 8 communities. PSE interventions were assessed using the Nutrition Environment Measures Survey Vending Assessment to see changes in the food environment. Baseline and follow-up assessments were conducted with 3 settings and a total of 19 machines. PSE changes resulted in increased availability of healthy options and decreased unhealthy options. Implementation of PSE interventions targeting the food environment can be an effective method of providing increased access to healthy foods and beverages with the goal of increasing consumption to decrease chronic diseases.

  10. The Development of a Framework for Target Diagnostic Centralized Control System (TDCCS) in ICF Experiments

    International Nuclear Information System (INIS)

    Zhang Chi; Wang Jian; Yu Xiaoqi; Yang Dong

    2008-01-01

    A framework for target diagnostic centralized control system (TDCCS) in inertial confinement fusion (ICF) experiment has been developed. The developed framework is based on the common object request broker architecture (CORBA) standard and part of the concept from the ICFRoot (a framework based on ROOT for ICF experiments) framework design. This framework is of a component architecture, including a message bus, command executer, status processor, parser and proxy. To test the function of the framework, a simplified prototype of the TDCCS has been developed as well.

  11. Multi-target consensus circle pursuit for multi-agent systems via a distributed multi-flocking method

    Science.gov (United States)

    Pei, Huiqin; Chen, Shiming; Lai, Qiang

    2016-12-01

    This paper studies the multi-target consensus pursuit problem of multi-agent systems. For solving the problem, a distributed multi-flocking method is designed based on the partial information exchange, which is employed to realise the pursuit of multi-target and the uniform distribution of the number of pursuing agents with the dynamic target. Combining with the proposed circle formation control strategy, agents can adaptively choose the target to form the different circle formation groups accomplishing a multi-target pursuit. The speed state of pursuing agents in each group converges to the same value. A Lyapunov approach is utilised to analyse the stability of multi-agent systems. In addition, a sufficient condition is given for achieving the dynamic target consensus pursuit, and which is then analysed. Finally, simulation results verify the effectiveness of the proposed approaches.

  12. Interpersonal and systemic aspects of emotional abuse at work: the target's perspective.

    Science.gov (United States)

    Keashly, L

    2001-06-01

    The most frequent form of workplace aggression is not physical, it is emotional and psychological in nature. Known by many names, emotional abuse at work is rapidly becoming recognized as pervasive and costly both in individual and organizational terms. Most of the research to date on emotional abuse at work has utilized survey and other quantitative methodologies in an effort to document the presence, prevalence, and impact of these behaviors. However, these methodologies are based on researchers' definitions and theories of what constitutes emotional abuse rather than on the meaning given to these experiences by the targets of these behaviors. A thorough understanding of this phenomenon requires a scholarly appreciation of the target's experience. Taking "feeling abused" as the criterion variable, this study examined target's experiences based on interviews with people who self-identifed as having experienced difficulties with a boss, coworker, or subordinate. The interpersonal aspects of emotional abuse focused on the nature of behaviors exhibited and the respondents' labeling of their experience. Consistent with elements of researchers' definitions, behaviors were defined as abusive when they were repetitive, resulted in injury or harm to target, and were experienced as a lack of recognition of the individual's integrity. Judgments of violation of standards of conduct and unsolicited nature of the behaviors were also related to respondents' experiences. Relative power differential was also an important element. However, contrary to researchers' definitions, actor intent was not central in defining the experience as abusive. The systemic aspect of emotional abuse was illustrated in the nature of organizational responding to concerns raised by respondents. These responses were of critical importance in respondents' labeling of their experiences as abusive. The focus on the meaning of the behaviors for the respondents provides an enriched picture of key

  13. Application of three-dimensional printing for colon targeted drug delivery systems.

    Science.gov (United States)

    Charbe, Nitin B; McCarron, Paul A; Lane, Majella E; Tambuwala, Murtaza M

    2017-01-01

    Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.

  14. Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

    Science.gov (United States)

    Sun, Bao-Liang; Wang, Li-Hua; Yang, Tuo; Sun, Jing-Yi; Mao, Lei-Lei; Yang, Ming-Feng; Yuan, Hui; Colvin, Robert A; Yang, Xiao-Yi

    2017-09-10

    The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange. Copyright © 2017. Published by Elsevier Ltd.

  15. Cytotoxic chromosomal targeting by CRISPR/Cas systems can reshape bacterial genomes and expel or remodel pathogenicity islands.

    Science.gov (United States)

    Vercoe, Reuben B; Chang, James T; Dy, Ron L; Taylor, Corinda; Gristwood, Tamzin; Clulow, James S; Richter, Corinna; Przybilski, Rita; Pitman, Andrew R; Fineran, Peter C

    2013-04-01

    In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas-mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA-targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity.

  16. Cytotoxic chromosomal targeting by CRISPR/Cas systems can reshape bacterial genomes and expel or remodel pathogenicity islands.

    Directory of Open Access Journals (Sweden)

    Reuben B Vercoe

    2013-04-01

    Full Text Available In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs and their associated (Cas proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2 involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas-mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA-targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity.

  17. Cytotoxic Chromosomal Targeting by CRISPR/Cas Systems Can Reshape Bacterial Genomes and Expel or Remodel Pathogenicity Islands

    Science.gov (United States)

    Vercoe, Reuben B.; Chang, James T.; Dy, Ron L.; Taylor, Corinda; Gristwood, Tamzin; Clulow, James S.; Richter, Corinna; Przybilski, Rita; Pitman, Andrew R.; Fineran, Peter C.

    2013-01-01

    In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas–mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA–targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity. PMID:23637624

  18. Magnetic Nanoparticles of Chitosan for Targeted Delivery System of Plasmids to the Lungs

    International Nuclear Information System (INIS)

    Baez, C.A.A.; Cruz, I.E.L.; Padilla, M.C.R.; Gonzalez, J.M.A.

    2014-01-01

    One of the major problems of gene therapy is the efficient, specific, and targeted delivery as well as the safety of the materials used in such systems. The specific targeted delivery of genes to the lung offers the possibility to treat a variety of specific diseases. We developed chitosan nanoparticles with the plasmid pCEM-Luc, which contains a promoter activated by magnetic field. Nanoparticles of 200-250 nm obtained by ionic gelation with a 99% retention rate were transfected in B16F10 cells and in vivo in the lungs of Balb/c mice by intratracheal administration. We observed that an external magnetic field increased the expression of the luciferase reporter gene in B16F10 cells transfected with magnetic nanoparticles and in homogenized lungs of mice which determined differences in levels of expression between different regions of the lungs (apical or distal and left or right). The highest levels of luciferase activity were observed in the apical left region. The magnetic nanoparticles prove an efficient delivery system to in vitro transfection of cells and lung tissue.

  19. Hypoxia-targeted suicidal gene therapy system enhances antitumor effects of radiotherapy

    International Nuclear Information System (INIS)

    Liu Junye; Guo Yao; Guo Guozhen

    2006-01-01

    Objective: To explore the effects of hypoxia-targeted suicidal gene therapy system combined with radiotherapy on pancreatic cancer. Methods: The recombinant adenovirus Ad-5HRE/hCMVmp-BCD was constructed by DNA recombinant technique. Western blot was used to detect hypoxia-induced expression of bacterial cytosine deaminase (BCD). Cell growth inhibition assay was used to determine the sensitivity of human pancreatic cancer cells MIA-PACA2 to 5-fluorocytosine (5-FC). Tumor xenograft growth delay assays was used to evaluate the effects of Ad-5HRE/hCMVmp-BCD/5-FC combined with radiotherapy on pancreatic cancer. Results: Western blot analysis demonstrated that hypoxia-induced BCD protein expression was achieved in MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD. With hypoxia treatment, the sensitivity of MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD to 5-FC significantly increased. Administration of either Ad-5HRE/hCMVmp-BCD/5-FC or radiotherapy could inhibit the growth of MIA-PACA2 xenografts in nude mice. Moreover, combination of Ad-5HRE/hCMVmp-BCD/5-FC could significantly enhance suppressing effects of radiotherapy on MIA-PACA2 xenografts. Conclusion: Hypoxia-targeted suicidal gene therapy system Ad-5HRE/hCMVmp-BCD/5-FC could enhance antitumor effects of radiotherapy on pancreatic cancer and can be used as a powerful adjunct to conventional radiotherapy. (authors)

  20. Immune system of the inner ear as a novel therapeutic target for sensorineural hearing loss

    Directory of Open Access Journals (Sweden)

    Takayuki eOkano

    2014-09-01

    Full Text Available Sensorineural hearing loss (SNHL is a common clinical condition resulting from dysfunction in one or more parts in the auditory pathway between the inner ear and auditory cortex. Despite the prevalence of SNHL, little is known about its etiopathology, although several mechanisms have been postulated including ischemia, viral infection or reactivation, and microtrauma. Immune-mediated inner ear disease has been introduced and accepted as one SNHL pathophysiology; it responds to immunosuppressive therapy and is one of the few reversible forms of bilateral SNHL. The concept of immune-mediated inner ear disease is straightforward and comprehensible, but criteria for clinical diagnosis and the precise mechanism of hearing loss have not been determined. Moreover, the therapeutic mechanisms of corticosteroids are unclear, leading to several misconceptions by both clinicians and investigators concerning corticosteroid therapy. This review addresses our current understanding of the immune system in the inner ear and its involvement in the pathophysiology in SNHL. Treatment of SNHL, including immune-mediated inner ear disorder, will be discussed with a focus on the immune mechanism and immunocompetent cells as therapeutic targets. Finally, possible interventions modulating the immune system in the inner ear to repair the tissue organization and improve hearing in patients with SNHL will be discussed. Tissue macrophages in the inner ear appear to be a potential target for modulating the immune response in the inner ear in the pathophysiology of SNHL.

  1. Target diagnostic control system implementation for the National Ignition Facility (invited)

    Energy Technology Data Exchange (ETDEWEB)

    Shelton, R. T.; Kamperschroer, J. H.; Lagin, L. J.; Nelson, J. R.; O' Brien, D. W. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States)

    2010-10-15

    The extreme physics of targets shocked by NIF's 192-beam laser is observed by a diverse suite of diagnostics. Many diagnostics are being developed by collaborators at other sites, but ad hoc controls could lead to unreliable and costly operations. A diagnostic control system (DCS) framework for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost WINDOWS XP processor and JAVA application. Each instrument is aggregated with others as needed in the supervisory system to form an integrated diagnostic. The JAVA framework provides data management, control services, and operator graphical user interface generation. DCS instruments are reusable by replication with reconfiguration for specific diagnostics in extensible markup language. Advantages include minimal application code, easy testing, and high reliability. Collaborators save costs by assembling diagnostics with existing DCS instruments. This talk discusses target diagnostic instrumentation used on NIF and presents the DCS architecture and framework.

  2. Target diagnostic control system implementation for the National Ignition Facility (invited)

    International Nuclear Information System (INIS)

    Shelton, R. T.; Kamperschroer, J. H.; Lagin, L. J.; Nelson, J. R.; O'Brien, D. W.

    2010-01-01

    The extreme physics of targets shocked by NIF's 192-beam laser is observed by a diverse suite of diagnostics. Many diagnostics are being developed by collaborators at other sites, but ad hoc controls could lead to unreliable and costly operations. A diagnostic control system (DCS) framework for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost WINDOWS XP processor and JAVA application. Each instrument is aggregated with others as needed in the supervisory system to form an integrated diagnostic. The JAVA framework provides data management, control services, and operator graphical user interface generation. DCS instruments are reusable by replication with reconfiguration for specific diagnostics in extensible markup language. Advantages include minimal application code, easy testing, and high reliability. Collaborators save costs by assembling diagnostics with existing DCS instruments. This talk discusses target diagnostic instrumentation used on NIF and presents the DCS architecture and framework.

  3. Lead-Bismuth Eutectic cooled experimental Accelerator Driven System. Windowless target unit thermal-hydraulic analysis

    International Nuclear Information System (INIS)

    Bianchi, F.; Ferri, R.; Moreau, V.

    2004-01-01

    A main concern related to the peaceful use of nuclear energy is the safe management of nuclear wastes, with particular attention to long-lived fission products. An increasing attention has recently been addressed to transmutation systems (Accelerator Driven System: ADS) able to 'burn' the actinides and some of the long-lived fission products (High-Level Waste: HLW), transforming them in short or medium-lived wastes that may be easier managed and stored in the geological disposal, with the consequent easier acceptability by population. An ADS consists of a subcritical-core coupled with an accelerator by means of a target. This paper deals with the thermal-hydraulic analysis, performed with STAR-CD and RELAP5 codes for the windowless target unit of Lead-Bismuth Eutectic (LBE) cooled experimental ADS (XADS), both to assess its behaviour during operational and accident sequences and to provide input data for the thermal-mechanical analyses. It also reports a description of modifications properly implemented in the codes used for the assessment of this kind of plants. (author)

  4. Target berthing and base reorientation of free-floating space robotic system after capturing

    Science.gov (United States)

    Xu, Wenfu; Li, Cheng; Liang, Bin; Xu, Yangsheng; Liu, Yu; Qiang, Wenyi

    2009-01-01

    Space robots are playing an increasingly important role in on-orbital servicing, including repairing, refueling, or de-orbiting the satellite. The target must be captured and berthed before the servicing task starts. However, the attitude of the base may lean much and needs re-orientating after capturing. In this paper, a method is proposed to berth the target, and re-orientate the base at the same time, using manipulator motion only. Firstly, the system state is formed of the attitude quaternion and joint variables, and the joint paths are parameterized by sinusoidal functions. Then, the trajectory planning is transformed to an optimization problem. The cost function, defined according to the accuracy requirements of system variables, is the function of the parameters to be determined. Finally, we solve the parameters using the particle swarm optimization algorithm. Two typical cases of the spacecraft with a 6-DOF manipulator are dynamically simulated, one is that the variation of base attitude is limited; the other is that both the base attitude and the joint rates are constrained. The simulation results verify the presented method.

  5. Target motifs affecting natural immunity by a constitutive CRISPR-Cas system in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Cristóbal Almendros

    Full Text Available Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR and CRISPR associated (cas genes conform the CRISPR-Cas systems of various bacteria and archaea and produce degradation of invading nucleic acids containing sequences (protospacers that are complementary to repeat intervening spacers. It has been demonstrated that the base sequence identity of a protospacer with the cognate spacer and the presence of a protospacer adjacent motif (PAM influence CRISPR-mediated interference efficiency. By using an original transformation assay with plasmids targeted by a resident spacer here we show that natural CRISPR-mediated immunity against invading DNA occurs in wild type Escherichia coli. Unexpectedly, the strongest activity is observed with protospacer adjoining nucleotides (interference motifs that differ from the PAM both in sequence and location. Hence, our results document for the first time native CRISPR activity in E. coli and demonstrate that positions next to the PAM in invading DNA influence their recognition and degradation by these prokaryotic immune systems.

  6. Connexin: a potential novel target for protecting the central nervous system?

    Directory of Open Access Journals (Sweden)

    Hong-yan Xie

    2015-01-01

    Full Text Available Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings regarding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer′s disease, Parkinson′s disease, X-linked Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.

  7. Research on Key Technologies of Network Centric System Distributed Target Track Fusion

    Directory of Open Access Journals (Sweden)

    Yi Mao

    2017-01-01

    Full Text Available To realize common tactical picture in network-centered system, this paper proposes a layered architecture for distributed information processing and a method for distributed track fusion on the basis of analyzing the characteristics of network-centered systems. Basing on the noncorrelation of three-dimensional measurement of surveillance and reconnaissance sensors under polar coordinates, it also puts forward an algorithm for evaluating track quality (TQ using statistical decision theory. According to simulation results, the TQ value is associated with the measurement accuracy of sensors and the motion state of targets, which is well matched with the convergence process of tracking filters. Besides, the proposed algorithm has good reliability and timeliness in track quality evaluation.

