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Sample records for icf target design

  1. Design and fabrication of a CH/Al dual-layer perturbation target for hydrodynamic instability experiments in ICF

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jun [Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Xie, Zhiyong [Shanghai Institute of Laser Plasma, Shanghai 201800 (China); Du, Ai [Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Ye, Junjian [Shanghai Institute of Laser Plasma, Shanghai 201800 (China); Zhang, Zhihua; Shen, Jun [Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Zhou, Bin, E-mail: zhoubin863@tongji.edu.cn [Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China)

    2014-04-15

    Highlights: • Sinusoidal perturbed Al foil was prepared by single-point diamond turning. • Perturbed Al foil was measured by surface profiler and white light interferometer. • Perturbed Al foil and CH layer adhered with each other via a hot-press process. • Parameters and cross-section of the CH–Al perturbation target was characterized. - Abstract: A polystyrene (CH)/aluminum (Al) dual-layer perturbation target for hydrodynamic instability experiments in inertial confinement fusion (ICF) was designed and fabricated. The target was composed of a perturbed 40 μm Al foil and a CH layer. The detailed fabrication method consisted of four steps. The 40 μm Al foil was first prepared by roll and polish process; the perturbation patterns were then introduced on the surface of the Al foil by the single-point diamond turning (SPDT) technology; the CH layer was prepared via a simple method which called spin-coating process; finally, the CH layer was directly coated on the perturbation surface of Al foil by a hot-press process to avoid the use of a sticker and to eliminate the gaps between the CH layer and the Al foil. The parameters of the target, such as the perturbation wavelength (T) and perturbation amplitude (A), were characterized by a QC-5000 tool microscope, an alpha-step 500 surface profiler and a NT1100 white light interferometer. The results showed that T and A of the target were about 52 μm and 7.34 μm, respectively. Thickness of the Al foil (H1), thickness of the CH layer (H2), and cross-section of the dual-layer target were characterized by a QC-5000 tool microscope and a scanning electron microscope (SEM). H1 and H2 were about 40 μm and 15 μm, respectively, the cross-sectional photographs of the target showed that the CH layer and the Al foil adhered perfectly with each other.

  2. Investigating ICF target conditions through spectroscopy

    Science.gov (United States)

    Hansen, Stephanie

    2011-10-01

    The fuel in inertial confinement fusion (ICF) targets is heated and compressed to extreme conditions, reaching multi-keV temperatures and higher-than-solid densities in a neutron- producing core with strong gradients and high velocities in the surrounding plasma. Measuring these conditions is an important step in understanding, accurately simulating, and, ultimately, controlling ICF target performance, whether the target is indirectly driven by laser-heated hohlraum emission or directly driven by lasers or magnetic fields. While neutron signals provide information about the core plasma, the emission and absorption spectra of high-energy x-rays can provide detailed information about core conditions, mix, gradients, velocities, and fields. We present modeled spectroscopic signatures of these quantities, demonstrate the importance of photon energy in diagnosing high-temperature core regions, and show how traditional atomic models must be modified to accurately describe x-ray emission from plasma at extreme densities. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. DOE's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  3. Field precision machining technology of target chamber in ICF lasers

    Science.gov (United States)

    Xu, Yuanli; Wu, Wenkai; Shi, Sucun; Duan, Lin; Chen, Gang; Wang, Baoxu; Song, Yugang; Liu, Huilin; Zhu, Mingzhi

    2016-10-01

    In ICF lasers, many independent laser beams are required to be positioned on target with a very high degree of accuracy during a shot. The target chamber provides a precision platform and datum reference for final optics assembly and target collimation and location system. The target chamber consists of shell with welded flanges, reinforced concrete pedestal, and lateral support structure. The field precision machining technology of target chamber in ICF lasers have been developed based on ShenGuangIII (SGIII). The same center of the target chamber is adopted in the process of design, fabrication, and alignment. The technologies of beam collimation and datum reference transformation are developed for the fabrication, positioning and adjustment of target chamber. A supporting and rotating mechanism and a special drilling machine are developed to bore the holes of ports. An adjustment mechanism is designed to accurately position the target chamber. In order to ensure the collimation requirements of the beam leading and focusing and the target positioning, custom-machined spacers are used to accurately correct the alignment error of the ports. Finally, this paper describes the chamber center, orientation, and centering alignment error measurements of SGIII. The measurements show the field precision machining of SGIII target chamber meet its design requirement. These information can be used on similar systems.

  4. Wetted foam liquid fuel ICF target experiments

    Science.gov (United States)

    Olson, R. E.; Leeper, R. J.; Yi, S. A.; Kline, J. L.; Zylstra, A. B.; Peterson, R. R.; Shah, R.; Braun, T.; Biener, J.; Kozioziemski, B. J.; Sater, J. D.; Biener, M. M.; Hamza, A. V.; Nikroo, A.; Berzak Hopkins, L.; Ho, D.; LePape, S.; Meezan, N. B.

    2016-05-01

    We are developing a new NIF experimental platform that employs wetted foam liquid fuel layer ICF capsules. We will use the liquid fuel layer capsules in a NIF sub-scale experimental campaign to explore the relationship between hot spot convergence ratio (CR) and the predictability of hot spot formation. DT liquid layer ICF capsules allow for flexibility in hot spot CR via the adjustment of the initial cryogenic capsule temperature and, hence, DT vapor density. Our hypothesis is that the predictive capability of hot spot formation is robust and 1D-like for a relatively low CR hot spot (CR∼15), but will become less reliable as hot spot CR is increased to CR>20. Simulations indicate that backing off on hot spot CR is an excellent way to reduce capsule instability growth and to improve robustness to low-mode x-ray flux asymmetries. In the initial experiments, we will test our hypothesis by measuring hot spot size, neutron yield, ion temperature, and burn width to infer hot spot pressure and compare to predictions for implosions with hot spot CR's in the range of 12 to 25. Larger scale experiments are also being designed, and we will advance from sub-scale to full-scale NIF experiments to determine if 1D-like behavior at low CR is retained as the scale-size is increased. The long-term objective is to develop a liquid fuel layer ICF capsule platform with robust thermonuclear burn, modest CR, and significant α-heating with burn propagation.

  5. Stability design of support systems in ICF lasers

    Science.gov (United States)

    Zhu, M. Z.; Wu, W. K.; Chen, G.; Zhan, H.; Xu, Y. L.; Chen, X. J.

    2016-10-01

    Within Inertial Confinement Fusion (ICF) laser systems, many independent laser beams are required to be positioned on target with a very high degree of accuracy until shots are complete. Optical elements that are capable of moving a laser beam on the target must meet the pointing error budget. Optical elements are typically supported by systems which consist of mounts, mount frames, support structures, and foundation. The stability design for support systems in ICF laser have been developed based on the designing and evaluating experience of ShenGuangIII (SGIII). This paper will provide the methodology of position error budget. The stability allocation is developed for evaluating the performance of support systems when they are subjected to multiple sources of excitations that can cause the motion of optical elements during alignment procedures and before shots. The vibrational stability design considerations of support systems are discussed on the fundamental frequency, ambient random vibration, and modal damping. The support structures of optical elements are the relatively large and massive hybrid structure of reinforced concrete and steel frame or vessels. While the reinforced concrete portions provide optical elements stability, the steel portions afford design flexibility. Finite element analyses of ambient random vibration are typically performed to evaluate the vibrational stability performances of support systems. Finally, this paper describes the ambient random vibration and beam pointing error measurements of SGIII. The measurements show the support systems of SGIII meet design requirement. These information can be used on similar systems.

  6. The Development of a Framework for Target Diagnostic Centralized Control System (TDCCS) in ICF Experiments

    Science.gov (United States)

    Zhang, Chi; Wang, Jian; Yu, Xiaoqi; Yang, Dong

    2008-02-01

    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.

  7. Teller Medal Lecture IFSA2001: Problems and solutions in the design and analysis of early laser driven high energy density and ICF target physics experiments (IFSA 2001)

    Science.gov (United States)

    Rosen, Mordecai D.

    2016-10-01

    The high energy density (HED) and inertial confinement fusion (ICF) physics community relies on increasingly sophisticated high power laser driven experiments to advance the field. We review early work in the design and analysis of such experiments, and discuss the problems encountered. By finding solutions to those problems we put the field on firmer ground, allowing the community to develop it to the exciting stage it is in today. Specific examples include: drive and preheat in complex hohlraum geometries with the complicating effects of sample motion; and issues in the successful design of laboratory soft x-ray lasers and in the invention of methods to reduce the required optical laser driver energy by several orders of magnitude.

  8. Improvements in ICF target fabrication through high precision assembly and nondestructive characterization

    Energy Technology Data Exchange (ETDEWEB)

    Obrey, Kimberly Ann Defriend [Los Alamos National Laboratory; Schmidt, Derek W [Los Alamos National Laboratory; Patterson, Brian M [Los Alamos National Laboratory; Day, Robert D [Los Alamos National Laboratory; Valdez, Adelaida C [Los Alamos National Laboratory; Capelli, Deanna [Los Alamos National Laboratory; Perea, Ron [Los Alamos National Laboratory; Randolph, Blaine [Los Alamos National Laboratory; Hatch, Doug [Los Alamos National Laboratory; Garcia, Felix [Los Alamos National Laboratory; Honnell, Diana [Los Alamos National Laboratory

    2009-01-01

    Current ICF and HED targets are fielded on Omega, Z, and Trident, and future campaigns will be fielded on NIF. NIF will only field less than 2 shots per day. With such few experiments, target fabrication and target alignment accuracy, enhanced metrology and advanced component machining will be even more important. Future target designs are also becoming more complex and more stringent in terms of accuracy. Several steps have been taken to improve the fabrication and characterization of targets, such as instituting an automated assembly station with 3 mm tolerances, utilizing nondestructive characterization tools for rapid component metrology and target assembly, and advancing machining capabilities. Recapitalization of target fabrication infrastructure is continuous.

  9. Improved algorithm of ray tracing in ICF cryogenic targets

    Science.gov (United States)

    Zhang, Rui; Yang, Yongying; Ling, Tong; Jiang, Jiabin

    2016-10-01

    The high precision ray tracing inside inertial confinement fusion (ICF) cryogenic targets plays an important role in the reconstruction of the three-dimensional density distribution by algebraic reconstruction technique (ART) algorithm. The traditional Runge-Kutta methods, which is restricted by the precision of the grid division and the step size of ray tracing, cannot make an accurate calculation in the case of refractive index saltation. In this paper, we propose an improved algorithm of ray tracing based on the Runge-Kutta methods and Snell's law of refraction to achieve high tracing precision. On the boundary of refractive index, we apply Snell's law of refraction and contact point search algorithm to ensure accuracy of the simulation. Inside the cryogenic target, the combination of the Runge-Kutta methods and self-adaptive step algorithm are employed for computation. The original refractive index data, which is used to mesh the target, can be obtained by experimental measurement or priori refractive index distribution function. A finite differential method is performed to calculate the refractive index gradient of mesh nodes, and the distance weighted average interpolation methods is utilized to obtain refractive index and gradient of each point in space. In the simulation, we take ideal ICF target, Luneberg lens and Graded index rod as simulation model to calculate the spot diagram and wavefront map. Compared the simulation results to Zemax, it manifests that the improved algorithm of ray tracing based on the fourth-order Runge-Kutta methods and Snell's law of refraction exhibits high accuracy. The relative error of the spot diagram is 0.2%, and the peak-to-valley (PV) error and the root-mean-square (RMS) error of the wavefront map is less than λ/35 and λ/100, correspondingly.

  10. The role of experimental science in ICF -- examples from X-ray diagnostics and targets

    Science.gov (United States)

    Kilkenny, J. D.

    2016-10-01

    The USA Inertial Confinement Fusion (ICF) Program evolved from the Nuclear Test Program which had restricted shot opportunities for experimentalists to develop sophisticated experimental techniques. In contrast the ICF program in the US was able to increase the shot availability on its large facilities, and develop sophisticated targets and diagnostics to measure and understand the properties of the high energy density plasmas (HEDP) formed. Illustrative aspects of this evolution at Lawrence Livermore National Laboratory (LLNL), with examples of the development of diagnostics and target fabrication are described.

  11. Burning the DT-plasma with inert impurities and non-cryogenic ICF-target with solid fuel

    OpenAIRE

    Gus'kov S.Yu.; Il'in D.V.; Sherman V.E.

    2013-01-01

    The ignition criterion, ignition energy and gain of DT-plasma of ICF-target in the presence of impurities of light atoms such as beryllium, carbon and lithium at their arbitrary concentration are found. It is shown that the most promising type of non-cryogenic solid thermonuclear fuel is DT-hydride of beryllium (BeDT). It is suggested to apply the targets with such a fuel as: (1) Fast-ignited ICF-target at the ignition energy of 25–50 kJ and compression driver energy of 2–3 MJ; (2) ICF-target...

  12. Kinetic model for DT ignition and burn in ICF targets

    Energy Technology Data Exchange (ETDEWEB)

    Anisimov, S.I.; Oparin, A.M.; Meyer-ter-Vehn, J. [Max-Planck-Institut fuer Quantenoptik, D-85748 Garching (Germany)]|[L.D. Landau Institute for Theoretical Physics, 117940 Moscow (Russia)

    1996-05-01

    Ignition and burn of DT targets is studied taking into account kinetic effects. Kinetic equations describing the interaction of the high-energy reaction products with target plasma are solved using the particle-in-cell (PIC) code for collisional plasma. Volume and spark ignition configurations are simulated for initial temperatures and {l_angle}{rho}{ital R}{r_angle} values of practical interest and target masses between 0.1 and 10 mg. Optically thick configurations igniting at temperatures below 5 keV are considered. Burn of the targets with reduced tritium content is simulated. It was shown that, for 25{percent} tritium concentration, the energy output is reduced only by 15{percent}. {copyright} {ital 1996 American Institute of Physics.}

  13. Target debris collection studies for inertial confinement fusion (ICF) experiments

    Science.gov (United States)

    Grim, G. P.; Archuleta, T. N.; Bradley, P. A.; Fowler, M. M.; Hayes, A. C.; Jungman, G.; Obst, A. W.; Rundberg, R. S.; Vieira, D. J.; Wang, Y. Q.; Wilhelmy, J. B.

    2010-08-01

    At the recently completed National Ignition Facility (NIF) at Lawrence Livermore National Laboratory, the initial set of diagnostics to be deployed are focused on measuring neutrons and γ's generated by d(t,n)α reactions in the imploded capsule. Although valuable for understanding pre-ignition experiments, this abbreviated diagnostic suite provides an incomplete picture of the plasma conditions obtained. Prompt radiochemical techniques, based on induced neutron and charged particle reactions within the imploded target, provide a novel and interesting new perspective. To enable these techniques requires the collection and assay of activated target material. In Nov. 2008, experiments were performed using the Omega Laser at the University of Rochester to study the efficiency of collecting debris from directly driven targets. Results from these experiments indicate that target debris was successfully collected, and the debris thermalization and transport scheme enhanced the debris collection up to 347% over direct collection.

  14. Target debris collection studies for inertial confinement fusion (ICF) experiments

    Energy Technology Data Exchange (ETDEWEB)

    Grim, G P; Archuleta, T N; Bradley, P A; Fowler, M M; Hayes, A C; Jungman, G; Obst, A W; Rundberg, R S; Vieira, D J; Wang, Y Q; Wilhelmy, J B, E-mail: gpgrim@lanl.go [Los Alamos National Laboratory, PO Box 1663, Los Alamos, NM 87545 (United States)

    2010-08-01

    At the recently completed National Ignition Facility (NIF) at Lawrence Livermore National Laboratory, the initial set of diagnostics to be deployed are focused on measuring neutrons and {gamma}'s generated by d(t,n){alpha} reactions in the imploded capsule. Although valuable for understanding pre-ignition experiments, this abbreviated diagnostic suite provides an incomplete picture of the plasma conditions obtained. Prompt radiochemical techniques, based on induced neutron and charged particle reactions within the imploded target, provide a novel and interesting new perspective. To enable these techniques requires the collection and assay of activated target material. In Nov. 2008, experiments were performed using the Omega Laser at the University of Rochester to study the efficiency of collecting debris from directly driven targets. Results from these experiments indicate that target debris was successfully collected, and the debris thermalization and transport scheme enhanced the debris collection up to 347% over direct collection.

  15. X-ray Digital Radiography and Computed Tomography of ICF and HEDP Materials, Subassemblies and Targets

    Energy Technology Data Exchange (ETDEWEB)

    Brown, W D; Martz Jr., H E

    2006-05-31

    Inertial confinement fusion (ICF) and high energy density physics (HEDP) research are being conducted at large laser facilities, such as the University of Rochester's Laboratory for Laser Energetics OMEGA facility and the Lawrence Livermore National Laboratory's (LLNL) National Ignition Facility (NIF). At such facilities, millimeter-sized targets with micrometer structures are studied in a variety of hydrodynamic, radiation transport, equation-of-state, inertial confinement fusion and high-energy density experiments. The extreme temperatures and pressures achieved in these experiments make the results susceptible to imperfections in the fabricated targets. Targets include materials varying widely in composition ({approx}3 < Z < {approx}82), density ({approx}0.03 to {approx}20 g/cm{sup 3}), geometry (planar to spherical) and embedded structures (joints to subassemblies). Fabricating these targets with structures to the tolerances required is a challenging engineering problem the ICF and HEDP community are currently undertaking. Nondestructive characterization (NDC) provides a valuable tool in material selection, component inspection, and the final pre-shot assemblies inspection. X-rays are a key method used to NDC these targets. In this paper we discuss X-ray attenuation, X-ray phase effects, and the X-ray system used, its performance and application to characterize low-temperature Raleigh-Taylor and non-cryogenic double-shell targets.

  16. Preparation and properties of polymer foams for ICF targets

    Energy Technology Data Exchange (ETDEWEB)

    Letts, S.A.; Lucht, L.M.

    1986-09-01

    Low density small cell sized foams were developed to localize the liquid DT layer in a direct drive wetted foam laser fusion target. We have developed foams made from ultrahigh molecular weight polyethylene gels and polystyrene inverse emulsions. Materials in the density range of from 0.020 to 0.300 g/cc were prepared and characterized for cell size, mechanical properties, machinability, specific surface area, and wetting. Foams with a density of 0.05 g/cc were made with a cell size of less than 5 ..mu..m. A cell structure model was developed which relates the density and specific surface area to cell size and cell wall thickness. Wetting tests in organic solvents and in liquid hydrogen were used to characterize the capillary pressure, pore structure and uniformity of the foams. 13 refs., 9 figs., 2 tabs.

  17. Ray-based calculations of laser backscatter in ICF targets

    CERN Document Server

    Strozzi, D J; Hinkel, D E; Froula, D H; London, R A; Callahan, D A

    2008-01-01

    A steady-state model for Brillouin and Raman backscatter along a laser ray path is presented. The daughter plasma waves are treated in the strong damping limit, and have amplitudes given by the (linear) kinetic response to the ponderomotive drive. Pump depletion, inverse-bremsstrahlung damping, bremsstrahlung emission, Thomson scattering off density fluctuations, and whole-beam focusing are included. The numerical code Deplete, which implements this model, is described. The model is compared with traditional linear gain calculations, as well as ``plane-wave'' simulations with the paraxial propagation code pF3D. Comparisons with Brillouin-scattering experiments at the Omega Laser Facility show that laser speckles greatly enhance the reflectivity over the Deplete results. An approximate upper bound on this enhancement is given by doubling the Deplete coupling coefficient. Analysis with Deplete of an ignition design for the National Ignition Facility (NIF), with a peak radiation temperature of 285 eV, shows enco...

  18. Burning the DT-plasma with inert impurities and non-cryogenic ICF-target with solid fuel

    Directory of Open Access Journals (Sweden)

    Gus'kov S.Yu.

    2013-11-01

    Full Text Available The ignition criterion, ignition energy and gain of DT-plasma of ICF-target in the presence of impurities of light atoms such as beryllium, carbon and lithium at their arbitrary concentration are found. It is shown that the most promising type of non-cryogenic solid thermonuclear fuel is DT-hydride of beryllium (BeDT. It is suggested to apply the targets with such a fuel as: (1 Fast-ignited ICF-target at the ignition energy of 25–50 kJ and compression driver energy of 2–3 MJ; (2 ICF-target spark-ignited by 15–20 MJ heavy ion driver; (3 Spark-ignited target by 5–7 MJ laser as a neutron source for hybrid fusion-fission.

  19. ND:GLASS LASER DESIGN FOR LASER ICF FISSION ENERGY (LIFE)

    Energy Technology Data Exchange (ETDEWEB)

    Caird, J A; Agrawal, V; Bayramian, A; Beach, R; Britten, J; Chen, D; Cross, R; Ebbers, C; Erlandson, A; Feit, M; Freitas, B; Ghosh, C; Haefner, C; Homoelle, D; Ladran, T; Latkowski, J; Molander, W; Murray, J; Rubenchik, S; Schaffers, K; Siders, C W; Stappaerts, E; Sutton, S; Telford, S; Trenholme, J; Barty, C J

    2008-10-28

    We have developed preliminary conceptual laser system designs for the Laser ICF (Inertial Confinement Fusion) Fission Energy (LIFE) application. Our approach leverages experience in high-energy Nd:glass laser technology developed for the National Ignition Facility (NIF), along with high-energy-class diode-pumped solid-state laser (HEC-DPSSL) technology developed for the DOE's High Average Power Laser (HAPL) Program and embodied in LLNL's Mercury laser system. We present laser system designs suitable for both indirect-drive, hot spot ignition and indirect-drive, fast ignition targets. Main amplifiers for both systems use laser-diode-pumped Nd:glass slabs oriented at Brewster's angle, as in NIF, but the slabs are much thinner to allow for cooling by high-velocity helium gas as in the Mercury laser system. We also describe a plan to mass-produce pump-diode lasers to bring diode costs down to the order of $0.01 per Watt of peak output power, as needed to make the LIFE application economically attractive.

  20. Wavelets, Curvelets and Multiresolution Analysis Techniques Applied to Implosion Symmetry Characterization of ICF Targets

    CERN Document Server

    Afeyan, Bedros; Starck, Jean Luc; Cuneo, Michael

    2012-01-01

    We introduce wavelets, curvelets and multiresolution analysis techniques to assess the symmetry of X ray driven imploding shells in ICF targets. After denoising X ray backlighting produced images, we determine the Shell Thickness Averaged Radius (STAR) of maximum density, r*(N, {\\theta}), where N is the percentage of the shell thickness over which to average. The non-uniformities of r*(N, {\\theta}) are quantified by a Legendre polynomial decomposition in angle, {\\theta}. Undecimated wavelet decompositions outperform decimated ones in denoising and both are surpassed by the curvelet transform. In each case, hard thresholding based on noise modeling is used. We have also applied combined wavelet and curvelet filter techniques with variational minimization as a way to select the significant coefficients. Gains are minimal over curvelets alone in the images we have analyzed.

  1. Large-scale 3D simulations of ICF and HEDP targets

    Science.gov (United States)

    Marinak, Michael M.

    2000-10-01

    The radiation hydrodynamics code HYDRA continues to be developed and applied to 3D simulations of a variety of targets for both inertial confinement fusion (ICF) and high energy density physics. Several packages have been added enabling this code to perform ICF target simulations with similar accuracy as two-dimensional codes of long-time historical use. These include a laser ray trace and deposition package, a heavy ion deposition package, implicit Monte Carlo photonics, and non-LTE opacities, derived from XSN or the linearized response matrix approach.(R. More, T. Kato, Phys. Rev. Lett. 81, 814 (1998), S. Libby, F. Graziani, R. More, T. Kato, Proceedings of the 13th International Conference on Laser Interactions and Related Plasma Phenomena, (AIP, New York, 1997).) LTE opacities can also be calculated for arbitrary mixtures online by combining tabular values generated by different opacity codes. Thermonuclear burn, charged particle transport, neutron energy deposition, electron-ion coupling and conduction, and multigroup radiation diffusion packages are also installed. HYDRA can employ ALE hydrodynamics; a number of grid motion algorithms are available. Multi-material flows are resolved using material interface reconstruction. Results from large-scale simulations run on up to 1680 processors, using a combination of massively parallel processing and symmetric multiprocessing, will be described. A large solid angle simulation of Rayleigh-Taylor instability growth in a NIF ignition capsule has resolved simultaneously the full spectrum of the most dangerous modes that grow from surface roughness. Simulations of a NIF hohlraum illuminated with the initial 96 beam configuration have also been performed. The effect of the hohlraum’s 3D intrinsic drive asymmetry on the capsule implosion will be considered. We will also discuss results from a Nova experiment in which a copper sphere is crushed by a planar shock. Several interacting hydrodynamic instabilities, including

  2. Ignition target design for the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Haan, S.W.; Pollaine, S.M.; Lindl, J.D. [Los Alamos National Laboratory, NM (United States)] [and others

    1996-06-01

    The goal of inertial confinement fusion (ICF) is to produce significant thermonuclear burn from a target driven with a laser or ion beam. To achieve that goal, the national ICF Program has proposed a laser capable of producing ignition and intermediate gain. The facility is called the National Ignition Facility (NIF). This article describes ignition targets designed for the NIF and their modeling. Although the baseline NIF target design, described herein, is indirect drive, the facility will also be capable of doing direct-drive ignition targets - currently being developed at the University of Rochester.

  3. A dual-PIXE tomography setup for reconstruction of Germanium in ICF target

    Science.gov (United States)

    Guo, N.; Lu, H. Y.; Wang, Q.; Meng, J.; Gao, D. Z.; Zhang, Y. J.; Liang, X. X.; Zhang, W.; Li, J.; Ma, X. J.; Shen, H.

    2017-08-01

    Inertial Confinement Fusion (ICF) is one type of fusion energy research which could initiate nuclear fusion reactions through heating and compressing thermonuclear fuel. Compared to a pure plastic target, Germanium doping into the CH ablator layer by Glow Discharge Polymer (GDP) technique can increase the ablation velocity and the standoff distance between the ablation front and laser-deposition region. During target fabrication process, quantitative doping of Ge should be accurately controlled. Particle Induced X-ray Emission Tomography (PIXE-T) can make not only quantification of the concentration, but also reconstruction of the spatial distribution of doped element. The Si (Li) detector for PIXE tomography technique had a disadvantage of low counting rate. To make up this deficiency, another detector of Si (Li) with the same configuration positioned at the opposite side with the same detective angle 135° have been implemented. Simultaneously acquired elemental maps of Ge obtained using two detectors may be different because of the X-ray absorption along the X-ray exit route in the target. In this paper, the X-ray detection efficiency is drastically improved by this dual-PIXE tomography system.

  4. Theranostic Approach for Metastatic Pigmented Melanoma Using ICF15002, a Multimodal Radiotracer for Both PET Imaging and Targeted Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Latifa Rbah-Vidal

    2017-01-01

    Full Text Available PURPOSE: This work reports, in melanoma models, the theranostic potential of ICF15002 as a single fluorinated and iodinated melanin-targeting compound. METHODS: Studies were conducted in the murine syngeneic B16BL6 model and in the A375 and SK-MEL-3 human xenografts. ICF15002 was radiolabeled with fluorine-18 for positron emission tomography (PET imaging and biodistribution, with iodine-125 for metabolism study, and iodine-131 for targeted radionuclide therapy (TRT. TRT efficacy was assessed by tumor volume measurement, with mechanistics and dosimetry parameters being determined in the B16BL6 model. Intracellular localization of ICF15002 was characterized by secondary ion mass spectrometry (SIMS. RESULTS: PET imaging with [18F]ICF15002 evidenced tumoral uptake of 14.33 ± 2.11%ID/g and 4.87 ± 0.93%ID/g in pigmented B16BL6 and SK-MEL-3 models, respectively, at 1 hour post inoculation. No accumulation was observed in the unpigmented A375 melanoma. SIMS demonstrated colocalization of ICF15002 signal with melanin polymers in melanosomes of the B16BL6 tumors. TRT with two doses of 20 MBq [131I]ICF15002 delivered an absorbed dose of 102.3 Gy to B16BL6 tumors, leading to a significant tumor growth inhibition [doubling time (DT of 2.9 ± 0.5 days in treated vs 1.8 ± 0.3 in controls] and a prolonged median survival (27 days vs 21 in controls. P53S15 phosphorylation and P21 induction were associated with a G2/M blockage, suggesting mitotic catastrophe. In the human SK-MEL-3 model, three doses of 25 MBq led also to a DT increase (26.5 ± 7.8 days vs 11.0 ± 3.8 in controls and improved median survival (111 days vs 74 in controls. CONCLUSION: Results demonstrate that ICF15002 fulfills suitable properties for bimodal imaging/TRT management of patients with pigmented melanoma.

  5. Target Diagnostic Technology Research and Development for the LLNL ICF and HED Programs

    Energy Technology Data Exchange (ETDEWEB)

    Bell, P; Bennett, C; Holder, J; Kimbrough, J; Landen, O; Lerche, D; Lowry, M; McDonald, J; Perry, T; Turner, B; Weber, F

    2003-08-22

    The National Ignition Facility (NIF) is under construction at LLNL for the Department of Energy Stockpile Stewardship Program. It will be used for experiments for Inertial Confinement Fusion (ICF) Ignition, High Energy Density (HED) science, and basic science. Many issues confront experimentalists who wish to design, fabricate, and install diagnostics on the NIF. To foster this process the ICF and HED programs at LLNL have formed a diagnostic research and development group to look at issues outside the charter of facility diagnostics (core diagnostics). We will present data from instrumentation and associated technology that is being developed by this group. A major portion of our instrumentation work is on improvements for readout systems. We have several efforts related to CCD device development. Work has been done in collaboration with the University of Arizona to backthin a large format CCD device (36mm{sup 2}). This work has shown good results. The device has very high quantum efficiency, low noise readout and high charge transfer efficiency. The device is being fielded in direct optical, direct x-ray and 13-15 RV electron readout applications. In addition to readout device development we have completed work on a CCD readout system. With a commercial vendor we have developed a large format, compact, Ethernet addressable CCD camera system. This system fits in shoebox size volume, is thermal electrically cooled, supports a variety of CCD devices and can be run from remote locations via TCP/IP protocol. We are also doing work to improve streak camera systems. We have coupled our large format CCD system to an MK2 Kentech streak tube. Improvements have been made to the resolution and dynamic range of the system. Similar improvements have been made to the LLNL optical streak camera systems. We will present data from the optical and x-ray streak camera work. In addition we will present data from single shot high-speed, high dynamic range data link work. In

  6. Design and analysis of a 2-DOF RFM for the mirror sub-assembly (MSA) of ICF facility

    Science.gov (United States)

    Wang, Baoxu; Zhu, Mingzhi; Chen, Xiaojuan; Chen, Gang; Fu, Xuenong

    2016-10-01

    This paper presents the design of a 2 degree-of-freedom (DOF) rotation flexure mechanism (RFM) that could be utilized as the pivot for the mirror sub-assembly (MSA) of transport mirrors in the target area of inertial confinement fusion (ICF) laser systems. The hybrid spring system is established as the analytical model of the 2-DOF RFM. With the suitable matrix in coordinate transformation, the overall compliance matrix is developed to reveal the compliance property of the mechanism and the compliance equations are obtained. The analytical results obtained from the compliance equations are validated by means of finite element analysis (FEA) with the accuracy of 1%. The compliance property and design tradeoffs of the 2-DOF RFM are discussed with the compliance equations. The 2-DOF RFM for the MSA of transport mirrors of ShenGuangIII (SGIII) facility is designed and optimized. Then, the MSA is modeled and analyzed by FEA. The analysis result shows that the 2-DOF RFM is feasible for the MSA design.

  7. Introducing the ICF: the development of an online resource to support learning, teaching and curriculum design.

    Science.gov (United States)

    Jones, Lester E

    2011-03-01

    The International Classification of Functioning, Disability and Health (ICF) was adopted as one of the key models to support early health professional learning across a suite of new preregistration health science courses. It was decided that an online resource should be developed to enable students, course designers and teaching staff, across all disciplines, to have access to the same definitions, government policies and other supporting information on disability. As part of the comprehensive curriculum review, enquiry-based learning was adopted as the educational approach. Enquiry-based learning promotes deeper learning by encouraging students to engage in authentic challenges. As such, it was important that the online resource was not merely a site for accessing content, but enabled students to make decisions about where else to explore for credible information about the ICF. The selection of a host location that all students and staff could access meant that the resource could not be located in the existing online learning management system. Construction using software being trialled by the library at La Trobe University allowed for the required access, as well as alignment with an enquiry-based learning approach. Consultation for the content of the online resource included formal and informal working groups on curriculum review. The published version included resources from the World Health Organization, examples of research completed within different disciplines, a test of knowledge and a preformatted search page. The format of the online resource allows for updating of information, and feedback on the utilisation of the software has been used to enhance the student experience. The key issues for the development of this online resource were accessibility for students and staff, alignment with the adopted educational approach, consultation with all disciplines, and ease of modification of information and format once published. Copyright © 2010 Chartered

  8. Analyses in support of the Laboratory Microfusion Facility and ICF commercial reactor designs

    Energy Technology Data Exchange (ETDEWEB)

    Meier, W.R.; Monsler, M.J.

    1988-12-28

    Our work on this contract was divided into two major categories; two thirds of the total effort was in support of the Laboratory Microfusion Facility (LMF), and one third of the effort was in support of Inertial Confinement Fusion (ICF) commercial reactors. This final report includes copies of the formal reports, memoranda, and viewgraph presentations that were completed under this contract.

  9. ICF ETF and its engineering development requirements

    Energy Technology Data Exchange (ETDEWEB)

    Blink, J.A.; Allen, W.O.; Billman, K.