  8. Optimization of the internal target system of the C V-28 cyclotron at IPEN-CNEN/SP

    International Nuclear Information System (INIS)

    Araujo, Sumair Gouveia de

    1996-01-01

    The C V-28 cyclotron at IPEN-CNEN/S P is used mainly for radioisotope production to be utilized in nuclear medicine for diagnostic purposes. Among these radioisotopes we can cite 67 Ga and 111 In, which are obtained by irradiation of Zn and Cd solid targets. Up to now, the irradiations were performed in the external beam line, which has limitations in beam current due to the extraction system, that can at best extract between 50 and 70% of the produced beam. This is a critical point for an efficient radioisotope production. A possible solution to achieve high beam currents is a system that allows the irradiation of these solid targets with the internal beam. In this case, the total produced beam can be used. For this, the objective of this work was to modify and improve the internal target system of the C V-28 Cyclotron, which had three critical points in the original project, that made the system useless. First, the transport of the target to the irradiation position was modified: the pneumatic tube was changed to a motor drive service. Secondly, the target cooling system was improved. Third and the most critical, the modification on the locking system of the target holder that could bring the cyclotron tank to atmosphere. These modifications implied on a change in all logical sequence of the target control. With these modifications the system became more versatile and showed more reproducibility and reliability than the original internal target system. The loss of mass in natural Zn targets irradiated with currents up to 80 μA was negligible. The production yield of 67 Ga obtained, at EOB, was 21.2 MBq/μAh (0.57 mCi/μAh), that is in good agreement with those obtained in the irradiation with external beams. (author)

  9. Targeting the Oxidative Stress Response System of Fungi with Redox-Potent Chemosensitizing Agents

    Science.gov (United States)

    Kim, Jong H.; Chan, Kathleen L.; Faria, Natália C. G.; Martins, M. de L.; Campbell, Bruce C.

    2012-01-01

    The cellular antioxidant system is a target in the antifungal action of amphotericin B (AMB) and itraconazole (ITZ), in filamentous fungi. The sakAΔ mutant of Aspergillus fumigatus, a mitogen-activated protein kinase (MAPK) gene deletion mutant in the antioxidant system, was found to be more sensitive to AMB or ITZ than other A. fumigatus strains, a wild type and a mpkCΔ mutant (a MAPK gene deletion mutant in the polyalcohol sugar utilization system). Complete fungal kill (≥99.9%) by ITZ or AMB was also achieved by much lower dosages for the sakAΔ mutant than for the other strains. It appears msnA, an Aspergillus ortholog to Saccharomyces cerevisiae MSN2 (encoding a stress-responsive C2H2-type zinc-finger regulator) and sakA and/or mpkC (upstream MAPKs) are in the same stress response network under tert-butyl hydroperoxide (t-BuOOH)-, hydrogen peroxide (H2O2)- or AMB-triggered toxicity. Of note is that ITZ-sensitive yeast pathogens were also sensitive to t-BuOOH, showing a connection between ITZ sensitivity and antioxidant capacity of fungi. Enhanced antifungal activity of AMB or ITZ was achieved when these drugs were co-applied with redox-potent natural compounds, 2,3-dihydroxybenzaldehyde, thymol or salicylaldehyde, as chemosensitizing agents. We concluded that redox-potent compounds, which target the antioxidant system in fungi, possess a chemosensitizing capacity to enhance efficacy of conventional drugs. PMID:22438852

  10. An Architecture for Interactive Target-Oriented e/m-Learning Systems

    Directory of Open Access Journals (Sweden)

    Cristina De Castro

    2009-12-01

    Full Text Available In this paper, an architecture is proposed for the development of an e/m-Learning system with the following features: (1 learning paths can be tailored to the user’s aims and, during the learning process, dynamically modified in order to meet his needs; (2 in context of m-Learning facilities, contents can be scaled and adapted to the user’s device and connection technology. As far as learning paths are concerned, each learner is allowed to specify his initial target and, if he decides to deepen some issues, is authorised to redefine such target over time. This process is guided by a “Path Decision Module” based on Petri Nets, which checks the user’s learning level and consequently decides whether further issues can be faced or not. As for access to the system, the following scenarios are considered: UMTS (e.g.: for PDAs, DSL (e.g.: at home, WiFi (e.g.: within study lounges and libraries, wired/fiber (e.g.: within laboratories. In order to satisfy such heterogeneous requirements, contents are dynamically adapted to available technologies by means of on the fly data format conversions. The whole system relies on a hybrid LDAP-SQL database, which benefits from the joint use of directory services and relational databases. LDAP is used for the storage of learning and assessment material, whereas dynamical paths are stored in the SQL system. Analytical calculations are also presented which show the access time in each scenario and, consequently, if a certain activity can be carried out or not efficiently.

  11. Reproductive toxicity: Male and female reproductive systems as targets for chemical injury

    Energy Technology Data Exchange (ETDEWEB)

    Mattison, D.R.; Plowchalk, D.R.; Meadows, M.J.; Al-Juburi, A.Z.; Gandy, J.; Malek, A. (Univ. of Arkansas for Medical Sciences, Little Rock (USA))

    1990-03-01

    On the basis of current knowledge of reproductive biology and toxicology, it is apparent that chemicals affecting reproduction may elicit their effects at a number of sites in both the male and the female reproductive system. This multiplicity of targets is attributable to the dynamic nature of the reproductive system, in which the hypothalamic-pituitary-gonadal axis is controlled by precise positive and negative feedback mechanisms among its components. Interference by a xenobiotic at any level in either the male or the female reproductive system may ultimately impair hypothalamic or pituitary function. Normal gonadal processes such as spermatogenesis or oogenesis, ejaculation or ovulation, hormone production by Leydig or granulosa cells, and the structure or function of the accessory reproductive structures (e.g., epididymis, fallopian tube) also appear vulnerable to xenobiotics. The reproductive system is a complex one that requires local and circulating hormones for control. This brief review illustrates a system for characterizing the mechanism of action of reproductive toxicants, as well as for defining the sites available for disruption of reproduction. Unfortunately, at present, data addressing the actual vulnerability of reproduction are sorely lacking. However, when experiments have been conducted and combined with epidemiologic data or clinical observation, it has been possible to demonstrate impairment of reproductive processes by xenobiotics. The role of environmental exposure to xenobiotics in the increase in infertility that has been observed remains to be defined. 87 references.

  12. Targeting of the Glutathione, Thioredoxin, and Nrf2 Antioxidant Systems in Head and Neck Cancer.

    Science.gov (United States)

    Roh, Jong-Lyel; Jang, Hyejin; Kim, Eun Hye; Shin, Daiha

    2017-07-10

    The glutathione (GSH), thioredoxin (Trx), and Nrf2 systems represent a major defense against reactive oxygen species (ROS), the cellular imbalance of which in cancer promotes growth and therapeutic resistance. This study investigated whether targeting the GSH, Trx, and Nrf2 antioxidant systems effectively eliminated head and neck cancer (HNC). At high concentrations, auranofin, but not buthionine sulfoximine (BSO) alone, decreased the viability of HNC, whereas even at low concentrations, auranofin plus BSO synergized to kill HNC cells. Dual silencing of the genes for GCLM and TrxR1 induced GSH depletion, Trx activity inhibition, and ROS accumulation, synergistically killing HNC cells. Inhibition of the GSH and Trx systems resulted in activation of the Nrf2-antioxidant response element (ARE) pathway, which may result in suboptimal GSH and Trx inhibition where HNC is resistant. Genetic inhibition of Nrf2 and/or HO-1 or trigonelline enhanced growth suppression, ROS accumulation, and cell death from GSH and Trx inhibition. The in vivo effects of GSH, Trx, and Nrf2 system inhibition were confirmed in a mouse HNC xenograft model by achieving growth inhibition >60% compared with those of control. Innovations: This study is the first to show that triple inhibition of GSH, Trx, and Nrf2 pathways could be an effective method to overcome the resistance of HNC. Inhibition of the Nrf2-ARE pathway in addition to dual inhibition of the GSH and Trx antioxidant systems can effectively eliminate resistant HNC. Antioxid. Redox Signal. 27, 106-114.

  13. Application of the target fish community model to an urban river system.

    Science.gov (United States)

    Meixler, Marcia S

    2011-04-01

    Several models have been developed to assess the biological integrity of aquatic systems using fish community data. One of these, the target fish community (TFC) model, has been used primarily to assess the biological integrity of larger, mainstem rivers in southern New England with basins characterized by dispersed human activities. We tested the efficacy of the TFC approach to specify the fish community in the highly urbanized Charles River watershed in eastern Massachusetts. To create a TFC for the Charles River we assembled a list of fish species that historically inhabited the Charles River watershed, identified geomorphically and zoogeographically similar reference rivers regarded as being in high quality condition, amassed fish survey data for the reference rivers, and extracted from the collections the information needed to define a TFC. We used a similarity measurement method to assess the extent to which the study river community complies with the TFC and an inference approach to summarize the manner in which the existing fish community differed from target conditions. The five most abundant species in the TFC were common shiners (34%), fallfish (17%) redbreast sunfish (11%), white suckers (8%), and American eel (7%). Three of the five species predicted to be most abundant in the TFC were scarce or absent in the existing river community. Further, the river was dominated by macrohabitat generalists (99%) while the TFC was predicted to contain 19% fluvial specialist species, 43% fluvial dependent species, and 38% macrohabitat generalist species. In addition, while the target community was dominated by fish intolerant (37%) and moderately tolerant (39%) of water quality degradation, the existing community was dominated by tolerant individuals (59%) and lacked intolerant species expected in the TFC. Similarity scores for species, habitat use specialization, and water quality degradation tolerance categories were 28%, 35% and 66%, respectively. The clear

  14. P2X receptors in the cardiovascular system and their potential as therapeutic targets in disease.

    Science.gov (United States)

    Ralevic, Vera

    2015-01-01

    This review considers the expression and roles of P2X receptors in the cardiovascular system in health and disease and their potential as therapeutic targets. P2X receptors are ligand gated ion channels which are activated by the endogenous ligand ATP. They are formed from the assembly of three P2X subunit proteins from the complement of seven (P2X1-7), which can associate to form homomeric or heteromeric P2X receptors. The P2X1 receptor is widely expressed in the cardiovascular system, being located in the heart, in the smooth muscle of the majority of blood vessels and in platelets. P2X1 receptors expressed in blood vessels can be activated by ATP coreleased with noradrenaline as a sympathetic neurotransmitter, leading to smooth muscle depolarisation and contraction. There is evidence that the purinergic component of sympathetic neurotransmission is increased in hypertension, identifying P2X1 receptors as a possible therapeutic target in this disorder. P2X3 and P2X2/3 receptors are expressed on cardiac sympathetic neurones and may, through positive feedback of neuronal ATP at this prejunctional site, amplify sympathetic neurotransmission. Activation of P2X receptors expressed in the heart increases cardiac myocyte contractility, and an important role of the P2X4 receptor in this has been identified. Deletion of P2X4 receptors in the heart depresses contractile performance in models of heart failure, while overexpression of P2X4 receptors has been shown to be cardioprotective, thus P2X4 receptors may be therapeutic targets in the treatment of heart disease. P2X receptors have been identified on endothelial cells. Although immunoreactivity for all P2X1-7 receptor proteins has been shown on the endothelium, relatively little is known about their function, with the exception of the endothelial P2X4 receptor, which has been shown to mediate endothelium-dependent vasodilatation to ATP released during shear stress. The potential of P2X receptors as therapeutic targets

  15. A road to food? : efficacy of nutrient management options targeted to heterogeneous soilscapes in the Teso farming system, Uganda

    NARCIS (Netherlands)

    Ebanyat, P.

    2009-01-01

    Key words: Land use change; Heterogeneity in soil fertility; Targeting; Integrated soil fertility management; Nutrient use efficiencies; Rehabilitation of degraded fields; Fertiliser requirements, Finger millet; QUEFTS model; Smallholder systems; sub-Saharan Africa.

    Poor soil fertility

  16. Preliminary study on the adjonction of a cooling system and internal target ring to the GEPL project

    International Nuclear Information System (INIS)

    Potaux, D.

    1983-01-01

    Various heavy particle storage rings (LEAR, Indiana, Uppsala) are planned for operation with combined electron cooling system and internal ultra-thin targets. The advantage of adding a similar device to the IPN cyclotron project is discussed [fr

  17. Hazard identification and risk assessment for biologics targeting the immune system.

    Science.gov (United States)

    Weir, Andrea B

    2008-01-01

    Biologic pharmaceuticals include a variety of products, such as monoclonal antibodies, fusion proteins and cytokines. Products in those classes include immunomodulatory biologics, which are intended to enhance or diminish the activity of the immune system. Immunomodulatory biologics have been approved by the U.S. FDA for a variety of indications, including cancer and inflammatory conditions. Prior to gaining approval for marketing, sponsoring companies for all types of products must demonstrate a product's safety in toxicology studies conducted in animals and show safety and efficacy in clinical trials conducted in patients. The overall goal of toxicology studies, which applies to immunomodulatory and other product types, is to identify the hazards that products pose to humans. Because biologics are generally highly selective for specific targets (receptors/epitopes), conducting toxicology studies in animal models with the target is essential. Such animals are referred to as pharmacologically relevant. Endpoints routinely included in toxicology studies, such as hematology, organ weight and histopathology, can be used to assess the effect of a product on the structure of the immune system. Additionally, specialized endpoints, such as immunophenotyping and immune function tests, can be used to define effects of immunomodulatory products on the immune system. Following hazard identification, risks posed to patients are assessed and managed. Risks can be managed through clinical trial design and risk communication, a practice that applies to immunomodulatory and other product types. Examples of risk management in clinical trial design include establishing a safe starting dose, defining the appropriate patient population and establishing appropriate patient monitoring. Risk communication starts during clinical trials and continues after product approval. A combination of hazard identification, risk assessment and risk management allows for drug development to proceed

  18. Noradrenergic System in Down Syndrome and Alzheimer's Disease A Target for Therapy.

    Science.gov (United States)

    Phillips, Cristy; Fahimi, Atoossa; Das, Devsmita; Mojabi, Fatemeh S; Ponnusamy, Ravikumar; Salehi, Ahmad

    2016-01-01

    Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimer's disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regions vital for cognition, mood, and executive function. While the mechanisms by which NE-ergic abnormalities contribute to cognitive dysfunction are not fully understood, emergent evidence suggests that rescue of NE-ergic system can attenuate neuropathology and cognitive decline in both AD and DS. Therapeutic strategies to enhance NE neurotransmission have undergone limited testing. Among those deployed to date are NE reuptake inhibitors, presynaptic α-adrenergic receptor antagonists, NE prodrugs, and β-adrenergic agonists. Here we examine alterations in the NE-ergic system in AD and DS and suggest that NE-ergic system rescue is a plausible treatment strategy for targeting cognitive decline in both disorders.

  19. Aluminum-doped zinc oxide thin films grown on various substrates using facing target sputtering system

    Science.gov (United States)

    Kim, Hwa-Min; Lee, Chang Hyun; Shon, Sun Young; Kim, Bong Hwan

    2017-11-01

    Aluminum-doped zinc oxide (AZO) films were fabricated on various substrates, such as glass, polyethylene naphthalate (PEN), and polyethylene terephthalate (PET), at room temperature using a facing target sputtering (FTS) system with hetero ZnO and Al2O3 targets, and their electrical and optical properties were investigated. The AZO film on glass exhibited compressive stress while the films on the plastic substrates showed tensile stress. These stresses negatively affected the crystalline quality of the AZO films, and it is suggested that the poor crystalline quality of the films may be related to the neutral Al-based defect complexes formed in the films; these complexes act as neutral impurity scattering centers. AZO films with good optoelectronic properties could be formed on the glass and plastic substrates by the FTS technique using the hetero targets. The AZO films deposited on the glass, PEN, and PET substrates showed very low resistivities, of 5.0 × 10-4 Ω cm, 7.0 × 10-4 Ω cm, and 7.4 × 10-4 Ω cm, respectively. Further, the figure merit of the AZO film formed on the PEN substrate in the visible range (400-700 nm) was significantly higher than that of the AZO film on PET and similar to that of the AZO film on glass. Finally, the average transmittances of the films in the visible range (400-700 nm) were 83.16% (on glass), 76.3% (on PEN), and 78.16% (on PET).

  20. Targeting the renin-angiotensin system as novel therapeutic strategy for pulmonary diseases.

    Science.gov (United States)

    Tan, Wan Shun Daniel; Liao, Wupeng; Zhou, Shuo; Mei, Dan; Wong, Wai-Shiu Fred

    2017-12-27

    The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects. Novel intervention is definitely needed to offer optimal therapeutic strategy and clinical outcome. This review compiles and analyses recent investigations targeting RAS for the treatment of inflammatory lung diseases. Inhibition of the upstream angiotensin (Ang) I/Ang II/angiotensin receptor type 1 (AT 1 R) pathway and activation of the downstream angiotensin-converting enzyme 2 (ACE2)/Ang (1-7)/Mas receptor pathway are two feasible strategies demonstrating efficacies in various pulmonary disease models. More recent studies favor the development of targeting the downstream ACE2/Ang (1-7)/Mas receptor pathway, in which diminazene aceturate, an ACE2 activator, GSK2586881, a recombinant ACE2, and AV0991, a Mas receptor agonist, showed much potential for further development. As the pathogenesis of pulmonary diseases is so complex that RAS modulation may be used alone or in combination with existing drugs like corticosteroids, pirfenidone/nintedanib or endothelin receptor antagonists for different pulmonary diseases. Personalized medicine through genetic screening and phenotyping for angiotensinogen or ACE would aid treatment especially for non-responsive patients. This review serves to provide an update on the latest development in the field of RAS targeting for pulmonary diseases, and offer some insights into future direction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Wenqing; Zhang, Baoxin; Duan, Dongzhu [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000 (China); Wu, Jincai [College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000 (China); Fang, Jianguo, E-mail: fangjg@lzu.edu.cn [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000 (China); College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000 (China)

    2012-08-01

    The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH, is ubiquitous in all cells and involved in many redox-dependent signaling pathways. Curcumin, a naturally occurring pigment that gives a specific yellow color in curry food, is consumed in normal diet up to 100 mg per day. This molecule has also been used in traditional medicine for the treatment of a variety of diseases. Curcumin has numerous biological functions, and many of these functions are related to induction of oxidative stress. However, how curcumin elicits oxidative stress in cells is unclear. Our previous work has demonstrated the way by which curcumin interacts with recombinant TrxR1 and alters the antioxidant enzyme into a reactive oxygen species (ROS) generator in vitro. Herein we reported that curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells. Curcumin-modified TrxR1 dose-dependently and quantitatively transfers electrons from NADPH to oxygen with the production of ROS. Also, curcumin can drastically down-regulate Trx1 protein level as well as its enzyme activity in HeLa cells, which in turn remarkably decreases intracellular free thiols, shifting the intracellular redox balance to a more oxidative state, and subsequently induces DNA oxidative damage. Furthermore, curcumin-pretreated HeLa cells are more sensitive to oxidative stress. Knockdown of TrxR1 sensitizes HeLa cells to curcumin cytotoxicity, highlighting the physiological significance of targeting TrxR1 by curcumin. Taken together, our data disclose a previously unrecognized prooxidant mechanism of curcumin in cells, and provide a deep insight in understanding how curcumin works in vivo. -- Highlights: ► Curcumin induces oxidative stress by targeting the thioredoxin system. ► Curcumin-modified TrxR quantitatively oxidizes NADPH to generate ROS. ► Knockdown of TrxR1 augments curcumin's cytotoxicity in HeLa cells.

  2. Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells

    International Nuclear Information System (INIS)

    Cai, Wenqing; Zhang, Baoxin; Duan, Dongzhu; Wu, Jincai; Fang, Jianguo

    2012-01-01

    The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH, is ubiquitous in all cells and involved in many redox-dependent signaling pathways. Curcumin, a naturally occurring pigment that gives a specific yellow color in curry food, is consumed in normal diet up to 100 mg per day. This molecule has also been used in traditional medicine for the treatment of a variety of diseases. Curcumin has numerous biological functions, and many of these functions are related to induction of oxidative stress. However, how curcumin elicits oxidative stress in cells is unclear. Our previous work has demonstrated the way by which curcumin interacts with recombinant TrxR1 and alters the antioxidant enzyme into a reactive oxygen species (ROS) generator in vitro. Herein we reported that curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells. Curcumin-modified TrxR1 dose-dependently and quantitatively transfers electrons from NADPH to oxygen with the production of ROS. Also, curcumin can drastically down-regulate Trx1 protein level as well as its enzyme activity in HeLa cells, which in turn remarkably decreases intracellular free thiols, shifting the intracellular redox balance to a more oxidative state, and subsequently induces DNA oxidative damage. Furthermore, curcumin-pretreated HeLa cells are more sensitive to oxidative stress. Knockdown of TrxR1 sensitizes HeLa cells to curcumin cytotoxicity, highlighting the physiological significance of targeting TrxR1 by curcumin. Taken together, our data disclose a previously unrecognized prooxidant mechanism of curcumin in cells, and provide a deep insight in understanding how curcumin works in vivo. -- Highlights: ► Curcumin induces oxidative stress by targeting the thioredoxin system. ► Curcumin-modified TrxR quantitatively oxidizes NADPH to generate ROS. ► Knockdown of TrxR1 augments curcumin's cytotoxicity in HeLa cells. ► Curcumin

  3. Optimum design of beam window's diameter and thickness of Hyper target system

    International Nuclear Information System (INIS)

    Cho, C. H.; Tak, N. I.; Song, T. Y.; Park, W. S.

    2002-01-01

    HYPER is designed to transmute long-lived TRU and fission products such as Tc-99 and I-129. Pb-Bi is used as the coolant and spallation target material at the same time. HYPER is expected to need about 20mA proton beam to sustain a 1000MW th power level. The cylindrical beam tube and spherical window is adopted as the basic window shape of HYPER. The window diameter and the window thickness are varied to find the maximum allowable current based on the design criteria : Pb-Bi temperature < 500 .deg. C, window temperature < 600 .deg. C, Pb-Bi velocity < 2m/s and window stress < 160MPa. The LAHET code is used to simulate heat generation. CFX is also used for the thermal-hydraulics calculation. Based on our design criteria, the maximum allowable current is calculated to be about 9.2mA, which is smaller than the required current. Therefore, an upgrade of the target system design is required

  4. Drug repurposing to target Ebola virus replication and virulence using structural systems pharmacology.

    Science.gov (United States)

    Zhao, Zheng; Martin, Che; Fan, Raymond; Bourne, Philip E; Xie, Lei

    2016-02-18

    The recent outbreak of Ebola has been cited as the largest in history. Despite this global health crisis, few drugs are available to efficiently treat Ebola infections. Drug repurposing provides a potentially efficient solution to accelerating the development of therapeutic approaches in response to Ebola outbreak. To identify such candidates, we use an integrated structural systems pharmacology pipeline which combines proteome-scale ligand binding site comparison, protein-ligand docking, and Molecular Dynamics (MD) simulation. One thousand seven hundred and sixty-six FDA-approved drugs and 259 experimental drugs were screened to identify those with the potential to inhibit the replication and virulence of Ebola, and to determine the binding modes with their respective targets. Initial screening has identified a number of promising hits. Notably, Indinavir; an HIV protease inhibitor, may be effective in reducing the virulence of Ebola. Additionally, an antifungal (Sinefungin) and several anti-viral drugs (e.g. Maraviroc, Abacavir, Telbivudine, and Cidofovir) may inhibit Ebola RNA-directed RNA polymerase through targeting the MTase domain. Identification of safe drug candidates is a crucial first step toward the determination of timely and effective therapeutic approaches to address and mitigate the impact of the Ebola global crisis and future outbreaks of pathogenic diseases. Further in vitro and in vivo testing to evaluate the anti-Ebola activity of these drugs is warranted.

  5. Analytical study of narrow channel flow for a spallation target system design

    Energy Technology Data Exchange (ETDEWEB)

    Islam, Md. Shafiqul; Monde, Masanori [Saga Univ., Saga (Japan); Terada, Atsuhiko; Kinoshita, Hidetaka; Hino, Ryutaro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2001-07-01

    Heat transfer and pressure drop characteristics under fully developed turbulent water flow condition were analyzed over a two-dimensional narrow rectangular channel whose height is H=1.2 mm. The channel configuration and water flow condition simulate forced convection cooling of a spallation target system components design such as a solid target and a proton beam window. The high-Reynolds number form of the standard k - {epsilon} and RNG k - {epsilon} models employing wall functions for the Reynolds number (Re) range of 7,000 to 22,000 were used in the analyses. As for heat transfer characteristics of a smooth channel, the Nusselt number obtained by the standard k - {epsilon} model agreed very well with the Dittus-Boelter correlation. No significant differences in friction factors for the smooth channel were observed for these two models, which agreed well with the Blasius correlation. However, the standard k - {epsilon} model could not predict friction factors well for the rib-roughened channel. (author)

  6. From Molecular Classification to Targeted Therapeutics: The Changing Face of Systemic Therapy in Metastatic Gastroesophageal Cancer

    Directory of Open Access Journals (Sweden)

    Adrian Murphy

    2015-01-01

    Full Text Available Histological classification of adenocarcinoma or squamous cell carcinoma for esophageal cancer or using the Lauren classification for intestinal and diffuse type gastric cancer has limited clinical utility in the management of advanced disease. Germline mutations in E-cadherin (CDH1 or mismatch repair genes (Lynch syndrome were identified many years ago but given their rarity, the identification of these molecular alterations does not substantially impact treatment in the advanced setting. Recent molecular profiling studies of upper GI tumors have added to our knowledge of the underlying biology but have not led to an alternative classification system which can guide clinician’s therapeutic decisions. Recently the Cancer Genome Atlas Research Network has proposed four subtypes of gastric cancer dividing tumors into those positive for Epstein-Barr virus, microsatellite unstable tumors, genomically stable tumors, and tumors with chromosomal instability. Unfortunately to date, many phase III clinical trials involving molecularly targeted agents have failed to meet their survival endpoints due to their use in unselected populations. Future clinical trials should utilize molecular profiling of individual tumors in order to determine the optimal use of targeted therapies in preselected patients.

  7. Optimized swimmer tracking system based on a novel multi-related-targets approach

    Science.gov (United States)

    Benarab, D.; Napoléon, T.; Alfalou, A.; Verney, A.; Hellard, P.

    2017-02-01

    Robust tracking is a crucial step in automatic swimmer evaluation from video sequences. We designed a robust swimmer tracking system using a new multi-related-targets approach. The main idea is to consider the swimmer as a bloc of connected subtargets that advance at the same speed. If one of the subtargets is partially or totally occluded, it can be localized by knowing the position of the others. In this paper, we first introduce the two-dimensional direct linear transformation technique that we used to calibrate the videos. Then, we present the classical tracking approach based on dynamic fusion. Next, we highlight the main contribution of our work, which is the multi-related-targets tracking approach. This approach, the classical head-only approach and the ground truth are then compared, through testing on a database of high-level swimmers in training, national and international competitions (French National Championships, Limoges 2015, and World Championships, Kazan 2015). Tracking percentage and the accuracy of the instantaneous speed are evaluated and the findings show that our new appraoach is significantly more accurate than the classical approach.

  8. Analytical study of narrow channel flow for a spallation target system design

    International Nuclear Information System (INIS)

    Islam, Md. Shafiqul; Monde, Masanori; Terada, Atsuhiko; Kinoshita, Hidetaka; Hino, Ryutaro

    2001-07-01

    Heat transfer and pressure drop characteristics under fully developed turbulent water flow condition were analyzed over a two-dimensional narrow rectangular channel whose height is H=1.2 mm. The channel configuration and water flow condition simulate forced convection cooling of a spallation target system components design such as a solid target and a proton beam window. The high-Reynolds number form of the standard k - ε and RNG k - ε models employing wall functions for the Reynolds number (Re) range of 7,000 to 22,000 were used in the analyses. As for heat transfer characteristics of a smooth channel, the Nusselt number obtained by the standard k - ε model agreed very well with the Dittus-Boelter correlation. No significant differences in friction factors for the smooth channel were observed for these two models, which agreed well with the Blasius correlation. However, the standard k - ε model could not predict friction factors well for the rib-roughened channel. (author)

  9. Heated uranium tetrafluoride target system to release non-rare gas fission products for the TRISTAN isotope separator

    International Nuclear Information System (INIS)

    Gill, R.L.

    1977-10-01

    Off-line experiments indicated that fluorides of As, Se, Br, Kr, Zr, Nb, Mo, Tc, Ru, Sb, Te, I and Xe could be volatilized, but except for Br, Kr, I and Xe, none of these elements were observed after mass separation in the on-line experiments. The results of the on-line experiments indicated a very low level of hydride contamination at ambient temperature and consequently, uranium tetrafluoride replaced uranyl stearate as the primary gaseous fission product target. Possible reasons for the failure of the heated target system to yield non-rare gas activities are discussed and suggestions for designing a new heated target system are presented

  10. A Colon Targeted Delivery System for Resveratrol Enriching in pH Responsive-Model

    DEFF Research Database (Denmark)

    Andishmand, Hashem; Hamishehkar, Hamed; Mohammadifar, Mohammad Amin

    2017-01-01

    Background: Resveratrol effects on the prevention and treatment of colon cancer have been well documented recently, but low solubility, rapid absorption and metabolism of resveratrol limit its beneficial effects on colon cancer. Designing a formulation that enhances the solubility of resveratrol......, protects resveratrol from oxidation and isomerization, and delivers it to the colon is a priority of food and drug industry. In this study, resveratrol-polyethylene glycol (PEG)-loaded pectin-chitosan polyelectrolyte complex was designed as a colon targeted delivery system. Methods: The effects of adding...... PEG, ultra-sonication time, pH, and pectin to chitosan ratio were investigated on particle size, polydispersity index (PDI), zeta potential by particle size analyzer, and scanning electron microscopy (SEM). Encapsulation efficiency (EE), release of resveratrol in simulated gastrointestinal fluid...

  11. Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome

    Directory of Open Access Journals (Sweden)

    V Raghunathan

    2017-01-01

    Full Text Available Hypertension is common in hemolytic uremic syndrome (HUS and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency.

  12. Gut-central nervous system axis is a target for nutritional therapies

    Directory of Open Access Journals (Sweden)

    Pimentel Gustavo D

    2012-04-01

    Full Text Available Abstract Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies.