    1980-10-01

    Inertial confinement fusion driver development and ICF target physics are being intensively explored both theoretically and experimentally. However, engineering considerations of harnessing the fusion energy pulses that are an ultimate product and goal of the ICF physics program are only being addressed on a small scale. Experience with development of other new technologies indicates that engineering development time will be substantial for ICF energy converters. The authors met at Livermore in July 1980 to form an ICF Reactor Technology Working Group to address this issue. This paper outlines the current state of planning for an ICF Engineering Test Facility (ETF) and the engineering development that must precede it.

  10. Beryllium ignition target design for indirect drive NIF experiments

    Science.gov (United States)

    Simakov, A. N.; Wilson, D. C.; Yi, S. A.; Kline, J. L.; Salmonson, J. D.; Clark, D. S.; Milovich, J. L.; Marinak, M. M.

    2016-03-01

    Beryllium (Be) ablator offers multiple advantages over carbon based ablators for indirectly driven NIF ICF ignition targets. These are higher mass ablation rate, ablation pressure and ablation velocity, lower capsule albedo, and higher thermal conductivity at cryogenic temperatures. Such advantages can be used to improve the target robustness and performance. While previous NIF Be target designs exist, they were obtained a long time ago and do not incorporate the latest improved physical understanding and models based upon NIF experiments. Herein, we propose a new NIF Be ignition target design at 1.45 MJ, 430 TW that takes all this knowledge into account.

  11. Suitability of Different Polyimide Capsule Materials for Use as ICF Targets

    Energy Technology Data Exchange (ETDEWEB)

    Knight, A.K.; Tsai, F.-Y.; Bonino, M.J.; Harding, D.R.

    2004-03-15

    OAK-B135 Previous research efforts to fabricate direct-drive polyimide shells have focused on identifying processes that maximize the mechanical and permeation properties of the polyimide material. A strong correlation exists between these properties and the processing conditions, which is ascribed to the crystallinity and segmental mobility of the polyimide chains. This correlation, together with the range of properties that have been demonstrated, will be reported. For example, the permeability of biaxially strained polyimide is three orders of magnitude higher than that of the normal Kapton formulation, decreasing the necessary fill time from 320 h to 0.66 h for an OMEGA target. Current research efforts focus on improving the smoothness of polyimide shells. The approach is to model the effect of different configurations of the equipment and processing parameters on the impinging mass flux of reactants onto the shell substrates. This is done using both computational fluid dynamics (FLUENT) and Monte Carlo codes to cover the relevant pressure regimes. Both molecular gas dynamics and surface chemistry are included in the models. These models are then cross-referenced to the measured smoothness of the shells.

  12. Ray-Based Calculations with DEPLETE of Laser Backscatter in ICF Targets

    Energy Technology Data Exchange (ETDEWEB)

    Strozzi, D J; Williams, E; Hinkel, D; Froula, D; London, R; Callahan, D

    2008-05-19

    A steady-state model for Brillouin and Raman backscatter along a laser ray path is presented. The daughter plasma waves are treated in the strong damping limit, and have amplitudes given by the (linear) kinetic response to the ponderomotive drive. Pump depletion, inverse-bremsstrahlung damping, bremsstrahlung emission, Thomson scattering off density fluctuations, and whole-beam focusing are included. The numerical code Deplete, which implements this model, is described. The model is compared with traditional linear gain calculations, as well as 'plane-wave' simulations with the paraxial propagation code pF3D. Comparisons with Brillouin-scattering experiments at the Omega Laser Facility show that laser speckles greatly enhance the reflectivity over the Deplete results. An approximate upper bound on this enhancement is given by doubling the Deplete coupling coefficient. Analysis with Deplete of an ignition design for the National Ignition Facility (NIF), with a peak radiation temperature of 285 eV, shows encouragingly low reflectivity. Doubling the coupling to bracket speckle effects suggests a less optimistic picture. Re-absorption of Raman light is seen to be significant in this design.

  13. Implementing Target Value Design.

    Science.gov (United States)

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

    2017-04-01

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

  14. Segmented Target Design

    Science.gov (United States)

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

    2013-10-01

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

  15. Advances and Challenges In Uncertainty Quantification with Application to Climate Prediction, ICF design and Science Stockpile Stewardship

    Science.gov (United States)

    Klein, R.; Woodward, C. S.; Johannesson, G.; Domyancic, D.; Covey, C. C.; Lucas, D. D.

    2012-12-01

    Uncertainty Quantification (UQ) is a critical field within 21st century simulation science that resides at the very center of the web of emerging predictive capabilities. The science of UQ holds the promise of giving much greater meaning to the results of complex large-scale simulations, allowing for quantifying and bounding uncertainties. This powerful capability will yield new insights into scientific predictions (e.g. Climate) of great impact on both national and international arenas, allow informed decisions on the design of critical experiments (e.g. ICF capsule design, MFE, NE) in many scientific fields, and assign confidence bounds to scientifically predictable outcomes (e.g. nuclear weapons design). In this talk I will discuss a major new strategic initiative (SI) we have developed at Lawrence Livermore National Laboratory to advance the science of Uncertainty Quantification at LLNL focusing in particular on (a) the research and development of new algorithms and methodologies of UQ as applied to multi-physics multi-scale codes, (b) incorporation of these advancements into a global UQ Pipeline (i.e. a computational superstructure) that will simplify user access to sophisticated tools for UQ studies as well as act as a self-guided, self-adapting UQ engine for UQ studies on extreme computing platforms and (c) use laboratory applications as a test bed for new algorithms and methodologies. The initial SI focus has been on applications for the quantification of uncertainty associated with Climate prediction, but the validated UQ methodologies we have developed are now being fed back into Science Based Stockpile Stewardship (SSS) and ICF UQ efforts. To make advancements in several of these UQ grand challenges, I will focus in talk on the following three research areas in our Strategic Initiative: Error Estimation in multi-physics and multi-scale codes ; Tackling the "Curse of High Dimensionality"; and development of an advanced UQ Computational Pipeline to enable

  16. Interaction of a self-focused laser beam with a DT fusion target in a plasma-loaded cone-guided ICF scheme

    Science.gov (United States)

    Saedjalil, N.; Mehrangiz, M.; Jafari, S.; Ghasemizad, A.

    2016-06-01

    In this paper, the interaction of a self-focused laser beam with a DT fusion target in a plasma-loaded cone-guided ICF scheme has been presented. We propose here to merge a plasma-loaded cone with the precompressed DT target in order to strongly focus the incident laser beam on the core to improve the fusion gain. The WKB approximation is used to derive a differential equation that governs the evolution of beamwidth of the incident laser beam with the distance of propagation in the plasma medium. The effects of initial plasma and laser parameters, such as initial plasma electron temperature, initial radius of the laser beam, initial laser beam intensity and plasma density, on self-focusing and defocusing of the Gaussian laser beam have been studied. Numerical results indicate that with increasing the plasma frequency (or plasma density) in the cone, the laser beam will be self-focused noticeably, while for a thinner laser beam (with small radius), it will diverge as propagate in the cone. By evaluating the energy deposition of the relativistic electron ignitors in the fuel, the importance of electron transportation in the cone-attached shell was demonstrated. Moreover, by lessening the least energy needed for ignition, the electrons coupling with the pellet enhances. Therefore, it increases the fusion efficiency. In this scheme, with employing a plasma-loaded cone, the fusion process improves without needing an ultrahigh-intensity laser beam in a conventional ICF.

  17. Study of high gain spherical shell ICF targets containing uniform layers of liquid deuterium tritium fuel. A numericial model for analyzing thermal layering of liquid mixtures of hydrogen isotopes inside a spherical inertial confinement fusion target: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, E.M.; Kim, Kyekyoon [Lawrence Livermore National Lab., CA (United States)

    1994-05-01

    A numerical model has been developed to describe the thermally induced behavior of a liquid layer of hydrogen isotopes inside a spherical Inertial Confinement Fusion (ICF) target and to calculate the far-field temperature gradient which will sustain a uniform liquid layer. This method is much faster than the trial-and-error method previously employed. The governing equations are the equations of continuity, momentum, energy, mass diffusion-convection, and conservation of the individual isotopic species. Ordinary and thermal diffusion equations for the diffusion of fluxes of the species are included. These coupled equations are solved by a finite-difference method using upwind schemes, variable mesh, and rigorous boundary conditions. The solution methodology unique to the present problem is discussed in detail. in particular, the significance of the surface tension gradient driven flows (also called Marangoni flows) in forming uniform liquid layers inside ICF targets is demonstrated. Using the theoretical model, the values of the externally applied thermal gradients that give rise to uniform liquid layers of hydrogen inside a cryogenic spherical-shell ICF target are calculated, and the results compared with the existing experimental data.

  18. Production Target Design Report

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-28

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

  19. Contributions to the Genesis and Progress of ICF

    Energy Technology Data Exchange (ETDEWEB)

    Nuckolls, J H

    2006-02-15

    Inertial confinement fusion (ICF) has progressed from the detonation of large-scale fusion explosions initiated by atomic bombs in the early 1950s to final preparations for initiating small-scale fusion explosions with giant lasers. The next major step after ignition will be development of high performance targets that can be initiated with much smaller, lower cost lasers. In the 21st century and beyond, ICF's grand challenge is to develop practical power plants that generate low cost, clean, inexhaustible fusion energy. In this chapter, I first describe the origin in 1960-61 of ICF target concepts, early speculations on laser driven 'Thermonuclear Engines' for power production and rocket propulsion, and encouraging large-scale nuclear explosive experiments conducted in 1962. Next, I recall the 40-year, multi-billion dollar ignition campaign - to develop a matched combination of sufficiently high-performance implosion lasers and sufficiently stable targets capable of igniting small fusion explosions. I conclude with brief comments on the NIF ignition campaign and very high-performance targets, and speculations on ICF's potential in a centuries-long Darwinian competition of future energy systems. My perspectives in this chapter are those of a nuclear explosive designer, optimistic proponent of ICF energy, and Livermore Laboratory leader. The perspectives of Livermore's post 1970 laser experts and builders, and laser fusion experimentalists are provided in a chapter written by John Holzrichter, a leading scientist and leader in Livermore's second generation laser fusion program. In a third chapter, Ray Kidder, a theoretical physicist and early laser fusion pioneer, provides his perspectives including the history of the first generation laser fusion program he led from 1962-1972.

  20. Target Area design basis and system performance for the National Ignition Facility. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Tobin, M.; Karpenko, V.; Hagans, K.; Anderson, A.; Latkowski, J.; Warren, R. [Lawrence Livermore National Lab., CA (United States); Wavrik, R.; Garcia, R.; Boyes, J. [Sandia National Labs., Albuquerque, NM (United States)

    1994-10-01

    The NIF Target Area is designed to confine the ICF target experiments leading up to and including fusion ignition and gain. The Target Area will provide appropriate in-chamber conditions before, during, and after each shot. The repeated introduction of large amounts of laser energy into the chamber and emission of fusion energy from targets represents a new challenge in ICF facility design. Prior to a shot, the facility provides proper illumination geometry, target chamber vacuum, and a stable platform for the target and its diagnostics. During a shot, the impact of the energy introduced into the chamber is minimized, and workers and the public are protected from excessive prompt radiation doses. After the shot, the residual radioactivation is managed to allow required accessibility. Tritium and other radioactive wastes are confined and disposed of. Diagnostic data is also retrieved, and the facility is readied for the next shot. The Target Area will accommodate yields up to 20 MJ, and its design lifetime is 30 years. The Target Area provides the personnel access needed to support the use precision diagnostics. The annual shot mix for design purposes is shown. Designing to this experimental envelope ensures the ability and flexibility to move through the experimental campaign to ignition efficiently.

  1. Core science and technology development plan for indirect-drive ICF ignition. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Powell, H.T.; Kilkenny, J.D. [eds.

    1995-12-01

    To define the development work needed to support inertial confinement fusion (ICF) program goals, the authors have assembled this Core Science and Technology (CS and T) Plan that encompasses nearly all science research and technology development in the ICF program. The objective of the CS and T Plan described here is to identify the development work needed to ensure the success of advanced ICF facilities, in particular the National Ignition Facility (NIF). This plan is intended as a framework to facilitate planning and coordination of future ICF programmatic activities. The CS and T Plan covers all elements of the ICF program including laser technology, optic manufacturing, target chamber, target diagnostics, target design and theory, target components and fabrication, and target physics experiments. The CS and T Plan has been divided into these seven different technology development areas, and they are used as level-1 categories in a work breakdown structure (WBS) to facilitate the organization of all activities in this plan. The scope of the CS and T Plan includes all research and development required to support the NIF leading up to the activation and initial operation as an indirect-drive facility. In each of the CS and T main development areas, the authors describe the technology and issues that need to be addressed to achieve NIF performance goals. To resolve all issues and achieve objectives, an extensive assortment of tasks must be performed in a coordinated and timely manner. The authors describe these activities and present planning schedules that detail the flow of work to be performed over a 10-year period corresponding to estimated time needed to demonstrate fusion ignition with the NIF. Besides the benefits to the ICF program, the authors also discuss how the commercial sector and the nuclear weapons science may profit from the proposed research and development program.

  2. Identification of candidate categories of the International Classification of Functioning Disability and Health (ICF for a Generic ICF Core Set based on regression modelling

    Directory of Open Access Journals (Sweden)

    Üstün Bedirhan T

    2006-07-01

    Full Text Available Abstract Background The International Classification of Functioning, Disability and Health (ICF is the framework developed by WHO to describe functioning and disability at both the individual and population levels. While condition-specific ICF Core Sets are useful, a Generic ICF Core Set is needed to describe and compare problems in functioning across health conditions. Methods The aims of the multi-centre, cross-sectional study presented here were: a to propose a method to select ICF categories when a large amount of ICF-based data have to be handled, and b to identify candidate ICF categories for a Generic ICF Core Set by examining their explanatory power in relation to item one of the SF-36. The data were collected from 1039 patients using the ICF checklist, the SF-36 and a Comorbidity Questionnaire. ICF categories to be entered in an initial regression model were selected following systematic steps in accordance with the ICF structure. Based on an initial regression model, additional models were designed by systematically substituting the ICF categories included in it with ICF categories with which they were highly correlated. Results Fourteen different regression models were performed. The variance the performed models account for ranged from 22.27% to 24.0%. The ICF category that explained the highest amount of variance in all the models was sensation of pain. In total, thirteen candidate ICF categories for a Generic ICF Core Set were proposed. Conclusion The selection strategy based on the ICF structure and the examination of the best possible alternative models does not provide a final answer about which ICF categories must be considered, but leads to a selection of suitable candidates which needs further consideration and comparison with the results of other selection strategies in developing a Generic ICF Core Set.

  3. Effect of thermal treatment temperature on plated ICF glass targets%热处理温度对化学镀磁性ICF玻璃靶丸特性的影响

    Institute of Scientific and Technical Information of China (English)

    杨文彬; 周元林; 卢忠远; 戴亚堂; 卢苇

    2009-01-01

    在300,700和1 000 ℃温度下,对化学镀Ni-P合金涂层后的磁性ICF玻璃靶丸进行热处理,通过X射线衍射仪(XRD)、扫描电子显微镜(SEM)和振动样品磁强计(VSM)对热处理后化学镀ICF玻璃靶丸的结构、形貌和磁性能进行了表征.结果表明:化学镀ICF玻璃靶丸经过热处理后,Ni-P涂层晶化为晶态合金层,涂层的组成颗粒直径和磁性能随着热处理温度的升高而不断增加,可望用于磁悬浮实验研究.%Plated ICF glass targets were treated under 300 ℃,700 ℃ and 1 000 ℃ for one hour,respectively.Structure,morphology and magnetic property of the plated ICF glass targets were characterized by X-ray diffraction(XRD),scanning electron microscopy(SEM) and vibrating sample magnetometry(VSM).The results show that the Ni-P plating on the surface of the ICF glass targets will be crystallized after the targets are thermally treated.The diameter of the crystalline grains and the corresponding magnetic parameters of the Ni-P plating increases with increasing the thermal treatment temperature.The treated ICF glass targets could be used in research of magnetic suspension experiment.

  4. The Edward Teller Medal Lecture: the Evolution Toward Indirect Drive and Two Decades of Progress Toward Icf Ignition and Burn (lirpp Vol. 11)

    Science.gov (United States)

    Lindl, John D.

    2016-10-01

    In 1972, I joined the Livermore ICF Theory and Target Design group led by John Nuckolls, shortly after publication of John's seminal Nature article on ICF. My primary role, working with others in the target design program including Mordy Rosen, Steve Haan, and Larry Suter, has been as a target designer and theorist who utilized the LASNEX code to perform numerical experiments, which along with analysis of laboratory and underground thermonuclear experiments allowed me to develop a series of models and physical insights which have been used to set the direction and priorities of the Livermore program...

  5. ICF Annual Report 1997

    Energy Technology Data Exchange (ETDEWEB)

    Correll, D

    1998-06-01

    The continuing objective of Lawrence Livermore National Laboratory's (LLNL's) Inertial Confinement Fusion (ICF) Program is the demonstration of thermonuclear fusion ignition and energy gain in the laboratory and to support the nuclear weapons program in its use of ICF facilities. The underlying theme of all ICF activities as a science research and development program is the Department of Energy's (DOE's) Defense Programs (DP) science-based Stockpile Stewardship Program (SSP). The mission of the US Inertial Fusion Program is twofold: (1) to address high-energy-density physics issues for the SSP and (2) to develop a laboratory microfusion capability for defense and energy applications. In pursuit of this mission, the ICF Program has developed a state-of-the-art capability to investigate high-energy-density physics in the laboratory. The near-term goals pursued by the ICF Program in support of its mission are demonstrating fusion ignition in the laboratory and expanding the Program's capabilities in high-energy-density science. The National Ignition Facility (NIF) project is a cornerstone of this effort.

  6. ICF Core Sets for stroke

    National Research Council Canada - National Science Library

    Szilvia Geyh; Alarcos Cieza; Jan Schouten; Hugh Dickson; Peter Frommelt; Zaliha Omar; Nenad Kostanjsek; Haim Ring; Gerold Stucki

    2004-01-01

    Objective: To report on the results of the consensus process integrating evidence from preliminary studies to develop the first version of the Comprehensive ICF Core Set and the Brief ICF Core Set for stroke. Methods...

  7. Fundamentals of ICF Hohlraums

    Energy Technology Data Exchange (ETDEWEB)

    Rosen, M D

    2005-09-30

    On the Nova Laser at LLNL, we demonstrated many of the key elements required for assuring that the next laser, the National Ignition Facility (NIF) will drive an Inertial Confinement Fusion (ICF) target to ignition. The indirect drive (sometimes referred to as ''radiation drive'') approach converts laser light to x-rays inside a gold cylinder, which then acts as an x-ray ''oven'' (called a hohlraum) to drive the fusion capsule in its center. On Nova we've demonstrated good understanding of the temperatures reached in hohlraums and of the ways to control the uniformity with which the x-rays drive the spherical fusion capsules. In these lectures we will be reviewing the physics of these laser heated hohlraums, recent attempts at optimizing their performance, and then return to the ICF problem in particular to discuss scaling of ICF gain with scale size, and to compare indirect vs. direct drive gains. In ICF, spherical capsules containing Deuterium and Tritium (DT)--the heavy isotopes of hydrogen--are imploded, creating conditions of high temperature and density similar to those in the cores of stars required for initiating the fusion reaction. When DT fuses an alpha particle (the nucleus of a helium atom) and a neutron are created releasing large amount amounts of energy. If the surrounding fuel is sufficiently dense, the alpha particles are stopped and can heat it, allowing a self-sustaining fusion burn to propagate radially outward and a high gain fusion micro-explosion ensues. To create those conditions the outer surface of the capsule is heated (either directly by a laser or indirectly by laser produced x-rays) to cause rapid ablation and outward expansion of the capsule material. A rocket-like reaction to that outward flowing heated material leads to an inward implosion of the remaining part of the capsule shell. The pressure generated on the outside of the capsule can reach nearly 100 megabar (100 million times

  8. Relationship between interRAI HC and the ICF: opportunity for operationalizing the ICF

    Directory of Open Access Journals (Sweden)

    Ljunggren Gunnar

    2009-03-01

    Full Text Available Abstract Background The International Classification of Functioning, Disability and Health (ICF is embraced as a framework to conceptualize human functioning and disability. Health professionals choose measures to represent the domains of the framework. The ICF coding classification is an administrative system but multiple studies have linked diverse clinical assessments to ICF codes. InterRAI-HC (home care is an assessment designed to assist planning of care for patients receiving home care. Examining the relationship between the ICF and the interRAI HC is of particular interest because the interRAI assessments are widely used in clinical practice and research, are computerized, and uploaded to databases that serve multiple purposes including public reporting of quality in Canada and internationally. The objective of this study was to examine the relationship between the interRAI HC (home care assessment and the ICF. Specifically, the goal was to determine the proportion of interRAI HC items that can be linked to each of the major domains of the ICF (Body Function, Body Structure, Activities and Participation, and the Environmental Factors, the chapters and the specific ICF codes. Methods Three coders who were familiar with both the home care assessment and the ICF independently assigned ICF codes to inter-RAI HC items. Subsequently, a series of teleconference meetings were held to reach consensus on the primary code and much later consensus was used to finalize codes for additional items added to the interRAI HC. Results Following exclusion of administrative and diagnostic sections, 175 interRAI items were examined for potential assignment of codes. Of these 52 were assigned codes related to body function, 43 to activities and participation, 34 to environment, 1 to body structure, 17 to not coded, and 26 to not defined. Considering all 3-digit ICF codes, interRAI items addressed 43.2% of Body Function and 50.6% of Activities and Participation

  9. Classification of functioning and impairment: the development of ICF core sets for autism spectrum disorder.

    Science.gov (United States)

    Bölte, Sven; de Schipper, Elles; Robison, John E; Wong, Virginia C N; Selb, Melissa; Singhal, Nidhi; de Vries, Petrus J; Zwaigenbaum, Lonnie

    2014-02-01

    Given the variability seen in Autism Spectrum Disorder (ASD), accurate quantification of functioning is vital to studying outcome and quality of life in affected individuals. The International Classification of Functioning, Disability and Health (ICF) provides a comprehensive, universally accepted framework for the description of health-related functioning. ICF Core Sets are shortlists of ICF categories that are selected to capture those aspects of functioning that are most relevant when describing a person with a specific condition. In this paper, the authors preview the process for developing ICF Core Sets for ASD, a collaboration with the World Health Organization and the ICF Research Branch. The ICF Children and Youth version (ICF-CY) was derived from the ICF and designed to capture the specific situation of the developing child. As ASD affects individuals throughout the life span, and the ICF-CY includes all ICF categories, the ICF-CY will be used in this project ("ICF(-CY)" from now on). The ICF(-CY) categories to be included in the ICF Core Sets for ASD will be determined at an ICF Core Set Consensus Conference, where evidence from four preparatory studies (a systematic review, an expert survey, a patient and caregiver qualitative study, and a clinical cross-sectional study) will be integrated. Comprehensive and Brief ICF Core Sets for ASD will be developed with the goal of providing useful standards for research and clinical practice and generating a common language for functioning and impairment in ASD in different areas of life and across the life span.

  10. ICF微靶装配体图像清晰度评价方法%Image Definition Evaluation Method of ICF Micro-target Assembly

    Institute of Scientific and Technical Information of China (English)

    聂凯; 刘文耀; 王晋疆

    2014-01-01

    During the process of evaluating ICF micro-target image with the current image definition evaluation function, owing to the changes in image contrast of different components of micro-target, the evaluation function may lose its ideal curve characteristics easily. This may not only result in the decrease of focus accuracy but also, in some cases, the failure of the entire focusing process. Based on the analysis of the causes for the blurring defocused image, we discovered that the primary reason for defocused image was structural distortion. With the characteristic of Zernike moment of descri-bing the image structure in mind, we propose a new function for evaluating the image definition of micro-target. The new evaluation function is consisted of Zernike moments weighting of different steps, and it is realized through the evaluation of image contrast for micro-targets of different defini-tions by regulating the weight coefficient. We confirm that the new evaluation function maintains the ideal curve characteristics during the process of evaluating the micro-target images compared to the current evaluation function. In the condition of low contrast, however, the new approach holds a distinct advantage in terms of sensitivity and noise immunity.%现有图像清晰度评价函数在对ICF微靶装配体图像的评价过程中,由于不同零件图像对比度的变化,评价函数极易失去其理想曲线特性,导致聚焦精度降低甚至调焦过程失败。针对这一问题,在分析离焦图像模糊原因的基础上,得出离焦图像究其本质为图像结构变化失真。利用Zernike矩具有描述图像结构特征这一特性,提出一种新的针对微靶装配体图像的清晰度评价函数。评价函数由图像不同阶Zernike矩的线性组合构成,通过调节权重系数来实现微靶装配体不同零件图像的清晰度评价。实验结果表明:相较于现有的评价函数,新的评价函数在对微靶

  11. Using the ICF in Ireland.

    LENUS (Irish Health Repository)

    Good, Anne

    2011-05-01

    This paper reflects on the use of ICF in Ireland, taking as a case study the experience of the first National Disability Survey (NDS). There were four clear effects in Ireland of using ICF as a framework for the NDS: a) that a broader range of people with disabilities was encompassed; b) that the environmental factors included from the ICF were comprehensive and policy relevant; c) that both barriers and facilitators were incorporated into the model; and d) that a focus on research ethics was encouraged. Some general conclusions regarding the benefits and limitations of ICF based on this experience are also drawn.

  12. Impact of First-Principles Property Calculations of Warm-Dense Deuterium/Tritium on Inertial Confinement Fusion Target Designs

    Science.gov (United States)

    Hu, S. X.

    2014-10-01

    Accurate knowledge of the properties of warm dense deuterium/tritium (DT) is essential to reliably design inertial confinement fusion (ICF) implosions. In the warm-dense-matter regime, routinely accessed by low-adiabat ICF implosions, strong-coupling and degeneracy effects play an important role in determining plasma properties. Using first-principles methods of both path-integral Monte Carlo and quantum molecular-dynamics (QMD), we have performed systematic investigation of the equation of state, thermal conductivity, and opacity for DT over a wide range of densities and temperatures. These first-principles properties have been incorporated into our hydrocodes. When compared to hydro simulations using standard plasma models, significant differences in 1-D target performance have been identified for simulations of DT implosions. For low-adiabat (α Administration under Award Number DE-NA0001944.

  13. Shock ignition: a brief overview and progress in the design of robust targets

    Science.gov (United States)

    Atzeni, S.; Marocchino, A.; Schiavi, A.

    2015-01-01

    Shock ignition is a laser direct-drive inertial confinement fusion (ICF) scheme in which the stages of compression and hot spot formation are partly separated. The fuel is first imploded at a lower velocity than in conventional ICF, reducing the threats due to Rayleigh-Taylor instability. Close to stagnation, an intense laser spike drives a strong converging shock, which contributes to hot spot formation. This paper starts with a brief overview of the theoretical studies, target design and experimental results on shock ignition. The second part of the paper illustrates original work aiming at the design of robust targets and computation of the relevant gain curves. Following Chang et al (2010 Phys. Rev. Lett. 104 135002) a safety factor for high gain, ITF* (analogous to the ignition threshold factor ITF introduced by Clark et al (2008 Phys. Plasmas 15 056305)), is evaluated by means of parametric 1D simulations with artificially reduced reactivity. SI designs scaled as in Atzeni et al (2013 New J. Phys. 15 045004) are found to have nearly the same ITF*. For a given target, such ITF* increases with implosion velocity and laser spike power. A gain curve with a prescribed ITF* can then be simply generated by upscaling a reference target with that value of ITF*. An interesting option is scaling in size by reducing the implosion velocity to keep the ratio of implosion velocity to self-ignition velocity constant. At a given total laser energy, targets with higher ITF* are driven to higher implosion velocity and achieve a somewhat lower gain. However, a 1D gain higher than 100 is achieved at an (incident) energy below 1 MJ, an implosion velocity below 300 km s-1 and a peak incident power below 400 TW. 2D simulations of mispositioned targets show that targets with a higher ITF* indeed tolerate larger displacements.

  14. Pediatric neurorehabilitation and the ICF.

    Science.gov (United States)

    Martinuzzi, Andrea; De Polo, Gianni; Bortolot, Sonia; Pradal, Monica

    2015-01-01

    One of the major intended uses of the International Classification of Functioning, Disability and Health (ICF) is the clinical world of rehabilitation. The intrinsic qualities of ICF, especially in its children and youth version (ICF-CY) seem to perfectly match the needs for the complex process of pediatric neurorehabilitation. We here report on the effect that the implementation of ICF-CY had on team members and families when it was used as a guiding structure in framing the rehabilitation project in a pediatric outpatient clinic dealing with adolescents with cerebral palsy and complex needs. The two-year experience was positive and an ad-hoc questionnaire delivered to team members and families returned very positive remarks. The main messages coming from this experience is on the feasibility of the introduction of ICF-CY language and the bio-psycho-social model in the described setting and on the positive response by the stakeholders.

  15. ICF Program: LDRD-ER Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Glenzer, S H

    2004-02-05

    In the 01-ERD-107 LDRD-ER project, we have performed novel Thomson scattering experiments at the Trident and Omega laser facilities and provided high quality spectral data. These results have led to the development of the first quantitative understanding of laser-plasma interactions for NIF plasmas. For this purpose an green/ultraviolet probe laser, built for Nova in 1998 [1] and successfully used to measure both temperature and plasma wave amplitudes [2], has been deployed on Omega. The Thomson scattering diagnostics has been used twofold: (1) it provided independent measurements of the plasma electron and ion temperature, the plasma flow velocity, or the electron distribution function; (2) it provided measurements of the primary plasma wave and their secondary non-linear decay wave products. These experiments at Omega provide definitive quantitative results on the nonlinear saturation of stimulated Raman scattering for green (2{omega}) beams. In addition, the experiments on the Trident laser have led to a quantitative understanding of the stimulated Brillouin scattering in low-Z plasmas. A nonlinear frequency detuning model has successfully explained all the experimental observable including the SBS reflectivity. This model has been implemented into the laser-plasma interaction code pF3D as a tool to design and optimize NIF target experiments with SBS and SRS losses included. The development of quantitative models for SBS and SRS for various regimes has now been adopted as part of the WBS1 project within the ICF program.

  16. Beam positioning error budget in ICF driver

    CERN Document Server

    Shi Zhi Quan; Su Jing Qin

    2002-01-01

    The author presents the method of linear weight sum to beam positioning budget on the basis of ICF request on targeting, the approach of equal or unequal probability to allocate errors to each optical element. Based on the relationship between the motion of the optical components and beam position on target, the position error of the optical components was evaluated, which was referred to as the maximum range. Lots of ray trace were performed, the position error budget were modified by law of the normal distribution. An overview of position error budget of the components is provided

  17. 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.

  18. 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.

  19. Moderators, mediators, and bidirectional relationships in the International Classification of Functioning, Disability and Health (ICF) framework: An empirical investigation using a longitudinal design and Structural Equation Modeling (SEM).

    Science.gov (United States)

    Rouquette, Alexandra; Badley, Elizabeth M; Falissard, Bruno; Dub, Timothée; Leplege, Alain; Coste, Joël

    2015-06-01

    The International Classification of Functioning, Disability and Health (ICF) published in 2001 describes the consequences of health conditions with three components of impairments in body structures or functions, activity limitations and participation restrictions. Two of the new features of the conceptual model were the possibility of feedback effects between each ICF component and the introduction of contextual factors conceptualized as moderators of the relationship between the components. The aim of this longitudinal study is to provide empirical evidence of these two kinds of effect. Structural equation modeling was used to analyze data from a French population-based cohort of 548 patients with knee osteoarthritis recruited between April 2007 and March 2009 and followed for three years. Indicators of the body structure and function, activity and participation components of the ICF were derived from self-administered standardized instruments. The measurement model revealed four separate factors for body structures impairments, body functions impairments, activity limitations and participation restrictions. The classic sequence from body impairments to participation restrictions through activity limitations was found at each assessment time. Longitudinal study of the ICF component relationships showed a feedback pathway indicating that the level of participation restrictions at baseline was predictive of activity limitations three years later. Finally, the moderating role of personal (age, sex, mental health, etc.) and environmental factors (family relationships, mobility device use, etc.) was investigated. Three contextual factors (sex, family relationships and walking stick use) were found to be moderators for the relationship between the body impairments and the activity limitations components. Mental health was found to be a mediating factor of the effect of activity limitations on participation restrictions.

  20. The ICF Core Sets for hearing loss: researcher perspective, Part II: Linking outcome measures to the International Classification of Functioning, Disability and Health (ICF).

    Science.gov (United States)

    Granberg, Sarah; Möller, Kerstin; Skagerstrand, Asa; Möller, Claes; Danermark, Berth

    2014-02-01

    To link outcome measures used in audiological research to the ICF classification and thereby describe audiological research from the ICF perspective. Through a peer-reviewed or a joint linking procedure, link outcome measures to the ICF classification system using standardized ICF linking rules. Additional linking rules were developed in combination with the established rules to overcome difficulties when connecting audiological data to ICF. Absolute and relative frequencies of ICF categories were reported. The identified outcome measures from the previous study (Part I) constituted the empirical material. In total, 285 ICF categories were identified. The most prevalent categories were related to listening, hearing functions, auditory perceptions, emotions and the physical environment, such as noise and hearing aids. Categories related to communication showed lower relative frequencies, as did categories related to the social and attitudinal environment. Based on the linked outcome measures, communication as a research topic is subordinated to other research topics. The same conclusion can be drawn for research targeting the social and attitudinal environment of adults with HL. Difficulties in the linking procedure were highlighted and discussed, and suggestions for future revisions of the ICF from the audiological perspective were described.

  1. The Nova Upgrade Facility for ICF ignition and gain

    Science.gov (United States)

    Lowdermilk, W. H.; Campbell, E. M.; Hunt, J. T.; Murray, J. R.; Storm, E.; Tobin, M. T.; Trenholme, J. B.

    1992-01-01

    Research on Inertial Confinement Fusion (ICF) is motivated by its potential defense and civilian applications, including ultimately the generation of electric power. The U.S. ICF Program was reviewed recently by the National Academy of Science (NAS) and the Fusion Policy Advisory Committee (FPAC). Both committees issued final reports in 1991 which recommended that first priority in the ICF program be placed on demonstrating fusion ignition and modest gain (G less than 10). The U.S. Department of Energy and Lawrence Livermore National Laboratory (LLNL) have proposed an upgrade of the existing Nova Laser Facility at LLNL to accomplish these goals. Both the NAS and FPAC have endorsed the upgrade of Nova as the optimal path to achieving ignition and gain. Results from Nova Upgrade Experiments will be used to define requirements for driver and target technology both for future high-yield military applications, such as the Laboratory Microfusion Facility (LMF) proposed by the Department of Energy, and for high-gain energy applications leading to an ICF engineering test facility. The central role and modifications which Nova Upgrade would play in the national ICF strategy are described.

  2. 3 MW solid rotating target design

    Science.gov (United States)

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

    2010-03-01

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

  3. The physics of radiation driven ICF hohlraums

    Energy Technology Data Exchange (ETDEWEB)

    Rosen, M.D.

    1995-08-07

    On the Nova Laser at LLNL, we have recently demonstrated many of the key elements required for assuring that the next proposed laser, the National Ignition Facility (NIF) will drive an Inertial Confinement Fusion (ICF) target to ignition. The target uses the recently declassified indirect drive (sometimes referred to as {open_quotes}radiation drive{close_quotes}) approach which converts laser light to x-rays inside a gold cylinder, which then acts as an x-ray {open_quotes}oven{close_quotes} (called a hohlraum) to drive the fusion capsule in its center. On Nova we`ve demonstrated good understanding of the temperatures reached in hohlraums and of the ways to control the uniformity with which the x-rays drive the spherical fusion capsules. In this lecture we briefly review the fundamentals of ICF, and describe the capsule implosion symmetry advantages of the hohlraum approach. We then concentrate on a quantitative understanding of the scaling of radiation drive with hohlraum size and wall material, and with laser pulse length and power. We demonstrate that coupling efficiency of x-ray drive to the capsule increases as we proceed from Nova to the NIF and eventually to a reactor, thus increasing the gain of the system.

  4. Technical Design Report, Second Target Station

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-01-01

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

  5. Design of the NIF Cryogenic Target System

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-06-10

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

  6. Heterochromatic Genes Undergo Epigenetic Changes and Escape Silencing in Immunodeficiency, Centromeric Instability, Facial Anomalies (ICF) Syndrome

    Science.gov (United States)

    Brun, Marie-Elisabeth; Lana, Erica; Rivals, Isabelle; Lefranc, Gérard; Sarda, Pierre; Claustres, Mireille; Mégarbané, André; De Sario, Albertina

    2011-01-01

    Immunodeficiency, Centromeric Instability, Facial Anomalies (ICF) syndrome is a rare autosomal recessive disorder that is characterized by a marked immunodeficiency, severe hypomethylation of the classical satellites 2 and 3 associated with disruption of constitutive heterochromatin, and facial anomalies. Sixty percent of ICF patients have mutations in the DNMT3B (DNA methyltransferase 3B) gene, encoding a de novo DNA methyltransferase. In the present study, we have shown that, in ICF lymphoblasts and peripheral blood, juxtacentromeric heterochromatic genes undergo dramatic changes in DNA methylation, indicating that they are bona fide targets of the DNMT3B protein. DNA methylation in heterochromatic genes dropped from about 80% in normal cells to approximately 30% in ICF cells. Hypomethylation was observed in five ICF patients and was associated with activation of these silent genes. Although DNA hypomethylation occurred in all the analyzed heterochromatic genes and in all the ICF patients, gene expression was restricted to some genes, every patient having his own group of activated genes. Histone modifications were preserved in ICF patients. Heterochromatic genes were associated with histone modifications that are typical of inactive chromatin: they had low acetylation on H3 and H4 histones and were slightly enriched in H3K9Me3, both in ICF and controls. This was also the case for those heterochromatic genes that escaped silencing. This finding suggests that gene activation was not generalized to all the cells, but rather was restricted to a clonal cell population that may contribute to the phenotypic variability observed in ICF syndrome. A slight increase in H3K27 monomethylation was observed both in heterochromatin and active euchromatin in ICF patients; however, no correlation between this modification and activation of heterochromatic genes was found. PMID:21559330

  7. Heterochromatic genes undergo epigenetic changes and escape silencing in immunodeficiency, centromeric instability, facial anomalies (ICF syndrome.

    Directory of Open Access Journals (Sweden)

    Marie-Elisabeth Brun

    Full Text Available Immunodeficiency, Centromeric Instability, Facial Anomalies (ICF syndrome is a rare autosomal recessive disorder that is characterized by a marked immunodeficiency, severe hypomethylation of the classical satellites 2 and 3 associated with disruption of constitutive heterochromatin, and facial anomalies. Sixty percent of ICF patients have mutations in the DNMT3B (DNA methyltransferase 3B gene, encoding a de novo DNA methyltransferase. In the present study, we have shown that, in ICF lymphoblasts and peripheral blood, juxtacentromeric heterochromatic genes undergo dramatic changes in DNA methylation, indicating that they are bona fide targets of the DNMT3B protein. DNA methylation in heterochromatic genes dropped from about 80% in normal cells to approximately 30% in ICF cells. Hypomethylation was observed in five ICF patients and was associated with activation of these silent genes. Although DNA hypomethylation occurred in all the analyzed heterochromatic genes and in all the ICF patients, gene expression was restricted to some genes, every patient having his own group of activated genes. Histone modifications were preserved in ICF patients. Heterochromatic genes were associated with histone modifications that are typical of inactive chromatin: they had low acetylation on H3 and H4 histones and were slightly enriched in H3K9Me(3, both in ICF and controls. This was also the case for those heterochromatic genes that escaped silencing. This finding suggests that gene activation was not generalized to all the cells, but rather was restricted to a clonal cell population that may contribute to the phenotypic variability observed in ICF syndrome. A slight increase in H3K27 monomethylation was observed both in heterochromatin and active euchromatin in ICF patients; however, no correlation between this modification and activation of heterochromatic genes was found.

  8. Design of the LBNF Beamline Target Station

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-10-01

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

  9. Designing divertor targets for uniform power load

    Science.gov (United States)

    Dekeyser, W.; Reiter, D.; Baelmans, M.

    2015-08-01

    Divertor design for next step fusion reactors heavily relies on 2D edge plasma modeling with codes as e.g. B2-EIRENE. While these codes are typically used in a design-by-analysis approach, in previous work we have shown that divertor design can alternatively be posed as a mathematical optimization problem, and solved very efficiently using adjoint methods adapted from computational aerodynamics. This approach has been applied successfully to divertor target shape design for more uniform power load. In this paper, the concept is further extended to include all contributions to the target power load, with particular focus on radiation. In a simplified test problem, we show the potential benefits of fully including the radiation load in the design cycle as compared to only assessing this load in a post-processing step.

  10. Review of the three candidate hohlraums in ICF

    CERN Document Server

    Li, Xin; Dai, Zhensheng; Zheng, Wudi; Zhao, Yiqing; Zhang, Huasen; Gu, Jianfa; Kang, Dongguo; Ge, Fengjun; Gu, Peijun; Zou, Shiyang

    2016-01-01

    In this paper, we give a review of three hohlraum geometries, including cylindrical, octahedral and six-cylinder-port hohlraums, in inertial confinement fusion (ICF) mainly from theoretical side. Every hohlraum has its own strengths and weaknesses. Although there is a problem of drive asymmetry in the cylindrical hohlraums due to some non-ideal factors, the success of ignition is still possible if more laser energy is available beyond the US National Ignition Facility (NIF) in the future. Octahedral hohlraums can provide the high symmetry flux on capsule. However, octahedral hohlraums suffer from several problems due to the complicated three-dimensional plasma conditions inside. And up to now, there is no one target design with the octahedral hohlraums in which each problem can be solved at the same time. Six-cylinder-port hohlraums combine the merits in theory of both cylindrical and octahedral hohlraums to a certain extent. We introduce a target design with good performance by using the six-cylinder-port ho...

  11. 29 mm Diameter Test Target Design Report

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dale, Gregory E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Olivas, Eric Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Naranjo, Angela Carol [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Romero, Frank Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-15

    The Northstar target for Mo99 production is made up of Mo100 disks in a stack separated by coolant gaps for helium flow. A number of targets have been tested at ANL for both production of Mo99 and for thermal-hydraulic performance. These have all been with a 12 mm diameter target, even while the production goals have increased the diameter to now 29 mm. A 29 mm diameter target has been designed that is consistent with the ANL beam capabilities and the capabilities of the helium circulation system currently in use at ANL. This target is designed for 500 μA at 35 MeV electrons. While the plant design calls for 42 MeV, the chosen design point is more favorable and higher power given the limits of the ANL accelerator. The intended beam spot size is 12 mm FWHM, but the thermal analysis presented herein conservatively assumed a 10 mm FWHM beam, which results in a 44% higher beam current density at beam center.

  12. ICF quarterly report October-December 1998 volume 8, number 1

    Energy Technology Data Exchange (ETDEWEB)

    Feit, M

    1998-09-08

    This issue of the ICF Quarterly Report focuses on the final section of the 192-arm, 1.8-MJ National Ignition Facility (NIF). We describe both technological advances necessary for optimal utilization of the delivered energy and the hohlraum physics resulting from extremely high energy densities. Two articles belong to the first category. The conversion of infrared light to ultraviolet occurs at the tripler in the NIF's Final Optics Assembly. It is then necessary to separate any unconverted (first- and second-harmonic) light from the tripled-frequency light passed to the target. Large-Aperture Color-Separation Gratings for Diverting Unconverted Light Away from the NIF Target describes the design and fabrication of novel diffraction gratings that fulfill this function. In both direct- and indirect-drive ICF, the symmetry of the capsule as it compresses is crucial. The NIF will have 48 clusters of four beams incident on targets. Optimization of Beam Angles for the National Ignition Facility (p. 15) presents the rationale used to assign beam angles for cylindrical indirect drive while still allowing direct-drive and tetrahedral indirect-drive experiments to be performed.

  13. Fabrication of Micro-column Array Filled With CH for ICF Target%微米柱阵列ICF埋点靶的制备

    Institute of Scientific and Technical Information of China (English)

    王衍斌; 唐永建; 朱效立; 张林; 陈志梅; 马小军

    2011-01-01

    微米柱阵列埋点靶是研究超短激光辐照靶激光吸收效率和等离子体产生过程及发展的1种重要靶型.本文结合采用电子束刻蚀、X射线刻蚀和微电镀等制备金微米点阵列,用CVD方法对阵列间隙填充无应力CH薄膜,用SEM、AFM与白光干涉仪等对制作过程和结果样品进行检测.结果表明,用电子束刻蚀方法制作的掩膜分辨率好、边缘光滑.用同步辐射的X光制作高质量样品,样品点柱高宽比为4,垂直度近于90°,点柱阵列周期为2×2μm,CH层厚约4μm.%The target with micro-column array embedded in CH is a kind of target which is important to research ps/fs laser absorbing efficiency and plasma generating and developing when laser irradiated it. A way to fabricate the target was implemented. The electronic beam-etching, X-ray etching and micro-plating were used to fabricate micrometer array and space was filled with CH in it. The SEM, AFM and white-light interferometer were used to characterize the sample. The result shows that the micro-column ratio of high and width is 4, the verticality is close to 90° and the space is 2×2 μm, and the thickness of CH is 4μm.

  14. Clinical application of ICF key codes to evaluate patients with dysphagia following stroke.

    Science.gov (United States)

    Dong, Yi; Zhang, Chang-Jie; Shi, Jie; Deng, Jinggui; Lan, Chun-Na

    2016-09-01

    This study was aimed to identify and evaluate the International Classification of Functioning (ICF) key codes for dysphagia in stroke patients. Thirty patients with dysphagia after stroke were enrolled in our study. To evaluate the ICF dysphagia scale, 6 scales were used as comparisons, namely the Barthel Index (BI), Repetitive Saliva Swallowing Test (RSST), Kubota Water Swallowing Test (KWST), Frenchay Dysarthria Assessment, Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). Multiple regression analysis was performed to quantitate the relationship between the ICF scale and the other 7 scales. In addition, 60 ICF scales were analyzed by the least absolute shrinkage and selection operator (LASSO) method. A total of 21 ICF codes were identified, which were closely related with the other scales. These included 13 codes from Body Function, 1 from Body Structure, 3 from Activities and Participation, and 4 from Environmental Factors. A topographic network map with 30 ICF key codes was also generated to visualize their relationships. The number of ICF codes identified is in line with other well-established evaluation methods. The network topographic map generated here could be used as an instruction tool in future evaluations. We also found that attention functions and biting were critical codes of these scales, and could be used as treatment targets.

  15. Expanding the mutation spectrum in ICF syndrome: Evidence for a gender bias in ICF2.

    Science.gov (United States)

    van den Boogaard, M L; Thijssen, P E; Aytekin, C; Licciardi, F; Kıykım, A A; Spossito, L; Dalm, V A S H; Driessen, G J; Kersseboom, R; de Vries, F; van Ostaijen-Ten Dam, M M; Ikinciogullari, A; Dogu, F; Oleastro, M; Bailardo, E; Daxinger, L; Nain, E; Baris, S; van Tol, M J D; Weemaes, C; van der Maarel, S M

    2017-01-27

    Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare, genetically heterogeneous, autosomal recessive disorder. Patients suffer from recurrent infections caused by reduced levels or absence of serum immunoglobulins. Genetically, 4 subtypes of ICF syndrome have been identified to date: ICF1 (DNMT3B mutations), ICF2 (ZBTB24 mutations), ICF3 (CDCA7 mutations), and ICF4 (HELLS mutations). To study the mutation spectrum in ICF syndrome. Genetic studies were performed in peripheral blood lymphocyte DNA from suspected ICF patients and family members. We describe 7 ICF1 patients and 6 novel missense mutations in DNMT3B, affecting highly conserved residues in the catalytic domain. We also describe 5 new ICF2 patients, one of them carrying a homozygous deletion of the complete ZBTB24 locus. In a meta-analysis of all published ICF cases, we observed a gender bias in ICF2 with 79% male patients. The biallelic deletion of ZBTB24 provides strong support for the hypothesis that most ICF2 patients suffer from a ZBTB24 loss of function mechanism and confirms that complete absence of ZBTB24 is compatible with human life. This is in contrast to the observed early embryonic lethality in mice lacking functional Zbtb24. The observed gender bias seems to be restricted to ICF2 as it is not observed in the ICF1 cohort. Our study expands the mutation spectrum in ICF syndrome and supports that DNMT3B and ZBTB24 are the most common disease genes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Giannarelli Diana

    2009-05-01

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

  17. The Prospects for High-Yield ICF with a Z-Pinch Driven Dynamic Hohlraum

    Energy Technology Data Exchange (ETDEWEB)

    CHANDLER, GORDON A.; CHRIEN, R.; COOPER, GARY WAYNE; DERZON, MARK S.; DOUGLAS, MELISSA R.; HEBRON, DAVID E.; LASH, JOEL S.; LEEPER, RAMON J.; MATZEN, M. KEITH; MEHLHORN, THOMAS A.; NASH, THOMAS J.; OLSON, RICHARD E.; PETERSON, D.L.; RUIZ, CARLOS L.; SANFORD, THOMAS W. L.; SLUTZ, STEPHEN A.

    1999-09-07

    Recent success with the Sandia Z machine has renewed interest in utilizing fast z-pinenes for ICF. One promising concept places the ICF capsule internal to the imploding z-pinch. At machine parameters relevant to achieving high yield, the imploding z-pinch mass has sufficient opacity to trap radiation giving rise to a dynamic hohlraum. The concept utilizes a 12 MJ, 54 MA z-pinch driver producing a capsule drive temperature exceeding 300 eV to realize a 550 MJ thermonuclear yield. They present the current high-yield design and its development that supports high-yield ICF with a z-pinch driven dynamic hohlraum.

  18. Test of a High Power Target Design

    CERN Multimedia

    2002-01-01

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

  19. Experimental techniques for measuring Rayleigh-Taylor instability in inertial confinement fusion (ICF)

    Energy Technology Data Exchange (ETDEWEB)

    Smalyuk, V A

    2012-06-07

    Rayleigh-Taylor (RT) instability is one of the major concerns in inertial confinement fusion (ICF) because it amplifies target modulations in both acceleration and deceleration phases of implosion, which leads to shell disruption and performance degradation of imploding targets. This article reviews experimental results of the RT growth experiments performed on OMEGA laser system, where targets were driven directly with laser light. RT instability was studied in the linear and nonlinear regimes. The experiments were performed in acceleration phase, using planar and spherical targets, and in deceleration phase of spherical implosions, using spherical shells. Initial target modulations consisted of 2-D pre-imposed modulations, and 2-D and 3-D modulations imprinted on targets by the non-uniformities in laser drive. In planar geometry, the nonlinear regime was studied using 3-D modulations with broadband spectra near nonlinear saturation levels. In acceleration-phase, the measured modulation Fourier spectra and nonlinear growth velocities are in good agreement with those predicted by Haan's model [Haan S W 1989 Phys. Rev. A 39 5812]. In a real-space analysis, the bubble merger was quantified by a self-similar evolution of bubble size distributions [Oron D et al 2001 Phys. Plasmas 8, 2883]. The 3-D, inner-surface modulations were measured to grow throughout the deceleration phase of spherical implosions. RT growth rates are very sensitive to the drive conditions, therefore they can be used to test and validate drive physics in hydrodynamic codes used to design ICF implosions. Measured growth rates of pre-imposed 2-D target modulations below nonlinear saturation levels were used to validate non-local thermal electron transport model in laser-driven experiments.

  20. ICF, individuelle planer og sociale tilbud

    DEFF Research Database (Denmark)

    Bonfils, Inge Storgaard; Wind, Thea

    Den Sociale Virksomhed i Region H. har siden 2008 arbejdet med at anvende ICF som grundlag for en funktionsevneudredning af brugerne af de sociale tilbud. Evalueringen viser, at arbejdet med ICF giver højere faglig kvalitet, et fælles sprog og er et godt værktøj til tværfagligt samarbejde....

  1. Computer simulation technology in inertial confinement (ICF)

    Energy Technology Data Exchange (ETDEWEB)

    Yabe, Takashi (Gunma Univ., Kiryu (Japan). Faculty of Engineering)

    1994-12-01

    Recent development of computational technologies in inertial confinement fusion (ICF) is reviewed with a special emphasis on hydrodynamic simulations. The CIP method developed for ICF simulations is one of the typical examples that are used in various fields of physics such as variety of computational fluid dynamics, astrophysics, laser applications, geophysics, and so on. (author).

  2. ICF and ICF-CY lessons learned: Pandora's box of personal factors.

    Science.gov (United States)

    Simeonsson, Rune J; Lollar, Don; Björck-Åkesson, Eva; Granlund, Mats; Brown, Scott C; Zhuoying, Qiu; Gray, David; Pan, Yi

    2014-01-01

    The aim of this article is to examine the component of "personal factors" described as a contextual factor in the ICF and ICF-CY. A critical examination of the construct of "personal factors" and description of the component was made with reference to conceptual and taxonomic criteria. The "personal factors" component in the ICF/ICF-CY is not defined, there is no taxonomy of codes, there is no explicit purpose stated for its use and no guidelines are provided for its application. In spite of these constraints, the component of "personal factors" is being applied as part of the classifications. Such uncontrolled applications constitute significant risks for the status of ICF/ICF-CY as the WHO reference classification in that: (a) the component is accepted for use by default simply by being applied; (b) component content is expanded with idiosyncratic exemplars by users; and (c) there is potential misuse of "personal factors" in documenting personal attributes, including "blaming the victim". In the absence of formal codes, any application of the component of "personal factors" lacks the legitimacy that documentation with a scientific taxonomy should provide. Given the growing use of the ICF/ICF-CY globally, a priority for the revision process should be to determine if there is in fact need for "personal" or any other factors in the ICF/ICF-CY. A central contribution of the ICF/ICF-CY is the universal language of codes for the components of body structure, body function, activities and participation and Environmental Factors. As such the codes provide taxonomical legitimacy and power for documenting dimensions of functioning and disability in clinical and rehabilitation contexts. As there are no codes of "personal factors", there is no basis for documentation of the component. Demographic information, if needed for identification, should be recorded in customary formats, independent of any component or codes of the ICF/ICF-CY.

  3. Designed nucleases for targeted genome editing.

    Science.gov (United States)

    Lee, Junwon; Chung, Jae-Hee; Kim, Ho Min; Kim, Dong-Wook; Kim, Hyongbum

    2016-02-01

    Targeted genome-editing technology using designed nucleases has been evolving rapidly, and its applications are widely expanding in research, medicine and biotechnology. Using this genome-modifying technology, researchers can precisely and efficiently insert, remove or change specific sequences in various cultured cells, micro-organisms, animals and plants. This genome editing is based on the generation of double-strand breaks (DSBs), repair of which modifies the genome through nonhomologous end-joining (NHEJ) or homology-directed repair (HDR). In addition, designed nickase-induced generation of single-strand breaks can also lead to precise genome editing through HDR, albeit at relatively lower efficiencies than that induced by nucleases. Three kinds of designed nucleases have been used for targeted DSB formation: zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases derived from the bacterial clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated) system. A growing number of researchers are using genome-editing technologies, which have become more accessible and affordable since the discovery and adaptation of CRISPR-Cas9. Here, the repair mechanism and outcomes of DSBs are reviewed and the three types of designed nucleases are discussed with the hope that such understanding will facilitate applications to genome editing.

  4. National Ignition Facility Target Design and Fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Cook, R C; Kozioziemski, B J; Nikroo, A; Wilkens, H L; Bhandarkar, S; Forsman, A C; Haan, S W; Hoppe, M L; Huang, H; Mapoles, E; Moody, J D; Sater, J D; Seugling, R M; Stephens, R B; Takagi, M; Xu, H W

    2007-12-10

    The current capsule target design for the first ignition experiments at the NIF Facility beginning in 2009 will be a copper-doped beryllium capsule, roughly 2 mm in diameter with 160-{micro}m walls. The capsule will have a 75-{micro}m layer of solid DT on the inside surface, and the capsule will driven with x-rays generated from a gold/uranium cocktail hohlraum. The design specifications are extremely rigorous, particularly with respect to interfaces, which must be very smooth to inhibit Rayleigh-Taylor instability growth. This paper outlines the current design, and focuses on the challenges and advances in capsule fabrication and characterization; hohlraum fabrication, and D-T layering and characterization.

  5. ICF gamma-ray reaction history diagnostics

    Science.gov (United States)

    Herrmann, H. W.; Young, C. S.; Mack, J. M.; Kim, Y. H.; McEvoy, A.; Evans, S.; Sedillo, T.; Batha, S.; Schmitt, M.; Wilson, D. C.; Langenbrunner, J. R.; Malone, R.; Kaufman, M. I.; Cox, B. C.; Frogget, B.; Miller, E. K.; Ali, Z. A.; Tunnell, T. W.; Stoeffl, W.; Horsfield, C. J.; Rubery, M.

    2010-08-01

    Reaction history measurements, such as nuclear bang time and burn width, are fundamental components of diagnosing ICF implosions and will be employed to help steer the National Ignition Facility (NIF) towards ignition. Fusion gammas provide a direct measure of nuclear interaction rate (unlike x-rays) without being compromised by Doppler spreading (unlike neutrons). Gas Cherenkov Detectors that convert fusion gamma rays to UV/visible Cherenkov photons for collection by fast optical recording systems have established their usefulness in illuminating ICF physics in several experimental campaigns at OMEGA. In particular, bang time precision better than 25 ps has been demonstrated, well below the 50 ps accuracy requirement defined by the NIF. NIF Gamma Reaction History (GRH) diagnostics are being developed based on optimization of sensitivity, bandwidth, dynamic range, cost, and NIF-specific logistics, requirements and extreme radiation environment. Implementation will occur in two phases. The first phase consists of four channels mounted to the outside of the target chamber at ~6 m from target chamber center (GRH-6m) coupled to ultra-fast photo-multiplier tubes (PMT). This system is intended to operate in the 1013-1017 neutron yield range expected during the early THD campaign. It will have high enough bandwidth to provide accurate bang times and burn widths for the expected THD reaction histories (> 80 ps fwhm). Successful operation of the first GRH-6m channel has been demonstrated at OMEGA, allowing a verification of instrument sensitivity, timing and EMI/background suppression. The second phase will consist of several channels located just inside the target bay shield wall at 15 m from target chamber center (GRH-15m) with optical paths leading through the cement shield wall to well-shielded streak cameras and PMTs. This system is intended to operate in the 1016-1020 yield range expected during the DT ignition campaign, providing higher temporal resolution for the

  6. Designing Optical Element of Beam Splitting Illumination for Adjusting Light path in ICF%用于ICF光路调整的分光照明元件设计

    Institute of Scientific and Technical Information of China (English)

    张超; 谭建军; 黄小霞; 赵曦; 高福华

    2013-01-01

    在惯性约束核聚变激光驱动装置中,光路庞大复杂且元器件众多,为保证激光系统正常运行需对光路进行精密调节.特别是装置中的多个4F系统,需调整激光光路使其聚焦后对准焦平面滤波小孔中心,以保证激光顺利通过并实现低通滤波作用.目前实际工程中采用凹透镜背光照明的方法判断光束是否准确过孔,但该方法步骤繁琐且调整精度较低,给实际光路调整带来了极大的不便.本文基于全息原理,提出了一种简单高效的4F系统光路调整方法,通过一特殊设计的分光照明衍射光学元件,可一步实现激光聚焦过孔的判断与调整,可有效解决现有4F系统光路调整的困难.%Numerous elements and huge laser system are existed in Inertial Confine Fusion driver (ICF).It is necessary to adjust light path accurately so as to ensure that the laser system can work normally.Expecially,the 4F system in ICF plays a role of low-pass filtering,so the purpose of adjusting is to make laser pass the center of filter hole in focus plane.Currently,the method in practical engineering is to use a concave lens for splitting light illumination to judge whether the beam pass the filter hole.However,the disadvantage of this method is tedious and low precision,which is inconvenient in actual adjusting.In this paper,a simple but effective way to adjust light path in 4F system is presented based on holography theory.With a specially designed diffractive optical element for splitting light illumination,judging and adjusting laser to pass the filter hole can be easily achieving.Thus,it can solve the difficulty of existing method.

  7. Targeted proteins for diabetes drug design

    Science.gov (United States)

    Doan Trang Nguyen, Ngoc; Thi Le, Ly

    2012-03-01

    Type 2 diabetes mellitus is a common metabolism disorder characterized by high glucose in the bloodstream, especially in the case of insulin resistance and relative insulin deficiency. Nowadays, it is very common in middle-aged people and involves such dangerous symptoms as increasing risk of stroke, obesity and heart failure. In Vietnam, besides the common treatment of insulin injection, some herbal medication is used but no unified optimum remedy for the disease yet exists and there is no production of antidiabetic drugs in the domestic market yet. In the development of nanomedicine at the present time, drug design is considered as an innovative tool for researchers to study the mechanisms of diseases at the molecular level. The aim of this article is to review some common protein targets involved in type 2 diabetes, offering a new idea for designing new drug candidates to produce antidiabetic drugs against type 2 diabetes for Vietnamese people.

  8. X-ray ablation measurements and modeling for ICF applications

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, A.T.

    1996-09-01

    X-ray ablation of material from the first wall and other components of an ICF (Inertial Confinement Fusion) chamber is a major threat to the laser final optics. Material condensing on these optics after a shot may cause damage with subsequent laser shots. To ensure the successful operation of the ICF facility, removal rates must be predicted accurately. The goal for this dissertation is to develop an experimentally validated x-ray response model, with particular application to the National Ignition Facility (NIF). Accurate knowledge of the x-ray and debris emissions from ICF targets is a critical first step in the process of predicting the performance of the target chamber system. A number of 1-D numerical simulations of NIF targets have been run to characterize target output in terms of energy, angular distribution, spectrum, and pulse shape. Scaling of output characteristics with variations of both target yield and hohlraum wall thickness are also described. Experiments have been conducted at the Nova laser on the effects of relevant x-ray fluences on various materials. The response was diagnosed using post-shot examinations of the surfaces with scanning electron microscope and atomic force microscope instruments. Judgments were made about the dominant removal mechanisms for each material. Measurements of removal depths were made to provide data for the modeling. The finite difference ablation code developed here (ABLATOR) combines the thermomechanical response of materials to x-rays with models of various removal mechanisms. The former aspect refers to energy deposition in such small characteristic depths ({approx} micron) that thermal conduction and hydrodynamic motion are significant effects on the nanosecond time scale. The material removal models use the resulting time histories of temperature and pressure-profiles, along with ancillary local conditions, to predict rates of surface vaporization and the onset of conditions that would lead to spallation.

  9. X-ray ablation measurements and modeling for ICF applications

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Andrew Thomas [Univ. of California, Berkeley, CA (United States)

    1996-09-01

    X-ray ablation of material from the first wall and other components of an ICF (Inertial Confinement Fusion) chamber is a major threat to the laser final optics. Material condensing on these optics after a shot may cause damage with subsequent laser shots. To ensure the successful operation of the ICF facility, removal rates must be predicted accurately. The goal for this dissertation is to develop an experimentally validated x-ray response model, with particular application to the National Ignition Facility (NIF). Accurate knowledge of the x-ray and debris emissions from ICF targets is a critical first step in the process of predicting the performance of the target chamber system. A number of 1-D numerical simulations of NIF targets have been run to characterize target output in terms of energy, angular distribution, spectrum, and pulse shape. Scaling of output characteristics with variations of both target yield and hohlraum wall thickness are also described. Experiments have been conducted at the Nova laser on the effects of relevant x-ray fluences on various materials. The response was diagnosed using post-shot examinations of the surfaces with scanning electron microscope and atomic force microscope instruments. Judgments were made about the dominant removal mechanisms for each material. Measurements of removal depths were made to provide data for the modeling. The finite difference ablation code developed here (ABLATOR) combines the thermomechanical response of materials to x-rays with models of various removal mechanisms. The former aspect refers to energy deposition in such small characteristic depths (~ micron) that thermal conduction and hydrodynamic motion are significant effects on the nanosecond time scale. The material removal models use the resulting time histories of temperature and pressure-profiles, along with ancillary local conditions, to predict rates of surface vaporization and the onset of conditions that would lead to spallation.

  10. Analytical opacity formulas for ICF elements

    Energy Technology Data Exchange (ETDEWEB)

    Minguez, E. E-mail: minguez@denim.upm.es; Martel, P.; Gil, J.M.; Rubiano, J.G.; Rodriguez, R

    2002-01-01

    Local Thermodynamic Equilibrium (LTE) opacity codes have been developed by the Instituto de Fusion Nuclear (DENIM) during the last years. JIMENA code (Laser and Particle Beams 6 (1998) 265; Laser and Particle Beams 10 (1992) 651) is an opacity code that solves self-consistently, for each temperature and density, the radial Dirac equation with a local spherically symmetrical potential. Very recently we have developed a new opacity code, called ANALOP, that uses an analytical potential (JQSRT 54 (1995) 621), which can include density and temperature effects for atomic data calculations. Opacities are determined with these two codes for selected elements at different plasma conditions. This work is focused on the determination of Rosseland and Planck mean analytical formulas for several single elements used in ICF targets. A scaling law of these mean opacities is given as a function of the plasma parameters: electron temperature and plasma density. These opacities have been tested with numerical results from other codes and with available experimental results.

  11. Design and Implementation of SCSI Target Emulator

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

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

  12. Genome-Wide DNA Methylation Analysis Identifies Novel Hypomethylated Non-Pericentromeric Genes with Potential Clinical Implications in ICF Syndrome.

    Science.gov (United States)

    Simo-Riudalbas, L; Diaz-Lagares, A; Gatto, S; Gagliardi, M; Crujeiras, A B; Matarazzo, M R; Esteller, M; Sandoval, J

    2015-01-01

    Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9), marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs) including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are supposed to be expressed in germ line and silenced in somatic tissues. In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific clinical biomarkers

  13. Genome-Wide DNA Methylation Analysis Identifies Novel Hypomethylated Non-Pericentromeric Genes with Potential Clinical Implications in ICF Syndrome.

    Directory of Open Access Journals (Sweden)

    L Simo-Riudalbas

    Full Text Available Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9, marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are supposed to be expressed in germ line and silenced in somatic tissues.In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific

  14. The Role of the WHO ICF as a Framework to Interpret Barriers and to Inclusion: Visually Impaired People's Views and Experiences of Personal Computers

    Science.gov (United States)

    Douglas, Graeme; Corcoran, Christine; Pavey, Sue

    2007-01-01

    This article describes how the World Health Organisation's International Classification of Functioning, Disability, and Health (ICF), 2001, was used as a framework for the design of the interview schedule used in the Network 1000 project. It is argued that the ICF offers a vocabulary to enable visually impaired participants to describe their lives…

  15. Developments in high-intensity two-step target design

    CERN Document Server

    Talbert, W L; Hsu, H H; Wilson, M T

    2003-01-01

    The two-step fission-product target concept is analyzed to design a prototype target for testing at the ISAC facility. A two-step target consists of an inner cylinder of heavy metal irradiated by an energetic light ion beam; neutrons produced emerge from the target into a coaxial secondary target (blanket) of fissionable material. With this approach, the production of fission product activities is enhanced compared to other products that can interfere in experiments, and significantly less energy is deposited in the secondary target than for direct irradiation. The design is mechanically simple and provides independent control of operating temperatures. The analysis determined appropriate target and blanket dimensions, and energy deposition profiles, temperature distributions and fission production rates. The production rates of some neutron-rich isotopes for selected elements are summarized. A conceptual design is presented, along with issues on cooling the primary target and heating of the secondary target.