  13. Development of Detector Systems for Internal and Fixed Target Heavy Ion Physics Experiments

    International Nuclear Information System (INIS)

    Golubev, Pavel

    2003-04-01

    This thesis deals with intermediate energy heavy ion reactions with the particular aim to study the nuclear matter equation of state which defines the relation between statistical parameters of a fermionic system. The development of equipment for two experiments, CA47 at The Svedberg Laboratory in Uppsala, Sweden and R16 at Kernfysisch Versneller Inst. (KVI), Groningen, The Netherlands, are described. CA47 contains the CHICSi detector, a modular, ultra-high vacuum (UHV) compatible, multi-detector system, covering a solid angle of 3pi sr around the collision point. Together with two auxiliary detector systems CHICSi is placed at the cluster-jet target chamber of the CELSIUS storage ring. This thesis gives a technical overview of the detector and the development carried out in order to achieve the desired detection performance. Some laboratory and in-beam tests are described and the analysis of the first experimental results is discussed. The nuclear intensity interferometry experiment (R16) was performed in a dedicated beam-line of the AGOR superconducting cyclotron. Small-angle two-particle correlations were measured for the E/A = 61 MeV 36 Ar + 27 Al, 112 Sn, 124 Sn reactions, together with singles spectra. The experimental energy distributions of neutrons and light charged particles for the 36 Ar + 27 Al reaction have been analyzed with a Maxwellian multi-source prescription. These results, together with correlation function data, are used to extract information on the size of the emitting sources and their time evolution

  14. Functions of flavonoids in the central nervous system: Astrocytes as targets for natural compounds.

    Science.gov (United States)

    Matias, Isadora; Buosi, Andrea Schmidt; Gomes, Flávia Carvalho Alcantara

    2016-05-01

    In the last decade, there have been major advances in the understanding of the role of glial cells as key elements in the formation, maintenance and refinement of synapses. Recently, the discovery of natural compounds capable of modulating nervous system function has revealed new perspectives on the restoration of the injured brain. Among these compounds, flavonoids stand out as molecules easily obtainable in the diet that have remarkable effects on cognitive performance and behavior. Nevertheless, little is known about the cellular and molecular mechanisms underlying the actions of flavonoids in the nervous system. The present review presents recent advances in the effects of natural compounds, particularly flavonoids, in the nervous system. We shed light on astrocytes as targets of flavonoids and discuss how this interaction might contribute to the effects of flavonoids on neuronal survival, differentiation and function. Finally, we discuss how the effects of flavonoids on astrocytes might contribute to the development of alternative therapeutic approaches to the treatment of neural diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. A system dynamics optimization framework to achieve population desired of average weight target

    Science.gov (United States)

    Abidin, Norhaslinda Zainal; Zulkepli, Jafri Haji; Zaibidi, Nerda Zura

    2017-11-01

    Obesity is becoming a serious problem in Malaysia as it has been rated as the highest among Asian countries. The aim of the paper is to propose a system dynamics (SD) optimization framework to achieve population desired weight target based on the changes in physical activity behavior and its association to weight and obesity. The system dynamics approach of stocks and flows diagram was used to quantitatively model the impact of both behavior on the population's weight and obesity trends. This work seems to bring this idea together and highlighting the interdependence of the various aspects of eating and physical activity behavior on the complex of human weight regulation system. The model was used as an experimentation vehicle to investigate the impacts of changes in physical activity on weight and prevalence of obesity implications. This framework paper provides evidence on the usefulness of SD optimization as a strategic decision making approach to assist in decision making related to obesity prevention. SD applied in this research is relatively new in Malaysia and has a high potential to apply to any feedback models that address the behavior cause to obesity.

  16. Modulation of the Endocannabinoid System: Vulnerability Factor and New Treatment Target for Stimulant Addiction.

    Directory of Open Access Journals (Sweden)

    Stéphanie eOlière

    2013-09-01

    Full Text Available Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamine. Interestingly, recent accumulating evidence points toward the involvement of the endocannabinoid system (ECBS in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep-insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. The aims of this article are to: 1 review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and 2 evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoid in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants.

  17. Visualizing multiple inter-organelle contact sites using the organelle-targeted split-GFP system.

    Science.gov (United States)

    Kakimoto, Yuriko; Tashiro, Shinya; Kojima, Rieko; Morozumi, Yuki; Endo, Toshiya; Tamura, Yasushi

    2018-04-18

    Functional integrity of eukaryotic organelles relies on direct physical contacts between distinct organelles. However, the entity of organelle-tethering factors is not well understood due to lack of means to analyze inter-organelle interactions in living cells. Here we evaluate the split-GFP system for visualizing organelle contact sites in vivo and show its advantages and disadvantages. We observed punctate GFP signals from the split-GFP fragments targeted to any pairs of organelles among the ER, mitochondria, peroxisomes, vacuole and lipid droplets in yeast cells, which suggests that these organelles form contact sites with multiple organelles simultaneously although it is difficult to rule out the possibilities that these organelle contacts sites are artificially formed by the irreversible associations of the split-GFP probes. Importantly, split-GFP signals in the overlapped regions of the ER and mitochondria were mainly co-localized with ERMES, an authentic ER-mitochondria tethering structure, suggesting that split-GFP assembly depends on the preexisting inter-organelle contact sites. We also confirmed that the split-GFP system can be applied to detection of the ER-mitochondria contact sites in HeLa cells. We thus propose that the split-GFP system is a potential tool to observe and analyze inter-organelle contact sites in living yeast and mammalian cells.

  18. Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

    Science.gov (United States)

    Hur, Eun-Mi; Lee, Byoung Dae

    2014-12-01

    Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

  19. Microtubule-Targeting Agents Enter the Central Nervous System (CNS: Double-edged Swords for Treating CNS Injury and Disease

    Directory of Open Access Journals (Sweden)

    Eun-Mi Hur

    2014-12-01

    Full Text Available Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

  20. OmniSearch: a semantic search system based on the Ontology for MIcroRNA Target (OMIT) for microRNA-target gene interaction data.

    Science.gov (United States)

    Huang, Jingshan; Gutierrez, Fernando; Strachan, Harrison J; Dou, Dejing; Huang, Weili; Smith, Barry; Blake, Judith A; Eilbeck, Karen; Natale, Darren A; Lin, Yu; Wu, Bin; Silva, Nisansa de; Wang, Xiaowei; Liu, Zixing; Borchert, Glen M; Tan, Ming; Ruttenberg, Alan

    2016-01-01

    As a special class of non-coding RNAs (ncRNAs), microRNAs (miRNAs) perform important roles in numerous biological and pathological processes. The realization of miRNA functions depends largely on how miRNAs regulate specific target genes. It is therefore critical to identify, analyze, and cross-reference miRNA-target interactions to better explore and delineate miRNA functions. Semantic technologies can help in this regard. We previously developed a miRNA domain-specific application ontology, Ontology for MIcroRNA Target (OMIT), whose goal was to serve as a foundation for semantic annotation, data integration, and semantic search in the miRNA field. In this paper we describe our continuing effort to develop the OMIT, and demonstrate its use within a semantic search system, OmniSearch, designed to facilitate knowledge capture of miRNA-target interaction data. Important changes in the current version OMIT are summarized as: (1) following a modularized ontology design (with 2559 terms imported from the NCRO ontology); (2) encoding all 1884 human miRNAs (vs. 300 in previous versions); and (3) setting up a GitHub project site along with an issue tracker for more effective community collaboration on the ontology development. The OMIT ontology is free and open to all users, accessible at: http://purl.obolibrary.org/obo/omit.owl. The OmniSearch system is also free and open to all users, accessible at: http://omnisearch.soc.southalabama.edu/index.php/Software.

  1. The glutamate and the immune systems: new targets for the pharmacological treatment of OCD.

    Science.gov (United States)

    Marazziti, Donatella; Albert, Umberto; Mucci, Federico; Piccinni, Armando

    2017-11-08

    In the last decades the pharmacological treatment of obsessive-compulsive disorder (OCD) has been significantly promoted by the effectiveness of selective serotonin (5-HT) reuptake inhibitors (SSRIs) and the subsequent development of the 5-HT hypothesis of OCD. However, since a large majority of patients (between 40% and 60 %) do not respond to SSRIs or strategies based on the modulation of the 5-HT system, it is now essential to search for other possible therapeutic targets. The aim of this paper was to review current literature through a PubMed and Google Scholar search of novel hypotheses and related compounds for the treatment of OCD, with a special focus on the glutammate and the immune systems. The literature would indicate that glutamate, the main excitatory neurotransmitter, might play an important role in the pathophysiology of OCD. In addition, a series of clinical study would also support the potential efficacy of drugs modulating the glutamate system. The role of the immune system alterations in OCD in both children and adults needs to be more deeply elucidated. In children, it has been widely described a subtype of OCD resulting from infections driven by group A streptococcus β-hemolitic and belonging to the so-called "pediatric autoimmune neuropsychiatric disorders associated with streptococcus" (PANDAS). In adults, available findings are meager and controversial, although interesting. The glutamate and the immune systems represent two intriguing topics of research that hold promises of development of open novel treatment strategies in OCD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Through-the-Wall Localization of a Moving Target by Two Independent Ultra Wideband (UWB Radar Systems

    Directory of Open Access Journals (Sweden)

    Jana Rovňáková

    2013-09-01

    Full Text Available In the case of through-the-wall localization of moving targets by ultra wideband (UWB radars, there are applications in which handheld sensors equipped only with one transmitting and two receiving antennas are applied. Sometimes, the radar using such a small antenna array is not able to localize the target with the required accuracy. With a view to improve through-the-wall target localization, cooperative positioning based on a fusion of data retrieved from two independent radar systems can be used. In this paper, the novel method of the cooperative localization referred to as joining intersections of the ellipses is introduced. This method is based on a geometrical interpretation of target localization where the target position is estimated using a properly created cluster of the ellipse intersections representing potential positions of the target. The performance of the proposed method is compared with the direct calculation method and two alternative methods of cooperative localization using data obtained by measurements with the M-sequence UWB radars. The direct calculation method is applied for the target localization by particular radar systems. As alternative methods of cooperative localization, the arithmetic average of the target coordinates estimated by two single independent UWB radars and the Taylor series method is considered.

  3. Efficient in planta gene targeting in tomato using geminiviral replicons and the CRISPR/Cas9 system.

    Science.gov (United States)

    Dahan-Meir, Tal; Filler-Hayut, Shdema; Melamed-Bessudo, Cathy; Bocobza, Samuel; Czosnek, Henryk; Aharoni, Asaph; Levy, Avraham A

    2018-04-18

    Current breeding relies mostly on random mutagenesis and recombination to generate novel genetic variation. However, targeted genome editing is becoming an increasingly important tool for precise plant breeding. Using the CRISPR-Cas system combined with the bean yellow dwarf virus rolling circle replicon we optimized a method for targeted mutagenesis and gene replacement in tomato. The carotenoid isomerase (CRTISO) and phytoene synthase 1 (PSY1) genes from the carotenoid biosynthesis pathway were chosen as targets due to their easily detectable change of phenotype. We took advantage of the geminiviral replicon amplification as a mean to provide a large amount of donor template for the repair of a CRISPR-Cas-induced DNA double strand break (DSB) in the target gene, via homologous recombination. Mutagenesis experiments, performed in the Micro-Tom variety achieved precise modification of the CRTISO and PSY1 loci at an efficiency of up to 90%. In the gene targeting experiments, our target was a fast-neutron-induced crtiso allele that contained a 281bp deletion. This deletion was repaired with the wildtype sequence through homologous recombination between the CRISPR-Cas-induced DSB in the crtiso target and the amplified donor in 25% of the plants transformed. This shows that efficient gene targeting can be achieved in the absence of selection markers or reporters using a single and modular construct that is adaptable to other tomato targets and other crops. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Targeting the oxidative stress response system of fungi with safe, redox-potent chemosensitizing agents

    Directory of Open Access Journals (Sweden)

    Jong H. eKim

    2012-03-01

    Full Text Available The cellular antioxidation system is a target in the antifungal action of amphotericin B (AMB and itraconazole (ITZ, in filamentous fungi. The sakAΔ mutant of Aspergillus fumigatus, a mitogen-activated protein kinase (MAPK gene deletion mutant in the antioxidation system, was found to be more sensitive to AMB or ITZ than other A. fumigatus strains, a wild type and a mpkCΔ mutant (MAPK gene deletion mutant in polyalcohol sugar utilization system. The sakAΔ mutant showed no growth at 0.5 μg mL-1 of ITZ or reduced growth at 1.0 to 2.0 μg mL-1 of AMB, while the other strains exhibited robust growth. Complete fungal kill (≥ 99.9% by ITZ or AMB was achieved by much lower dosages for the sakAΔ mutant than for the other strains. SakA and MpkC appear to have overlapping roles in marshalling the oxidative stress response under treatment by an organic peroxide, tert-butyl hydroperoxide (t-BuOOH, or hydrogen peroxide (H2O2. The SakA signalling pathway was found to be responsible for fungal tolerance to AMB or ITZ toxicity. It appears msnA, an Aspergillus ortholog to Saccharomyces cerevisiae MSN2 (encoding a stress-responsive C2H2-type zinc-finger regulator and sakA and/or mpkC (upstream MAPKs are in the same stress response network under t-BuOOH-, H2O2- or AMB-triggered toxicity. Of note is that ITZ-sensitive yeast pathogens (Candida krusei and Cryptococcus neoformans were also sensitive to t-BuOOH, showing a connection between ITZ toxicity and oxidative stress response. This was shown by enhanced antifungal activity of AMB or ITZ when co-applied with redox-potent natural compounds, 2,3-dihydroxybenzaldehyde, thymol or salicylaldehyde, as chemosensitizing agents. Hence, redox compounds, which target the antioxidation system in fungi, possess a potent chemosensitizing capacity to enhance efficacy of conventional drugs inducing oxidative stress. Such chemosensitization can reduce costs and alleviate negative side effects associated with current

  5. Safety-technical lay-out of the operational environment of a high-power spallation target system of the megawatt class with mercury as target material

    International Nuclear Information System (INIS)

    Butzek, M.

    2005-06-01

    This thesis is concerning the safety relevant layout of the environment of a mercury based 5-Megawatt-spallation target. All safety relevant aspects related to construction, operation and dismantling as well as economical issues were taken into account. Safety concerns are basically driven by the toxic and radioactive inventory as well as the kind and intensity of radiation produced by the spallation process. Due to significant differences in inventory and radiation between a spallation source and a fission reactor, for the design of the spallation source mentioned above the safety philosophy of a fission reactor must not be used unchanged. Rather than this a systematic study of all safety related boundary conditions is necessary. Within this thesis all safety relevant boundary conditions for this specific type of machine are given. Beside the spatial distribution of different areas inside the target station, influence of medias to be used as well as arising radiation and handling requirements are discussed in detail. A general layout of the target station is presented, serving as a basis for all further component and system development. An enclosure concept for the target station was developed, taking into account the safety relevant issues concerning the mercury used as target materials, the water cooling loops containing massive amounts of tritium as well as the materials used for the moderators potentially forming explosive mixtures. Concept and detailed technical layout of the enclosure system was chosen to guarantee safe operation of the source as well as taking care of requirement arising for handling needs. For design of the shielding different suitable materials have been discussed. A design for assembling the shielding is shown taking into account the safety relevant requirements during operation as well as during dismantling. The neutron beam shutters, buried inside the shielding were designed to optimize handling and positioning issued of the inner part

  6. Study on the knowledge base system for the identification of typical target

    International Nuclear Information System (INIS)

    Qin Kai; Zhao Yingjun

    2008-01-01

    Based on the research on target knowledge base, target database, texture analysis, shape analysis, this paper proposed a new knowledge based method for typical target identification from remote sensing image. By extracting the texture characters and shape characters, joining with spatial analysis in GIS, reasoning according to the prior knowledge in the knowledge base, this method can identify and ex- tract typical target from remote sensing images. (authors)

  7. Conceptual design of the handling and storage system of the spent target vessel for neutron scattering facility 2

    International Nuclear Information System (INIS)

    Adachi, Junichi; Kaminaga, Masanori; Sasaki, Shinobu; Haga, Katsuhiro; Aso, Tomokazu; Kinoshita, Hidetaka; Hino, Ryutaro

    2002-01-01

    In designing the neutron scattering facility, a spent target vessel should be replaced with remote handling devices in order to protect radioactive exposure, since it would be highly activated through the high energy neutron irradiation caused by the spallation reaction between mercury of the target material and the MW-class proton beam. In the storage of the spent target vessel, it is necessary to consider decay heat of the target vessel and mercury contamination caused by vaporization of the residual mercury in the vessel. A conceptual design has been carried out to establish basic concept and to clarify its specification of main equipments on handling and storage systems for the spent target vessel. This report presents the basic concept and a system plot plan based on latest design works of remote handling devices such as a spent target vessel storage cask and a target vessel exchange trolley, which aim at reasonability and simplification. In addition, storage systems for the spent moderator vessel, the spent proton beam window and the spent reflector vessel are also investigated based on the plot plan. (author)

  8. Fusion-based multi-target tracking and localization for intelligent surveillance systems

    Science.gov (United States)

    Rababaah, Haroun; Shirkhodaie, Amir

    2008-04-01

    In this paper, we have presented two approaches addressing visual target tracking and localization in complex urban environment. The two techniques presented in this paper are: fusion-based multi-target visual tracking, and multi-target localization via camera calibration. For multi-target tracking, the data fusion concepts of hypothesis generation/evaluation/selection, target-to-target registration, and association are employed. An association matrix is implemented using RGB histograms for associated tracking of multi-targets of interests. Motion segmentation of targets of interest (TOI) from the background was achieved by a Gaussian Mixture Model. Foreground segmentation, on other hand, was achieved by the Connected Components Analysis (CCA) technique. The tracking of individual targets was estimated by fusing two sources of information, the centroid with the spatial gating, and the RGB histogram association matrix. The localization problem is addressed through an effective camera calibration technique using edge modeling for grid mapping (EMGM). A two-stage image pixel to world coordinates mapping technique is introduced that performs coarse and fine location estimation of moving TOIs. In coarse estimation, an approximate neighborhood of the target position is estimated based on nearest 4-neighbor method, and in fine estimation, we use Euclidean interpolation to localize the position within the estimated four neighbors. Both techniques were tested and shown reliable results for tracking and localization of Targets of interests in complex urban environment.