  16. The development and application of advanced analytical methods to commercial ICF reactor chambers. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Cousseau, P.; Engelstad, R.; Henderson, D.L. [and others

    1997-10-01

    Progress is summarized in this report for each of the following tasks: (1) multi-dimensional radiation hydrodynamics computer code development; (2) 2D radiation-hydrodynamic code development; (3) ALARA: analytic and Laplacian adaptive radioactivity analysis -- a complete package for analysis of induced activation; (4) structural dynamics modeling of ICF reactor chambers; and (5) analysis of self-consistent target chamber clearing.

  17. Experiments in ICF, materials science, and astrophysics

    Directory of Open Access Journals (Sweden)

    Remington Bruce A.

    2013-11-01

    Full Text Available We have been developing HED experiments on high power ICF lasers over the past two decades that span (1 the radiative hydrodynamics of ICF capsule physics; (2 the high pressure, high strain rate, solid-state dynamics relevant to novel concepts for ICF and hypervelocity impacts in space and on Earth; and (3 the shock driven turbulence of exploding stars (supernovae. These different regimes are separated by many orders of magnitude in length, time, and temperature, yet there are common threads that run through all of these phenomena, such as the occurrence of hydrodynamic instabilities. Examples from each of these three seemingly very disparate regimes are given, and the common theme of hydrodynamic instability evolution is explored.

  18. The ICF and Postsurgery Occupational Therapy after Traumatic Hand Injury

    Science.gov (United States)

    Fitinghoff, Helene; Lindqvist, Birgitta; Nygard, Louise; Ekholm, Jan; Schult, Marie-Louise

    2011-01-01

    Recent studies have examined the effectiveness of hand rehabilitation programmes and have linked the outcomes to the concept of ICF but not to specific ICF category codes. The objective of this study was to gain experience using ICF concepts to describe occupational therapy interventions during postsurgery hand rehabilitation, and to describe…

  19. The ICF and Postsurgery Occupational Therapy after Traumatic Hand Injury

    Science.gov (United States)

    Fitinghoff, Helene; Lindqvist, Birgitta; Nygard, Louise; Ekholm, Jan; Schult, Marie-Louise

    2011-01-01

    Recent studies have examined the effectiveness of hand rehabilitation programmes and have linked the outcomes to the concept of ICF but not to specific ICF category codes. The objective of this study was to gain experience using ICF concepts to describe occupational therapy interventions during postsurgery hand rehabilitation, and to describe…

  20. Design of the Next Generation Spallation Target

    Energy Technology Data Exchange (ETDEWEB)

    Ferres, Laurent [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-06-13

    The purpose of this summary is to detail the studies that enable new nuclear physics experiments currently limited by neutron intensity or energy resolution available at LANSCE. The target is being redesigned so that the Flight Paths (FP) in the upper tier provide a higher intensity in the epithermal and medium energy ranges.

  1. Effect of initial conditions and Mach number on the Richtmyer-Meshkov instability in ICF like conditions

    Science.gov (United States)

    Rao, Pooja; She, Dan; Lim, Hyunkyung; Glimm, James

    2015-11-01

    The qualitative and quantitative effect of initial conditions (linear and non-linear) and high Mach number (1.3 and 1.45) is studied on the turbulent mixing induced by the Richtmyer-Meshkov instability in idealized ICF conditions. The Richtmyer-Meshkov instability seeds Rayleigh-taylor instabilities in ICF experiments and is one of the factors that contributes to reduced performance of ICF experiments. Its also found in collapsing cores of stars and supersonic combustion. We use the Stony Brook University code, FronTier, which is verified via a code comparison study against the AMR multiphysics code FLASH, and validated against vertical shock tube experiments done by the LANL Extreme Fluids Team. These simulations are designed as a step towards simulating more realistic ICF conditions and quantifying the detrimental effects of mixing on the yield.

  2. Laser pulse spatial-temporal inversion technology for ICF laser facility

    Science.gov (United States)

    Zhang, Ying; Geng, Yuanchao; Chen, Lin; Huang, Wanqing; Zhao, Junpu; Wang, Wenyi; Liu, Lanqin; Zheng, Kuixing; Zhu, Qihua; Wei, Xiaofeng

    2017-05-01

    The laser pulse should be shaped to satisfy the ICF physical requirement and the profile should be flattened to increase the extraction efficiency of the disk amplifiers and to ensure system safety in ICF laser facility. The spatial-temporal distribution of the laser pulse is affected by the gain saturation, uniformity gain profile of the amplifiers, and the frequency conversion process. The pulse spatial-temporal distribution can't be described by simply analytic expression, so new iteration algorithms are needed. We propose new inversion method and iteration algorithms in this paper. All of these algorithms have been integrated in SG99 software and the validity has been demonstrated. The result could guide the design of the ICF laser facility in the future.

  3. Accommodation Outcomes and the ICF Framework

    Science.gov (United States)

    Schreuer, Naomi

    2009-01-01

    Accommodation of the environment and technology is one of the key mediators of adjustment to disability and participation in community. In this article, accommodations are tested empirically as facilitators of return to work and participation, as defined by the "International Classification of Disability, Function, and Health" (ICF) and…

  4. Driver beam-led EURISOL target design constraints

    CERN Document Server

    Noah, Etam; Catherall, Richard; Kadi, Yacine; Kharoua, Cyril; Lettry, Jacques

    2008-01-01

    The EURISOL (European Isotope Separation Online) Design Study is addressing new high power target design challenges. A three-step method [1] was proposed to split the high power linac proton driver beam into one $H^{-}$ branch for the 4 $MW_{b}$ [2] mercury target that produces radioactive ion beams (RIB) via spallation neutroninduced fission in a secondary actinide target and three 100 $kW_{b}$ $H^{+}$ branches for the direct targets producing RIBs via fragmentation and spallation reactions. This scheme minimises transient thermo-mechanical stresses on targets and preserves the cw nature of the driver beam in the four branches. The heat load for oxides, carbides, refractory metal foils and liquid metals is driven by the incident proton driver beam while for actinides, exothermic fission reactions are an additional contribution. This paper discusses the constraints that are specific to each class of material and the target design strategies.

  5. Development of the Data Processing and Analysis System Framework for ICF Experiments

    Institute of Scientific and Technical Information of China (English)

    Yang Dong; Yu Xiaoqi; Zhang Chi

    2005-01-01

    An idea is presented about the development of a data processing and analysis system for ICF experiments, which is based on an object oriented framework. The design and preliminary implementation of the data processing and analysis framework based on the ROOT system have been completed. Software for unfolding soft X-ray spectra has been developed to test the functions of this framework.

  6. BPS-ICF model, a tool to measure biopsychosocial functioning and disability within ICF concepts: theory and practice updated.

    Science.gov (United States)

    Talo, Seija A; Rytökoski, Ulla M

    2016-03-01

    The transformation of International Classification of Impairments, Disabilities and Handicaps into International Classification of Functioning, Disability and Health (ICF) meant a lot for those needing to communicate in terms of functioning concept in their daily work. With ICF's commonly understood language, the decades' uncertainty on what concepts and terms describe functioning and disabilities seemed to be dispelled. Instead, operationalizing ICF to measure the level of functioning along with the new nomenclature has not been as unambiguous. Transforming linguistic terms into quantified functioning seems to need another type of theorizing. Irrespective of challenging tasks, numerous projects were formulated during the past decades to apply ICF for measurement purposes. This article updates one of them, the so-called biopsychosocial-ICF model, which uses all ICF categories but classifies them into more components than ICF for measurement purposes. The model suggests that both disabilities and functional resources should be described by collecting and organizing functional measurement data in a multidisciplinary, biopsychosocial data matrice.

  7. Kr X-ray spectroscopy to diagnose NIF ICF implosions

    Science.gov (United States)

    Dasgupta, A.; Ouart, N.; Giuliani, J. L.; Clark, R. W.; Schneider, M. B.; Scott, H. A.; Chen, H.; Ma, T.; Apruzese, J. P.

    2016-10-01

    X ray spectroscopy is used on the NIF to diagnose the plasma conditions in the ignition target in indirect drive ICF implosions. High-energy emission spectra from mid to high atomic number elements can provide estimates of electron temperature near stagnation of an ICF implosion. A platform is being developed at NIF where small traces of krypton are used as a dopant to the fuel gas for spectroscopic diagnostics using krypton line emissions. The fraction of krypton dopant was varied in the experiments and was selected so as not to perturb the implosion. Simulations of the krypton spectra using a 1 in 104 atomic fraction of krypton in direct-drive exploding pusher with a range of electron temperatures and densities show discrepancies when different atomic models are used. We use our non-LTE atomic model with a detailed fine-structure level atomic structure and collisional-radiative rates to investigate the krypton spectra at the same conditions. Synthetic spectra are generated with a detailed multi-frequency radiation transport scheme from the emission regions of interest to analyze the experimental data and compare and contrast with the existing simulations at LLNL. Work supported by DOE/NNSA and under the auspices of DOE by LLNL under Contract # DE-AC52-07NA27344.

  8. ICF quarterly report January - March 1997 volume 7, number 3

    Energy Technology Data Exchange (ETDEWEB)

    Murray, J

    1998-04-09

    The National Ignition Facility Project The mission of the National Ignition Facility (NIF) is to produce ignition and modest energy gain in inertial confinement fusion (ICF) targets. Achieving these goals will maintain U.S. world leadership in ICF and will directly benefit the U.S. Department of Energy (DOE) missions in national security, science and technology, energy resources, and industrial competitiveness. Development and operation of the NIF are consistent with DOE goals for environmental quality, openness to the community, and nuclear nonproliferation and arms control. Although the primary mission of inertial fusion is for defense applications, inertial fusion research will provide critical information for the development of inertial fusion energy. The NIF, under construction at Lawrence Livermore National Laboratory (LLNL), is a cornerstone of the DOE's science-based Stockpile Stewardship Program for addressing high-energy-density physics issues in the absence of nuclear weapons testing. In pursuit of this mission, the DOE's Defense Programs has developed a state-of-the-art capability with the NIF to investigate high-energy-density physics in the laboratory with a microfusion capability for defense and energy applications. As a Strategic System Acquisition, the NIF Project has a separate and disciplined reporting chain to DOE as shown below.

  9. An international qualitative study of ability and disability in ADHD using the WHO-ICF framework.

    Science.gov (United States)

    Mahdi, Soheil; Viljoen, Marisa; Massuti, Rafael; Selb, Melissa; Almodayfer, Omar; Karande, Sunil; de Vries, Petrus J; Rohde, Luis; Bölte, Sven

    2017-03-28

    This is the third in a series of four cross-cultural empirical studies designed to develop International Classification of Functioning, Disability and Health (ICF, and Children and Youth version, ICF(-CY) Core Sets for Attention-Deficit Hyperactivity Disorder (ADHD). To explore the perspectives of individuals diagnosed with ADHD, self-advocates, immediate family members and professional caregivers on relevant areas of impairment and functional abilities typical for ADHD across the lifespan as operationalized by the ICF(-CY). A qualitative study using focus group discussions or semi-structured interviews of 76 participants, divided into 16 stakeholder groups. Participants from five countries (Brazil, India, Saudi Arabia, South Africa and Sweden) were included. A deductive qualitative content analysis was conducted to extract meaningful functioning and disability concepts from verbatim material. Extracted concepts were then linked to ICF(-CY) categories by independent researchers using a standardized linking procedure. In total, 82 ICF(-CY) categories were identified, of which 32 were related to activities and participation, 25 to environmental factors, 23 to body functions and 2 to body structures. Participants also provided opinions on experienced positive sides to ADHD. A high level of energy and drive, creativity, hyper-focus, agreeableness, empathy, and willingness to assist others were the most consistently reported strengths associated with ADHD. Stakeholder perspectives highlighted the need to appraise ADHD in a broader context, extending beyond diagnostic criteria into many areas of ability and disability as well as environmental facilitators and barriers. This qualitative study, along with three other studies (comprehensive scoping review, expert survey and clinical study), will provide the scientific basis to define ICF(-CY) Core Sets for ADHD, from which assessment tools can be derived for use in clinical and research setting, as well as in health care

  10. Evolutionary Multiobjective Design Targeting a Field Programmable Transistor Array

    Science.gov (United States)

    Aguirre, Arturo Hernandez; Zebulum, Ricardo S.; Coello, Carlos Coello

    2004-01-01

    This paper introduces the ISPAES algorithm for circuit design targeting a Field Programmable Transistor Array (FPTA). The use of evolutionary algorithms is common in circuit design problems, where a single fitness function drives the evolution process. Frequently, the design problem is subject to several goals or operating constraints, thus, designing a suitable fitness function catching all requirements becomes an issue. Such a problem is amenable for multi-objective optimization, however, evolutionary algorithms lack an inherent mechanism for constraint handling. This paper introduces ISPAES, an evolutionary optimization algorithm enhanced with a constraint handling technique. Several design problems targeting a FPTA show the potential of our approach.

  11. Hemozoin Formation as a Target for Antimalarial Drug Design

    Science.gov (United States)

    2005-02-01

    AD Award Number: DAMD17-03-1-0030 TITLE: Hemozoin Formation as a Target for Antimalarial Drug Design PRINCIPAL INVESTIGATOR: Michael K. Riscoe, Ph.D...Formation as a Target for Antimalarial Drug Design DAMD17-03-1-0030 6. A UTHOR(S) Michael K. Riscoe, Ph.D. 7. PERFORMING ORGANIZA TION NAME(S) AND ADDRESS...Report: by Principal Investigator - Michael K. Riscoe, Ph.D. DAMD1 7-03-1-0030: "Hemozoin Formation as a Target for Antimalarial Drug Design " INTRODUCTION

  12. The design, construction and performance of the MICE target

    CERN Document Server

    Booth, C N; Howlett, L; Nicholson, R; Overton, E; Robinson, M; Smith, P J; Apollonio, M; Barber, G; Dobbs, A; Leaver, J; Long, K R; Shepherd, B; Adams, D; Capocci, E; McCarron, E; Tarrant, J

    2012-01-01

    The pion-production target that serves the MICE Muon Beam consists of a titanium cylinder that is dipped into the halo of the ISIS proton beam. The design and construction of the MICE target system are described along with the quality-assurance procedures, electromagnetic drive and control systems, the readout electronics, and the data-acquisition system. The performance of the target is presented together with the particle rates delivered to the MICE Muon Beam. Finally, the beam loss in ISIS generated by the operation of the target is evaluated as a function of the particle rate, and the operating parameters of the target are derived.

  13. Target based drug design - a reality in virtual sphere.

    Science.gov (United States)

    Verma, Saroj; Prabhakar, Yenamandra S

    2015-01-01

    The target based drug design approaches are a series of computational procedures, including visualization tools, to support the decision systems of drug design/discovery process. In the essence of biological targets shaping the potential lead/drug molecules, this review presents a comprehensive position of different components of target based drug design which include target identification, protein modeling, molecular dynamics simulations, binding/catalytic sites identification, docking, virtual screening, fragment based strategies, substructure treatment of targets in tackling drug resistance, in silico ADMET, structural vaccinology, etc along with the key issues involved therein and some well investigated case studies. The concepts and working of these procedures are critically discussed to arouse interest and to advance the drug research.

  14. New schools design: Acoustics as main target

    Science.gov (United States)

    Maffei, Luigi; Lembo, Paola

    2005-04-01

    The effects of poor intelligibility and high background noise levels on the cognitive development of school children and on the dissatisfaction of teachers has been largely investigated. National standards have been implemented and attempts to harmonize these standards in international guidelines are ongoing. All these activities have led to the awareness that design of new schools must be centered on the achievement of a good acoustic environment. At this point a strong research effort to study and implement best solutions must be conducted, in collaboration, by architects, acousticians, pedagogues, psychologists, builders and acoustic materials producers. Recently an international competition for the planning of new primary schools in Rome, Italy has been announced. The aim of the competition is to study new architectural and running features of primary schools to obtain, among other parameters such as lighting, low cost energy solutions and air quality, the control of reverberation time, sound insulation and mechanical equipments noise. In these school buildings, as innovative requirement, children must be also able to elaborate interpretative hypothesis of physical phenomena such as sound emission and perception and be aware of their influence on these phenomena. Different possible solutions are presented.

  15. Target Value Design: The Challenge of Value Generation

    OpenAIRE

    Gomes Miron, Luciana; Kaushik, Amit; Koskela, Lauri

    2015-01-01

    Target Value Design (TVD) is a management approach that aims to maximize value in the framework of a pre-established cost target. TVD views AEC (Architecture, Engineering and Construction) as a complex system and transforms the current design practice upside down. In spite of the existing studies, applying TVD in the context of AEC still represents a major challenge. Creating a structure that enables and measures value generation to the client is part of this challenge. However, despite the c...

  16. Design of the next generation target at Lujan center, LANSCE.

    Energy Technology Data Exchange (ETDEWEB)

    Ferres, Laurent [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-07-27

    This is a presentation given at Los Alamos National Laboratory (LANL) on the design of the next generation target at Lujan center, LANSCE. The motivation for this design is to enable new nuclear physics experiments (defense program applications (DANCE)) that are currently limited by neutron intensity or energy resolution available at LANSCE. The target is being redesigned so that the Flight Paths in the upper tier provide a higher intensity in the epithermal and medium energy ranges.

  17. Computational design of nanoparticle drug delivery systems for selective targeting.

    Science.gov (United States)

    Duncan, Gregg A; Bevan, Michael A

    2015-10-01

    Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ρR, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ρL. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting diseased cells and tissues.

  18. Inertial confinement fusion. 1995 ICF annual report, October 1994--September 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-06-01

    Lawrence Livermore National Laboratory`s (LLNL`s) Inertial Confinement Fusion (ICF) Program is a Department of Energy (DOE) Defense Program research and advanced technology development program focused on the goal of demonstrating thermonuclear fusion ignition and energy gain in the laboratory. During FY 1995, the ICF Program continued to conduct ignition target physics optimization studies and weapons physics experiments in support of the Defense Program`s stockpile stewardship goals. It also continued to develop technologies in support of the performance, cost, and schedule goals of the National Ignition Facility (NIF) Project. The NIF is a key element of the DOE`s Stockpile Stewardship and Management Program. In addition to its primary Defense Program goals, the ICF Program provides research and development opportunities in fundamental high-energy-density physics and supports the necessary research base for the possible long-term application to inertial fusion energy (IFE). Also, ICF technologies have had spin-off applications for industrial and governmental use. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  19. Investigating the International Classification of Functioning, Disability, and Health (ICF) Framework to Capture User Needs in the Concept Stage of Rehabilitation Technology Development.

    Science.gov (United States)

    Sivan, Manoj; Gallagher, Justin; Holt, Ray; Weightman, Andy; Levesley, Martin; Bhakta, Bipin

    2014-01-01

    This study evaluates whether the International Classification of Functioning, Disability, and Health (ICF) framework provides a useful basis to ensure that key user needs are identified in the development of a home-based arm rehabilitation system for stroke patients. Using a qualitative approach, nine people with residual arm weakness after stroke and six healthcare professionals with expertise in stroke rehabilitation were enrolled in the user-centered design process. They were asked, through semi-structured interviews, to define the needs and specification for a potential home-based rehabilitation device to facilitate self-managed arm exercise. The topic list for the interviews was derived by brainstorming ideas within the clinical and engineering multidisciplinary research team based on previous experience and existing literature in user-centered design. Meaningful concepts were extracted from questions and responses of these interviews. These concepts obtained were matched to the categories within the ICF comprehensive core set for stroke using ICF linking rules. Most of the concepts extracted from the interviews matched to the existing ICF Core Set categories. Person factors like gender, age, interest, compliance, motivation, choice, and convenience that might determine device usability are yet to be categorized within the ICF comprehensive core set. The results suggest that the categories of the comprehensive ICF Core Set for stroke provide a useful basis for structuring interviews to identify most users needs. However some personal factors (related to end users and healthcare professionals) need to be considered in addition to the ICF categories.

  20. ICF Ignition, the Lawson Criterion, and Comparison with MFE Ignition

    Science.gov (United States)

    Betti, R.

    2009-11-01

    The Lawson criterion, which determines the onset of thermonuclear ignition, is usually expressed through the product pτ > 10 atm . s, where p is the plasma pressure in atm and τ is the energy confinement time in seconds. In magnetic fusion devices, both the pressure and confinement time are routinely measured and the performance of each discharge can be assessed by comparing the value of pτ with respect to the ignition value (10 atm . s). In inertial confinement fusion, both p and τ cannot be directly measured and the performance of surrogate and/or subignited ICF implosions cannot be assessed with respect to the ignition condition. This makes it difficult to compare the performance of ICF implosions with that of magnetic fusion energy (MFE) discharges. Here, we define the meaning of ignition in ICF implosions and compare it to MFE ignition. We then show that a multidimensional ignition condition for inertial confinement fusion can be cast in a form that depends on three measurable parameters of the compressed-fuel assembly: the hot-spot ion temperature T, the neutron yield normalized to the 1-D prediction (yield over clean or YOC) and the total areal density ρR, which includes the cold shell's contribution. A family of marginal-ignition curves are derived in the ρR--T plane.footnotetext C. D. Zhou and R. Betti, Phys. Plasmas 15, 102707 (2008). On this plane, hydrodynamic-equivalent curves show how a given implosion would perform with respect to the ignition condition when the laser-driver energy is varied. Such a criterion can be used to measure the ignition marginfootnotetext D. S. Clark, S. W. Haan, and J. D. Salmonson, Phys. Plasmas 15, 056305 (2008). of NIF targets and to predict the performance of OMEGA targets when scaled up to NIF energies. This work has been supported by the US Department of Energy under Cooperative Agreement Nos. DE-FC02-ER54789 and DE-FC52-08NA28302.

  1. LBNF 1.2 MW TARGET: CONCEPTUAL DESIGN & FABRICATION

    Energy Technology Data Exchange (ETDEWEB)

    Crowley, Cory F. [Fermilab; Ammigan, K. [Fermilab; Anderson, K. [Fermilab; Hartsell, B. [Fermilab; Hurh, P. [Fermilab; Hylen, J. [Fermilab; Zwaska, R. [Fermilab

    2015-06-29

    Fermilab’s Long-Baseline Neutrino Facility (LBNF) will utilize a modified design based on the NuMI low energy target that is reconfigured to accommodate beam operation at 1.2 MW. Achieving this power with a graphite target material and ancillary systems originally rated for 400 kW requires several design changes and R&D efforts related to material bonding and electrical isolation. Target cooling, structural design, and fabrication techniques must address higher stresses and heat loads that will be present during 1.2 MW operation, as the assembly will be subject to cyclic loads and thermal expansion. Mitigations must be balanced against compromises in neutrino yield. Beam monitoring and subsystem instrumentation will be updated and added to ensure confidence in target positioning and monitoring. Remote connection to the target hall support structure must provide for the eventual upgrade to a 2.4 MW target design, without producing excessive radioactive waste or unreasonable exposure to technicians during reconfiguration. Current designs and assembly layouts will be presented, in addition to current findings on processes and possibilities for prototype and final assembly fabrication.

  2. Approximate Design of Alloy Composition of Cathode Target

    Institute of Scientific and Technical Information of China (English)

    Jun ZHANG; Yu ZHANG; Li LI; Guoqiang LIN; Chuang DONG

    2006-01-01

    An empirical formula for composition demixing analysis in cathodic arc ion plating using alloy target is established based on the concepts of average charged state and relative demixing parameter. The level of composition demixing effect is presented by demixing degree of one element. For binary constituent alloy target, the composition change trend in coating is discussed and the limit of demixing degree for each element is determined. The content of one element with higher average charged state gets larger in coating than in alloy target, at meantime, the content of one element with lower average charged state gets less. For each one of the two constituents, the less the atom percent in alloy target, the larger the difference of its contents between the coating and the target. For triple constituent alloy target, the content change of one element with moderate average charged state is discussed in detail. Its content in coating getting larger or less is determined by the combination result of the contents of the other two elements in alloy target. For a given content of the element with moderate average charged state in triple alloy target, the content deviation level of that element from coating to alloy target will be not larger than that using binary alloy target containing only that element and one of the two others. According to the wanted coating composition, the composition design of alloy target is easily deduced from the formula.

  3. Monte Carlo Methods in ICF (LIRPP Vol. 13)

    Science.gov (United States)

    Zimmerman, George B.

    2016-10-01

    Monte Carlo methods appropriate to simulate the transport of x-rays, neutrons, ions and electrons in Inertial Confinement Fusion targets are described and analyzed. The Implicit Monte Carlo method of x-ray transport handles symmetry within indirect drive ICF hohlraums well, but can be improved SOX in efficiency by angular biasing the x-rays towards the fuel capsule. Accurate simulation of thermonuclear burn and burn diagnostics involves detailed particle source spectra, charged particle ranges, inflight reaction kinematics, corrections for bulk and thermal Doppler effects and variance reduction to obtain adequate statistics for rare events. It is found that the effects of angular Coulomb scattering must be included in models of charged particle transport through heterogeneous materials.

  4. Exploring use of the ICF in health education.

    Science.gov (United States)

    Bornbaum, Catherine C; Day, Adam M B; Izaryk, Kristen; Morrison, Stephanie J; Ravenek, Michael J; Sleeth, Lindsay E; Skarakis-Doyle, Elizabeth

    2015-01-01

    Currently, little is known regarding use of the International Classification of Functioning, Disability and Health (ICF) in health education applications. Therefore, this review sought to examine the scope of work that has been conducted regarding the application of the ICF in health education. A review of the current literature related to use of the ICF in health education programs was conducted. Twelve electronic databases were searched in accordance with a search protocol developed by a health sciences librarian. In total, 17,878 records were reviewed, and 18 articles met the criteria for inclusion in this review. Current evidence regarding use of the ICF in healthcare education revealed that program and participant properties can be essential facilitators or barriers to successful education programs. In addition, gaps in comprehensive outcome measurement were revealed as areas for future attention. Educational applications of the ICF are very much a work in progress as might be expected given the ICF's existence for only a little over a decade. To advance use of the ICF in education, it is important to incorporate the measurement of both knowledge acquisition and behavior change related to ICF-based programs. Ultimately, widespread implementation of the ICF represents not only a substantial opportunity but also poses a significant challenge.

  5. Toolbox of multiple-item measures aligning with the ICF Core Sets for children and youth with cerebral palsy.

    Science.gov (United States)

    Schiariti, Verónica; Tatla, Sandy; Sauve, Karen; O'Donnell, Maureen

    2017-03-01

    Selecting appropriate measure(s) for clinical and/or research applications for children and youth with Cerebral Palsy (CP) poses many challenges. The newly developed International Classification of Functioning, Disability and Health (ICF) Core Sets for children and youth with CP serve as universal guidelines for assessment, intervention and follow-up. The aims of this study were: 1) to identify valid and reliable measures used in studies with children and youth with CP, 2) to characterize the content of each measure using the ICF Core Sets for children and youth with CP as a framework, and finally 3) to create a toolbox of psychometrically sound measures covering the content of each ICF Core Set for children and youth with CP. All clearly defined multiple-item measures used in studies with CP between 1998 and 2015 were identified. Psychometric properties were extracted when available. Construct of the measures were linked to the ICF Core Sets. Overall, 83 multiple-item measures were identified. Of these, 68 measures (80%) included reliability and validity testing. The majority of the measures were discriminative, generic and designed for school-aged children. The degree to which measures with proven psychometric properties represented the ICF Core Sets for children and youth with CP varied considerably. Finally, 25 valid and reliable measures aligned highly with the content of the ICF Core Sets, and as such, these measures are proposed as a novel ICF Core Sets-based toolbox of measures for CP. Our results will guide professionals seeking appropriate measures to meet their research and clinical needs worldwide. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  6. Quantitative modeling of selective lysosomal targeting for drug design

    DEFF Research Database (Denmark)

    Trapp, Stefan; Rosania, G.; Horobin, R.W.;

    2008-01-01

    Lysosomes are acidic organelles and are involved in various diseases, the most prominent is malaria. Accumulation of molecules in the cell by diffusion from the external solution into cytosol, lysosome and mitochondrium was calculated with the Fick–Nernst–Planck equation. The cell model considers....... This demonstrates that the cell model can be a useful tool for the design of effective lysosome-targeting drugs with minimal off-target interactions....

  7. Design of a covert RFID tag network for target discovery and target information routing.

    Science.gov (United States)

    Pan, Qihe; Narayanan, Ram M

    2011-01-01

    Radio frequency identification (RFID) tags are small electronic devices working in the radio frequency range. They use wireless radio communications to automatically identify objects or people without the need for line-of-sight or contact, and are widely used in inventory tracking, object location, environmental monitoring. This paper presents a design of a covert RFID tag network for target discovery and target information routing. In the design, a static or very slowly moving target in the field of RFID tags transmits a distinct pseudo-noise signal, and the RFID tags in the network collect the target information and route it to the command center. A map of each RFID tag's location is saved at command center, which can determine where a RFID tag is located based on each RFID tag's ID. We propose the target information collection method with target association and clustering, and we also propose the information routing algorithm within the RFID tag network. The design and operation of the proposed algorithms are illustrated through examples. Simulation results demonstrate the effectiveness of the design.

  8. [The Prognostic Significance of ICF Data with Regard to Realization of Recommendations Given in the Medical Discharge Report after In-Patient Psychosomatic Rehabilitation].

    Science.gov (United States)

    Oster, Jörg; von Wietersheim, Jörn; Müller, Gottfried; Braunger, Carina

    2017-05-01

    Target In this trial, the prognostic significance of ICF-related diagnostics compared to social and medical, disease-related and personal factors with regard to realization of recommendations given in the medical discharge report after the in-patient psychosomatic rehabilitation should be examined. Methodology ICF-related, social and medical, disease-related and personal prognostic factors were surveyed by questionnaires and interviews, on admission, discharge and 6 months after discharge from rehabilitation (time of catamnesis). As target criteria, realizations of recommendations from the fields of sports and exercise, psychotherapy and social medicine were chosen, they could be evaluated by telephone from N=344 participants at the time of catamnesis. For determination of relevant predictors, bivariate and multi-variate analyses were performed. Results 70% of patients realized the recommended sports and exercise, 45% the recommended psychotherapy and 44% a social and medical recommendation. With regard to the target criterion for the realization of recommended sports and exercise, the elevated prognostic factors had only a low prognostic value. For the prognosis of the target criterion of realizing a recommended psychotherapy, interpersonal problems and a low ability to interact in groups (Mini-ICF-APP) turned out to be relevant ICF-related predictors. Different problems (e. g., job-related conditions) appeared as relevant, ICF-related predictors concerning the realization of social and medical recommendations. Disturbances of reliability, self-evaluated by means of ICF AT-50 Psych, showed in the bivariate analyses significant correlations with the target criteria. Conclusion Besides other variables, also ICF-supported attributes turned out to be suitable for the prognosis of target criteria. They should be evaluated and considered in the rehabilitation process. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Target value design: applications to newborn intensive care units.

    Science.gov (United States)

    Rybkowski, Zofia K; Shepley, Mardelle McCuskey; Ballard, H Glenn

    2012-01-01

    There is a need for greater understanding of the health impact of various design elements in neonatal intensive care units (NICUs) as well as cost-benefit information to make informed decisions about the long-term value of design decisions. This is particularly evident when design teams are considering the transition from open-bay NICUs to single-family-room (SFR) units. This paper introduces the guiding principles behind target value design (TVD)-a price-led design methodology that is gaining acceptance in healthcare facility design within the Lean construction methodology. The paper also discusses the role that set-based design plays in TVD and its application to NICUs.

  10. Towards an ICF core set for ADHD: a worldwide expert survey on ability and disability.

    Science.gov (United States)

    de Schipper, Elles; Mahdi, Soheil; Coghill, David; de Vries, Petrus J; Gau, Susan Shur-Fen; Granlund, Mats; Holtmann, Martin; Karande, Sunil; Levy, Florence; Almodayfer, Omar; Rohde, Luis; Tannock, Rosemary; Bölte, Sven

    2015-12-01

    This is the second in a series of four empirical studies designed to develop International Classification of Functioning, Disability and Health (ICF and Children and Youth version, ICF-CY) core sets for attention deficit hyperactivity disorder (ADHD). The objective of this stage was to gather the opinions from international experts on which ability and disability concepts were considered relevant to functioning in ADHD. An email-based survey was carried out amongst international experts in ADHD. Relevant functional ability and disability concepts were extracted from their responses and linked to the ICF/-CY categories by two independent researchers using a standardised linking procedure. 174 experts from 11 different disciplines and 45 different countries completed the survey. Meaningful concepts identified in their responses were linked to 185 ICF/-CY categories. Of these, 83 categories were identified by at least 5 % of the experts and considered the most relevant to ADHD: 30 of these were related to Body functions (most identified: attention functions, 85 %), 30 to Activities and Participation (most identified: school education, 52 %), 20 to Environmental factors (most identified: support from immediate family, 61 %), and 3 to Body structures (most identified: structure of brain, 83 %). Experts also provided their views on particular abilities related to ADHD, naming characteristics such as high-energy levels, flexibility and resiliency. Gender differences in the expression of ADHD identified by experts pertained mainly to females showing more internalising (e.g. anxiety, low self-esteem) and less externalising behaviours (e.g. hyperactivity), leading to a risk of late- and under-diagnosis in females. Results indicate that the impact of ADHD extends beyond the core symptom domains, into all areas of life and across the lifespan. The current study in combination with three additional preparatory studies (comprehensive scoping review, focus groups, clinical study

  11. ICF-CY: A Universal Tool for Documentation of Disability

    Science.gov (United States)

    Simeonsson, Rune J.

    2009-01-01

    The "International Classification of Functioning, Disability and Health--ICF" (ICF-CY) conceptual framework offers a new paradigm and taxonomy of human functioning disability, which can be used to guide holistic and interdisciplinary approaches to assessment and intervention. In settings serving children, youth, or adults with disabilities, the…

  12. Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives

    Directory of Open Access Journals (Sweden)

    Avinaba Mukherjee

    2016-03-01

    Full Text Available Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the ‘apicoplast’, which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle’s function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug

  13. Plasma Viscosity with Mass Transport in Spherical ICF Implosion Simulations

    CERN Document Server

    Vold, Erik L; Ortega, Mario I; Moll, Ryan; Fenn, Daniel; Molvig, Kim

    2015-01-01

    The effects of viscosity and small-scale atomic-level mixing on plasmas in inertial confinement fusion (ICF) currently represent challenges in ICF research. Many current ICF hydrodynamic codes ignore the effects of viscosity though recent research indicates viscosity and mixing by classical transport processes may have a substantial impact on implosion dynamics. We have implemented a Lagrange hydrodynamic code in one-dimensional spherical geometry with plasma viscosity and mass transport and including a three temperature model for ions, electrons, and radiation treated in a gray radiation diffusion approximation. The code is used to study ICF implosion differences with and without plasma viscosity and to determine the impacts of viscosity on temperature histories and neutron yield. It was found that plasma viscosity has substantial impacts on ICF shock dynamics characterized by shock burn timing, maximum burn temperatures, convergence ratio, and time history of neutron production rates. Plasma viscosity reduc...

  14. Oak Ridge Spallation Neutron Source (ORSNS) target station design integration

    Energy Technology Data Exchange (ETDEWEB)

    McManamy, T.; Booth, R.; Cleaves, J.; Gabriel, T. [and others

    1996-06-01

    The conceptual design for a 1- to 3-MW short pulse spallation source with a liquid mercury target has been started recently. The design tools and methods being developed to define requirements, integrate the work, and provide early cost guidance will be presented with a summary of the current target station design status. The initial design point was selected with performance and cost estimate projections by a systems code. This code was developed recently using cost estimates from the Brookhaven Pulsed Spallation Neutron Source study and experience from the Advanced Neutron Source Project`s conceptual design. It will be updated and improved as the design develops. Performance was characterized by a simplified figure of merit based on a ratio of neutron production to costs. A work breakdown structure was developed, with simplified systems diagrams used to define interfaces and system responsibilities. A risk assessment method was used to identify potential problems, to identify required research and development (R&D), and to aid contingency development. Preliminary 3-D models of the target station are being used to develop remote maintenance concepts and to estimate costs.

  15. ENGINEERING DESIGN OF THE EURISOL MULTI-MW SPALLATION TARGET

    CERN Document Server

    Adonai Herrera-Martinez*, Yacine Kadi, Morteza Ashrafi-Nik, Karel Samec, Janis Freibergs, Ernests Platacis

    The European Isotope Separation On-Line Radioactive Ion Beam project (EURISOL) is set to design the ‘next-generation’ European Isotope Separation On-Line (ISOL) Radioactive Ion Beam (RIB) facility. It will extend and amplify current research on nuclear physics, nuclear astrophysics and fundamental interactions beyond the year 2010. In EURISOL, four target stations are foreseen, three direct targets of approximately 100 kW of beam power and one multi-MW target assembly, all driven by a high-power particle accelerator. In this high power target station, high-intensity RIBs of neutron-rich isotopes will be obtained by inducing fission in several actinide targets surrounding a liquid metal spallation neutron source. This article summarises the work carried out within Task 2 of the EURISOL Design Study, with special attention to the coupled neutronics of the mercury proton-to-neutron converter and the fission targets. The overall performance of the facility, which will sustain fast neutron fluxes of the order ...

  16. Engineering design of the EURISOL multi-MW spallation target

    CERN Document Server

    Herrera-Martínez, A; Ashrafi-Nik, M; Samec, K; Freibergs, J; Platacis, E

    2007-01-01

    The European Isotope Separation On-Line Radioactive Ion Beam project (EURISOL) is set to design the 'next-generation' European Isotope Separation On-Line (ISOL) Radioactive Ion Beam (RIB) facility. It will extend and amplify current research on nuclear physics, nuclear astrophysics and fundamental interactions beyond the year 2010. In EURISOL, four target stations are foreseen, three direct targets of approximately 100 kW of beam power and one multi-MW target assembly, all driven by a high-power particle accelerator. In this high power target station, high-intensity RIBs of neutron-rich isotopes will be obtained by inducing fission in several actinide targets surrounding a liquid metal spallation neutron source. This article summarises the work carried out within Task 2 of the EURISOL Design Study, with special attention to the coupled neutronics of the mercury proton-to-neutron converter and the fission targets. The overall performance of the facility, which will sustain fast neutron fluxes of the order of 1...

  17. International Classification of Functioning, Disability and Health (ICF) Core Set for patients with vertigo, dizziness and balance disorders.

    Science.gov (United States)

    Grill, Eva; Bronstein, Adolfo; Furman, Joseph; Zee, David S; Müller, Martin

    2012-01-01

    Vertigo, dizziness and balance disorders have major impact on independence, employability, activities and participation. There are many measures for the assessment of the impact of vertigo, but no consensus exists on which aspects should be measured. The objective of this study was to develop international standards (ICF Core Sets) for patients with vertigo and dizziness to describe functioning. The development of the ICF Core Sets involved a formal decision-making and consensus process, integrating evidence from preparatory studies including qualitative interviews with patients, a systematic review of the literature, a survey with health professionals, and empirical data collection from patients. Twenty-seven experts selected 100 second level categories for the comprehensive Core Set and 29 second level categories for the Brief Core Set. The largest number of categories was selected from the ICF component Activities and Participation (40). Twenty-five categories were selected from the component Body Functions, six from Body Structures, and 29 from Environmental Factors. The ICF Core Set for vertigo is designed for physicians, nurses, therapists and other health professionals working in inpatient or ambulatory settings. ICF Core Sets create patient-relevant outcomes that can be used as evidence for the success of treatments.

  18. Designing Multi-target Compound Libraries with Gaussian Process Models.

    Science.gov (United States)

    Bieler, Michael; Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Kriegl, Jan M; Schneider, Gisbert

    2016-05-01

    We present the application of machine learning models to selecting G protein-coupled receptor (GPCR)-focused compound libraries. The library design process was realized by ant colony optimization. A proprietary Boehringer-Ingelheim reference set consisting of 3519 compounds tested in dose-response assays at 11 GPCR targets served as training data for machine learning and activity prediction. We compared the usability of the proprietary data with a public data set from ChEMBL. Gaussian process models were trained to prioritize compounds from a virtual combinatorial library. We obtained meaningful models for three of the targets (5-HT2c , MCH, A1), which were experimentally confirmed for 12 of 15 selected and synthesized or purchased compounds. Overall, the models trained on the public data predicted the observed assay results more accurately. The results of this study motivate the use of Gaussian process regression on public data for virtual screening and target-focused compound library design.

  19. VISRAD, 3-D Target Design and Radiation Simulation Code

    Science.gov (United States)

    Golovkin, Igor; Macfarlane, Joseph; Golovkina, Viktoriya

    2016-10-01

    The 3-D view factor code VISRAD is widely used in designing HEDP experiments at major laser and pulsed-power facilities, including NIF, OMEGA, OMEGA-EP, ORION, LMJ, Z, and PLX. It simulates target designs by generating a 3-D grid of surface elements, utilizing a variety of 3-D primitives and surface removal algorithms, and can be used to compute the radiation flux throughout the surface element grid by computing element-to-element view factors and solving power balance equations. Target set-up and beam pointing are facilitated by allowing users to specify positions and angular orientations using a variety of coordinates systems (e.g., that of any laser beam, target component, or diagnostic port). Analytic modeling for laser beam spatial profiles for OMEGA DPPs and NIF CPPs is used to compute laser intensity profiles throughout the grid of surface elements. We will discuss recent improvements to the software package and plans for future developments.

  20. Ignition and burn of a small magnetized fuel target

    Energy Technology Data Exchange (ETDEWEB)

    Kirkpatrick, Ronald C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2012-06-01

    The crucial step for inertial confinement fusion (ICF) is ignition, which leads to sufficiently high gain to enable design of a power producing system. Thus far, this step has not been demonstrated. Magnetized targets may provide an alternative path to ignition. In addition, the 1-D calculations presented here suggest that this approach may provide the gain and other characteristics needed for a practical fusion reactor.

  1. Drive Asymmetry and the Origin of Turbulence in an ICF Implosion

    CERN Document Server

    Thomas, V A; 10.1103/PhysRevLett.109.075004

    2012-01-01

    2D and 3D numerical simulations with the adaptive mesh refinement Eulerian radiation-hydrocode RAGE at unprecedented spatial resolution are used to investigate the connection between drive asymmetry and the generation of turbulence in the DT fuel in a simplified inertial-confinement fusion (ICF) implosion. Long-wavelength deviations from spherical symmetry in the pressure drive lead to the generation of coherent vortical structures in the DT gas and it is the three-dimensional instability of these structures that in turn leads to turbulence and mix. The simulations sug-gest that this mechanism may be an additional important source of mix in ICF implosions. Applications to target ignition at the National Ignition Facility are briefly discussed.

  2. X-ray spectroscopic signatures of ion species separation in ICF implosions on OMEGA

    Science.gov (United States)

    Hakel, Peter; Hsu, Scott; Herrmann, Hans; Kim, Yong Ho; Schmitt, Mark; Kagan, Grigory; McEvoy, Aaron; Colgan, James; Fontes, Christopher; Kilcrease, David; Sherrill, Manolo; Rauenzahn, Rick

    2015-11-01

    This work aims to provide a direct measurement of the species separation through experimental inference of the ion density profiles, and comparisons of the data with simulations that explicitly model multi-ion-species diffusion. We also describe the development of a new code capable of modeling x-ray spectral emission from ICF capsules that accounts for the effects of spatial gradients in species distributions throughout the target. This new code named FESTR also allows the inclusion of NLTE, opacity, and Stark broadening effects on x-ray spectral line emissions. We show preliminary results from an OMEGA campaign to obtain direct measurements of ion species separation via advanced analysis of x-ray spectroscopy and spectrally resolved imaging data. These were symmetric direct-drive implosions of CH capsules with deuterium and trace argon gas fills. The implosions were designed to be in a collisional, diffusive regime and to take advantage of interspecies diffusion between the D and Ar driven by temperature gradients in the hot spot. X-ray spectral line emissions and narrowband images from He-like and H-like Ar ions are used to infer the spatial separation of Ar from D.

  3. Designing to target cost: one approach to design/construction integration

    DEFF Research Database (Denmark)

    Jørgensen, Bo

    2005-01-01

    One approach to a more integrated construction delivery process is the concept of ‘designing to target cost’ of which the first examples of application within a lean construction framework have recently been seen. This paper introduces the main principles of the design to target cost method...... and discusses the applicability of this approach to construction. The low degree of organizational and technical continuity from one construction project to the next limits the applicability of the design for target cost approach when compared to its origin in product development of mass manufactured artefacts...

  4. Target selection and transfer trajectories design for exploring asteroid mission

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Technique of target selection and profiles of transfer trajectory for Chinese asteroid exploring mission are studied systemically.A complete set of approaches to selecting mission targets and designing the transfer trajectory is proposed.First,when selecting a target for mission,some factors regarded as the scientific motivations are discussed.Then,when analyzing the accessibility of targets,instead of the classical strategy,the multiple gravity-assist strategy is provided.The suitable and possible targets,taking into account scientific value and technically feasible,are obtained via selection and estimation.When designing the transfer trajectory for exploring asteroid mission,an approach to selecting gravity-assist celestial body is proposed.Finally,according to the mission constraints,the trajectory profile with 2-years △V-EGA for exploring asteroid is presented.Through analyzing the trajectory profile,unexpected result that the trajectory would pass by two main-belts asteroids is found.So,the original proposal is extended to the multiple flybys mission.It adds the scientific return for asteroid mission.

  5. Optimum nuclear design of target fuel rod for Mo-99 production in HANARO

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Myung Hyun [Kyung Hee University, Seoul (Korea)

    1998-04-01

    Nuclear target design for Mo-99 production in HANARO was performed, KAERI proposed target design was analyzed and its feasibility was shown. Three commercial target designs of Cintichem, ANL and KAERI were tested for the HANARO irradiation an d they all satisfied with design specification. A parametric study was done for target design options and Mo-99 yields ratio and surface heat flux were compared. Tested parameters were target fuel thickness, irradiation location, target axial length, packing density of powder fuel, size of target radius, target geometry, fuel enrichment, fuel composition, and cladding material. Optimized target fuel was designed for both LEU and HEU options. (author). 17 refs., 33 figs., 42 tabs.

  6. 42 CFR 440.150 - Intermediate care facility (ICF/MR) services.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Intermediate care facility (ICF/MR) services. 440....150 Intermediate care facility (ICF/MR) services. (a) “ICF/MR services” means those items and services... level of room and board; (2) The primary purpose of the ICF/MR is to furnish health or rehabilitative...

  7. MPD: multiplex primer design for next-generation targeted sequencing.

    Science.gov (United States)

    Wingo, Thomas S; Kotlar, Alex; Cutler, David J

    2017-01-05

    Targeted resequencing offers a cost-effective alternative to whole-genome and whole-exome sequencing when investigating regions known to be associated with a trait or disease. There are a number of approaches to targeted resequencing, including microfluidic PCR amplification, which may be enhanced by multiplex PCR. Currently, there is no open-source software that can design next-generation multiplex PCR experiments that ensures primers are unique at a genome-level and efficiently pools compatible primers. We present MPD, a software package that automates the design of multiplex PCR primers for next-generation sequencing. The core of MPD is implemented in C for speed and uses a hashed genome to ensure primer uniqueness, avoids placing primers over sites of known variation, and efficiently pools compatible primers. A JavaScript web application ( http://multiplexprimer.io ) utilizing the MPD Perl package provides a convenient platform for users to make designs. Using a realistic set of genes identified by genome-wide association studies (GWAS), we achieve 90% coverage of all exonic regions using stringent design criteria. Using the first 47 primer pools for wet-lab validation, we sequenced ~25Kb at 99.7% completeness with a mean coverage of 300X among 313 samples simultaneously and identified 224 variants. The number and nature of variants we observe are consistent with high quality sequencing. MPD can successfully design multiplex PCR experiments suitable for next-generation sequencing, and simplifies retooling targeted resequencing pipelines to focus on new targets as new genetic evidence emerges.

  8. The multi megawatt target station integration of the MAFF/PIAFE fission target design

    CERN Document Server

    Kharoua, C; Herrera-Martinez, A; Lettry, J; Ashrafi-Nik, M; Groeschel, F; Samec, K; Zanini, L; Alyakriskiy, O; Barbui, M; Tecchio, Luigi; Freibergs, J; Gross, M; Nebel, F; Thirolf, P; Negoita, F; Serbina, L; Romanets, Y; Vaz, P; Lindroos, M; Kadi, Y

    The European Isotope Separation On-Line Radioactive Ion Beam Facility (EURISOL) is set to be the ‘next-generation’ European Isotope Separation On-Line (ISOL) Radioactive Ion Beam (RIB) facility. It will extend and amplify current research on nuclear physics, nuclear astrophysics and fundamental interactions beyond the year 2010.In EURISOL, four target stations are foreseen, three direct targets of approximately 100 kW of beam power and one multi-MW liquid metal proton-to-neutron converter, all driven by a high-power particle accelerator. In the aforementioned multi-MW target assembly, high-intensity RIBs of neutron-rich isotopes will be obtained by inducing fission in several actinide targets surrounding a liquid metal spallation neutron source.This article summarises the work carried out within Task 2 of the EURISOL Design Study, with special attention to the coupled neutronics of the liquid converter and fission target (MAFF/PIAFE design like) and the overall performance of the facility, which will sust...

  9. Rational design of Rho GTPase-targeting inhibitors.

    Science.gov (United States)

    Shang, Xun; Zheng, Yi

    2012-01-01

    Rho GTPases have been implicated in diverse cellular functions and are potential therapeutic targets in inflammation, cancer, and neurologic diseases. Virtual screening of compounds that fit into surface grooves of RhoA known to be critical for guanine nucleotide exchange factor (GEF) interaction produced chemical candidates with minimized docking energy. Subsequent screening for inhibitory activity of RhoA binding to the Rho-GEF, LARG, identified a Rho-specific inhibitor as a lead compound capable of blocking RhoA-LARG interaction and RhoA activation by LARG specifically and dose dependently. A microscale thermophoresis analysis was applied to directly quantify the binding interaction of the lead inhibitor with RhoA target. The lead inhibitor highlights the principle that rational targeting of subfamily members of Rho GTPases is feasible and potentially useful in future drug design effort.

  10. Medicinal chemistry design principles for liver targeting through OATP transporters.

    Science.gov (United States)

    Tu, Meihua; Mathiowetz, Alan M; Pfefferkorn, Jeffrey A; Cameron, Kimberly O; Dow, Robert L; Litchfield, John; Di, Li; Feng, Bo; Liras, Spiros

    2013-01-01

    The tissue distribution of a drug can have significant impact on both its efficacy and safety. As a consequence, selective tissue targeting has become an attractive approach for optimizing the window between efficacy and safety for drug targets that are ubiquitously expressed and important in key physiological processes. Given the liver's key role in metabolic regulation and the fact that it is the principal tissue affected by diseases such as hepatitis B and C viruses as well as hepatocellular carcinoma, designing drugs with hepatoselective distribution profiles is an important strategy in developing safe cardiovascular, metabolic, antiviral and oncology drug candidates. In this paper, we analyze a diverse set of compounds from four different projects within Pfizer that specifically pursued liver targeting strategies. A number of key in vitro and in vivo ADME endpoints were collected including in vivo tissue exposure, oral bioavailability, clearance in preclinical species and in vitro hepatic OATP uptake, in vitro rat liver microsomal stability, permeability, solubility, logD, and others. From this analysis, we determined a set of general structure-liver-selectivity guides for designing orally bioavailable, liver-targeted candidates using liver specific OATP transporters. The guidelines have been formulated using straightforward molecular descriptors and in vitro properties that medicinal chemists routinely optimize. Our analysis emphasizes the need to focus on a chemical space with balanced lipophilicity, high aqueous solubility and low passive permeability in order to achieve the desired hepatoselectivity while maintaining fraction absorbed.

  11. Target Station Design for the Mu2e Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Pronskikh, Vitaly [Fermilab; Ambrosio, Giorgio [Fermilab; Campbell, Michael [Fermilab; Coleman, Richard [Fermilab; Ginther, George [Fermilab; Kashikhin, Vadim [Fermilab; Krempetz, Kurt [Fermilab; Lamm, Michael [Fermilab; Lee, Ang [Fermilab; Leveling, Anthony [Fermilab; Mokhov, Nikolai [Fermilab; Nagaslaev, Vladimir [Fermilab; Stefanik, Andrew [Fermilab; Striganov, Sergei [Fermilab; Werkema, Steven [Fermilab; Bartoszek, Larry [Technicare; Densham, Chris [Rutherford; Loveridge, Peter [Rutherford; Lynch, Kevin [BMCC, New York; Popp, James [BMCC, New York

    2014-07-01

    The Mu2e experiment at Fermilab is devoted to search for the conversion of a negative muon into an electron in the field of a nucleus without emission of neutrinos. One of the main parts of the Mu2e experimental setup is its Target Station in which negative pions are generated in interactions of the 8-GeV primary proton beam with a tungsten target. A large-aperture 5-T superconducting production solenoid (PS) enhances pion collection, and an S-shaped transport solenoid (TS) delivers muons and pions to the Mu2e detector. The heat and radiation shield (HRS) protects the PS and the first TS coils. A beam dump absorbs the spent beam. In order for the PS superconducting magnet to operate reliably the sophisticated HRS was designed and optimized for performance and cost. The beam dump was designed to absorb the spent beam and maintaining its temperature and air activation in the hall at the allowable level. Comprehensive MARS15 simulations have been carried out to optimize all the parts while maximizing muon yield. Results of simulations of critical radiation quantities and their implications on the overall Target Station design and integration will be reported.

  12. Selection and trajectory design to mission secondary targets

    Science.gov (United States)

    Victorino Sarli, Bruno; Kawakatsu, Yasuhiro

    2017-02-01

    Recently, with new trajectory design techniques and use of low-thrust propulsion systems, missions have become more efficient and cheaper with respect to propellant. As a way to increase the mission's value and scientific return, secondary targets close to the main trajectory are often added with a small change in the transfer trajectory. As a result of their large number, importance and facility to perform a flyby, asteroids are commonly used as such targets. This work uses the Primer Vector theory to define the direction and magnitude of the thrust for a minimum fuel consumption problem. The design of a low-thrust trajectory with a midcourse asteroid flyby is not only challenging for the low-thrust problem solution, but also with respect to the selection of a target and its flyby point. Currently more than 700,000 minor bodies have been identified, which generates a very large number of possible flyby points. This work uses a combination of reachability, reference orbit, and linear theory to select appropriate candidates, drastically reducing the simulation time, to be later included in the main trajectory and optimized. Two test cases are presented using the aforementioned selection process and optimization to add and design a secondary flyby to a mission with the primary objective of 3200 Phaethon flyby and 25143 Itokawa rendezvous.

  13. The Health and Functioning ICF-60: development and psychometric properties.

    Science.gov (United States)

    Tutelyan, V A; Chatterji, S; Baturin, A K; Pogozheva, A V; Kishko, O N; Akolzina, S E

    2014-01-01

    This paper describes the development and psychometric properties of the Health and Functioning ICF-60 (HF-ICF-60) measure, based on the World Health Organization (WHO) 'International Classification of Functioning, Disability and Health: ICF' (2001). The aims of the present study were to test psychometric properties of the HF-ICF-60, developed as a measure that would be responsive to change in functioning through changes in health and nutritional status, as a prospective measure to monitor health and nutritional status of populations and to explore the relationship of the HF-ICF-60 with quality of life measures such as the World Health Organization WHOQOL-BREF quality of life assessment in relation to non-communicable diseases. The HF-ICF-60 measure consists of 60 items selected from the ICF by an expert panel, which included 18 items that cover Body Functions, 21 items that cover Activities and Participation, rated on five-point scales, and 21 items that cover Environmental Factors (seven items cover Individual Environmental Factors and 14 items cover Societal Environmental Factors), rated on nine-point scales. The HF-ICF-60 measure was administered to the Russian nationally representative sample within the Russian National Population Quality of Life, Health and Nutrition Survey, in 2004 (n = 9807) and 2005 (n = 9560), as part of the two waves of the Russian Longitudinal Monitoring Survey (RLMS). The statistical analyses were carried out with the use of both classical and modern psychometric methods, such as factor analysis, and based on Item Response Theory, respectively. The HF-ICF-60 questionnaire is a new measure derived directly from the ICF and covers the ICF components as follows: Body Functions, Activities and Participation, and Environmental Factors (Individual Environmental Factors and Societal Environmental Factors). The results from the factor analyses (both Exploratory Factor Analyses and Confirmatory Factor Analyses) show good support for the

  14. Experiments in ICF, materials science, and astrophysics

    Science.gov (United States)

    Remington, Bruce A.

    2016-10-01

    We have been developing RED experiments on high power TCF lasers over the past two decades that span (1) the radiative hydrodynamics of TCF capsule physics; (2) the high pressure, high strain rate, solid-state dynamics relevant to novel concepts for ICF and hypervelocity impacts in space and on Earth; and (3) the shock driven turbulence of exploding stars (supernovae). These different regimes are separated by many orders of magnitude in length, time, and temperature, yet there are common threads that run through all of these phenomena, such as the occurrence of hydrodynamic instabilities. Examples from each of these three seemingly very disparate regimes are given, and the common theme of hydrodynamic instability evolution is explored.

  15. Progress on LMJ targets for ignition

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-12-15

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

  16. Ion kinetic dynamics in strongly-shocked plasmas relevant to ICF

    Science.gov (United States)

    Rinderknecht, H. G.; Amendt, P. A.; Rosenberg, M. J.; Li, C. K.; Frenje, J. A.; Gatu Johnson, M.; Sio, H.; Séguin, F. H.; Petrasso, R. D.; Zylstra, A. B.; Kagan, G.; Hoffman, N. M.; Svyatsky, D.; Wilks, S. C.; Glebov, V. Yu.; Stoeckl, C.; Sangster, T. C.

    2017-06-01

    Implosions of thin-shell capsules produce strongly-shocked (M  >  10), low-density (ρ ˜ 1 mg cc-1), high-temperature ({{T}\\text{i}}˜ keV) plasmas, comparable to those produced in the strongly-shocked DT-vapor in inertial confinement fusion (ICF) experiments. A series of thin-glass targets filled with mixtures of deuterium and Helium-3 gas ranging from 7% to 100% deuterium was imploded to investigate the impact of multi-species ion kinetic mechanisms in ICF-relevant plasmas over a wide range of Knudsen numbers ({{N}\\text{K}}\\equiv {λ\\text{ii}}/R ). Slightly kinetic implosions ({{N}\\text{K}}˜ 0.01 -0.05) follow the expected yield trend with experimentally-inferred N K, suggesting effects associated with long mean-free-paths (such as energetic tail-ion loss) provide the dominant yield reduction mechanisms. In contrast, highly kinetic implosions (Rinderknecht et al 2015 Phys. Rev. Lett. 114 025001) with inferred {{N}\\text{K}}>0.5 produce the opposite yield trend from the Knudsen-number prediction, confirming the dominance of multi-species physics in these experiments. The impact of the observed kinetic physics mechanisms on the formation of the hotspot in ICF experiments is discussed.

  17. [Can ICF core sets be helpful in preparing a social-medical expert report due to incapacity to work?--a first proposal].

    Science.gov (United States)

    Kirschneck, M; Legner, R; Armbrust, W; Nowak, D; Cieza, A

    2015-04-01

    Social-medical expert reports from the German statutory pension insurance are essential for the German statutory pension regulatory authority to decide whether to grant services regarding participation as well as retirement pensions due to incapacity to work.The objective of this investigation is to determine whether the ICF Core Sets and other international approaches, such as the EUMASS Core Sets or ICF Core Set for vocational rehabilitation cover the content of the social-medical expert reports as well as to propose an approach how the ICF can be economically used by the social medicine practitioner when writing a social-medical expert report. A retrospective quantitative study design was used to translate a total of 294 social-medical expert reports from patients with low back pain (LBP) or chronic widespread pain (CWP) into the language of the ICF (linking) by 2 independent health professionals and compare the results with the ICF Core Sets for specific health conditions and other international approaches. The content of social-medical expert reports was largely reflected by the condition specific brief ICF Core Sets, brief ICF Core Sets for vocational rehabilitation and EUMASS Core Sets. The weighted Kappa statistic for the agreement between the 2 health professionals who translated the expert reports were in CWP 0.69 with a bootstrapped confidence interval of 0.67-0.71 and in LBP 0.73 (0.71-0.74). The analyses show that the content of social-medical expert reports varies enormously. A combination of a condition specific brief ICF Core Set as well as vocational rehabilitation and EUMASS ICF Core Sets as well as all ICF-categories from the expert reports that were named at least in 50% of it can largely provide a basis for preparing expert reports. Within the scope of implementation the need for a specific ICF Core Set for expert reports of the German statutory pension insurance should be further analyzed and discussed. © Georg Thieme Verlag KG Stuttgart

  18. Health measurement using the ICF: Test-retest reliability study of ICF codes and qualifiers in geriatric care

    Directory of Open Access Journals (Sweden)

    Takahashi Tai

    2005-07-01

    Full Text Available Abstract Background The International Classification of Functioning, Disability and Health (ICF was published by the World Health Organization (WHO to standardize descriptions of health and disability. Little is known about the reliability and clinical relevance of measurements using the ICF and its qualifiers. This study examines the test-retest reliability of ICF codes, and the rate of immeasurability in long-term care settings of the elderly to evaluate the clinical applicability of the ICF and its qualifiers, and the ICF checklist. Methods Reliability of 85 body function (BF items and 152 activity and participation (AP items of the ICF was studied using a test-retest procedure with a sample of 742 elderly persons from 59 institutional and at home care service centers. Test-retest reliability was estimated using the weighted kappa statistic. The clinical relevance of the ICF was estimated by calculating immeasurability rate. The effect of the measurement settings and evaluators' experience was analyzed by stratification of these variables. The properties of each item were evaluated using both the kappa statistic and immeasurability rate to assess the clinical applicability of WHO's ICF checklist in the elderly care setting. Results The median of the weighted kappa statistics of 85 BF and 152 AP items were 0.46 and 0.55 respectively. The reproducibility statistics improved when the measurements were performed by experienced evaluators. Some chapters such as genitourinary and reproductive functions in the BF domain and major life area in the AP domain contained more items with lower test-retest reliability measures and rated as immeasurable than in the other chapters. Some items in the ICF checklist were rated as unreliable and immeasurable. Conclusion The reliability of the ICF codes when measured with the current ICF qualifiers is relatively low. The result in increase in reliability according to evaluators' experience suggests proper

  19. SMET: systematic multiple enzyme targeting - a method to rationally design optimal strains for target chemical overproduction.

    Science.gov (United States)

    Flowers, David; Thompson, R Adam; Birdwell, Douglas; Wang, Tsewei; Trinh, Cong T

    2013-05-01

    Identifying multiple enzyme targets for metabolic engineering is very critical for redirecting cellular metabolism to achieve desirable phenotypes, e.g., overproduction of a target chemical. The challenge is to determine which enzymes and how much of these enzymes should be manipulated by adding, deleting, under-, and/or over-expressing associated genes. In this study, we report the development of a systematic multiple enzyme targeting method (SMET), to rationally design optimal strains for target chemical overproduction. The SMET method combines both elementary mode analysis and ensemble metabolic modeling to derive SMET metrics including l-values and c-values that can identify rate-limiting reaction steps and suggest which enzymes and how much of these enzymes to manipulate to enhance product yields, titers, and productivities. We illustrated, tested, and validated the SMET method by analyzing two networks, a simple network for concept demonstration and an Escherichia coli metabolic network for aromatic amino acid overproduction. The SMET method could systematically predict simultaneous multiple enzyme targets and their optimized expression levels, consistent with experimental data from the literature, without performing an iterative sequence of single-enzyme perturbation. The SMET method was much more efficient and effective than single-enzyme perturbation in terms of computation time and finding improved solutions.

  20. Designing to target cost: one approach to design/construction integration

    DEFF Research Database (Denmark)

    Jørgensen, Bo

    2005-01-01

    One approach to a more integrated construction delivery process is the concept of ‘designing to target cost’ of which the first examples of application within a lean construction framework have recently been seen. This paper introduces the main principles of the design to target cost method...... and discusses the applicability of this approach to construction. The low degree of organizational and technical continuity from one construction project to the next limits the applicability of the design for target cost approach when compared to its origin in product development of mass manufactured artefacts....... The approach can, however, be applied as a way of substantially involving the production organisation from the earliest phases of schematic design and thus contribute to enhanced value and reduced waste for the overall project delivery as well as for the many assignments of which it is ultimately composed...

  1. Design, Operations, and Safety Report for the MERIT Target System

    Energy Technology Data Exchange (ETDEWEB)

    Graves, Van B [ORNL; Spampinato, Philip Thomas [ORNL

    2007-09-01

    The Mercury Intense Target Project (MERIT) is a proof-of-principal experiment to determine the feasibility of using a free-jet of Hg as a spallation target in a Neutrino Factory or a Muon Collider facility. The 1-cm-diameter, 20-m/sec jet will be generated inside a 15-Tesla magnetic field, and high-speed optical diagnostics will be used to photograph the interaction between the Hg jet and a 24-GeV proton beam.The experiment is scheduled to be conducted at CERN in 2007. ORNL is responsible for the design, fabrication, and testing of a system to deliver the Hg jet within the confines of the 15-cm magnet bore. This report documents the functional and safety requirements of the Hg system along with descriptions of its interfaces to the other experimental equipment.

  2. Polyamide platinum anticancer complexes designed to target specific DNA sequences.

    Science.gov (United States)

    Jaramillo, David; Wheate, Nial J; Ralph, Stephen F; Howard, Warren A; Tor, Yitzhak; Aldrich-Wright, Janice R

    2006-07-24

    Two new platinum complexes, trans-chlorodiammine[N-(2-aminoethyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-2) and trans-chlorodiammine[N-(6-aminohexyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-6) have been synthesized as proof-of-concept molecules in the design of agents that can specifically target genes in DNA. Coordinate covalent binding to DNA was demonstrated with electrospray ionization mass spectrometry. Using circular dichroism, these complexes were found to show greater DNA binding affinity to the target sequence: d(CATTGTCAGAC)(2), than toward either d(GTCTGTCAATG)(2,) which contains different flanking sequences, or d(CATTGAGAGAC)(2), which contains a double base pair mismatch sequence. DJ1953-2 unwinds the DNA helix by around 13 degrees , but neither metal complex significantly affects the DNA melting temperature. Unlike simple DNA minor groove binders, DJ1953-2 is able to inhibit, in vitro, RNA synthesis. The cytotoxicity of both metal complexes in the L1210 murine leukaemia cell line was also determined, with DJ1953-6 (34 microM) more active than DJ1953-2 (>50 microM). These results demonstrate the potential of polyamide platinum complexes and provide the structural basis for designer agents that are able to recognize biologically relevant sequences and prevent DNA transcription and replication.

  3. Measurement of activity limitations and participation restrictions: examination of ICF-linked content and scale properties of the FIM and PC-PART instruments.