  9. Development of a Novel Antimicrobial Screening System Targeting the Pyoverdine-Mediated Iron Acquisition System and Xenobiotic Efflux Pumps

    Directory of Open Access Journals (Sweden)

    Kazuki Sato

    2015-04-01

    Full Text Available The iron acquisition systems in Pseudomonas aeruginosa are inducible in response to low-iron conditions and important for growth of this organism under iron limitation. OprM is the essential outer membrane subunit of the MexAB-OprM xenobiotic efflux pump. We designed and constructed a new model antimicrobial screening system targeting both the iron-uptake system and xenobiotic efflux pumps. The oprM gene was placed immediately downstream of the ferri-pyoverdine receptor gene, fpvA, in the host lacking chromosomal oprM and the expression of oprM was monitored by an antibiotic susceptibility test under iron depleted and replete conditions. The recombinant cells showed wild-type susceptibility to pump substrate antibiotics, e.g., aztreonam, under iron limitation and became supersusceptible to them under iron repletion, suggesting that expression of oprM is under control of the iron acquisition system. Upon screening of a chemical library comprising 2952 compounds using this strain, a compound—ethyl 2-(1-acetylpiperidine-4-carboxamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate—was found to enhance the efficacy of aztreonam under iron limitation, suggesting that the compound inhibits either the iron acquisition system or the MexAB-OprM efflux pump. This compound was subsequently found to inhibit the growth of wild-type cells in the presence of sublethal amounts of aztreonam, regardless of the presence or absence of dipyridyl, an iron-chelator. The compound was eventually identified to block the function of the MexAB-OprM efflux pump, showing the validity of this new method.

  10. Development of a novel antimicrobial screening system targeting the pyoverdine-mediated iron acquisition system and xenobiotic efflux pumps.

    Science.gov (United States)

    Sato, Kazuki; Ushioda, Kenichi; Akiba, Keiji; Matsumoto, Yoshimi; Maseda, Hideaki; Ando, Tasuke; Isogai, Emiko; Nakae, Taiji; Yoneyama, Hiroshi

    2015-04-29

    The iron acquisition systems in Pseudomonas aeruginosa are inducible in response to low-iron conditions and important for growth of this organism under iron limitation. OprM is the essential outer membrane subunit of the MexAB-OprM xenobiotic efflux pump. We designed and constructed a new model antimicrobial screening system targeting both the iron-uptake system and xenobiotic efflux pumps. The oprM gene was placed immediately downstream of the ferri-pyoverdine receptor gene, fpvA, in the host lacking chromosomal oprM and the expression of oprM was monitored by an antibiotic susceptibility test under iron depleted and replete conditions. The recombinant cells showed wild-type susceptibility to pump substrate antibiotics, e.g., aztreonam, under iron limitation and became supersusceptible to them under iron repletion, suggesting that expression of oprM is under control of the iron acquisition system. Upon screening of a chemical library comprising 2952 compounds using this strain, a compound-ethyl 2-(1-acetylpiperidine-4-carboxamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate-was found to enhance the efficacy of aztreonam under iron limitation, suggesting that the compound inhibits either the iron acquisition system or the MexAB-OprM efflux pump. This compound was subsequently found to inhibit the growth of wild-type cells in the presence of sublethal amounts of aztreonam, regardless of the presence or absence of dipyridyl, an iron-chelator. The compound was eventually identified to block the function of the MexAB-OprM efflux pump, showing the validity of this new method.

  11. Shilling Attacks Detection in Recommender Systems Based on Target Item Analysis.

    Science.gov (United States)

    Zhou, Wei; Wen, Junhao; Koh, Yun Sing; Xiong, Qingyu; Gao, Min; Dobbie, Gillian; Alam, Shafiq

    2015-01-01

    Recommender systems are highly vulnerable to shilling attacks, both by individuals and groups. Attackers who introduce biased ratings in order to affect recommendations, have been shown to negatively affect collaborative filtering (CF) algorithms. Previous research focuses only on the differences between genuine profiles and attack profiles, ignoring the group characteristics in attack profiles. In this paper, we study the use of statistical metrics to detect rating patterns of attackers and group characteristics in attack profiles. Another question is that most existing detecting methods are model specific. Two metrics, Rating Deviation from Mean Agreement (RDMA) and Degree of Similarity with Top Neighbors (DegSim), are used for analyzing rating patterns between malicious profiles and genuine profiles in attack models. Building upon this, we also propose and evaluate a detection structure called RD-TIA for detecting shilling attacks in recommender systems using a statistical approach. In order to detect more complicated attack models, we propose a novel metric called DegSim' based on DegSim. The experimental results show that our detection model based on target item analysis is an effective approach for detecting shilling attacks.

  12. One-dimensional MHD simulations of MTF systems with compact toroid targets and spherical liners

    Science.gov (United States)

    Khalzov, Ivan; Zindler, Ryan; Barsky, Sandra; Delage, Michael; Laberge, Michel

    2017-10-01

    One-dimensional (1D) MHD code is developed in General Fusion (GF) for coupled plasma-liner simulations in magnetized target fusion (MTF) systems. The main goal of these simulations is to search for optimal parameters of MTF reactor, in which spherical liquid metal liner compresses compact toroid plasma. The code uses Lagrangian description for both liner and plasma. The liner is represented as a set of spherical shells with fixed masses while plasma is discretized as a set of nested tori with circular cross sections and fixed number of particles between them. All physical fields are 1D functions of either spherical (liner) or small toroidal (plasma) radius. Motion of liner and plasma shells is calculated self-consistently based on applied forces and equations of state. Magnetic field is determined by 1D profiles of poloidal and toroidal fluxes - they are advected with shells and diffuse according to local resistivity, this also accounts for flux leakage into the liner. Different plasma transport models are implemented, this allows for comparison with ongoing GF experiments. Fusion power calculation is included into the code. We performed a series of parameter scans in order to establish the underlying dependencies of the MTF system and find the optimal reactor design point.

  13. Use of the target diagnostic control system in the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Shelton, R; Lagin, L; Nelson, J

    2011-07-25

    The extreme physics of targets shocked by NIF's 192-beam laser are observed by a diverse suite of diagnostics including optical backscatter, time-integrated, time resolved and gated X-ray sensors, laser velocity interferometry, and neutron time of flight. Diagnostics to diagnose fusion ignition implosion and neutron emissions have been developed. A Diagnostic Control System (DCS) for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost Window XP processor and Java application. Instruments are aggregated as needed in the supervisory system to form an integrated diagnostic. The Java framework provides data management, control services and operator GUI generation. During the past several years, over thirty-six diagnostics have been deployed using this architecture in support of the National Ignition Campaign (NIC). The DCS architecture facilitates the expected additions and upgrades to diagnostics as more experiments are performed. This paper presents the DCS architecture, framework and our experiences in using it during the NIC to operate, upgrade and maintain a large set of diagnostic instruments.

  14. Use of the target diagnostic control system in the National Ignition Facility

    International Nuclear Information System (INIS)

    Shelton, R.; Lagin, L.; Nelson, J.

    2011-01-01

    The extreme physics of targets shocked by NIF's 192-beam laser are observed by a diverse suite of diagnostics including optical backscatter, time-integrated, time resolved and gated X-ray sensors, laser velocity interferometry, and neutron time of flight. Diagnostics to diagnose fusion ignition implosion and neutron emissions have been developed. A Diagnostic Control System (DCS) for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost Window XP processor and Java application. Instruments are aggregated as needed in the supervisory system to form an integrated diagnostic. The Java framework provides data management, control services and operator GUI generation. During the past several years, over thirty-six diagnostics have been deployed using this architecture in support of the National Ignition Campaign (NIC). The DCS architecture facilitates the expected additions and upgrades to diagnostics as more experiments are performed. This paper presents the DCS architecture, framework and our experiences in using it during the NIC to operate, upgrade and maintain a large set of diagnostic instruments.

  15. Experimental research on laser tracking system with galvanometer scanner for measuring spatial coordinates of moving target

    Science.gov (United States)

    Wang, Jia; Hu, Zhaohui; Liu, Yongdong; Liang, Jinwen

    2000-10-01

    The spatial position of industrial object, such as robot end- effector, is an important geometric parameter whose accuracy determines whether robot can perform accurately. Therefore, we have established a laser tracking and coordinate measuring system with galvanometer scanner for high accuracy, large range, non- contact, and spatial dynamic measurement. In this paper, the laser tracking system and its setup are illuminated at first. Then, the formulae for calculating coordinates are deduced, and the calibration method of the initial distance from tracking mirror to target is presented. After that, two preliminary experiments in different distances are described. One is on CMM; the other is with grating ruler as reference. In the former, the maximum measurement error of coordinates is 70micrometers and the maximum error of length is 35micrometers in the 85x100x100mm3 measurement volume, and in the 1m initial distance. In the later, the maximum error of length is 140micrometers in the range of 480mm, and in the 5m initial distance. At the end of the paper, the error sources are analyzed and simulated.

  16. Shilling Attacks Detection in Recommender Systems Based on Target Item Analysis

    Science.gov (United States)

    Zhou, Wei; Wen, Junhao; Koh, Yun Sing; Xiong, Qingyu; Gao, Min; Dobbie, Gillian; Alam, Shafiq

    2015-01-01

    Recommender systems are highly vulnerable to shilling attacks, both by individuals and groups. Attackers who introduce biased ratings in order to affect recommendations, have been shown to negatively affect collaborative filtering (CF) algorithms. Previous research focuses only on the differences between genuine profiles and attack profiles, ignoring the group characteristics in attack profiles. In this paper, we study the use of statistical metrics to detect rating patterns of attackers and group characteristics in attack profiles. Another question is that most existing detecting methods are model specific. Two metrics, Rating Deviation from Mean Agreement (RDMA) and Degree of Similarity with Top Neighbors (DegSim), are used for analyzing rating patterns between malicious profiles and genuine profiles in attack models. Building upon this, we also propose and evaluate a detection structure called RD-TIA for detecting shilling attacks in recommender systems using a statistical approach. In order to detect more complicated attack models, we propose a novel metric called DegSim’ based on DegSim. The experimental results show that our detection model based on target item analysis is an effective approach for detecting shilling attacks. PMID:26222882

  17. Energy Storage System Control Algorithm by Operating Target Power to Improve Energy Sustainability of Smart Home

    Directory of Open Access Journals (Sweden)

    Byeongkwan Kang

    2018-01-01

    Full Text Available As energy issues are emerging around the world, a variety of smart home technologies aimed at realizing zero energy houses are being introduced. Energy storage system (ESS for smart home energy independence is increasingly gaining interest. However, limitations exist in that most of them are controlled according to time schedules or used in conjunction with photovoltaic (PV generation systems. In consideration of load usage patterns and PV generation of smart home, this study proposes an ESS control algorithm that uses constant energy of energy network while making maximum use of ESS. Constant energy means that the load consumes a certain amount of power under all conditions, which translates to low variability. The proposed algorithm makes a smart home a load of energy network with low uncertainty and complexity. The simulation results show that the optimal ESS operating target power not only makes the smart home use power constantly from the energy network, but also maximizes utilization of the ESS. In addition, since the smart home is a load that uses constant energy, it has the advantage of being able to operate an efficient energy network from the viewpoint of energy providers.

  18. A novel folate-modified self-microemulsifying drug delivery system of curcumin for colon targeting

    Directory of Open Access Journals (Sweden)

    Zhang L

    2012-01-01

    Full Text Available Lin Zhang1*, Weiwei Zhu2*, Chunfen Yang1, Hongxia Guo1, Aihua Yu1, Jianbo Ji3, Yan Gao1, Min Sun1, Guangxi Zhai11Department of Pharmaceutical Engineering, College of Pharmacy, Shandong University, Jinan; 2Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai; 3Department of Pharmacology, College of Pharmacy, Shandong University, Jinan, China*These authors contributed equally to the workBackground: The objective of this study was to prepare, characterize, and evaluate a folate-modified self-microemulsifying drug delivery system (FSMEDDS with the aim to improve the solubility of curcumin and its delivery to the colon, facilitating endocytosis of FSMEDDS mediated by folate receptors on colon cancer cells.Methods: Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of curcumin-loaded SMEDDS was optimized by a simplex lattice experiment design. Then, three lipophilic folate derivatives (folate-polyethylene glycol-distearoylphosphatidylethanolamine, folate-polyethylene glycol-cholesteryl hemisuccinate, and folate-polyethylene glycol-cholesterol used as a surfactant were added to curcumin-loaded SMEDDS formulations. An in situ colon perfusion method in rats was used to optimize the formulation of FSMEDDS. Curcumin-loaded FSMEDDS was then filled into colon-targeted capsules and the in vitro release was investigated. Cytotoxicity studies and cellular uptake studies was used in this research.Results: The optimal formulation of FSMEDDS obtained with the established in situ colon perfusion method in rats was comprised of 57.5% Cremophor® EL, 32.5% Transcutol® HP, 10% Capryol™ 90, and a small amount of folate-polyethylene glycol-cholesteryl hemisuccinate (the weight ratio of folate materials to Cremophor EL was 1:100. The in vitro release results indicated that the obtained formulation of curcumin could reach the colon efficiently and release the drug immediately. Cellular

  19. Analyses of Brucella pathogenesis, host immunity, and vaccine targets using systems biology and bioinformatics

    Directory of Open Access Journals (Sweden)

    Yongqun eHe

    2012-02-01

    Full Text Available Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of ten classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning.

  20. Analyses of Brucella Pathogenesis, Host Immunity, and Vaccine Targets using Systems Biology and Bioinformatics

    Science.gov (United States)

    He, Yongqun

    2011-01-01

    Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of 10 classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics) and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning. PMID:22919594

  1. Sleep and Sedative States Induced by Targeting the Histamine and Noradrenergic Systems

    Directory of Open Access Journals (Sweden)

    Xiao Yu

    2018-01-01

    Full Text Available Sedatives target just a handful of receptors and ion channels. But we have no satisfying explanation for how activating these receptors produces sedation. In particular, do sedatives act at restricted brain locations and circuitries or more widely? Two prominent sedative drugs in clinical use are zolpidem, a GABAA receptor positive allosteric modulator, and dexmedetomidine (DEX, a selective α2 adrenergic receptor agonist. By targeting hypothalamic neuromodulatory systems both drugs induce a sleep-like state, but in different ways: zolpidem primarily reduces the latency to NREM sleep, and is a controlled substance taken by many people to help them sleep; DEX produces prominent slow wave activity in the electroencephalogram (EEG resembling stage 2 NREM sleep, but with complications of hypothermia and lowered blood pressure—it is used for long term sedation in hospital intensive care units—under DEX-induced sedation patients are arousable and responsive, and this drug reduces the risk of delirium. DEX, and another α2 adrenergic agonist xylazine, are also widely used in veterinary clinics to sedate animals. Here we review how these two different classes of sedatives, zolpidem and dexmedetomideine, can selectively interact with some nodal points of the circuitry that promote wakefulness allowing the transition to NREM sleep. Zolpidem enhances GABAergic transmission onto histamine neurons in the hypothalamic tuberomammillary nucleus (TMN to hasten the transition to NREM sleep, and DEX interacts with neurons in the preoptic hypothalamic area that induce sleep and body cooling. This knowledge may aid the design of more precise acting sedatives, and at the same time, reveal more about the natural sleep-wake circuitry.

  2. Study of particle transport in a high power spallation target for an accelerator-driven transmutation system

    International Nuclear Information System (INIS)

    Shetty, Nikhil Vittal

    2013-01-01

    AGATE is a project envisaged to demonstrate the feasibility of transmutation in a gas (helium) cooled accelerator-driven system using solid spallation target. Development of the spallation target module and assessing its safety aspects are studied in this work. According to the AGATE concept parameters, 600 MeV protons are delivered on to the segmented tungsten spallation target. The Monte Carlo toolkit Geant4 has been used in the simulation of particle transport. Binary cascade is used to simulate intra-nuclear cascades, along with the G4NDL neutron data library for low energy neutrons (<20 MeV).

  3. Study of particle transport in a high power spallation target for an accelerator-driven transmutation system

    Energy Technology Data Exchange (ETDEWEB)

    Shetty, Nikhil Vittal

    2013-01-31

    AGATE is a project envisaged to demonstrate the feasibility of transmutation in a gas (helium) cooled accelerator-driven system using solid spallation target. Development of the spallation target module and assessing its safety aspects are studied in this work. According to the AGATE concept parameters, 600 MeV protons are delivered on to the segmented tungsten spallation target. The Monte Carlo toolkit Geant4 has been used in the simulation of particle transport. Binary cascade is used to simulate intra-nuclear cascades, along with the G4NDL neutron data library for low energy neutrons (<20 MeV).

  4. Determination of solar flare accelerated ion angular distributions from SMM gamma ray and neutron measurements and determination of the He-3/H ratio in the solar photosphere from SMM gamma ray measurements

    Science.gov (United States)

    Lingenfelter, Richard E.

    1989-01-01

    Comparisons of Solar Maximum Mission (SMM) observations of gamma-ray line and neutron emission with theoretical calculation of their expected production by flare accelerated ion interactions in the solar atmosphere have led to significant advances in the understanding of solar flare particle acceleration and interaction, as well as the flare process itself. These comparisons have enabled the determination of, not only the total number and energy spectrum of accelerated ions trapped at the sun, but also the ion angular distribution as they interact in the solar atmosphere. The Monte Carlo program was modified to include in the calculations of ion trajectories the effects of both mirroring in converging magnetic fields and of pitch angle scattering. Comparing the results of these calculations with the SMM observations, not only the angular distribution of the interacting ions can be determined, but also the initial angular distribution of the ions at acceleration. The reliable determination of the solar photospheric He-3 abundance is of great importance for understanding nucleosynthesis in the early universe and its implications for cosmology, as well as for the study of the evolution of the sun. It is also essential for the determinations of the spectrum and total number of flare accelerated ions from the SMM/GRS gamma-ray line measurements. Systematic Monte Carlo calculations of the time dependence were made as a function of the He-3 abundance and other variables. A new series of calculations were compared for the time-dependent flux of 2.223 MeV neutron capture line emission and the ratio of the time-integrated flux in the 2.223 MeV line to that in the 4.1 to 6.4 MeV nuclear deexcitation band.

  5. An experiment to study CP violation in the B system using an internal target at the HERA proton ring

    International Nuclear Information System (INIS)

    Hofmann, W.

    1993-01-01

    Using the HERA proton beam striking an internal wire target, sufficient numbers of B mesons are produced to allow the search for CP violation in B decays with a sensitivity Δsin(2β)∼0.05, provided that the detector can accept and separate multiple interactions per bunch crossing. This report summarizes our present views concerning the layout of the target, of the spectrometer, and of the trigger system, which selects events containing J/ψ candidates. (orig.)

  6. Synergistic target combination prediction from curated signaling networks: Machine learning meets systems biology and pharmacology.

    Science.gov (United States)

    Chua, Huey Eng; Bhowmick, Sourav S; Tucker-Kellogg, Lisa

    2017-10-01

    Given a signaling network, the target combination prediction problem aims to predict efficacious and safe target combinations for combination therapy. State-of-the-art in silico methods use Monte Carlo simulated annealing (mcsa) to modify a candidate solution stochastically, and use the Metropolis criterion to accept or reject the proposed modifications. However, such stochastic modifications ignore the impact of the choice of targets and their activities on the combination's therapeutic effect and off-target effects, which directly affect the solution quality. In this paper, we present mascot, a method that addresses this limitation by leveraging two additional heuristic criteria to minimize off-target effects and achieve synergy for candidate modification. Specifically, off-target effects measure the unintended response of a signaling network to the target combination and is often associated with toxicity. Synergy occurs when a pair of targets exerts effects that are greater than the sum of their individual effects, and is generally a beneficial strategy for maximizing effect while minimizing toxicity. mascot leverages on a machine learning-based target prioritization method which prioritizes potential targets in a given disease-associated network to select more effective targets (better therapeutic effect and/or lower off-target effects); and on Loewe additivity theory from pharmacology which assesses the non-additive effects in a combination drug treatment to select synergistic target activities. Our experimental study on two disease-related signaling networks demonstrates the superiority of mascot in comparison to existing approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Development of Detector Systems for Internal and Fixed Target Heavy Ion Physics Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Golubev, Pavel

    2003-04-01

    This thesis deals with intermediate energy heavy ion reactions with the particular aim to study the nuclear matter equation of state which defines the relation between statistical parameters of a fermionic system. The development of equipment for two experiments, CA47 at The Svedberg Laboratory in Uppsala, Sweden and R16 at Kernfysisch Versneller Inst. (KVI), Groningen, The Netherlands, are described. CA47 contains the CHICSi detector, a modular, ultra-high vacuum (UHV) compatible, multi-detector system, covering a solid angle of 3pi sr around the collision point. Together with two auxiliary detector systems CHICSi is placed at the cluster-jet target chamber of the CELSIUS storage ring. This thesis gives a technical overview of the detector and the development carried out in order to achieve the desired detection performance. Some laboratory and in-beam tests are described and the analysis of the first experimental results is discussed. The nuclear intensity interferometry experiment (R16) was performed in a dedicated beam-line of the AGOR superconducting cyclotron. Small-angle two-particle correlations were measured for the E/A = 61 MeV {sup 36}Ar + {sup 27}Al, {sup 112}Sn, {sup 124}Sn reactions, together with singles spectra. The experimental energy distributions of neutrons and light charged particles for the {sup 36}Ar + {sup 27}Al reaction have been analyzed with a Maxwellian multi-source prescription. These results, together with correlation function data, are used to extract information on the size of the emitting sources and their time evolution.

  8. System effectiveness of a targeted free mass distribution of long lasting insecticidal nets in Zanzibar, Tanzania

    Directory of Open Access Journals (Sweden)

    Abass Ali K

    2010-06-01

    Full Text Available Abstract Background Insecticide-treated nets (ITN and long-lasting insecticidal treated nets (LLIN are important means of malaria prevention. Although there is consensus regarding their importance, there is uncertainty as to which delivery strategies are optimal for dispensing these life saving interventions. A targeted mass distribution of free LLINs to children under five and pregnant women was implemented in Zanzibar between August 2005 and January 2006. The outcomes of this distribution among children under five were evaluated, four to nine months after implementation. Methods Two cross-sectional surveys were conducted in May 2006 in two districts of Zanzibar: Micheweni (MI on Pemba Island and North A (NA on Unguja Island. Household interviews were conducted with 509 caretakers of under-five children, who were surveyed for socio-economic status, the net distribution process, perceptions and use of bed nets. Each step in the distribution process was assessed in all children one to five years of age for unconditional and conditional proportion of success. System effectiveness (the accumulated proportion of success and equity effectiveness were calculated, and predictors for LLIN use were identified. Results The overall proportion of children under five sleeping under any type of treated net was 83.7% (318/380 in MI and 91.8% (357/389 in NA. The LLIN usage was 56.8% (216/380 in MI and 86.9% (338/389 in NA. Overall system effectiveness was 49% in MI and 87% in NA, and equity was found in the distribution scale-up in NA. In both districts, the predicting factor of a child sleeping under an LLIN was caretakers thinking that LLINs are better than conventional nets (OR = 2.8, p = 0.005 in MI and 2.5, p = 0.041 in NA, in addition to receiving an LLIN (OR = 4.9, p Conclusions Targeted free mass distribution of LLINs can result in high and equitable bed net coverage among children under five. However, in order to sustain high effective coverage, there

  9. Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus.

    Science.gov (United States)

    Guan, Jing; Wang, Wanying; Sun, Baolin

    2017-01-01

    CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCC mec ). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5' tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCC mec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and consecutive

  10. Tuberculosis therapeutics: Engineering of nanomedicinal systems for local delivery of targeted drug cocktails

    Science.gov (United States)

    D'Addio, Suzanne M.

    In this thesis, a multifunctional nanocarrier drug delivery system was investigated and optimized to improve tuberculosis therapy by promoting the intracellular delivery of high payloads of antibiotics. To meet the needs of a patient population which continues to grow by close to 10 million people a year, innovative therapeutics must be formulated by robust and scalable processes. We use Flash NanoPrecipitation for the continuous precipitation of nanocarriers by block copolymer directed assembly, which enables the development of nanocarriers with tunable properties. Stable nanocarriers of Rifampicin and a hydrophobic Rifampicin prodrug have efficacy against tuberculosis in vitro that is equivalent to the soluble Rifampicin. To overcome poor in vivo efficacy of the recently discovered antitubercular drug SQ641, we co-encapsulate SQ641 and Cyclosporine A in a stable aqueous nanocarrier suspension, which enables drug administration and also enhances intracellular accumulation and antitubercular efficacy relative to SQ641 in solution. Since the mannose receptor is involved in the phagocytosis of tuberculosis bacilli, we modify the surface of nanocarriers with mannoside residues to target specific intracellular accumulation in macrophages. The surface density of mannoside terminated polyethylene glycol chains was controlled between 0 and 75% and in vitro cellular association reveals a 9% surface density is optimal for internalization mediated by the mannose receptor. We explore the preparation of large, porous aerosol carrier particles of with tunable deposition characteristics by spray freeze drying with ultrasonic atomization for direct dosing to the lungs. Nanocarriers are loaded at 3 - 50 wt% in mannitol particles with constant size, limited nanocarrier aggregation, and 63% dose delivered to the lungs, as determined by in vitro cascade impaction. There has been a lag in the development of new technologies to facilitate development and commercialization of

  11. A new screening method to identify inhibitors of the Lol (localization of lipoproteins) system, a novel antibacterial target.

    Science.gov (United States)

    Ito, Hideaki; Ura, Atsushi; Oyamada, Yoshihiro; Yoshida, Hiroaki; Yamagishi, Jun-Ichi; Narita, Shin-Ichiro; Matsuyama, Shin-Ichi; Tokuda, Hajime

    2007-01-01

    As the Lol system, which is involved in localization of lipoproteins, is essential for Escherichia coli growth and widely conserved among gram-negative bacteria, it is considered to be a promising target for the development of anti-gram-negative bacterial agents. However, no high-throughput screening method has so far been developed to screen for Lol system inhibitors. By combining three assay systems (anucleate cell blue assay, Lpp assay, and LolA-dependent release inhibition assay) and a drug susceptibility test, we have successfully developed a new screening method for identification of compounds that inhibit the Lol system. Using this new screening method, we screened 23,600 in-house chemical compounds and found 2 Lol system inhibitors. We therefore conclude that our new screening method can efficiently identify new antibacterial agents that target the Lol system.

  12. A lentivirus-free inducible CRISPR-Cas9 system for efficient targeting of human genes.

    Science.gov (United States)

    Bisht, Kamlesh; Grill, Sherilyn; Graniel, Jacqueline; Nandakumar, Jayakrishnan

    2017-08-01

    CRISPR-Cas9 is a cutting-edge tool for modifying genomes. The efficacy with which Cas9 recognizes its target has revolutionized the engineering of knockouts. However this efficacy complicates the knocking out of important genes in cultured cells. Unedited cells holding a survival advantage within an edited population can confound the knockout phenotype. Here we develop a HeLa-based system that overcomes this limitation, incorporating several attractive features. First, we use Flp-recombinase to generate clones stably integrated for Cas9 and guide RNAs, eliminating the possibility of unedited cells. Second, Cas9 can be induced uniformly in the clonal cultures using doxycycline to measure the knockout phenotype. Third, two genes can be simultaneously knocked out using this approach. Finally, by not involving lentiviruses, our method is appealing to a broad research audience. Using this methodology we generated an inducible AGO2-knockout cell line showing normal RNA interference in the absence of doxycycline. Upon induction of Cas9, the AGO2 locus was cleaved, the AGO2 protein was depleted, and RNA interference was compromised. In addition to generating inducible knockouts, our technology can be adapted to improve other applications of Cas9, including transcriptional/epigenetic modulation and visualization of cellular DNA loci. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia Essential Oil on Central Nervous System Targets

    Directory of Open Access Journals (Sweden)

    Víctor López

    2017-05-01

    Full Text Available Lavender essential oil is traditionally used and approved by the European Medicines Agency (EMA as herbal medicine to relieve stress and anxiety. Some animal and clinical studies reveal positive results in models of anxiety and depression although very little research has been done on molecular mechanisms. Our work consisted of evaluating the effects of lavender (Lavandula angustifolia essential oil on central nervous system well-established targets, such as MAO-A, SERT, GABAAand NMDA receptors as well as in vitro models of neurotoxicity. The results showed that lavender essential oil and its main components exert affinity for the glutamate NMDA-receptor in a dose-dependent manner with an IC50 value of 0.04 μl/mL for lavender oil. In addition, lavender and linalool were also able to bind the serotonin transporter (SERT whereas they did not show affinity for GABAA-benzodiazepine receptor. In three different models of neurotoxicity, lavender did not enhance the neurotoxic insult and improved viability of SH-SY5Y cells treated with hydrogen peroxide. According to our data, the anxiolytic and antidepressant-like effects attributed to lavender may be due to an antagonism on the NMDA-receptor and inhibition of SERT. This study suggests that lavender essential oil may exert pharmacological properties via modulating the NMDA receptor, the SERT as well as neurotoxicity induced by hydrogen peroxide.

  14. A Tumor-Targeted Nanodelivery System to Improve Early MRI Detection of Cancer

    Directory of Open Access Journals (Sweden)

    Kathleen F. Pirollo

    2006-01-01

    Full Text Available The development of improvements in magnetic resonance imaging (MRI that would enhance sensitivity, leading to earlier detection of cancer and visualization of metastatic disease, is an area of intense exploration. We have devised a tumor-targeting, liposomal nanodelivery platform for use in gene medicine. This systemically administered nanocomplex has been shown to specifically and efficiently deliver both genes and oligonucleotides to primary and metastatic tumor cells, resulting in significant tumor growth inhibition and even tumor regression. Here we examine the effect on MRI of incorporating conventional MRI contrast agent Magnevist® into our anti-transferrin receptor single-chain antibody (TfRscFv liposomal complex. Both in vitro and in an in vivo orthotopic mouse model of pancreatic cancer, we show increased resolution and image intensity with the complexed Magnevist®. Using advanced microscopy techniques (scanning electron microscopy and scanning probe microscopy, we also established that the Magnevist® is in fact encapsulated by the liposome in the complex and that the complex still retains its nanodimensional size. These results demonstrate that this TfRscFv-liposome-Magnevist® nanocomplex has the potential to become a useful tool in early cancer detection.

  15. Emerging Targets in Pituitary Adenomas: Role of the CXCL12/CXCR4-R7 System

    Directory of Open Access Journals (Sweden)

    Federica Barbieri

    2014-01-01

    Full Text Available Chemokines are chemotactic regulators of immune surveillance in physiological and pathological conditions such as inflammation, infection, and cancer. Several chemokines and cognate receptors are constitutively expressed in the central nervous system, not only in glial and endothelial cells but also in neurons, controlling neurogenesis, neurite outgrowth, and axonal guidance during development. In particular, the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, form a functional network that controls plasticity in different brain areas, influencing neurotransmission, neuromodulation, and cell migration, and the dysregulation of this chemokinergic axis is involved in several neurodegenerative, neuroinflammatory, and malignant diseases. CXCR4 primarily mediates the transduction of proliferative signals, while CXCR7 seems to be mainly responsible for scavenging CXCL12. Importantly, the multiple intracellular signalling generated by CXCL12 interaction with its receptors influences hypothalamic modulation of neuroendocrine functions, although a direct modulation of pituitary functioning via autocrine/paracrine mechanisms was also reported. Both CXCL12 and CXCR4 are constitutively overexpressed in pituitary adenomas and their signalling induces cell survival and proliferation, as well as hormonal hypersecretion. In this review we focus on the physiological and pathological functions of immune-related cyto- and chemokines, mainly focusing on the CXCL12/CXCR4-7 axis, and their role in pituitary tumorigenesis. Accordingly, we discuss the potential targeting of CXCR4 as novel pharmacological approach for pituitary adenomas.