    Science.gov (United States)

    Darzins, Susan W; Imms, Christine; Di Stefano, Marilyn

    2017-05-01

    To explore the operationalization of activity and participation-related measurement constructs through comparison of item phrasing, item response categories and scoring (scale properties) for two separate instruments targeting activities of daily living. Personal Care Participation Assessment and Resource Tool (PC-PART) item content was linked to ICF categories using established linking rules. Previously reported ICF-linked FIM content categories and ICF-linked PC-PART content categories were compared to identify common ICF categories between the instruments. Scale properties of both instruments were compared using a patient scenario to explore the instruments' separate measurement constructs. The PC-PART and FIM shared 15 of the 53 level two ICF-linked categories identified across both instruments. Examination of the instruments' scale properties for items with overlapping ICF content, and exploration through a patient scenario, provided supportive evidence that the instruments measure different constructs. While the PC-PART and FIM share common ICF-linked content, they measure separate constructs. Measurement construct was influenced by the instruments' scale properties. The FIM was observed to measure activity limitations and the PC-PART measured participation restrictions. Scrutiny of instruments' scale properties in addition to item content is critical in the operationalization of activity and participation-related measurement constructs. Implications for Rehabilitation When selecting outcome measures for use in rehabilitation it is necessary to examine both the content of the instruments' items and item phrasing, response categories and scoring, to clarify the construct being measured. Measurement of activity limitations as well as participation restrictions in activities of daily living required for community life provides a more comprehensive measurement of rehabilitation outcomes than measurement of either construct alone. To measure the effects of

  4. The ICF Status and Plans in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Moses, E; Miller, G; Kauffman, R

    2005-10-12

    The United States continues to maintain its leadership in ICF as it moves toward the goal of ignition. The flagship of the program is the National Ignition Facility (NIF) presently under construction at LLNL. Experiments had begun on the first four beams of the National Ignition Facility just at the time of the last IFSA Conference. Several new successful campaigns have been conducted since then in planar hydrodynamics and hohlraums as well as activating the VISAR diagnostic for equation of state experiments. Highlights of these results will be reviewed. Presently, the four beam experimental capability has been suspended while the first eight beams are being installed as the first step in building out the project. Meanwhile, much progress has been made in developing ignition designs for using NIF. An array of designs having several ablator materials have been shown computationally to ignite with energies ranging from the design energy to as low as 1 MJ of laser energy. Alternative direct drive designs in the NIF indirect drive configuration have been developed by LLE. This wide array of design choices has increased the chance of achieving ignition sooner on the facility. Plans are now being developed to begin an ignition experimental campaign on NIF in 2010, a little over a year after completion of the facility. Other US facilities are also implementing improved capabilities. Petawatt lasers are now under construction at the University of Rochester and Sandia National Laboratory. The Z pulsed power machine at Sandia National Laboratory is being refurbished to improve its performance. The ongoing research program at the OMEGA laser at the University of Rochester and the Z machine at Sandia National Laboratory as well as at the Nike, Trident and Janus lasers remain strong, performing experiments supporting the NIF ignition plan and direct drive ignition. There also is an active program in the broader field of high energy density science on these facilities. These

  5. Auto Target Tracking Robot Design Based on Smartphone

    Directory of Open Access Journals (Sweden)

    Shuen De Wu

    2016-03-01

    Full Text Available This paper describes a robot tracking control design based on a smartphone using a commercial microprocessor. The system hardware consists of four major parts: an Android smartphone with an embedded camera, a Microchip microprocessor, a motor driver circuit and an Attacknid robot. First, an image of the surrounding environment is captured by the high definition camera embedded in the smartphone. The target is then recognized from the image using an algorithm developed in Android OS and OpenCV library. Third, motion control and laser activation strategies are achieved using the proposed algorithm implemented in Java. Fourth, the motion commands are delivered to the microchip processor through a USB interface. Finally, the processor produces a pulse width modulation (PWM voltage to control the robot’s motion and activate the laser diode according commands sent from the smart phone. Experimental results demonstrate the feasibility of this proposed architecture.

  6. ICF-DOC: the ICF dedicated checklist for evaluating functioning and disability in people with disorders of consciousness.

    Science.gov (United States)

    Leonardi, Matilde; Covelli, Venusia; Giovannetti, Ambra M; Raggi, Alberto; Sattin, Davide

    2014-09-01

    Clinicians need a comprehensive description of patients' functioning state to capture the complex interaction between symptoms and environmental factors, and to determine the actual level of functioning in patients in a vegetative state or a minimally conscious state. The aim of this study is to develop an International Classification of Functioning, Disability, and Health (ICF) checklist for patients with disorders of consciousness (DOC) so as to capture and describe, with a tailored list of categories, the most common health, disability, and functioning issues of adult patients with DOC. The WHO ICF checklist was used as a basis for collecting data. This was an observational, cross-sectional, multicenter study conducted in 69 Italian centers. Specific methodological procedures were used to identify the most appropriate categories for DOC patients to be added to or deleted from the ICF checklist so as to develop the ICF-DOC checklist. A total of 566 adult patients were enrolled: 398 in a vegetative state and 168 in a minimally conscious state. A total of 127 ICF categories reached the threshold of 20% concerning the presence of a problem: 37 categories from the body functions chapter, 13 from the body structures chapter, 46 from the activities and participations chapter, and 31 from the environmental factors chapter. ICF categories identified in this study can be useful guidelines for clinicians and researchers to collect data on functioning and disability of adult patients with DOC. The new ICF-DOC checklist allows monitoring of the effects of interventions on functional areas and possible changes in each patient in follow-up studies.

  7. Design of Thymidine Analogues Targeting Thymidilate Kinase of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Luc Calvin Owono Owono

    2013-01-01

    Full Text Available We design here new nanomolar antituberculotics, inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt, by means of structure-based molecular design. 3D models of TMPKmt-inhibitor complexes have been prepared from the crystal structure of TMPKmt cocrystallized with the natural substrate deoxythymidine monophosphate (dTMP (1GSI for a training set of 15 thymidine analogues (TMDs with known activity to prepare a QSAR model of interaction establishing a correlation between the free energy of complexation and the biological activity. Subsequent validation of the predictability of the model has been performed with a 3D QSAR pharmacophore generation. The structural information derived from the model served to design new subnanomolar thymidine analogues. From molecular modeling investigations, the agreement between free energy of complexation (ΔΔGcom and Ki values explains 94% of the TMPKmt inhibition (pKi=-0.2924ΔΔGcom+3.234;R2=0.94 by variation of the computed ΔΔGcom and 92% for the pharmacophore (PH4 model (pKi=1.0206×pKipred-0.0832,  R2=0.92. The analysis of contributions from active site residues suggested substitution at the 5-position of pyrimidine ring and various groups at the 5′-position of the ribose. The best inhibitor reached a predicted Ki of 0.155 nM. The computational approach through the combined use of molecular modeling and PH4 pharmacophore is helpful in targeted drug design, providing valuable information for the synthesis and prediction of activity of novel antituberculotic agents.

  8. Design study of ITER-like divertor target for DEMO

    Energy Technology Data Exchange (ETDEWEB)

    Crescenzi, Fabio, E-mail: fabio.crescenzi@enea.it [ENEA, Unità Tecnica Fusione, ENEA C. R. Frascati, via E. Fermi 45, 00044 Frascati (Roma) (Italy); Bachmann, C. [EFDA, Power Plant Physics and Technology, Boltzmannstraße 2, 85748 Garching (Germany); Richou, M. [CEA, IRFM, F-13108 Saint Paul Lez Durance (France); Roccella, S.; Visca, E. [ENEA, Unità Tecnica Fusione, ENEA C. R. Frascati, via E. Fermi 45, 00044 Frascati (Roma) (Italy); You, J.-H. [Max-Planck-Institut für Plasmaphysik, Boltzmannstr. 2, 85748 Garching (Germany)

    2015-10-15

    Highlights: • ‘DEMO’ is a near-term Power Plant Conceptual Study (PPCS). • The ITER-like design concept represents a promising solution also for DEMO plasma facing units. • The optimization of PFUs aims to enhance the thermo-mechanical behaviour of the component. • The optimized geometry was evaluated by ITER SDC-IC criteria and in terms of low cycle fatigue (LCF). - Abstract: A near-term water-cooled target solution has to be evaluated together with the required technologies and its power exhaust limit under ‘DEMO’ conditions. The ITER-like design concept based on the mono-block technology using W as armour material and the CuCrZr-IG as structural material with an interlayer of pure copper represents a promising solution also for DEMO. This work reports the design study of an “optimized” ITER-like Water Cooled Divertor able to withstand a heat flux of 10 MW m{sup −2}, as requested for DEMO operating conditions. The optimization of plasma facing unit (PFU) aims to enhance the thermo-mechanical behaviour of the component by varying some geometrical parameters (monoblock size, interlayer thickness and, tube diameter and thickness). The optimization was performed by means of the multi-variable optimization algorithms using the FEM code ANSYS. The coolant hydraulic conditions (inlet pressure, temperature and velocity) were fixed for simplicity. This study is based on elastic analysis and 3 dimensional modelling. The resulting optimized geometry was evaluated on the basis of the ITER SDC-IC criteria and in terms of low cycle fatigue (LCF). The margin to the critical heat flux (CHF) was also estimated. Further design study (taking into account the effect of neutron radiation on the material properties) together with mock-up fabrication and high-heat-flux (HHF) tests are foreseen in next work programmes.

  9. Application of the International Classification of Functioning, Disability and Health (ICF) framework in record keeping by occupational therapists and physiotherapists at central hospitals in Harare.

    Science.gov (United States)

    Chigweremba, R A; Chikwanha, T M; January, J; Chikwasha, V

    2014-01-01

    The International Classification of Functioning, Disability and Health (ICF) is a framework that provides a detailed outline of the information that should be included in patient records. Whilst the World Federation of occupational therapists and the World Confederation of Physiotherapists have recommended use of this framework in clinical practice, the extent to which Zimbabwean therapists are applying this framework in patients' assessment and treatment is unknown. This study was conducted to determine the extent to which the ICF framework is being applied in recording information on patient assessment and treatment by occupational therapists and physiotherapists in Zimbabwe. A descriptive cross sectional study was carried out in rehabilitation departments at three central hospitals in Harare. Thirty therapists were interviewed on their record keeping practices. Sixty randomly selected records for in-patients receiving rehabilitation services were also evaluated for completeness using a checklist developed using ICF guidelines. Data were analysed using Microsoft excel and Epi info. Forty-three percent (12) of the records were rated as good and another (43%) as satisfactory. None of the records reviewed were 100% complete according to the ICF guidelines. Personal factors were the most recorded (82%) component and the least recorded were environmental factors (18%) affecting patient functioning. There were no statistically significant associations between application of the ICF framework and profession (p = 0.680), ICF application and years in clinical practice (p = 0.557) and training and record keeping practices (p = 1.000). Standard guidelines for evaluating patients with different conditions derived from the ICF checklist should be designed for occupational therapists and physiotherapists to standardise information recorded during management of patients seeking rehabilitation services.

  10. Toward developing a specific outcome instrument for spine trauma: an empirical cross-sectional multicenter ICF-based study by AOSpine Knowledge Forum Trauma.

    Science.gov (United States)

    Oner, F Cumhur; Sadiqi, Said; Lehr, A Mechteld; Aarabi, Bizhan; Dunn, Robert N; Dvorak, Marcel F; Fehlings, Michael G; Kandziora, Frank; Post, Marcel W; Rajasekaran, S; Vialle, Luiz; Vaccaro, Alexander R

    2015-09-01

    Empirical cross-sectional multicenter study. To identify the most commonly experienced problems by patients with traumatic spinal column injuries, excluding patients with complete paralysis. There is no disease or condition-specific outcome instrument available that is designed or validated for patients with spine trauma, contributing to the present lack of consensus and ongoing controversies in the optimal treatment and evaluation of many types of spine injuries. Therefore, AOSpine Knowledge Forum Trauma started a project to develop such an instrument using the International Classification of Functioning, Disability and Health (ICF) as its basis. Patients with traumatic spinal column injuries, within 13 months after discharge from hospital were recruited from 9 trauma centers in 7 countries, representing 4 AOSpine International world regions. Health professionals collected the data using the general ICF Checklist. The responses were analyzed using frequency analysis. Possible differences between the world regions and also between the subgroups of potential modifiers were analyzed using descriptive statistics and Fisher exact test. In total, 187 patients were enrolled. A total of 38 (29.7%) ICF categories were identified as relevant for at least 20% of the patients. Categories experienced as a difficulty/impairment were most frequently related to activities and participation (n = 15), followed by body functions (n = 6), and body structures (n = 5). Furthermore, 12 environmental factors were considered to be a facilitator in at least 20% of the patients. Of 128 ICF categories of the general ICF Checklist, 38 ICF categories were identified as relevant. Loss of functioning and limitations in daily living seem to be more relevant for patients with traumatic spinal column injuries rather than pain during this time frame. This study creates an evidence base to define a core set of ICF categories for outcome measurement in adult spine trauma patients. 4.

  11. Prevalence and features of ICF-disability in Spain as captured by the 2008 National Disability Survey

    Science.gov (United States)

    2011-01-01

    Background Since 1986, the study of disability in Spain has been mainly addressed by National Disability Surveys (NDSs). While international attempts to frame NDS designs within the International Classification of Functioning, Disability and Health (ICF) have progressed, in general, the ICF has hardly been used in either the NDS or epidemiological studies. This study sought to identify ICF Activity- and Participation-related content in the most recent Spanish NDS, the 2008 Survey on Disabilities, Independence and Dependency Situations (Encuesta sobre discapacidades, autonomía personal y situaciones de Dependencia - EDAD 2008), and estimate the prevalence of such ICF-framed disability. Methods EDAD 2008 methods and questions were perused. Of the 51 EDAD items analysed, 29 were backcoded to specific d2-d7 domains of the ICF Checklist and, by rating the recorded difficulty to perform specific tasks with or without help, these were then taken as performance and capacity respectively. A global ICF score was also derived, albeit lacking data for d1, "Learning and applying knowledge", d8, "Major Life Areas" and d9, "Community, Social and Civic Life". Data were grouped by sex, age, residence and initial positive screening, and prevalence figures were calculated by disability level both for the general population, using the originally designed weights, and for the population that had screened positive to disability. Data for institutionalised persons were processed separately. Results Crude prevalence of ICF severe/complete and moderate disability among the community-dwelling population aged ≥6 years was 0.9%-2.2% respectively, and that of severe/complete disability among persons living in sheltered accommodation was 0.3%. Prevalence of severe/complete disability was: higher in women than in men, 0.8% vs. 0.4%; increased with age; and was particularly high in domains such as "Domestic Life", 3.4%, "Mobility", 1.8%, and "Self-care", 1.9%, in which prevalence decreased

  12. Prevalence and features of ICF-disability in Spain as captured by the 2008 National Disability Survey.

    Science.gov (United States)

    Maierhofer, Sarah; Almazán-Isla, Javier; Alcalde-Cabero, Enrique; de Pedro-Cuesta, Jesús

    2011-11-28

    Since 1986, the study of disability in Spain has been mainly addressed by National Disability Surveys (NDSs). While international attempts to frame NDS designs within the International Classification of Functioning, Disability and Health (ICF) have progressed, in general, the ICF has hardly been used in either the NDS or epidemiological studies. This study sought to identify ICF Activity- and Participation-related content in the most recent Spanish NDS, the 2008 Survey on Disabilities, Independence and Dependency Situations (Encuesta sobre discapacidades, autonomía personal y situaciones de Dependencia - EDAD 2008), and estimate the prevalence of such ICF-framed disability. EDAD 2008 methods and questions were perused. Of the 51 EDAD items analysed, 29 were backcoded to specific d2-d7 domains of the ICF Checklist and, by rating the recorded difficulty to perform specific tasks with or without help, these were then taken as performance and capacity respectively. A global ICF score was also derived, albeit lacking data for d1, "Learning and applying knowledge", d8, "Major Life Areas" and d9, "Community, Social and Civic Life". Data were grouped by sex, age, residence and initial positive screening, and prevalence figures were calculated by disability level both for the general population, using the originally designed weights, and for the population that had screened positive to disability. Data for institutionalised persons were processed separately. Crude prevalence of ICF severe/complete and moderate disability among the community-dwelling population aged ≥6 years was 0.9%-2.2% respectively, and that of severe/complete disability among persons living in sheltered accommodation was 0.3%.Prevalence of severe/complete disability was: higher in women than in men, 0.8% vs. 0.4%; increased with age; and was particularly high in domains such as "Domestic Life", 3.4%, "Mobility", 1.8%, and "Self-care", 1.9%, in which prevalence decreased when measured by reference to

  13. Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects.

    NARCIS (Netherlands)

    Weemaes, C.M.R.; Tol, M.J. van; Wang, J.; Ostaijen-ten Dam, M.M. van; Eggermond, M.C. van; Thijssen, P.E.; Aytekin, C.; Brunetti-Pierri, N.; Burg, M. van der; aham Davies, E. Gr; Ferster, A.; Furthner, D.; Gimelli, G.; Gennery, A.; Kloeckener-Gruissem, B.; Meyn, S.; Powell, C.; Reisli, I.; Schuetz, C.; Schulz, A.; Shugar, A.; Elsen, P.J. van den; Maarel, S.M. van der

    2013-01-01

    Immunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a primary immunodeficiency, predominantly characterized by agammaglobulinemia or hypoimmunoglobulinemia, centromere instability and facial anomalies. Mutations in two genes have been discovered to cause ICF syndrome

  14. Designer interface peptide grafts target estrogen receptor alpha dimerization

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, S. [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Asare, B.K. [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States); Biswas, P.K., E-mail: pbiswas@tougaloo.edu [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Rajnarayanan, R.V., E-mail: rajendra@buffalo.edu [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States)

    2016-09-09

    The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

  15. Colocated MIMO Radar: Beamforming, Waveform design, and Target Parameter Estimation

    KAUST Repository

    Jardak, Seifallah

    2014-04-01

    Thanks to its improved capabilities, the Multiple Input Multiple Output (MIMO) radar is attracting the attention of researchers and practitioners alike. Because it transmits orthogonal or partially correlated waveforms, this emerging technology outperformed the phased array radar by providing better parametric identifiability, achieving higher spatial resolution, and designing complex beampatterns. To avoid jamming and enhance the signal to noise ratio, it is often interesting to maximize the transmitted power in a given region of interest and minimize it elsewhere. This problem is known as the transmit beampattern design and is usually tackled as a two-step process: a transmit covariance matrix is firstly designed by minimizing a convex optimization problem, which is then used to generate practical waveforms. In this work, we propose simple novel methods to generate correlated waveforms using finite alphabet constant and non-constant-envelope symbols. To generate finite alphabet waveforms, the proposed method maps easily generated Gaussian random variables onto the phase-shift-keying, pulse-amplitude, and quadrature-amplitude modulation schemes. For such mapping, the probability density function of Gaussian random variables is divided into M regions, where M is the number of alphabets in the corresponding modulation scheme. By exploiting the mapping function, the relationship between the cross-correlation of Gaussian and finite alphabet symbols is derived. The second part of this thesis covers the topic of target parameter estimation. To determine the reflection coefficient, spatial location, and Doppler shift of a target, maximum likelihood estimation yields the best performance. However, it requires a two dimensional search problem. Therefore, its computational complexity is prohibitively high. So, we proposed a reduced complexity and optimum performance algorithm which allows the two dimensional fast Fourier transform to jointly estimate the spatial location

  16. Progress on LMJ targets for ignition

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-08-01

    Targets designed to produce ignition on the Laser MegaJoule are presented. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-shaped cocktail hohlraum. 1D and 2D robustness evaluations of these different targets shed light on critical points for ignition, that can be traded off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

  17. 42 CFR 431.154 - Informal reconsideration for ICFs/MR.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Informal reconsideration for ICFs/MR. 431.154... SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS STATE ORGANIZATION AND GENERAL ADMINISTRATION Appeals Process for NFs and ICFs/MR § 431.154 Informal reconsideration for ICFs/MR. The informal...

  18. 42 CFR 442.118 - Denial of payments for new admissions to an ICF/MR.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Denial of payments for new admissions to an ICF/MR... of payments for new admissions to an ICF/MR. (a) Basis for denial of payments. The Medicaid agency may deny payment for new admissions to an ICF/MR that no longer meets the applicable conditions of...

  19. Sensitivity of ICF ignition conditions to non-Maxwellian DT fusion reactivity

    Directory of Open Access Journals (Sweden)

    Garbett W.J.

    2013-11-01

    Full Text Available The hotspot ignition conditions in ICF are determined by considering the power balance between fusion energy deposition and energy loss terms. Uncertainty in any of these terms has potential to modify the ignition conditions, changing the optimum ignition capsule design. This paper considers the impact of changes to the DT fusion reaction rate due to non-thermal ion energy distributions. The DT fusion reactivity has been evaluated for a class of non-Maxwellian distributions representing a perturbation to the tail of a thermal distribution. The resulting reactivity has been used to determine hotspot ignition conditions as a function of the characteristic parameter of the modified distribution.

  20. Advances in target design and fabrication for experiments on NIF

    OpenAIRE

    Obrey K.; Schmidt D.; Hamilton C.; Capelli D.; Williams J.; Randolph R.; Fierro F.; Hatch D.; Havrilla G.; Patterson B.

    2013-01-01

    The ability to build target platforms for National Ignition Facility (NIF) is a key feature in LANL's (Los Alamos National Laboratory) Target Fabrication Program. We recently built and manufactured the first LANL targets to be fielded on NIF in March 2011. Experiments on NIF require precision component manufacturing and accurate knowledge of the materials used in the targets. The characterization of foams and aerogels, the Be ignition capsule, and machining unique components are of main mater...

  1. Designing block copolymer architectures for targeted membrane performance

    KAUST Repository

    Dorin, Rachel Mika

    2014-01-01

    Using a combination of block copolymer self-assembly and non-solvent induced phase separation, isoporous ultrafiltration membranes were fabricated from four poly(isoprene-b-styrene-b-4-vinylpyridine) triblock terpolymers with similar block volume fractions but varying in total molar mass from 43 kg/mol to 115 kg/mol to systematically study the effect of polymer size on membrane structure. Small-angle X-ray scattering was used to probe terpolymer solution structure in the dope. All four triblocks displayed solution scattering patterns consistent with a body-centered cubic morphology. After membrane formation, structures were characterized using a combination of scanning electron microscopy and filtration performance tests. Membrane pore densities that ranged from 4.53 × 1014 to 1.48 × 1015 pores/m 2 were observed, which are the highest pore densities yet reported for membranes using self-assembly and non-solvent induced phase separation. Hydraulic permeabilities ranging from 24 to 850 L m-2 h-1 bar-1 and pore diameters ranging from 7 to 36 nm were determined from permeation and rejection experiments. Both the hydraulic permeability and pore size increased with increasing molar mass of the parent terpolymer. The combination of polymer characterization and membrane transport tests described here demonstrates the ability to rationally design macromolecular structures to target specific performance characteristics in block copolymer derived ultrafiltration membranes. © 2013 Elsevier Ltd. All rights reserved.

  2. Targeting Plasmodium Metabolism to Improve Antimalarial Drug Design.

    Science.gov (United States)

    Avitia-Domínguez, Claudia; Sierra-Campos, Erick; Betancourt-Conde, Irene; Aguirre-Raudry, Miriam; Vázquez-Raygoza, Alejandra; Luevano-De la Cruz, Artemisa; Favela-Candia, Alejandro; Sarabia-Sanchez, Marie; Ríos-Soto, Lluvia; Méndez-Hernández, Edna; Cisneros-Martínez, Jorge; Palacio-Gastélum, Marcelo Gómez; Valdez-Solana, Mónica; Hernández-Rivera, Jessica; De Lira-Sánchez, Jaime; Campos-Almazán, Mara; Téllez-Valencia, Alfredo

    2016-01-01

    Malaria is one of the main infectious diseases in tropical developing countries and represents high morbidity and mortality rates nowadays. The principal etiological agent P. falciparum is transmitted through the bite of the female Anopheles mosquito. The issue has escalated due to the emergence of resistant strains to most of the antimalarials used for the treatment including Chloroquine, Sulfadoxine-Pyrimethamine, and recently Artemisinin derivatives, which has led to diminished effectiveness and by consequence increased the severity of epidemic outbreaks. Due to the lack of effective compounds to treat these drug-resistant strains, the discovery or development of novel anti-malaria drugs is important. In this context, one strategy has been to find inhibitors of enzymes, which play an important role for parasite survival. Today, promising results have been obtained in this regard, involving the entire P. falciparum metabolism. These inhibitors could serve as leads in the search of a new chemotherapy against malaria. This review focuses on the achievements in recent years with regard to inhibition of enzymes used as targets for drug design against malaria.

  3. Waveform design for cognitive radar: target detection in heavy clutter

    Science.gov (United States)

    Kirk, Benjamin H.; Narayanan, Ram M.; Martone, Anthony F.; Sherbondy, Kelly D.

    2016-05-01

    In many applications of radar systems, detection of targets in environments with heavy clutter and interference can be difficult. It is desired that a radar system should detect targets at a further range as well as be able to detect these targets with very few false positive or negative readings. In a cognitive radar system, there are ways that these negative effects can be mitigated and target detection can be significantly improved. An important metric to focus on for increasing target detectability is the signal-to-clutter ratio (SCR). Cognitive radar offers solutions to issues such as this with the use of a priori knowledge of targets and environments as well as real time adaptations. A feature of cognitive radar that is of interest is the ability to adapt and optimize transmitted waveforms to a given situation. A database is used to hold a priori and dynamic knowledge of the operational environment and targets to be detected, such as clutter characteristics and target radar cross-section (RCS) estimations. Assuming this knowledge is available or can be estimated in real-time, the transmitted waveform can be tailored using methods such as transmission of a spectrum corresponding to the target-to-clutter ratio (TCR). These methods provide significant improvement in distinguishing targets from clutter or interference.

  4. ICF Core Set for Head and Neck Cancer: Do the Categories Discriminate Among Clinically Relevant Subgroups of Patients?

    Science.gov (United States)

    Tschiesner, Uta; Oberhauser, Cornelia; Cieza, Alarcos

    2011-01-01

    The multidisciplinary assessment of functioning in patients with head and neck cancer (HNC) according to the "ICF Core Set for Head and Neck Cancer" (ICF-HNC) was developed in an international and multi-disciplinary approach. The ICF-HNC is an application of the ICF that was adopted by the World Health Organization. The objective of this study was…

  5. Validation of the ICF core set for neuromuscular diseases

    NARCIS (Netherlands)

    Bos, Isaac; Stallinga, H. A.; Middel, B.; Kuks, J. B. M.; Wynia, K.

    Background. Understanding of the consequences of a neuromuscular disease (NMD) can improve when a valid sample of disease-specific categories based on the International Classification of Functioning, Disabilities, and Health (ICF) is available. Objective. To examine the content validity of the

  6. Criteria for selection of target materials and design of high-efficiency-release targets for radioactive ion beam generation

    CERN Document Server

    Alton, G D; Liu, Y

    1999-01-01

    In this report, we define criteria for choosing target materials and for designing, mechanically stable, short-diffusion-length, highly permeable targets for generation of high-intensity radioactive ion beams (RIBs) for use at nuclear physics and astrophysics research facilities based on the ISOL principle. In addition, lists of refractory target materials are provided and examples are given of a number of successful targets, based on these criteria, that have been fabricated and tested for use at the Holifield Radioactive Ion Beam Facility (HRIBF).

  7. Alternative positron-target design for electron-positron colliders

    Energy Technology Data Exchange (ETDEWEB)

    Donahue, R.J. (Lawrence Berkeley Lab., CA (United States)); Nelson, W.R. (Stanford Linear Accelerator Center, Menlo Park, CA (United States))

    1991-04-01

    Current electron-positron linear colliders are limited in luminosity by the number of positrons which can be generated from targets presently used. This paper examines the possibility of using an alternate wire-target geometry for the production of positrons via an electron-induced electromagnetic cascade shower. 39 refs., 38 figs., 5 tabs.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Design, fabrication and measurement of a novel cooling arm for fusion energy source

    CERN Document Server

    Jiang, Shui-Dong; Mei, Jia-Bin; Yang, Bin; Yang, Chun-Sheng

    2012-01-01

    The issues of energy and environment are the main constraint of sustainable development in worldwide. Nuclear energy source is one important optional choice for long term sustainable development. The nuclear energy consists of fusion energy and fission energy. Compared with fission, inertial confinement fusion (ICF) is a kind of clean fusion energy and can generate large energy and little environmental pollution. ICF mainly consists of peripheral driver unit and target. The cooling arm is an important component of the target, which cools the hohlraum to maintain the required temperature and positions the thermal-mechanical package (TMP) assembly. This paper mainly investigates the cooling arm, including the structural design, the verticality of sidewall and the mechanical properties. The TMP assembly is uniformly clamped in its radial when using (111) crystal orientation silicon to fabricate cooling arm. The finite element method is used to design the structure of cooling arm with 16 clamping arms, and the ME...

  10. The ignition design space of magnetized target fusion

    Energy Technology Data Exchange (ETDEWEB)

    Lindemuth, Irvin R. [2490 North Grannen Road, Tucson, Arizona 85745 (United States)

    2015-12-15

    The simple magnetized target implosion model of Lindemuth and Kirkpatrick [Nucl. Fusion 23, 263 (1983)] has been extended to survey the potential parameter space in which three types of magnetized targets—cylindrical with axial magnetic field, cylindrical with azimuthal magnetic field, and spherical with azimuthal magnetic field—might achieve ignition and produce large gain at achievable radial convergence ratios. The model has been used to compute the dynamic, time-dependent behavior of many initial parameter sets that have been based upon projected ignition conditions using the quasi-adiabatic and quasi-flux-conserving properties of magnetized target implosions. The time-dependent calculations have shown that energy gains greater than 30 can potentially be achieved for each type of target. By example, it is shown that high gain may be obtained at extremely low convergence ratios, e.g., less than 15, for appropriate initial conditions. It is also shown that reaching the ignition condition, i.e., when fusion deposition rates equal total loss rates, does not necessarily lead to high gain and high fuel burn-up. At the lower densities whereby fusion temperatures can be reached in magnetized targets, the fusion burn rate may be only comparable with the hydrodynamic heating/cooling rates. On the other hand, when the fusion burn rates significantly exceed the hydrodynamic rates, the calculations show a characteristic rapid increase in temperature due to alpha particle deposition with a subsequent increased burn rate and high gain. A major result of this paper is that each type of target operates in a different initial density-energy-velocity range. The results of this paper provide initial target plasma parameters and driver parameters that can be used to guide plasma formation and driver development for magnetized targets. The results indicate that plasmas for spherical, cylindrical with azimuthal field, and cylindrical with axial field targets must have an initial

  11. The implementation of the ICF among Israeli rehabilitation centers--the case of physical therapy.

    Science.gov (United States)

    Jacob, Tamar

    2013-10-01

    The extent of the implementation of the International Classification of Functioning, Disability and Health (ICF), developed by the WHO, in rehabilitation units and in physical therapy (PT) departments is unknown. The study aims to describe the extent to which the ICF has been implemented in PT services within rehabilitation units in Israel. To update data on ICF implementation since its inception. An online semi-structured survey was administered to 25 physiotherapists in charge of PT departments in all rehabilitation units throughout Israel. Rehabilitation units were grouped into three categories: general, geriatric and pediatric. The questionnaire included items regarding the ICF implementation, its strengths, and weaknesses. Twenty two physiotherapists (88%) completed the questionnaire. The majority was familiar with the ICF and nearly two thirds reported partial implementation in their units. Implementation focused mostly on adopting the biopsychosocial concepts and using ICF terms. The ICF was not used either for evaluating patients, or for reporting or encoding patient information. Physiotherapists, directors of most Israeli PT departments in rehabilitation units are familiar with the ICF; however, its clinical implementation is very limited. There is need for further research into the processes of knowledge transfer and implementation of the ICF, in order to better understand the factors that facilitate and those that impede ICF implementation.

  12. Rehabilitation and control of cerebral injury and palsy disability by application of multiple integration methods of preventive treatment of disease and ICF theoretical design%应用治未病与ICF理论设计多元融合式康复控制脑损伤脑瘫残疾

    Institute of Scientific and Technical Information of China (English)

    陈世英

    2013-01-01

    Objective It is to observe the effect of rehabilitation and control of cerebral injury and palsy disability by application of effective and multiple integration methods of preventive treatment of disease and ICF theoretical design. Methods 131 infants who meet the diagnosis of cerebral injury and palsy were randomly paired and divided into two groups, the multiple integration rehabilitation was used in observation group, the intensive physical type rehabilitation was used in control group. By assessment of Gese11 Developmental Scale, emotion and behaviors nervimotion and Infant-Junior High School Student' s Social Living Ability Scale and the disability assessment criteria, the comprehensive efficacies of two groups were compared. Results The average adaptive developmental quotients of the observation group were higher, their emotional behavior symptoms were reduced, the mental deficiency was lower and admission rate of the kindergarten was higher. Conclusion The multiple integration type rehabilitation by design and application can improve the overall rehabilitation effect and reduce the cerebral injury and palsy disability.%目的 观察应用治未病与ICF理论设计的高效、多元融合式康复方法控制脑损伤脑瘫的效果.方法 将符合脑损伤脑瘫诊断的131例婴儿随机配对分为2组:观察组采用多元融合式方法康复,对照组采用运动强化式方法康复.以Gesell发育量表、情绪和行为神经运动测评、婴儿-初中生社会生活适应量表和残疾评定标准评定2组综合疗效.结果 观察组平均适应性发育商较高,情绪行为症状减少,智残率低,入园率高.结论 多元融合式康复能提高整体康复效果,减少脑损伤脑瘫残疾.