  16. Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia) Essential Oil on Central Nervous System Targets

    Science.gov (United States)

    López, Víctor; Nielsen, Birgitte; Solas, Maite; Ramírez, Maria J.; Jäger, Anna K.

    2017-01-01

    Lavender essential oil is traditionally used and approved by the European Medicines Agency (EMA) as herbal medicine to relieve stress and anxiety. Some animal and clinical studies reveal positive results in models of anxiety and depression although very little research has been done on molecular mechanisms. Our work consisted of evaluating the effects of lavender (Lavandula angustifolia) essential oil on central nervous system well-established targets, such as MAO-A, SERT, GABAAand NMDA receptors as well as in vitro models of neurotoxicity. The results showed that lavender essential oil and its main components exert affinity for the glutamate NMDA-receptor in a dose-dependent manner with an IC50 value of 0.04 μl/mL for lavender oil. In addition, lavender and linalool were also able to bind the serotonin transporter (SERT) whereas they did not show affinity for GABAA-benzodiazepine receptor. In three different models of neurotoxicity, lavender did not enhance the neurotoxic insult and improved viability of SH-SY5Y cells treated with hydrogen peroxide. According to our data, the anxiolytic and antidepressant-like effects attributed to lavender may be due to an antagonism on the NMDA-receptor and inhibition of SERT. This study suggests that lavender essential oil may exert pharmacological properties via modulating the NMDA receptor, the SERT as well as neurotoxicity induced by hydrogen peroxide. PMID:28579958

  17. Liposomes as potential carrier system for targeted delivery of polyene antibiotics.

    Science.gov (United States)

    Naik, Suresh R; Desai, Sandhya K; Shah, Priyank D; Wala, Santosh M

    2013-09-01

    The development of new therapeutic modalities involves the use of drug carrier, such as liposomes, which can modify pharmacokinetic and bio-distribution of drug profile. Polyene antibiotics incorporation into liposomes improves its availability at the site, bio-distribution and therapeutic index mainly through the engulfment of liposomes by circulating monocytes/macrophages and transportation to the site of infection. Polyene antibiotics (AmB, SJA-95, HA-1-92) and other antibiotics (streptomycin, tobramycin, quinolones, anti-tubercular and anti-cancer drugs), liposomal preparations are described with possible advantages from therapeutic efficacy and toxicity point of view. The polyene macrolide antibiotics liposomal preparations proved to be more effective in the treatment of systemic mycosis. The AmB-cyclodextrin derivatives inclusion complex is a major breakthrough in liposomal preparation which can be converted into aqueous phase of liposome. Liposomal drug incorporated preparation has been one of the important areas of research for developing the existing polyene antibiotics into useful chemotherapeutic agents in clinical medicine. In recent past other antibiotics have also been incorporated into liposomes using wide variety of materials, phosphatidylethanolamine derivatives (pegylated liposomes, enzyme sensitive conjugates, fluidosomes of anti-cancer drugs and poly lactic/glycolic acid microspheres for anti-tuberculosis drugs). In addition, attempts were also made to extend the receptor mediated drug targeting and to review some relevant patents.

  18. Mechanistic Systems Modeling to Improve Understanding and Prediction of Cardiotoxicity Caused by Targeted Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Jaehee V. Shim

    2017-09-01

    Full Text Available Tyrosine kinase inhibitors (TKIs are highly potent cancer therapeutics that have been linked with serious cardiotoxicity, including left ventricular dysfunction, heart failure, and QT prolongation. TKI-induced cardiotoxicity is thought to result from interference with tyrosine kinase activity in cardiomyocytes, where these signaling pathways help to control critical processes such as survival signaling, energy homeostasis, and excitation–contraction coupling. However, mechanistic understanding is limited at present due to the complexities of tyrosine kinase signaling, and the wide range of targets inhibited by TKIs. Here, we review the use of TKIs in cancer and the cardiotoxicities that have been reported, discuss potential mechanisms underlying cardiotoxicity, and describe recent progress in achieving a more systematic understanding of cardiotoxicity via the use of mechanistic models. In particular, we argue that future advances are likely to be enabled by studies that combine large-scale experimental measurements with Quantitative Systems Pharmacology (QSP models describing biological mechanisms and dynamics. As such approaches have proven extremely valuable for understanding and predicting other drug toxicities, it is likely that QSP modeling can be successfully applied to cardiotoxicity induced by TKIs. We conclude by discussing a potential strategy for integrating genome-wide expression measurements with models, illustrate initial advances in applying this approach to cardiotoxicity, and describe challenges that must be overcome to truly develop a mechanistic and systematic understanding of cardiotoxicity caused by TKIs.

  19. The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target?

    Science.gov (United States)

    Lansdown, Andrew; Rees, D Aled

    2012-12-01

    Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with long-term health risks, including type 2 diabetes and vascular dysfunction in addition to reproductive sequelae. Many of the common features of PCOS, such as central obesity, hyperinsulinaemia and obstructive sleep apnoea (OSA), are associated with chronic sympathetic overactivity, suggesting that sympathoexcitation may be involved in the pathogenesis of this condition. Rodent models of polycystic ovaries have shown that ovarian sympathetic outflow may be increased, accompanied by elevated intra-ovarian synthesis of nerve growth factor (NGF) which may be involved in initiation of ovarian pathology. Patients with PCOS have evidence of increased muscle sympathetic nerve activity (MSNA), altered heart rate variability and attenuated heart rate recovery postexercise, compared with age- and BMI-matched controls, suggesting a generalized increase in sympathetic nerve activity. Active weight loss can reduce MSNA and whole body noradrenaline spillover, whereas low-frequency electroacupuncture decreased MSNA in overweight women with PCOS. Treatment of OSA with continuous positive airways pressure may reduce plasma noradrenaline levels and diastolic blood pressure and improve cardiac sympathovagal balance. Renal sympathetic denervation also reduced MSNA, noradrenaline spillover and blood pressure in two PCOS subjects with hypertension, accompanied by improved insulin sensitivity. The sympathetic nervous system may thus offer a new therapeutic target in PCOS but larger and longer-term studies are needed before these treatments can be considered in clinical practice. © 2012 Blackwell Publishing Ltd.

  20. Universal method for effusive-flow characterization target ion source/vapor transport systems for radioactive ion beam generation (abstract)

    International Nuclear Information System (INIS)

    Alton, G.D.; Bilheux, J.-C.; Liu, Y.; Cole, J. A.; Williams, C.

    2004-01-01

    Worldwide interest in the use of accelerated radioactive ion beams (RIBs) for exploring reactions important in understanding the structure of the nucleus and nuclear astrophysical phenomena has motivated the construction of facilities dedicated to their production and acceleration. Many facilities utilize the isotope-separator-on-line (ISOL) method in which species of interest are generated within a solid or liquid target matrix. Experimentally useful RIBs are often difficult to generate by this technique because of the times required for diffusion from the interior of the target material, and to effusively transport the species of interest to the ion source following diffusion release in relation to its lifetime. Therefore, these delay times must be minimized. We have developed an experimental method that can be used to determine effusive-flow times of arbitrary geometry target/vapor transport systems. The technique utilizes a fast valve to measure effusive-flow times as short as 0.1 ms for any chemically active or inactive species through any target system, independent of size, geometry and materials of construction. In this report, we provide a theoretical basis for effusive flow through arbitrary geometry vapor transport systems, describe a universal experimental apparatus for measuring effusive-flow times, and provide time spectra for noble gases through prototype RIB target/vapor-transport systems

  1. Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system

    Science.gov (United States)

    Holzer, Peter

    2011-01-01

    Approximately 20 of the 30 mammalian transient receptor potential (TRP) channel subunits are expressed by specific neurons and cells within the alimentary canal. They subserve important roles in taste, chemesthesis, mechanosensation, pain and hyperalgesia and contribute to the regulation of gastrointestinal motility, absorptive and secretory processes, blood flow, and mucosal homeostasis. In a cellular perspective, TRP channels operate either as primary detectors of chemical and physical stimuli, as secondary transducers of ionotropic or metabotropic receptors, or as ion transport channels. The polymodal sensory function of TRPA1, TRPM5, TRPM8, TRPP2, TRPV1, TRPV3 and TRPV4 enables the digestive system to survey its physical and chemical environment, which is relevant to all processes of digestion. TRPV5 and TRPV6 as well as TRPM6 and TRPM7 contribute to the absorption of Ca2+ and Mg2+, respectively. TRPM7 participates in intestinal pacemaker activity, and TRPC4 transduces muscarinic acetylcholine receptor activation to smooth muscle contraction. Changes in TRP channel expression or function are associated with a variety of diseases/disorders of the digestive system, notably gastro-esophageal reflux disease, inflammatory bowel disease, pain and hyperalgesia in heartburn, functional dyspepsia and irritable bowel syndrome, cholera, hypomagnesemia with secondary hypocalcemia, infantile hypertrophic pyloric stenosis, esophageal, gastrointestinal and pancreatic cancer, and polycystic liver disease. These implications identify TRP channels as promising drug targets for the management of a number of gastrointestinal pathologies. As a result, major efforts are put into the development of selective TRP channel agonists and antagonists and the assessment of their therapeutic potential. PMID:21420431

  2. Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges

    Directory of Open Access Journals (Sweden)

    Attila Oláh

    2017-11-01

    Full Text Available It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the “phytocannabinoids” [pCBs; e.g., (−-trans-Δ9-tetrahydrocannabinol (THC, (−-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances [“endocannabinoids” (eCB, e.g., arachidonoylethanolamine (anandamide, AEA, 2-arachidonoylglycerol (2-AG, etc.]. These ligands, together with multiple receptors (e.g., CB1 and CB2 cannabinoid receptors, etc., and a complex enzyme and transporter apparatus involved in the synthesis and degradation of the ligands constitute the endocannabinoid system (ECS, a recently emerging regulator of several physiological processes. The ECS is widely expressed in the human body, including several members of the innate and adaptive immune system, where eCBs, as well as several pCBs were shown to deeply influence immune functions thereby regulating inflammation, autoimmunity, antitumor, as well as antipathogen immune responses, etc. Based on this knowledge, many in vitro and in vivo studies aimed at exploiting the putative therapeutic potential of cannabinoid signaling in inflammation-accompanied diseases (e.g., multiple sclerosis or in organ transplantation, and to dissect the complex immunological effects of medical and “recreational” marijuana consumption. Thus, the objective of the current article is (i to summarize the most recent findings of the field; (ii to highlight the putative therapeutic potential of targeting cannabinoid signaling; (iii to identify open questions and key challenges; and (iv to suggest promising future directions for cannabinoid-based drug development.

  3. A Colon Targeted Delivery System for Resveratrol Enriching in pH Responsive-Model

    Directory of Open Access Journals (Sweden)

    Hashem Andishmand, Hamed Hamishehkar, Afshin Babazadeh, Arezou Taghvimi, Mohammad Amin Mohammadifar, Mahnaz Tabibiazar

    2017-03-01

    Full Text Available Background: Resveratrol effects on the prevention and treatment of colon cancer have been well documented recently, but low solubility, rapid absorption and metabolism of resveratrol limit its beneficial effects on colon cancer. Designing a formulation that enhances the solubility of resveratrol, protects resveratrol from oxidation and isomerization, and delivers it to the colon is a priority of food and drug industry. In this study, resveratrol-polyethylene glycol (PEG-loaded pectin-chitosan polyelectrolyte complex was designed as a colon targeted delivery system. Methods: The effects of adding PEG, ultra-sonication time, pH, and pectin to chitosan ratio were investigated on particle size, polydispersity index (PDI, zeta potential by particle size analyzer, and scanning electron microscopy (SEM. Encapsulation efficiency (EE, release of resveratrol in simulated gastrointestinal fluid, and different pHs were analyzed via High Performance Liquid Chromatography (HPLC. Antioxidant activity was measured by (2, 2-diphenyl-1-picryl-hydrazyl-hydrate DPPH free-radical method. Results: Results showed that colloidal stable micro-particles (725 ± 20 nm with PDI < 0.3 and zeta potential +27 ± 2 mV was formed in the ratio of 5:1 of pectin to chitosan w/v % after a 10-min sonication. Encapsulation efficiency was 81 ± 7 %. The reduction of antioxidant activity of resveratrol loaded micro-particles after one month was less than 13%. Micro-particles released about 33% of resveratrol in the simulated gastric and intestinal fluids. Conclusion: Two-thirds of the loaded resveratrol in Pectin-Chitosan complex reached colon. The developed system had enough specification for enriching fruit based drinks due to remarkable colloidal stability in the pH range of 3.5 to 4.5.

  4. Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus

    OpenAIRE

    Guan, Jing; Wang, Wanying; Sun, Baolin

    2017-01-01

    ABSTRACT CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show...

  5. Biallelic targeting of expressed genes in mouse embryonic stem cells using the Cas9 system

    NARCIS (Netherlands)

    Zhang, Yu; Vanoli, Fabio; LaRocque, Jeannine R.; Krawczyk, Przemek M.; Jasin, Maria

    2014-01-01

    Gene targeting - homologous recombination between transfected DNA and a chromosomal locus - is greatly stimulated by a DNA break in the target locus. Recently, the RNA-guided Cas9 endonuclease, involved in bacterial adaptive immunity, has been modified to function in mammalian cells. Unlike other

  6. Reimbursement of targeted cancer therapies within 3 different European health care systems

    NARCIS (Netherlands)

    Mihajlović, Jovan; Dolk, Christiaan; Tolley, Keith; Simoens, Steven; Postma, Maarten J.

    2015-01-01

    PURPOSE: Targeted cancer therapies (TCTs) are drugs that specifically act on molecular targets within the cancer cell, causing its regression and/or destruction. Although TCTs offer clinically important gains in survival in one of the most challenging therapeutic areas, these gains are followed by

  7. A Large-Acceptance Detector System for Electron Scattering from Polarized Internal targets.

    NARCIS (Netherlands)

    Passchier, E.; Bouwhuis, M.; Choi, S.; Zhou, Z.L.; Alarcon, R.; Anghinolfi, M.; Botto, T.; van den Brand, J.F.J.; Bulten, H.J.; Dimitroyannis, D.; Doets, M.; Ent, R.; Ferro Luzzi, M.M.E.; Higinbotham, D.W.; de Jager, C.W.; Lang, J.; de Lange, D.J.; Nikolenko, D.; Nooren, G.J.; Papadakis, N.; Passchier, I.; Popov, S.G.; Rachek, I.; Ripani, M.; Steijger, J.J.M.; Taiuti, M.; Vodinas, N.; de Vries, H.