  13. The design and performance of an improved target for MICE

    CERN Document Server

    Booth, C N; Langlands, J; Overton, E; Robinson, M; Smith, P J; Barber, G; Long, K R; Shepherd, B; Capocci, E; MacWaters, C; Tarrant, J

    2016-01-01

    The linear motor driving the target for the Muon Ionisation Cooling Experiment has been redesigned to improve its reliability and performance. A new coil-winding technique is described which produces better magnetic alignment and improves heat transport out of the windings. Improved field-mapping has allowed the more precise construction to be demonstrated, and an enhanced controller exploits the full features of the hardware, enabling increased acceleration and precision. The new user interface is described and analysis of performance data to monitor friction is shown to allow quality control of bearings and a measure of the ageing of targets during use.

  14. Design of targeting ligands in medicinal inorganic chemistry.

    Science.gov (United States)

    Storr, Tim; Thompson, Katherine H; Orvig, Chris

    2006-06-01

    This tutorial review will highlight recent advances in medicinal inorganic chemistry pertaining to the use of multifunctional ligands for enhanced effect. Ligands that adequately bind metal ions and also include specific targeting features are gaining in popularity due to their ability to enhance the efficacy of less complicated metal-based agents. Moving beyond the traditional view of ligands modifying reactivity, stabilizing specific oxidation states, and contributing to substitution inertness, we will discuss recent work involving metal complexes with multifunctional ligands that target specific tissues, membrane receptors, or endogenous molecules, including enzymes.

  15. Advances in target design and fabrication for experiments on NIF

    Directory of Open Access Journals (Sweden)

    Obrey K.

    2013-11-01

    Full Text Available The ability to build target platforms for National Ignition Facility (NIF is a key feature in LANL's (Los Alamos National Laboratory Target Fabrication Program. We recently built and manufactured the first LANL targets to be fielded on NIF in March 2011. Experiments on NIF require precision component manufacturing and accurate knowledge of the materials used in the targets. The characterization of foams and aerogels, the Be ignition capsule, and machining unique components are of main material focus. One important characterization metric the physics' have determined is that the knowledge of density gradients in foams is important. We are making strides in not only locating these density gradients in aerogels and foams as a result of how they are manufactured and machined but also quantifying the density within the foam using 3D confocal micro x-ray fluorescence (μXRF imaging and 3D x-ray computed tomography (CT imaging. In addition, collaborative efforts between General Atomics (GA and LANL in the characterization of the NIF Ignition beryllium capsule have shown that the copper in the capsule migrates radially from the capsule center.

  16. Mechanic Design of the Radial Probe Target for CYCIAE-100

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The radial probe target is an important diagnostic component of CYCIAE-100 that adopts blocking measurement. The probe placed in the median plane of sector gap of the cyclotron is mainly used to measure both the radial and vertical cross-sections of the beam,

  17. Advances in target design and fabrication for experiments on NIF

    Science.gov (United States)

    Obrey, K.; Schmidt, D.; Hamilton, C.; Capelli, D.; Williams, J.; Randolph, R.; Fierro, F.; Hatch, D.; Havrilla, G.; Patterson, B.

    2013-11-01

    The ability to build target platforms for National Ignition Facility (NIF) is a key feature in LANL's (Los Alamos National Laboratory) Target Fabrication Program. We recently built and manufactured the first LANL targets to be fielded on NIF in March 2011. Experiments on NIF require precision component manufacturing and accurate knowledge of the materials used in the targets. The characterization of foams and aerogels, the Be ignition capsule, and machining unique components are of main material focus. One important characterization metric the physics' have determined is that the knowledge of density gradients in foams is important. We are making strides in not only locating these density gradients in aerogels and foams as a result of how they are manufactured and machined but also quantifying the density within the foam using 3D confocal micro x-ray fluorescence (μXRF) imaging and 3D x-ray computed tomography (CT) imaging. In addition, collaborative efforts between General Atomics (GA) and LANL in the characterization of the NIF Ignition beryllium capsule have shown that the copper in the capsule migrates radially from the capsule center.

  18. National Ignition Facility subsystem design requirements target diagnostics subsystem SSDR 1.8.3

    Energy Technology Data Exchange (ETDEWEB)

    Lee, D.

    1996-10-28

    This SSDR establishes the performance, design, development and test requirements for the Target Experimental System`s Diagnostic, WBS 1.8. 3. This includes the individual diagnostic components, the Target Diagnostic Data Acquisition System (Target DAS), the diagnostic vacuum system, the timing/fiducial system, and the EMI protection system.

  19. An ICF-Based Model for Implementing and Standardizing Multidisciplinary Obesity Rehabilitation Programs within the Healthcare System.

    Science.gov (United States)

    Brunani, Amelia; Raggi, Alberto; Sirtori, Anna; Berselli, Maria Elisa; Villa, Valentina; Ceriani, Francesca; Corti, Stefania; Leonardi, Matilde; Capodaglio, Paolo

    2015-05-29

    In this study, we aimed to design an ICF-based individual rehabilitation project for obese patients with comorbidities (IRPOb) integrated into the Rehab-CYCLE to standardize rehabilitative programs. This might facilitate the different health professionals involved in the continuum of care of obese patients to standardize rehabilitation interventions. After training on the ICF and based on the relevant studies, ICF categories were identified in a formal consensus process by our multidisciplinary team. Thereafter, we defined an individual rehabilitation project based on a structured multi-disciplinary approach to obesity. the proposed IRPOb model identified the specific intervention areas (nutritional, physiotherapy, psychology, nursing), the short-term goals, the intervention modalities, the professionals involved and the assessment of the outcomes. Information was shared with the patient who signed informed consent. The model proposed provides the following advantages: (1) standardizes rehabilitative procedures; (2) facilitates the flow of congruent and updated information from the hospital to outpatient facilities, relatives, and care givers; (3) addresses organizational issues; (4) might serve as a benchmark for professionals who have limited specific expertise in rehabilitation of comorbid obese patients.

  20. A tool to enhance occupational therapy reasoning from ICF perspective: The Hasselt Occupational Performance Profile (H-OPP).

    Science.gov (United States)

    Ghysels, R; Vanroye, E; Westhovens, M; Spooren, A

    2017-03-01

    In order to enhance occupational therapy reasoning in clinical practice, different elements such as client-centred approach, evidence-based care and interdisciplinary work should be taken into account, but is a challenge. To describe the development of the digital Hasselt Occupational Performance Profile (H-OPP(©)) that enhances occupational therapy reasoning from ICF perspective. A participative qualitative design was used to create the H-OPP(©) in an iterative way in which occupational therapy lectures, ICF experts, students and occupational therapists in the field were involved. After linking occupational therapy terminology to the ICF, different stages of the H-OPP were identified and elaborated with main features: generating an occupational performance profile based on inventarization of problems and possibilities, formulating an occupational performance diagnosis and enabling to create an intervention plan. In all stages, both the perspectives of the client and the occupational therapist were taken into account. To increase practical use, the tool was further elaborated and digitalized. The H-OPP(©) is a digital coach that guides and facilitates professional reasoning in (novice) occupational therapists. It augments involvement of the client system. Furthermore, it enhances interdisciplinary communication and evidence-based care.

  1. Effects of hippotherapy on body functions, activities and participation in children with cerebral palsy based on ICF-CY assessments.

    Science.gov (United States)

    Hsieh, Yueh-Ling; Yang, Chen-Chia; Sun, Shih-Heng; Chan, Shu-Ya; Wang, Tze-Hsuan; Luo, Hong-Ji

    2017-08-01

    To evaluate the effects of hippotherapy on body functions, activities, and participation in children with CP of various functional levels by using the International Classification of Functioning, Disability and Health-Children and Youth (ICF-CY) checklist. Fourteen children with cerebral palsy (CP) (3-8 years of age) were recruited for a 36-week study composed of baseline, intervention, and withdrawal phases (12 weeks for each phase, ABA design). Hippotherapy was implemented for 30 min once weekly for 12 consecutive weeks during the intervention phase. Body Functions (b) and Activities and Participation (d) components of the ICF-CY checklist were used as outcome measures at the initial interview and at the end of each phase. Over the 12 weeks of hippotherapy, significant improvements in ICF-CY qualifiers were found in neuromusculoskeletal and movement-related functions (b7), mobility (d4) and major life areas (d8) and, in particular, mobility of joint functions (b710), muscle tone functions (b735), involuntary movement reaction functions (b755), involuntary movement functions (b765), and play (d811) (all p functions, activities, and participation in children with CP. Implications for Rehabilitation ICF-CY provides a comprehensive overview of functioning and disability and constitutes a universal language for identifying the benefits of hippotherapy in areas of functioning and disability in children with CP. In children with CP, hippotherapy encourages a more complementary approach that extends beyond their impairments and limitations in body functions, activities, and participation. The effect of hippotherapy was distinct from GMFCS levels and the majority of improvements were present in children with GMFCS levels I-III.

  2. Analysis Of Wetted-Foam ICF Capsule Perormance

    Science.gov (United States)

    Peterson, R.; Olson, R.; Zylstra, A.; Haines, B.; Yi, A.; Bradley, P.; Yin, L.; Leeper, R.; Kline, J.

    2016-10-01

    The performance of wetted-foam ICF capsules is investigated with the RAGE Eulerian radiation-hydrodynamics computer code. We are developing an experimental platform on NIF that employs a wetted foam liquid DT fuel layer ICF capsules. By varying the capsule temperature, the vapor density in the capsule can be prescribed, and the hot spot convergence ratio (CR) of the capsule implosion can be controlled. This allows us to investigate the fidelity of RAGE in modeling of capsule implosions as the value of CR is varied. In the NIF experiments, CR can be varied from 12 to 25. This presentation will cover simulations with RAGE of three NIF shots performed in 2016; a DD and a DT liquid fuel shot with CR =14 and a DT shot with CR =16. It will also discuss analysis of future experiments. This work was performed under auspices of the U. S. DOE by LANL.

  3. Change in design targets for building energy towards smart cities

    DEFF Research Database (Denmark)

    Heller, Alfred; Gianniou, Panagiota; Katsigiannis, Emmanouil

    2014-01-01

    Designing cities from an overall energy optimization system point of view, demands changes in engineering procedures. Traditionally the design was driven independently between the involved domains and energy system components. By modelling the whole energy system in one, it is expected that there......Designing cities from an overall energy optimization system point of view, demands changes in engineering procedures. Traditionally the design was driven independently between the involved domains and energy system components. By modelling the whole energy system in one, it is expected...... so is, to move demands from high demand periods to low demand periods and hereby to avoid “peak” demands. This is called “flexibility” within the terminology of “smart grids”. In early solutions the search was for energy capacities within the domain of the electrical grid, hence car batteries where...

  4. Secretases as targets for drug design in Alzheimer's disease

    NARCIS (Netherlands)

    Hendriksen, JVRB; Nottet, HSLM; Smits, HA; Smits, H.J.

    Alzheimer's disease accounts for the majority of dementia in the elderly. Worldwide, approximately 20 million people are suffering from this devastating disease, with no effective treatment currently available. For efficient drug design, it is important to identify the molecular mechanisms

  5. [Assement of incapacity to work and the Mini-ICF-APP].

    Science.gov (United States)

    Habermeyer, Benedikt; Kaiser, Stefan; Kawohl, Wolfram; Seifritz, Erich

    2017-08-30

    According to recent recommendations the Mini-ICF Rating for Limitations of Activities and Participation in Psychological Disorders (Mini-ICF-APP) should be used in the assessment of incapacity to work. However evidence from empirical research in the field is missing. The application of the Mini-ICF-APP in the psychiatric assessment of 121 cases was analysed. A significant correlation between capacity to work and the duration of sick-leave with the Mini-ICF-APP sum-score was confirmed. The probability that criteria for disability insurance compensations was fulfilled according to the assessor increased with the Mini-ICF-APP-sum-score. Our study provides first empirical evidence regarding the application of the Mini-ICF-APP in the psychiatric assessment of incapacity to work.

  6. FUNCTIONAL PROFILE OF ACTIVE OLDER ADULTS WITH LOW BACK PAIN, ACCORDING TO THE ICF

    Directory of Open Access Journals (Sweden)

    Andersom Ricardo Fréz

    Full Text Available ABSTRACT Introduction: The International Classification of Functioning, Disability and Health (ICF considers multiples aspects of functionality. It is believed that this tool can help to classify the functionality of older adults with low back pain (LBP . Objectives: To describe the functionality of active older adults with LBP according to the ICF. Methods: A transversal study was conducted using the brief ICF core set for low back pain, to establish functional profiles of 40 older adults. The ICF categories were considered valid when ≥20% of participants showed some disability. Results: Thirty-two of the 35 categories of the brief ICF core set could be considered representative of the sample. Conclusion: The brief ICF core set for LBP results demonstrated that this classification system is representative for describing the functional profile of the sample.

  7. Rational design of non-resistant targeted cancer therapies

    Science.gov (United States)

    Martínez-Jiménez, Francisco; Overington, John P.; Al-Lazikani, Bissan; Marti-Renom, Marc A.

    2017-01-01

    Drug resistance is one of the major problems in targeted cancer therapy. A major cause of resistance is changes in the amino acids that form the drug-target binding site. Despite of the numerous efforts made to individually understand and overcome these mutations, there is a lack of comprehensive analysis of the mutational landscape that can prospectively estimate drug-resistance mutations. Here we describe and computationally validate a framework that combines the cancer-specific likelihood with the resistance impact to enable the detection of single point mutations with the highest chance to be responsible of resistance to a particular targeted cancer therapy. Moreover, for these treatment-threatening mutations, the model proposes alternative therapies overcoming the resistance. We exemplified the applicability of the model using EGFR-gefitinib treatment for Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Cancer (LSCC) and the ERK2-VTX11e treatment for melanoma and colorectal cancer. Our model correctly identified the phenotype known resistance mutations, including the classic EGFR-T790M and the ERK2-P58L/S/T mutations. Moreover, the model predicted new previously undescribed mutations as potentially responsible of drug resistance. Finally, we provided a map of the predicted sensitivity of alternative ERK2 and EGFR inhibitors, with a particular highlight of two molecules with a low predicted resistance impact. PMID:28436422

  8. Design of a cone target for fast ignition

    Directory of Open Access Journals (Sweden)

    Sunahara Atsushi

    2013-11-01

    Full Text Available We propose a new type of target for the fast ignition of inertial confinement fusion. Pre-formed plasma inside a cone target can significantly reduce the energy coupling efficiency from the ultra-high intense short-pulse laser to the imploded core plasma. Also, in order to protect the tip of the cone and reduce generation of pre-formed plasma, we propose pointed shaped cone target. In our estimation, the shock traveling time can be delayed 20–30 ps by lower-Z material with larger areal density compared to the conventional gold flat tip. Also, the jet flow can sweep the blow-off plasma from the tip of the cone, and the implosion performance is not drastically affected by the existence of pointed tip. In addition, the self-generated magnetic field is generated along the boundary of cone tip and surrounding CD or DT plasma. This magnetic field can confine fast electrons and focus to the implosion core plasma. Resultant heating efficiency is improved by 30% compared to that with conventional gold flat tip.

  9. Pleiotropic effects of statins: new therapeutic targets in drug design.

    Science.gov (United States)

    Bedi, Onkar; Dhawan, Veena; Sharma, P L; Kumar, Puneet

    2016-07-01

    The HMG Co-enzyme inhibitors and new lipid-modifying agents expand their new therapeutic target options in the field of medical profession. Statins have been described as the most effective class of drugs to reduce serum cholesterol levels. Since the discovery of the first statin nearly 30 years ago, these drugs have become the main therapeutic approach to lower cholesterol levels. The present scientific research demonstrates numerous non-lipid modifiable effects of statins termed as pleiotropic effects of statins, which could be beneficial for the treatment of various devastating disorders. The most important positive effects of statins are anti-inflammatory, anti-proliferative, antioxidant, immunomodulatory, neuroprotective, anti-diabetes, and antithrombotic, improving endothelial dysfunction and attenuating vascular remodeling besides many others which are discussed under the scope of this review. In particular, inhibition of Rho and its downstream target, Rho-associated coiled-coil-containing protein kinase (ROCK), and their agonistic action on peroxisome proliferator-activated receptors (PPARs) can be viewed as the principle mechanisms underlying the pleiotropic effects of statins. With gradually increasing knowledge of new therapeutic targets of statins, their use has also been advocated in chronic inflammatory disorders for example rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE). In the scope of review, we highlight statins and their pleiotropic effects with reference to their harmful and beneficial effects as a novel approach for their use in the treatment of devastating disorders. Graphical abstract Pleiotropic effect of statins.

  10. Recent Measurements of DT Gamma to Neutron Branching Ratio at ICF Conditions

    Science.gov (United States)

    Kim, Yongho

    2011-10-01

    The total T(d,g)5He/T(d,n)4He branching ratio of (4.5 +/- 0.5)E-5 has been measured on Inertial Confinement Fusion (ICF) implosions at the OMEGA laser facility. Recent measurements have shown that the DT branching ratio at ICF is 2 - 3 times less than that of previously measured at particle accelerator facilities. Measurements were done at ion temperatures of (5 +/- 2) keV, which is quite low compared to previous measurements. Implication of the recent founding is that nuclear properties such as DT branching ratio might be reconsidered at low temperature ICF and stellar conditions. In practical sense, precise measurements of the branching ratio T(d,g)5He relative to T(d,n)4He are important in order to diagnose target areal density and resultant fusion yield of cryogenically-layered implosions at the National Ignition Facility (NIF). In this work, we have used LANL's Gas Cherenkov Detector (GCD), which provides a high bandwidth, energy thresholding capability for gamma-ray detection using gamma/electron/Cherenkov conversion. High-bandwidth aids the detection of D-T fusion gamma rays before the arrival of associated 14.1 MeV neutron-induced gammas; energy thresholding gives further protection against such undesirable backgrounds. In addition, to reduce systematic uncertainty, we have applied three independent calibration methods to characterize GCD response such as (1) D-3He gamma-rays generated at Omega laser where no absolute detector calibration was required because quite similar gamma spectrum from D3He and DT, (2) mono-energetic gamma rays generated at Duke University's High Intensity Gamma-ray Source (HIgS), and (3) 14-MeV neutron-induced inelastic gamma-rays generated at OMEGA using puck materials of known areal density placed near target center. In conjunction with an independent neutron yield measurements and ACCEPT and GEANT4 simulation codes, the resultant DT branching ratio was inferred. This work was performed by Los Alamos National Laboratory under the

  11. Shoulder pain within the ICF framework; patient experiences of functioning and assessment methods

    OpenAIRE

    Røe, Yngve

    2014-01-01

    Introduction: Shoulder pain is a common, persistent and disabling disease. The restoration of abnormal movement-patterns is often an important goal in the treatment of patients with shoulder pain. The International Classification of Functioning, Disability and Health (ICF) is a conceptual framework and classification that has been developed by the World Health Organisation. The ICF is a common, multi-disciplinary language that allows identification of condition-specific codes (ICF categories)...

  12. Designing Nonlinear Turbo Codes with a Target Ones Density

    CERN Document Server

    Wang, Jiadong; Chen, Tsung-Yi; Xie, Bike; Wesel, Richard

    2011-01-01

    Certain binary asymmetric channels, such as Z-channels in which one of the two crossover probabilities is zero, demand optimal ones densities different from 50%. Some broadcast channels, such as broadcast binary symmetric channels (BBSC) where each component channel is a binary symmetric channel, also require a non-uniform input distribution due to the superposition coding scheme, which is known to achieve the boundary of capacity region. This paper presents a systematic technique for designing nonlinear turbo codes that are able to support ones densities different from 50%. To demonstrate the effectiveness of our design technique, we design and simulate nonlinear turbo codes for the Z-channel and the BBSC. The best nonlinear turbo code is less than 0.02 bits from capacity.

  13. TRPV1: A Target for Rational Drug Design

    Directory of Open Access Journals (Sweden)

    Vincenzo Carnevale

    2016-08-01

    Full Text Available Transient Receptor Potential Vanilloid 1 (TRPV1 is a non-selective, Ca2+ permeable cation channel activated by noxious heat, and chemical ligands, such as capsaicin and resiniferatoxin (RTX. Many compounds have been developed that either activate or inhibit TRPV1, but none of them are in routine clinical practice. This review will discuss the rationale for antagonists and agonists of TRPV1 for pain relief and other conditions, and strategies to develop new, better drugs to target this ion channel, using the newly available high-resolution structures.

  14. Design and synthesis of threading intercalators to target DNA.

    Science.gov (United States)

    Howell, Lesley A; Gulam, Rosul; Mueller, Anja; O'Connell, Maria A; Searcey, Mark

    2010-12-01

    Threading intercalators are high affinity DNA binding agents that bind by inserting a chromophore into the duplex and locating one group in each groove. The first threading intercalators that can be conjugated to acids, sulfonic acids and peptides to target them to duplex DNA are described, based upon the well studied acridine-3- or 4-carboxamides. Cellular uptake of the parent acridine is rapid and it can be visualized in the nucleus of cells. Both the parent compounds and their conjugates maintain antitumor activity.

  15. Design and implementation of location-based wireless targeted advertising

    Science.gov (United States)

    Li, Benjamin; Xu, Deyin

    2001-10-01

    As advertisements are time and location sensitive, a challenge for wireless marketing is to have advertisements delivered when and where they are most convenient. In this paper we introduce a two-stage auction model for location-based wireless targeted advertising. This system extends the notion of location-based service by using location information to target advertising, and does so specifically by enabling advertisers to specify their preferences and bid for advertisement delivery, where those preferences are then used in a subsequent automated auction of actual deliveries to wireless data users. The automated auction in the second stage is especially effective because it can use information about the individual user profile data, including customer relationship management system contents as well as location from the wireless system's location management service, including potentially location history such as current trajectory from recent history and longer-term historical trip records for that user. Through two-stage auction, real-time bidding by advertisers and matching ads contents to mobile users help advertising information reach maximal value.

  16. In silico design of targeted SRM-based experiments

    Directory of Open Access Journals (Sweden)

    Nahnsen Sven

    2012-11-01

    Full Text Available Abstract Selected reaction monitoring (SRM-based proteomics approaches enable highly sensitive and reproducible assays for profiling of thousands of peptides in one experiment. The development of such assays involves the determination of retention time, detectability and fragmentation properties of peptides, followed by an optimal selection of transitions. If those properties have to be identified experimentally, the assay development becomes a time-consuming task. We introduce a computational framework for the optimal selection of transitions for a given set of proteins based on their sequence information alone or in conjunction with already existing transition databases. The presented method enables the rapid and fully automated initial development of assays for targeted proteomics. We introduce the relevant methods, report and discuss a step-wise and generic protocol and we also show that we can reach an ad hoc coverage of 80 % of the targeted proteins. The presented algorithmic procedure is implemented in the open-source software package OpenMS/TOPP.

  17. Representing Targets of Measurement within Evidence-Centered Design

    Science.gov (United States)

    Ewing, Maureen; Packman, Sheryl; Hamen, Cynthia; Thurber, Allison Clark

    2010-01-01

    In the last few years, the Advanced Placement (AP) Program[R] has used evidence-centered assessment design (ECD) to articulate the knowledge, skills, and abilities to be taught in the course and measured on the summative exam for four science courses, three history courses, and six world language courses; its application to calculus and English…

  18. Mediating effects of the ICF domain of function and the gross motor function measure on the ICF domains of activity, and participation in children with cerebral palsy.

    Science.gov (United States)

    Lee, Byoung-Hee; Kim, Yu-Mi; Jeong, Goo-Churl

    2015-10-01

    [Purpose] This study aimed to evaluate the mediating effect of gross motor function, measured using the Gross Motor Function Measure (GMFM) and of general function, measured using the International Classification of Functioning, Disability and Health-Child and Youth Check List (ICF-CY), on the ICF domains of activity and participation in children with cerebral palsy (CP). [Subjects] Ninety-five children with CP, from Seoul, Korea, participated in the study. [Methods] The GMFM was administered in its entirety to patients without orthoses or mobility aids. The ICF-CY was used to evaluate the degree of disability and health of subjects. [Results] GMFM score and ICF-CY function were negatively correlated to ICF-CY activity and participation. ICF-CY partially mediated the effects of the GMFM on activity and participation. [Conclusion] When establishing a treatment plan for a child with CP, limitations in activity and participation, as described by the ICF-CY, should be considered in addition to the child's physical abilities and development. In addition, the treatment plan should focus on increasing the child's activity and participation level, as well as his/her physical level.

  19. 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)

  20. White Paper on Ion Beam Transport for ICF: Issues, R&D Need,and Tri-Lab Plans

    Energy Technology Data Exchange (ETDEWEB)

    Olson, C.; Lee, E.; Langdon, B.

    2005-05-04

    To date, most resources for ion beam fusion have been devoted to development of accelerators and target physics; relatively few resources have gone into ion beam transport development. Because of theoretical studies and substantial experience with electron beam transport, the ion beam transport community is now poised to develop and optimize ion beam transport for ICF. Because of this Tri-Lab effort, a path for coordinated development of ion beam transport has been established. The rate of progress along this path will now be determined largely by the availability of resources.

  1. Constraints on target chamber first wall and target designs that will enable NIF debris shields to survive

    Science.gov (United States)

    Burnham, Alan K.; Gerassimenko, Michel; Scott, J. M.; Latkowski, Jeff F.; Whitman, Pamela K.; Genin, Francois Y.; Hibbard, Wilthea; Peterson, P. F.; Tokheim, R. E.; Curran, D. R.

    1999-07-01

    The NIF target chamber interior materials and target designs themselves have to be compatible with survival of the final- optics debris shields. To meet the planned maintenance and refinishing rate, the contamination of the debris shields cannot exceed about 1 nm equivalent thickness per shot of total material. This implies that he target mass must be limited to no more than 1 gram and the ablated mass released to the chamber from all other components must not exceed 3 grams. In addition, the targets themselves must either completely vaporize or send any minor amounts of shrapnel towards the chamber waist to prevent excessive catering of the debris shields. The constraints on the first-wall debris will remobilize at a rate fast enough to require cleaning every 3 weeks, about three times more frequent than possible with planned robotics. Furthermore, a comparison of ablatants from B4C and stainless-steel louvers suggest that remobilization of target debris by x-rays will be greater than that of the base material in both cases, thereby reducing the performance advantage of clean B4C over much cheaper stainless steel. Neutronics calculations indicate that activation of thin Ni-free stainless steel is not a significant source of maintenance personnel radiation dose. Consequently, the most attractive first wall design consists of stainless-steel louvers. Evaluation of various unconverted-light beam dump designs indicates that stainless steel louvers generate no more debris than other matrices, so one single design can serve as both first wall and beam dumps, eliminating beam steering restrictions caused by size and location of the beam dumps. One reservation is that the allowable contamination rate of the debris shield is not yet completely understood. Consequently, it is likely that either a protruding beam tube, a rapid post-shot gas purge of the final optics assembly, or thin polymeric pre-shield will be required to prevent low-velocity contamination from reaching

  2. Targeting B cell responses in universal influenza vaccine design

    Science.gov (United States)

    Kaur, Kaval; Sullivan, Meghan; Wilson, Patrick C

    2011-01-01

    Since its first administration in the 1940s, the influenza vaccine has provided tremendous relief against influenza infections. However, time has revealed the vaccine’s ultimate limit and the call for its reinvention has now come, just as we are beginning to appreciate the antibody immune responses vital in preventing infections. New strategies to design the influenza vaccine rely on selectively inducing broadly neutralizing antibodies that are specific for highly conserved viral epitopes. Such approaches take us away from the limited range of protection provided by current seasonal influenza vaccines and towards a future with a pan-influenza vaccine capable of providing universal strain coverage. PMID:21940217

  3. Inertial confinement fusion. ICF quarterly report, October 1993--December 1993, Volume 4, Number 1

    Energy Technology Data Exchange (ETDEWEB)

    Powell, H.T.; Schleich, D.P.; Murphy, P.W. [eds.

    1994-05-01

    In the 1990 National Academy of Sciences (NAS) report of its review of the U.S. Inertial Confinement Fusion (ICF) Program, it was recommended that a high priority be placed on completing the Precision Nova Project and its associated experimental campaign. Since fiscal year 1990, the lab has therefore campaigned vigorously on Nova and in its supporting laboratories to develop the Precision Nova capabilities needed to perform the stressful target experiments recommended in the 1990 NAS report. The activities to enable these experiments have been directed at improvements in three areas - the Nova laser, target fabrication capabilities, and target diagnostics. As summarized in the five articles in this report, the Precision Nova improvements have been successfully completed. These improvements have had a positive impact on target performance and on the ability to diagnose the results, as evidenced by the HEP-1 experimental results. The five articles generally concentrate on improvements to the capabilities rather than on the associated target physics experiments. Separate abstracts are included for each paper.

  4. Towards system-wide implementation of the International Classification of Functioning, Disability and Health (ICF) in routine practice: Developing simple, intuitive descriptions of ICF categories in the ICF Generic and Rehabilitation Set.

    Science.gov (United States)

    Prodinger, Birgit; Reinhardt, Jan D; Selb, Melissa; Stucki, Gerold; Yan, Tiebin; Zhang, Xia; Li, Jianan

    2016-06-13

    A national, multi-phase, consensus process to develop simple, intuitive descriptions of International Classification of Functioning, Disability and Health (ICF) categories contained in the ICF Generic and Rehabilitation Sets, with the aim of enhancing the utility of the ICF in routine clinical practice, is presented in this study. A multi-stage, national, consensus process was conducted. The consensus process involved 3 expert groups and consisted of a preparatory phase, a consensus conference with consecutive working groups and 3 voting rounds (votes A, B and C), followed by an implementation phase. In the consensus conference, participants first voted on whether they agreed that an initially developed proposal for simple, intuitive descriptions of an ICF category was in fact simple and intuitive. The consensus conference was held in August 2014 in mainland China. Twenty-one people with a background in physical medicine and rehabilitation participated in the consensus process. Four ICF categories achieved consensus in vote A, 16 in vote B, and 8 in vote C. This process can be seen as part of a larger effort towards the system-wide implementation of the ICF in routine clinical and rehabilitation practice to allow for the regular and comprehensive evaluation of health outcomes most relevant for the monitoring of quality of care.

  5. Sustainable Process Design under uncertainty analysis: targeting environmental indicators

    DEFF Research Database (Denmark)

    2015-01-01

    from algae biomass is used as a case study. The results indicate there are considerable uncertainties in the calculated environmental indicators as revealed by CDFs. The underlying sources of these uncertainties are indeed the significant variation in the databases used for the LCA analysis......This study focuses on uncertainty analysis of environmental indicators used to support sustainable process design efforts. To this end, the Life Cycle Assessment methodology is extended with a comprehensive uncertainty analysis to propagate the uncertainties in input LCA data to the environmental...... indicators. The resulting uncertainties in the environmental indicators are then represented by empirical cumulative distribution function, which provides a probabilistic basis for the interpretation of the indicators. In order to highlight the main features of the extended LCA, the production of biodiesel...

  6. Computational design of high efficiency release targets for use at ISOL facilities

    CERN Document Server

    Liu, Y

    1999-01-01

    This report describes efforts made at the Oak Ridge National Laboratory to design high-efficiency-release targets that simultaneously incorporate the short diffusion lengths, high permeabilities, controllable temperatures, and heat-removal properties required for the generation of useful radioactive ion beam (RIB) intensities for nuclear physics and astrophysics research using the isotope separation on-line (ISOL) technique. Short diffusion lengths are achieved either by using thin fibrous target materials or by coating thin layers of selected target material onto low-density carbon fibers such as reticulated-vitreous-carbon fiber (RVCF) or carbon-bonded-carbon fiber (CBCF) to form highly permeable composite target matrices. Computational studies that simulate the generation and removal of primary beam deposited heat from target materials have been conducted to optimize the design of target/heat-sink systems for generating RIBs. The results derived from diffusion release-rate simulation studies for selected t...

  7. European heavy ion ICF driver development

    CERN Document Server

    Plass, Günther

    1996-01-01

    Approaches in Europe to heavy ion induced Inertial Confinement Fusion are oriented toward the linac-plus- storage ring technique. Despite the very limited support of this work, technical pro gress was achieved in some important areas. For the immediate future, a substantial intensity upgrade of the GSI accelerator facilities at Darmstadt is being implemented, leading to specific energy depositions of the order of 100 kJ/g and plasma temperatures of 10 to 20 eV. For the longer term, a conceptual design study of a heavy ion based Ignition Facility is being initiated.

  8. A coordinate transformation method for calculating the 3D light intensity distribution in ICF hohlraum

    Science.gov (United States)

    Lin, Zhili; Li, Xiaoyan; Zhao, Kuixia; Chen, Xudong; Chen, Mingyu; Pu, Jixiong

    2016-06-01

    For an inertial confinement fusion (ICF) system, the light intensity distribution in the hohlraum is key to the initial plasma excitation and later laser-plasma interaction process. Based on the concept of coordinate transformation of spatial points and vector, we present a robust method with a detailed procedure that makes the calculation of the three dimensional (3D) light intensity distribution in hohlraum easily. The method is intuitive but powerful enough to solve the complex cases of random number of laser beams with arbitrary polarization states and incidence angles. Its application is exemplified in the Shenguang III Facility (SG-III) that verifies its effectiveness and it is useful for guiding the design of hohlraum structure parameter.

  9. Inertial confinement fusion target component fabrication and technology development support: Annual report, October 1, 1995--September 30, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, M. [ed.