    1997-01-01

    The design and the performance of a non-magnetic detector setup for internal target physics at the NIKHEF electron-scattering facility is described. The detector setup, used in the first internal-target experiment at the AmPS ring, measures the spin dependence in the elastic and break-up reaction

  8. Genomic Targets and Features of BarA-UvrY (-SirA Signal Transduction Systems.

    Directory of Open Access Journals (Sweden)

    Tesfalem R Zere

    Full Text Available The two-component signal transduction system BarA-UvrY of Escherichia coli and its orthologs globally regulate metabolism, motility, biofilm formation, stress resistance, virulence of pathogens and quorum sensing by activating the transcription of genes for regulatory sRNAs, e.g. CsrB and CsrC in E. coli. These sRNAs act by sequestering the RNA binding protein CsrA (RsmA away from lower affinity mRNA targets. In this study, we used ChIP-exo to identify, at single nucleotide resolution, genomic sites for UvrY (SirA binding in E. coli and Salmonella enterica. The csrB and csrC genes were the strongest targets of crosslinking, which required UvrY phosphorylation by the BarA sensor kinase. Crosslinking occurred at two sites, an inverted repeat sequence far upstream of the promoter and a site near the -35 sequence. DNAse I footprinting revealed specific binding of UvrY in vitro only to the upstream site, indicative of additional binding requirements and/or indirect binding to the downstream site. Additional genes, including cspA, encoding the cold-shock RNA-binding protein CspA, showed weaker crosslinking and modest or negligible regulation by UvrY. We conclude that the global effects of UvrY/SirA on gene expression are primarily mediated by activating csrB and csrC transcription. We also used in vivo crosslinking and other experimental approaches to reveal new features of csrB/csrC regulation by the DeaD and SrmB RNA helicases, IHF, ppGpp and DksA. Finally, the phylogenetic distribution of BarA-UvrY was analyzed and found to be uniquely characteristic of γ-Proteobacteria and strongly anti-correlated with fliW, which encodes a protein that binds to CsrA and antagonizes its activity in Bacillus subtilis. We propose that BarA-UvrY and orthologous TCS transcribe sRNA antagonists of CsrA throughout the γ-Proteobacteria, but rarely or never perform this function in other species.

  9. Emissions and targets of greenhouse gases not included in the Emission Trading System 2013-2020

    Energy Technology Data Exchange (ETDEWEB)

    Verdonk, M.

    2011-06-15

    This report evaluates the European Commission's (EC) proposal to calculate Member States' targets for emissions not included in the Emission Trading System (ETS) (as announced in the so-called Effort Sharing Decision). The calculation procedures and data sources proposed by the EC have been used for calculating non-ETS emission targets for the Netherlands, for the years from 2013 to 2020. In order to compare results, an alternative approach also was introduced and evaluated. In this approach more transparent data sources were used. Furthermore, the report updates the emission forecast of non-ETS emission levels in the Netherlands, for 2020, and evaluates the consequences of excluding uncertainties related to monitoring from the (updated) emission forecast. It is concluded that, for the Netherlands, the non-ETS emission caps as proposed by the EC would result in an emission cap of 105 Mt CO2 equivalent by 2020. This is higher than in the alternative approach, which would result in a cap of 103 Mt CO2 equivalents. The difference is explained by the different data sources that were used. A drawback of the data sources used in the EC proposal is the lack of transparency of part of the data, which resulted in an additional uncertainty as not all issues could be verified. However, other Member States may not have similar data sources available, in case the EC decides to adopt the alternative approach. The calculated emission caps are to be considered as estimates based on the most recent (but sometimes uncertain) statistics. The EC will determine the definite caps by the end of 2012. Based on a 2010 forecast, and including both an updated division of emissions into ETS and non-ETS emissions and a revised methodology for calculating nitrous oxide emissions, we estimate that non-ETS emissions in the Netherlands would be 104 Mt CO2 equivalents by 2020, with an uncertainty range of between 96 and 112 Mt CO2 equivalents. It is our conclusion that non-ETS emission

  10. An integrated structure- and system-based framework to identify new targets of metabolites and known drugs

    KAUST Repository

    Naveed, Hammad

    2015-08-18

    Motivation: The inherent promiscuity of small molecules towards protein targets impedes our understanding of healthy versus diseased metabolism. This promiscuity also poses a challenge for the pharmaceutical industry as identifying all protein targets is important to assess (side) effects and repositioning opportunities for a drug. Results: Here, we present a novel integrated structure- and system-based approach of drug-target prediction (iDTP) to enable the large-scale discovery of new targets for small molecules, such as pharmaceutical drugs, co-factors and metabolites (collectively called ‘drugs’). For a given drug, our method uses sequence order–independent structure alignment, hierarchical clustering, and probabilistic sequence similarity to construct a probabilistic pocket ensemble (PPE) that captures promiscuous structural features of different binding sites on known targets. A drug’s PPE is combined with an approximation of its delivery profile to reduce false positives. In our cross-validation study, we use iDTP to predict the known targets of eleven drugs, with 63% sensitivity and 81% specificity. We then predicted novel targets for these drugs—two that are of high pharmacological interest, the nuclear receptor PPARγ and the oncogene Bcl-2, were successfully validated through in vitro binding experiments. Our method is broadly applicable for the prediction of protein-small molecule interactions with several novel applications to biological research and drug development.

  11. Reducing uncertainty of estimated nitrogen load reductions to aquatic systems through spatially targeting agricultural mitigation measures using groundwater nitrogen reduction

    DEFF Research Database (Denmark)

    Hashemi, Fatemeh; Olesen, Jørgen Eivind; Jabloun, Mohamed

    2018-01-01

    variation across the landscape in natural N-reduction (denitrification) of leached nitrate in the groundwater and surface water systems. A critical basis for including spatial targeting in regulation of N-load in Denmark is the uncertainty associated with the effect of spatially targeting measures, since......The need to further abate agricultural nitrate (N)-loadings to coastal waters in Denmark represents the main driver for development of a new spatially targeted regulation that focus on locating N-mitigation measures in agricultural areas with high N-load. This targeting makes use of the spatial...... the effect will be critically affected by uncertainty in the quantification of the spatial variation in N-reduction. In this study, we used 30 equally plausible N-reduction maps, at 100 m grid and sub-catchment resolutions, for the 85-km2 groundwater dominated Norsminde catchment in Denmark, applying set...

  12. Target Localization by Resolving the Time Synchronization Problem in Bistatic Radar Systems Using Space Fast-Time Adaptive Processor

    Directory of Open Access Journals (Sweden)

    D. Madurasinghe

    2009-01-01

    Full Text Available The proposed technique allows the radar receiver to accurately estimate the range of a large number of targets using a transmitter of opportunity as long as the location of the transmitter is known. The technique does not depend on the use of communication satellites or GPS systems, instead it relies on the availability of the direct transmit copy of the signal from the transmitter and the reflected paths off the various targets. An array-based space-fast time adaptive processor is implemented in order to estimate the path difference between the direct signal and the delayed signal, which bounces off the target. This procedure allows us to estimate the target distance as well as bearing.

  13. CRISPRseek: a bioconductor package to identify target-specific guide RNAs for CRISPR-Cas9 genome-editing systems.

    Directory of Open Access Journals (Sweden)

    Lihua J Zhu

    Full Text Available CRISPR-Cas systems are a diverse family of RNA-protein complexes in bacteria that target foreign DNA sequences for cleavage. Derivatives of these complexes have been engineered to cleave specific target sequences depending on the sequence of a CRISPR-derived guide RNA (gRNA and the source of the Cas9 protein. Important considerations for the design of gRNAs are to maximize aimed activity at the desired target site while minimizing off-target cleavage. Because of the rapid advances in the understanding of existing CRISPR-Cas9-derived RNA-guided nucleases and the development of novel RNA-guided nuclease systems, it is critical to have computational tools that can accommodate a wide range of different parameters for the design of target-specific RNA-guided nuclease systems. We have developed CRISPRseek, a highly flexible, open source software package to identify gRNAs that target a given input sequence while minimizing off-target cleavage at other sites within any selected genome. CRISPRseek will identify potential gRNAs that target a sequence of interest for CRISPR-Cas9 systems from different bacterial species and generate a cleavage score for potential off-target sequences utilizing published or user-supplied weight matrices with position-specific mismatch penalty scores. Identified gRNAs may be further filtered to only include those that occur in paired orientations for increased specificity and/or those that overlap restriction enzyme sites. For applications where gRNAs are desired to discriminate between two related sequences, CRISPRseek can rank gRNAs based on the difference between predicted cleavage scores in each input sequence. CRISPRseek is implemented as a Bioconductor package within the R statistical programming environment, allowing it to be incorporated into computational pipelines to automate the design of gRNAs for target sequences identified in a wide variety of genome-wide analyses. CRISPRseek is available under the GNU General

  14. Modelling the impacts of challenging 2020 non-ETS GHG emissions reduction targets on Ireland′s energy system

    International Nuclear Information System (INIS)

    Chiodi, Alessandro; Gargiulo, Maurizio; Deane, J.P.; Lavigne, Denis; Rout, Ullash K.; Ó Gallachóir, Brian P.

    2013-01-01

    This paper focuses on Ireland's ambitious target for 2020 to reduce greenhouse gas (GHG) emissions by 20% below 2005 levels for sectors not covered by ETS (Non-ETS). Ireland is an interesting case study due to the role of agriculture (a particularly challenging sector with regard to GHG emissions reduction), that represents 29% of Ireland's GHG emissions compared with less than 10% for the EU. The analysis is carried out with the Irish TIMES model, a bottom-up energy systems modelling tool with detailed characterization of Ireland's energy system. The paper uses scenario analysis to provide pathways that demonstrate how Ireland can meet the non-ETS target at least cost. The paper considers the impacts (in terms of different technology choices and higher marginal abatement costs) arising from higher targets for the energy system to compensate for growth in agriculture activity and low mitigation potential in that sector. The results point to a need to reconsider Ireland's renewable energy focus, with a need for increased effort in renewable transport and renewable heat in particular. The results also point to significant electrification of residential heating. The results also point to a high marginal abatement cost (€213/tCO 2 ), which challenges the analysis carried out at EU level to establish Ireland's non-ETS target. - Highlights: • Techno-economic energy model to deliver EU GHG mitigation target by 2020 in Ireland. • Agriculture represents nearly half of Non-ETS emissions in Ireland. • The target set for Non-ETS GHG for Ireland is far from a cost optimal target. • The results point to a need to reconsider Ireland's renewable energy focus. • Key pathways: electrification of heating in buildings and biofuels in transport

  15. An amplified promoter system for targeted expression of calcium indicator proteins in the cerebellar cortex

    Directory of Open Access Journals (Sweden)

    Bernd eKuhn

    2012-07-01

    Full Text Available Recording of identified neuronal network activity using genetically encoded calcium indicators (GECIs requires labeling that is cell type-specific and bright enough for the detection of functional signals. However, specificity and strong expression are often not achievable using the same promoter. Here we present a combinatorial approach for targeted expression and single-cell-level quantification in which a weak promoter is used to drive trans-amplification under a strong general promoter. We demonstrated this approach using recombinant adeno-associated viruses (rAAVs to deliver the sequence of the GECI D3cpv in the mouse cerebellar cortex. Direct expression under the human synapsin promoter (hSYN led to high levels of expression (50-100 µM in five interneuron types of the cerebellar cortex but not in Purkinje cells (PCs (≤10 μM, yielding sufficient contrast to allow functional signals to be recorded from somata and processes in awake animals using two-photon microscopy. When the hSYN promoter was used to drive expression of the tetracycline transactivator (tTA, a second rAAV containing the bidirectional TET promoter (Ptetbi could drive strong D3cpv expression in PCs (10-300 µM, enough to allow reliable complex spike detection in the dendritic arbor. An amplified approach should be of use in monitoring neural processing in selected cell types and boosting expression of optogenetic probes. Additionally, we overcome cell toxicity associated with rAAV injection and/or local GECI overexpression by combining the virus injection with systemic pre-injection of hyperosmotic D-mannitol, and by this double the time window for functional imaging.

  16. The application of state machine based on labview for solid target transfer control system at BATAN’s cyclotron

    International Nuclear Information System (INIS)

    Heranudin; Rajiman; Parwanto; Edy Slamet R

    2015-01-01

    Software programming for the new solid target transfer control system referred to the working principle of the whole each sub system. System modeling with state machine diagram was chosen because this simplified a complex design of the control system. State machine implementation of this system was performed by creating basic state drawn from the working system of each sub system. All states with their described inputs, outputs and algorithms were compiled in the sequential state machine diagram. In order to ease the operation, three modes namely automatic, major states and micro states were created. Testing of the system has been conducted and as a result, the system worked properly. The implementation of State machine based on LabView has several advantages such as faster, easier programming and the capability for further developments. (author)

  17. Chemistry and biology of radiotracers that target changes in sympathetic and parasympathetic nervous systems in heart disease.

    Science.gov (United States)

    Eckelman, William C; Dilsizian, Vasken

    2015-06-01

    Following the discovery of the sympathetic and parasympathetic nervous system, numerous adrenoceptor drugs were radiolabeled and potent radioligands were prepared in order to image the β-adrenergic and the muscarinic systems. But the greatest effort has been in preparing noradrenaline analogs, such as norepinephrine, (11)C-metahydroxyephedrine, and (123)I-metaiodobenzylguanidine that measure cardiac sympathetic nerve varicosities. Given the technical and clinical challenges in designing and validating targeted adrenoceptor-binding radiotracers, namely the heavily weighted flow dependence and relatively low target-to-background ratio, both requiring complicated mathematic analysis, and the inability of targeted adrenoceptor radioligands to have an impact on clinical care of heart disease, the emphasis has been on radioligands monitoring the norepinephrine pathway. The chemistry and biology of such radiotracers, and the clinical and prognostic impact of these innervation imaging studies in patients with heart disease, are examined. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  18. Integrin Targeting and Toxicological Assessment of Peptide-Conjugated Liposome Delivery Systems to Activated Endothelial Cells

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Villadsen, Klaus; Østrem, Ragnhild Garborg

    2017-01-01

    constructed with the aim of targeting integrins (i.e. vitronectin and/or fibronectin receptors) on activated endothelial cells. The peptide-conjugated liposomes induced only cytotoxicity at the highest concentration in non-activated or activated endothelial cells, as well as in co-culture of endothelial cells...... and macrophages. There was unaltered secretion of cytokines following exposure of peptide-conjugated liposomes to endothelial cells, indicating that the materials were not inflammogenic. Liposomes with a peptide targeting the fibronectin receptor (integrin α5β1) were more effective in targeting of activated....... Therefore, this study demonstrates the feasibility of constructing a peptide-conjugated cationic liposome, which displays targeting to activated endothelial cells at concentrations that are not cytotoxic or inflammogenic to the cells....

  19. IMPACT OF ENERGY GROUP STRUCTURE ON NUCLEAR DATA TARGET ACCURACY REQUIREMENTS FOR ADVANCED REACTOR SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    G. Palmiotti; M. Salvatores; H. Hiruta

    2011-06-01

    A target accuracy assessment study using both a fine and a broad energy structure has shown that less stringent nuclear data accuracy requirements are needed for the latter energy structure. However, even though a reduction is observed, still the requirements will be very difficult to be met unless integral experiments are also used to reduce nuclear data uncertainties. Target accuracy assessment is the inverse problem of the uncertainty evaluation. To establish priorities and target accuracies on data uncertainty reduction, a formal approach can be adopted by defining target accuracy on design parameters and finding out required accuracy on data in order to meet them. In fact, the unknown uncertainty data requirements can be obtained by solving a minimization problem where the sensitivity coefficients in conjunction with the constraints on the integral parameters provide the needed quantities for finding the solutions.

  20. Nanopreparations for mitochondria targeting drug delivery system: Current strategies and future prospective

    Directory of Open Access Journals (Sweden)

    Zhenjie Wang

    2017-11-01

    Full Text Available Mitochondria are a novel and promising therapeutic target for diagnosis, treatment and prevention of a lot of human diseases such as cancer, metabolic diseases and neurodegenerative disease. Owing to the mitochondrial special bilayer structure and highly negative potential nature, therapeutic molecules have multiple difficulties in reaching mitochondria. To overcome multiple barriers for targeting mitochondria, the researchers developed various pharmaceutical preparations such as liposomes, polymeric nanoparticles and inorganic nanoparticles modified by mitochondriotropic moieties like dequalinium (DQA, triphenylphosphonium (TPP, mitochondrial penetrating peptides (MPPs and mitochondrial protein import machinery that allow specific targeting. The targeted formulations exhibited enhanced pharmacological effect and better therapeutic effect than their untargeted counterpart both in vitro and in vivo. Nanocarriers may be used for bio-therapeutic delivery into specific mitochondria that possess a great potential treatment of mitochondria related diseases.