    1997-02-01

    On December 30, 1990, the U.S. Department of Energy entered into a contract with General Atomics (GA) to be the Inertial Confinement Fusion (ICF) Target Component Fabrication and Technology Development Support contractor. In September 1995 this contract ended and a second contract was issued for us to continue this ICF target support work. This report documents the technical activities of the period October 1, 1995 through September 30, 1996. During this period, GA and our partners WJ Schafer Associates (WJSA) and Soane Technologies, Inc. (STI) were assigned 14 formal tasks in support of the Inertial Confinement Fusion program and its five laboratories. A portion of the effort on these tasks included providing direct {open_quotes}Onsite Support{close_quotes} at Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), and Sandia National Laboratory Albuquerque (SNLA). We fabricated and delivered over 800 gold-plated hohlraum mandrels to LLNL, LANL and SNLA. We produced nearly 1,200 glass and plastic target capsules for LLNL, LANL, SNLA and University of Rochester/Laboratory for Laser Energetics (UR/LLE). We also delivered over 100 flat foil targets for Naval Research Lab (NRL) and SNLA in FY96. This report describes these target fabrication activities and the target fabrication and characterization development activities that made the deliveries possible. The ICF program is anticipating experiments at the OMEGA laser and the National Ignition Facility (NIF) which will require capsules containing cryogenic layered D{sub 2} or deuterium-tritium (DT) fuel. We are part of the National Cryogenic Target Program to create and demonstrate viable ways to generate and characterize cryogenic layers. Substantial progress has been made on ways to both create and characterize viable layers. During FY96, significant progress was made in the design of the OMEGA Cryogenic Target System that will field cryogenic targets on OMEGA.

  10. Efficient Targeted Mutagenesis in Medaka Using Custom-Designed Transcription Activator-Like Effector Nucleases

    OpenAIRE

    Ansai, Satoshi; Sakuma, Tetsushi; Yamamoto, Takashi; Ariga, Hiroyoshi; Uemura, Norihito; Takahashi, Ryosuke; Kinoshita, Masato

    2013-01-01

    Transcription activator-like effector nucleases (TALENs) have become powerful tools for targeted genome editing. Here we demonstrate efficient targeted mutagenesis in medaka (Oryzias latipes), which serves as an excellent vertebrate model for genetics and genomics. We designed and constructed a pair of TALENs targeting the medaka DJ-1 gene, a homolog of human DJ-1 (PARK7). These TALENs induced a number of insertions and deletions in the injected embryos with extremely high efficiency. This in...

  11. Design and test of a graphite target system for in-flight fragment separator

    Science.gov (United States)

    Hong, S. G.; Kim, J. H.; Kim, M. J.; Song, J. S.; Kim, J. W.

    2014-07-01

    A graphite target system to produce rare isotope beams using in-flight fragmentation method has been designed for the rare isotope science project in Korea. A main primary beam to bombard the target is 238U in the energy of 200 MeV/u with a maximum power of 400 kW, in which the beam power deposit on the target amounts up to 100 kW. A multi-slice target concept was adopted to enhance radiation cooling effect. A finite element program ANSYS was used to analyze thermo-mechanical behavior of a single and multi-slice targets. To validate the design, an electron beam at the energy of 50 keV was used to test a single slice target. A good agreement of the hot spot temperature was achieved between the simulation and measurement. For multi-slice targets a series of ANSYS analysis was performed in search of the optimal design. Target design parameters for the isotope beam production, which can sustain an incident 400-kW 238U beam, have been found.

  12. Design and test of a graphite target system for in-flight fragment separator

    Energy Technology Data Exchange (ETDEWEB)

    Hong, S.G.; Kim, J.H.; Kim, M.J.; Song, J.S. [Rare Isotope Science Project, Institute for Basic Science, Daejeon 305-811 (Korea, Republic of); Department of Physics, Han-Nam University, Daejeon 306-791 (Korea, Republic of); Kim, J.W., E-mail: jwkim@ibs.re.kr [Rare Isotope Science Project, Institute for Basic Science, Daejeon 305-811 (Korea, Republic of)

    2014-07-01

    A graphite target system to produce rare isotope beams using in-flight fragmentation method has been designed for the rare isotope science project in Korea. A main primary beam to bombard the target is {sup 238}U in the energy of 200 MeV/u with a maximum power of 400 kW, in which the beam power deposit on the target amounts up to 100 kW. A multi-slice target concept was adopted to enhance radiation cooling effect. A finite element program ANSYS was used to analyze thermo-mechanical behavior of a single and multi-slice targets. To validate the design, an electron beam at the energy of 50 keV was used to test a single slice target. A good agreement of the hot spot temperature was achieved between the simulation and measurement. For multi-slice targets a series of ANSYS analysis was performed in search of the optimal design. Target design parameters for the isotope beam production, which can sustain an incident 400-kW {sup 238}U beam, have been found.

  13. Strategies for designing and monitoring malaria vaccines targeting diverse antigens

    Directory of Open Access Journals (Sweden)

    Alyssa E Barry

    2014-07-01

    Full Text Available After more than 50 years of intensive research and development, only one malaria vaccine candidate, RTS,S, has progressed to Phase 3 clinical trials. Despite only partial efficacy, this candidate is now forecast to become the first licensed malaria vaccine. Hence, more efficacious second-generation malaria vaccines that can significantly reduce transmission are urgently needed. This review will focus on a major obstacle hindering development of effective malaria vaccines: parasite antigenic diversity. Despite extensive genetic diversity in leading candidate antigens, vaccines have been and continue to be formulated using recombinant antigens representing only one or two strains. These vaccine strains represent only a small fraction of the diversity circulating in natural parasite populations, leading to escape of non-vaccine strains and challenging investigators’ abilities to measure strain-specific efficacy in vaccine trials. Novel strategies are needed to overcome antigenic diversity in order for vaccine development to succeed. Many studies have now catalogued the global diversity of leading Plasmodium falciparum and Plasmodium vivax vaccine antigens. In this review, we describe how population genetic approaches can be applied to this rich data source to predict the alleles that best represent antigenic diversity, polymorphisms that contribute to it, and to identify key polymorphisms associated with antigenic escape. We also suggest an approach to summarise the known global diversity of a given antigen to predict antigenic diversity, how to select variants that best represent the strains circulating in natural parasite populations and how to investigate the strain-specific efficacy of vaccine trials. Use of these strategies in the design and monitoring of vaccine trials will not only shed light on the contribution of genetic diversity to the antigenic diversity of malaria, but will also maximise the potential of future malaria vaccine

  14. [Use of the ICF in medical rehabilitation in Germany: claims and reality].

    Science.gov (United States)

    Wenzel, Tobias-Raphael; Morfeld, Matthias

    2017-04-01

    The International Classification of Functioning, Disability and Health (ICF) is being used in the medical rehabilitation practice in different ways. The World Health Organization (WHO) and many other stakeholders have formulated claims and expectations for its use. A comparative presentation of the claims of various stakeholders for the use of the ICF with examples in current practice. Database searches (PubMed, REHADAT, and Google Scholar) were conducted for studies concerning claims and the current use of the ICF in practice. There are different requirements regarding the use of the ICF. While lawmakers and social insurance agencies remain very cautious and vague, other stakeholders (research institutions, organizations, stakeholders, service providers) formulate higher expectations and call for greater use of the ICF. In practice, the ICF is used in the form of a bio-psycho-social model, a common language and many different adaptations. The different requirements for the use of ICF demonstrate the motivations and interests of the stakeholders. Signals must now be sent both by politics and by social insurance agencies that go far beyond non-binding declarations. Furthermore it is necessary to systematize and evaluate the many use adaptations that are primarily being used by service providers. Research is needed on the concrete use of ICF-based instruments and its intended and unintended effects.

  15. Anbefaling vedrørende brug af ICF på fysioterapeutuddannelsen UCN

    DEFF Research Database (Denmark)

    Østergaard, Gert Værge; Larsen, Lars Henrik; Brogner, Heidi Marie

    2015-01-01

    Basis-fys-fagteamets anbefalinger til hvordan ICF ønskes brugt på uddannelsen, både i den teoretiske, såvel som i den kliniske undervisning......Basis-fys-fagteamets anbefalinger til hvordan ICF ønskes brugt på uddannelsen, både i den teoretiske, såvel som i den kliniske undervisning...

  16. Disability and Functional Profiles of Patients with Migraine Measured with ICF Classification

    Science.gov (United States)

    Raggi, Alberto

    2010-01-01

    To describe the functional profiles of patients with migraine, and the relationships between symptoms, activities and environmental factors, using WHO's International Classification of Functioning (ICF). Patients were consecutively enrolled at the Besta Institute of Milan. The ICF checklist was administered and two count-based indexes developed:…

  17. An ICF-CY-Based Content Analysis of the Vineland Adaptive Behavior Scales-II

    Science.gov (United States)

    Gleason, Kara; Coster, Wendy

    2012-01-01

    Background: The International Classification of Functioning, Disability and Health (ICF), and its version for children and youth (ICF-CY), has been increasingly adopted as a system to describe function and disability. A content analysis of the Vineland Adaptive Behavior Scales-II (VABS-II) was conducted to examine congruence with the functioning…

  18. ICF quarterly report, October-December 1998, volume 8, number 4

    Energy Technology Data Exchange (ETDEWEB)

    Kaufmann, B

    1998-09-30

    The ICF Quarterly Report is pub-lished four times each fiscal year by the Inertial Confinement Fusion/National Ignition Facility and High-Energy-Density Experimental Science (ICF/NIF/ HEDES) Program at the Lawrence Livermore National Laboratory (LLNL). The journal summarizes selected current research achievements of the LLNLICF/NIF/HEDES Program.

  19. The design status of the liquid lithium target facility of IFMIF at the end of the engineering design activities

    Energy Technology Data Exchange (ETDEWEB)

    Nitti, F.S., E-mail: francesco.nitti@enea.it [IFMIF/EVEDA Project Team, Rokkasho Japan (Japan); Ibarra, A. [CIEMAT, Madrid (Spain); Ida, M. [IHI Corporation, Tokyo (Japan); Favuzza, P. [ENEA Research Center Firenze (Italy); Furukawa, T. [JAEA Research Center, Tokai-mura, Ibaraki (Japan); Groeschel, F. [KIT Research Center, Karlsruhe (Germany); Heidinger, R. [F4E Research Center, Garching (Germany); Kanemura, T. [JAEA Research Center, Tokai-mura, Ibaraki (Japan); Knaster, J. [IFMIF/EVEDA Project Team, Rokkasho Japan (Japan); Kondo, H. [JAEA Research Center, Tokai-mura, Ibaraki (Japan); Micchiche, G. [ENEA Research Center, Brasimone (Italy); Sugimoto, M. [JAEA Research Center, Rokkasho Japan (Japan); Wakai, E. [JAEA Research Center, Tokai-mura, Ibaraki (Japan)

    2015-11-15

    Highlights: • Results of validation and design activity for the Li loop facility of IFMIF. • Demonstration of Li target stability, with surface disturbance <1 mm. • Demonstration of start-up and shut down procedures of Li loop. • Complete design of the heat removal system and C and O purification system. • Conceptual design of N and H isotopes purification systems. - Abstract: The International Fusion Material Irradiation Facility (IFMIF) is an experimental facility conceived for qualifying and characterizing structural materials for nuclear fusion applications. The Engineering Validation and Engineering Design Activity (EVEDA) is a fundamental step towards the final design. It presented two mandates: the Engineering Validation Activities (EVA), still on-going, and the Engineering Design Activities (EDA) accomplished on schedule in June 2013. Five main facilities are identified in IFMIF, among which the Lithium Target Facility constituted a technological challenge overcome thanks to the success of the main validation challenges impacting the design. The design of the liquid Lithium Target Facility at the end of the EDA phase is here detailed.

  20. Selecting an optimal abbreviated ICF set for clinical practice among rehabilitants with subacute stroke: retrospective analysis of patient records.

    Science.gov (United States)

    Saltychev, Mikhail; Tarvonen-Schröder, Sinikka; Eskola, Merja; Laimi, Katri

    2013-06-01

    To evaluate the adequacy of abbreviated versions of International Classification of Functioning, Disability and Health (ICF) (the WHO ICF Checklist and the ICF Comprehensive Core Set for Stroke) with respect to the specific clinical needs of a stroke rehabilitation unit before their implementation at a practical level. Common descriptions of functional limitations were identified from patient records of 10 subsequent subacute stroke patients referred to an inpatient multiprofessional rehabilitation unit of a university hospital. These descriptions were then converted into ICF categories, and the list was compared with the ICF Checklist of the WHO and the ICF Comprehensive and Brief Core Sets for Stroke developed by the ICF Research Branch. From the study population (50% women), 71 different, second-level ICF categories were identified, averaging 36.4 categories/patient (SD 5.8, range 28-46). Except for one category, all of the categories identified were also found in the ICF Comprehensive Core Set for Stroke. Of the categories identified, 49 (69%) were found in the WHO ICF Checklist. All except one category included in the ICF Brief Core Set for Stroke were also in our list. The Comprehensive Core Set for Stroke was found to be a good potential starting point for the practical implementation of the ICF in a stroke rehabilitation unit.

  1. Autonomous Rover Traverse and Precise Arm Placement on Remotely Designated Targets

    Science.gov (United States)

    Nesnas, Issa A.; Pivtoraiko, Mihail N.; Kelly, Alonzo; Fleder, Michael

    2012-01-01

    This software controls a rover platform to traverse rocky terrain autonomously, plan paths, and avoid obstacles using its stereo hazard and navigation cameras. It does so while continuously tracking a target of interest selected from 10 20 m away. The rover drives and tracks the target until it reaches the vicinity of the target. The rover then positions itself to approach the target, deploys its robotic arm, and places the end effector instrument on the designated target to within 2-3-cm accuracy of the originally selected target. This software features continuous navigation in a fairly rocky field in an outdoor environment and the ability to enable the rover to avoid large rocks and traverse over smaller ones. Using point-and-click mouse commands, a scientist designates targets in the initial imagery acquired from the rover s mast cameras. The navigation software uses stereo imaging, traversability analysis, path planning, trajectory generation, and trajectory execution. It also includes visual target tracking of a designated target selected from 10 m away while continuously navigating the rocky terrain. Improvements in this design include steering while driving, which uses continuous curvature paths. There are also several improvements to the traversability analyzer, including improved data fusion of traversability maps that result from pose estimation uncertainties, dealing with boundary effects to enable tighter maneuvers, and handling a wider range of obstacles. This work advances what has been previously developed and integrated on the Mars Exploration Rovers by using algorithms that are capable of traversing more rock-dense terrains, enabling tight, thread-the-needle maneuvers. These algorithms were integrated on the newly refurbished Athena Mars research rover, and were fielded in the JPL Mars Yard. Forty-three runs were conducted with targets at distances ranging from 5 to 15 m, and a success rate of 93% was achieved for placement of the instrument within

  2. Computer Aided Drug Design for Multi-Target Drug Design: SAR /QSAR, Molecular Docking and Pharmacophore Methods.

    Science.gov (United States)

    Abdolmaleki, Azizeh; Ghasemi, Jahan B; Ghasemi, Fatemeh

    2017-01-01

    Multi-target drugs against particular multiple targets get better protection, resistance profiles and curative influence by cooperative rules of a key beneficial target with resistance behavior and compensatory elements. Computational techniques can assist us in the efforts to design novel drugs (ligands) with a preferred bioactivity outline and alternative bioactive molecules at an early stage. A number of in silico methods have been explored extensively in order to facilitate the investigation of individual target agents and to propose a selective drug. A different, progressively more significant field which is used to predict the bioactivity of chemical compounds is the data mining method. Some of the previously mentioned methods have been investigated for multi-target drug design (MTDD) to find drug leads interact simultaneously with multiple targets. Several cheminformatics methods and structure-based approaches try to extract information from units working cooperatively in a biomolecular system to fulfill their task. To dominate the difficulties of the experimental specification of ligand-target structures, rational methods, namely molecular docking, SAR and QSAR are vital substitutes to obtain knowledge for each structure in atomic insight. These procedures are logically successful for the prediction of binding affinity and have shown promising potential in facilitating MTDD. Here, we review some of the important features of the multi-target therapeutics discoveries using the computational approach, highlighting the SAR, QSAR, docking and pharmacophore methods to discover interactions between drug-target that could be leveraged for curative benefits. A summary of each, followed by examples of its applications in drug design has been provided. Computational efficiency of each method has been represented according to its main strengths and limitations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Design of targeted libraries against the human Chk1 kinase using PGVL Hub.

    Science.gov (United States)

    Peng, Zhengwei; Hu, Qiyue

    2011-01-01

    PGVL Hub is a Pfizer internal desktop tool for chemical library and singleton design. In this chapter, we give a short introduction to PGVL Hub, the core workflow it supports, and the rich design capabilities it provides. By re-creating two legacy targeted libraries against the human checkpoint kinase 1 (Chk1) as a showcase, we illustrate how PGVL Hub could be used to help library designers carry out the steps in library design and realize design objectives such as SAR expansion and improvement in both kinase selectivity and compound aqueous solubility. Finally we share several tips about library design and usage of PGVL Hub.

  4. Content comparison of haemophilia specific patient-rated outcome measures with the international classification of functioning, disability and health (ICF, ICF-CY)

    Science.gov (United States)

    2010-01-01

    Background Patient-Reported Outcomes (PROs) are considered important outcomes because they reflect the patient's experience in clinical trials. PROs have been included in the field of haemophilia only recently. Purpose Comparing the contents of PROs measures used in haemophilia, based on the ICF/ICF-CY as frame of reference. Methods Haemophilia-specific PROs for adults and children were selected on the grounds of international accessibility. The content of the selected instruments were examined by linking the concepts within the items of these instruments to the ICF/ICF-CY. Results Within the 5 selected instruments 365 concepts were identified, of which 283 concepts were linked to the ICF/ICF CY and mapped into 70 different categories. The most frequently used categories were "b152: Emotional functions" and "e1101: Drugs". Conclusions The present paper provides an overview on current PROs in haemophilia and facilitates the selection of appropriate instruments for specific purposes in clinical and research settings. This work was made possible by the grant of the European Murinet Project (Multidisciplinary Research Network on Health and Disability in Europe). PMID:21108796

  5. Design and Optimization for the Windowless Target of the China Nuclear Waste Transmutation Reactor

    Directory of Open Access Journals (Sweden)

    Desheng Cheng

    2016-04-01

    Full Text Available A windowless spallation target can provide a neutron source and maintain neutron chain reaction for a subcritical reactor, and is a key component of China's nuclear waste transmutation of coupling accelerator and subcritical reactor. The main issue of the windowless target design is to form a stable and controllable free surface that can ensure that energy spectrum distribution is acquired for the neutron physical design when the high energy proton beam beats the lead–bismuth eutectic in the spallation target area. In this study, morphology and flow characteristics of the free surface of the windowless target were analyzed through the volume of fluid model using computational fluid dynamics simulation, and the results show that the outlet cross section size of the target is the key to form a stable and controllable free surface, as well as the outlet with an arc transition. The optimization parameter of the target design, in which the radius of outlet cross section is 60 ± 1 mm, is verified to form a stable and controllable free surface and to reduce the formation of air bubbles. This work can function as a reference for carrying out engineering design of windowless target and for verification experiments.

  6. Design and optimization for the windowless target of the China Nuclear Waste Transmutation Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, De Sheng; Wang, Weihua; Yang, Shi Jun; Deng, Haifei; Wang, Rong Fei; Wang, Bin Jun [Institute Applied Physics of AOA, Hefei (China)

    2016-04-15

    A windowless spallation target can provide a neutron source and maintain neutron chain reaction for a subcritical reactor, and is a key component of China's nuclear waste transmutation of coupling accelerator and subcritical reactor. The main issue of the windowless target design is to form a stable and controllable free surface that can ensure that energy spectrum distribution is acquired for the neutron physical design when the high energy proton beam beats the lead-bismuth eutectic in the spallation target area. In this study, morphology and flow characteristics of the free surface of the windowless target were analyzed through the volume of fluid model using computational fluid dynamics simulation, and the results show that the outlet cross section size of the target is the key to form a stable and controllable free surface, as well as the outlet with an arc transition. The optimization parameter of the target design, in which the radius of outlet cross section is 60 ± 1 mm, is verified to form a stable and controllable free surface and to reduce the formation of air bubbles. This work can function as a reference for carrying out engineering design of windowless target and for verification experiments.

  7. Magnet Design for the ISIS Second Target Station Proton Beam Line

    CERN Document Server

    Thomas, Chris; Jago, Stephen

    2005-01-01

    The ISIS facility, based at the Rutherford Appleton Laboratory in the UK, is an intense source of neutrons and muons for condensed matter research. The accelerator facility delivers an 800 MeV proton beam of 2.5x1013 protons per pulse at 50 Hz to the present target station. As part of a facility upgrade, it is planned to share the source with a second, 10 Hz, target station. The beam line supplying this target will extract from the existing target station beam line. Electromagnetic Finite Element Modelling techniques have been used to design the magnets required to meet the specified beam line optics. Kicker, septum, dipole, quadrupole, and steering magnets are covered. The magnet design process, involving 2D and 3D modelling, the calculation of ideal shims and chamfers, choice of steel, design of conducting coils, handling of heating issues and eddy current effects, is discussed.

  8. Design of photon converter and photoneutron target for High power electron accelerator based BNCT.

    Science.gov (United States)

    Rahmani, Faezeh; Seifi, Samaneh; Anbaran, Hossein Tavakoli; Ghasemi, Farshad

    2015-12-01

    An electron accelerator, ILU-14, with current of 10 mA and 100 kW in power has been considered as one of the options for neutron source in Boron Neutron Capture Therapy (BNCT). The final design of neutron target has been obtained using MCNPX to optimize the neutron production. Tungsten in strip shape and D2O in cylindrical form have been proposed as the photon converter and the photoneutron target, respectively. In addition calculation of heat deposition in the photon target design has been considered to ensure mechanical stability of target. The results show that about 8.37×10(12) photoneutron/s with average energy of 615 keV can be produced by this neutron source design. In addition, using an appropriate beam shaping assembly an epithermal neutron flux of the order of 1.24×10(8) cm(-2) s(-1) can be obtained for BNCT applications.

  9. Early oncology clinical trial design in the era of molecular-targeted agents.

    Science.gov (United States)

    Brunetto, Andre T; Kristeleit, Rebecca S; de Bono, Johann S

    2010-08-01

    The introduction of molecularly targeted agents has changed the concept of drug development. The field has evolved over the last decade and therapeutic drugs are now being rationally designed to affect specific intracellular or extracellular pathways that are thought to be important for cancer progression. Traditionally, toxicity has been the primary end point for dose definition and escalation; however, novel targeted compounds are characterized by the lack of significant clinical toxicity compared with conventional chemotherapy. Alternative trial designs and pharmacodynamic-driven biomarkers that assess drug-target effect and allow demonstration of proof-of-concept for intended target modulation and achievement of desired biological effects have emerged to guide dose selection. This must be facilitated by validated preclinical tumor models and biomarker assays that are critical to aid understanding of which agents are likely to be beneficial in different cancer subtype patients and which biomarkers should be implemented into early trial design.

  10. Design and construction of the cluster-jet target for PANDA

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-01

    Cluster-jet targets are highly suited as internal targets for storage ring experiments. Hence, the first target to be operated at the PANDA experiment at the future accelerator center FAIR will be a cluster-jet target. In such a target the cluster beam itself is formed due to the expansion of pre-cooled gases within a Laval nozzle. Afterwards an orifice, the skimmer, separates the cluster beam from the residual gas and a second orifice, the collimator, defines its final size and shape. A prototype for the cluster-jet target for PANDA has already been built up in full PANDA geometry at the University of Muenster and operates successfully for years. In combination with a nozzle tilting system allowing for an adjustment of the nozzle system relative to the experimental setup, the prototype provides a target thickness of more than 2 x 10{sup 15} atoms/cm{sup 2}. Based on the results of the performance of this prototype, the final cluster-jet target source was designed and constructed in Muenster as well. In this presentation an overview of the cluster-jet target design, various special features and first performance results are presented and discussed.

  11. Opacity spectra of silicon and carbon in ICF plasmas

    Science.gov (United States)

    Benredjem, D.; Calisti, A.; Ferri, S.; Gilleron, F.; Mondet, G.; Pain, J.-C.

    2017-03-01

    The knowledge of opacity is very important when one investigates the radiative properties of ICF and astrophysical plasmas. Germanium and silicon are good candidates as dopants in the ablator of some ICF schemes (LMJ in France, NIF at Livermore). In this work we calculate the opacity spectra of silicon and carbon mixtures. Two competitive methods were used. The first one is based on a detailed line calculation in which the atomic database is provided by the MCDF code. A lineshape code based on a fast algorithm was then adapted to the calculation of opacity profiles. All major line broadening mechanisms, including Zeeman splitting and Stark effect, are taken into account. This approach provides accurate opacity spectra but becomes rapidly prohibitive when the number of lines is large. To account for systems involving many ionic stages and thousands of lines, a second approach combines detailed line calculations and statistical calculations. This approach necessitates much smaller calculation times than the first one and is then more appropriate for extensive calculations. The monochromatic opacity and the Rosseland and Planck mean opacities are calculated for relevant densities and temperatures.

  12. Barriers, activities and participation: Incorporating ICF into service planning datasets.

    LENUS (Irish Health Repository)

    O'Donovan, MA

    2009-05-21

    Purpose. Guided by the World Health Organization\\'s International Classification of Functioning, Disability and Health (ICF), a measure of activity and participation (MAP) was developed and incorporated into the National Physical and Sensory Disability Database in Ireland. The aims of this article are to investigate and explore the relationship between the barriers, participation restriction and functioning levels experienced by people with disabilities. Method. Seven thousand five hundred and sixty-two personal interviews with people meeting specific eligibility criteria for registering onto the database were conducted across four health service executive regions in Ireland. Results. Overall, differences in barriers, participation restriction and activity limitations experienced by people with different types of disabilities were found to be significant. Furthermore, low functioning and experience of barriers were indicators of participation restriction. Conclusions. This article has shown that elements of the ICF have been successfully operationalised in a service planning tool through the development of the MAP. This provides a more holistic view of disability and will enable the impact of service interventions to be measured over time.

  13. Initiation of extended arc discharge in ICF reactor dense atmospheres

    Energy Technology Data Exchange (ETDEWEB)

    Kislev, H.

    1986-01-01

    Reduced density plasma channels are essential for LIB transport from external diodes to an ICF pellet centered in the 2-4 MPa superheated steamfilled cavity of the Heavy Water ICF Reactor. Forming such channels by ohmic heating requires the initiation of straight arc discharges along each beamline. The goal of this thesis is to evaluate the threshold beamline preionization and applied electric field for arc initiation. The capability of several preionizers to produce a straight preionized trail is evaluated through a ten-group Boltzmann equation solver. Electron densities around 10/sup 17/ m/sup -3/ could be maintained in the trail by monojoule output external preionizers. Trail preionization through the co-application of UV and CO/sub 2/ lasers appears to be the most promising technique. UV laser preionization of NO(a/sup 4/..pi..) formed in the fireball shows also good prospective. The large divergence of soft x-ray sources reduces their attractivity. The E/N dependent electron transport properties are used to construct the first streamer model capable of evaluating the steady state streamer wave shape. The streamers-induced highly ionized filament transition into a multi-kA carrying plasma channel is simulated by a modified radiation-MHD one-dimensional code.

  14. Improved ICF implosion performance through precision engineering features

    Science.gov (United States)

    Weber, Christopher

    2016-10-01

    The thin membrane that holds the capsule in-place in the hohlraum is recognized as one of the most significant contributors to reduced performance in indirect drive inertial confinement fusion (ICF) experiments on the National Ignition Facility (NIF). This membrane, known as the ``tent'', seeds a perturbation that is amplified by Rayleigh-Taylor and can rupture the capsule. The ICF program is undertaking a major effort to develop a less damaging capsule support mechanism. Possible alternatives include micron-scale rods spanning the hohlraum width and supporting either the capsule or stiffening the fill-tube, a larger fill-tube to both fill and support the capsule, or a low-density foam layer that protects the capsule from the tent impact. In addition to the challenges presented by nano and microscale engineering, it is difficult to model and experimentally verify improvement from these changes. The 3D nature of the proposed replacements and the radiation shadows they cast on the capsule prohibit direct simulation. Therefore a combination of reduced models and experimental verification are used to set requirements and down-select the options. Ultimately the improved capsule support will be used to repeat a DT-layered implosion and demonstrate improved performance. Work performed under the auspices of the U.S. D.O.E. by Lawrence Livermore National Laboratory under Contract No. DE-AC52-07NA27344.

  15. Improving ICF implosion performance with alternative capsule supports

    Science.gov (United States)

    Weber, C. R.; Casey, D. T.; Clark, D. S.; Hammel, B. A.; MacPhee, A.; Milovich, J.; Martinez, D.; Robey, H. F.; Smalyuk, V. A.; Stadermann, M.; Amendt, P.; Bhandarkar, S.; Chang, B.; Choate, C.; Crippen, J.; Felker, S. J.; Field, J. E.; Haan, S. W.; Johnson, S.; Kroll, J. J.; Landen, O. L.; Marinak, M.; Mcinnis, M.; Nikroo, A.; Rice, N.; Sepke, S. M.

    2017-05-01

    The thin membrane that holds the capsule in-place in the hohlraum is recognized as one of the most significant contributors to reduced performance in indirect drive inertial confinement fusion (ICF) experiments on the National Ignition Facility. This membrane, known as the "tent," seeds a perturbation that is amplified by Rayleigh-Taylor and can rupture the capsule. A less damaging capsule support mechanism is under development. Possible alternatives include the micron-scale rods spanning the hohlraum width and supporting either the capsule or stiffening the fill-tube, a larger fill-tube to both fill and support the capsule, or a low-density foam layer that protects the capsule from the tent impact. Experiments are testing these support features to measure their imprint on the capsule. These experiments are revealing unexpected aspects about perturbation development in indirect drive ICF, such as the importance of shadows coming from bright spots in the hohlraum. Two dimensional and 3D models are used to explain these features and assess the impact on implosion performance. Experiments and modeling suggest that the fill-tube supported by a perpendicular rod can mount the capsule without any additional perturbation beyond that of the fill tube.

  16. Wetted Foam Liquid DT Layer ICF Experiments at the NIF

    Science.gov (United States)

    Olson, R. E.; Leeper, R. J.; Peterson, R. R.; Yi, S. A.; Zylstra, A. B.; Kline, J. L.; Bradley, P. A.; Yin, L.; Wilson, D. C.; Haines, B. M.; Batha, S. H.

    2016-10-01

    A key physics issue in indirect-drive ICF relates to the understanding of the limitations on hot spot convergence ratio (CR), principally set by the hohlraum drive symmetry, the capsule mounting hardware (the ``tent''), and the capsule fill tube. An additional key physics issue relates to the complex process by which a hot spot must be dynamically formed from the inner ice surface in a DT ice-layer implosion. These physics issues have helped to motivate the development of a new liquid DT layer wetted foam platform at the NIF that provides an ability to form the hot spot from DT vapor and experimentally study and understand hot spot formation at a variety of CR's in the range of 12ICF ignition. This work was performed under the auspices of the U. S. DOE by LANL under contract DE-AC52-06NA25396.

  17. The Communication Supports Inventory-Children & Youth (CSI-CY), a new instrument based on the ICF-CY.

    Science.gov (United States)

    Rowland, Charity; Fried-Oken, Melanie; Bowser, Gayl; Granlund, Mats; Lollar, Donald; Phelps, Randall; Simeonsson, Rune J; Steiner, Sandra A M

    2016-09-01

    Two studies are presented that evaluated the Communication Supports Inventory-Children & Youth (CSI-CY), an instrument designed to facilitate the development of communication-related educational goals for students with complex communication needs (CCN). The CSI-CY incorporates a code set based on the ICF-CY. The studies were designed to determine the effect of using the CSI-CY on IEP goals for students with CCN and to evaluate consumer satisfaction. In Study 1, sixty-one educators and speech-language pathologists were randomly assigned to either (a) provide a student's current IEP (control group) or (b) complete the CSI-CY prior to preparing a student's next IEP and to submit the new IEP (experimental group). Study 2 was a field test to generate consumer satisfaction data. Study 1 showed that IEP goals submitted by participants in the experimental group referenced CSI-CY-related content significantly more frequently than did those submitted by control participants. Study 2 revealed high satisfaction with the instrument. The code set basis of the CSI-CY extends the common language of the ICF-CY to practical educational use for children with CCN across diagnostic groups. The CSI-CY is well regarded as an instrument to inform the content of communication goals related to CCN. Implications for Rehabilitation The CSI-CY will guide rehabilitation professionals to develop goals for children with complex communication impairments. The CSI-CY is a new instrument that is based on the ICF-CY for documentation of communication goals.

  18. Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site

    Energy Technology Data Exchange (ETDEWEB)

    Strauch, Eva-Maria; Bernard, Steffen M.; La, David; Bohn, Alan J.; Lee, Peter S.; Anderson, Caitlin E.; Nieusma, Travis; Holstein, Carly A.; Garcia, Natalie K.; Hooper, Kathryn A.; Ravichandran, Rashmi; Nelson, Jorgen W.; Sheffler, William; Bloom, Jesse D.; Lee, Kelly K.; Ward, Andrew B.; Yager, Paul; Fuller, Deborah H.; Wilson, Ian A.; Baker , David (UWASH); (Scripps); (FHCRC)

    2017-06-12

    Many viral surface glycoproteins and cell surface receptors are homo-oligomers1, 2, 3, 4, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites5, 6, 7, 8. In the first step, a small protein is designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.

  19. Molecular drug targets and structure based drug design: A holistic approach

    OpenAIRE

    Singh, Shailza; Malik, Balwant Kumar; Sharma, Durlabh Kumar

    2006-01-01

    Access to the complete human genome sequence as well as to the complete sequences of pathogenic organisms provides information that can result in an avalanche of therapeutic targets. Structure-based design is one of the first techniques to be used in drug design. Structure based design refers specifically to finding and complementing the 3D structure (binding and/or active site) of a target molecule such as a receptor protein. The aim of this review is to give an outline of studies in the fie...

  20. Designs Characteristics and Main Inherent Concerns of the Antiproton Decelerator Target

    CERN Document Server

    Torregrosa, C; Calviani, M

    2015-01-01

    In the context of AD area consolidation activities a redesign of the AD-target is planned. The information presented in this report is a starting point to this purpose. The current design dates from late 80’s and it was obtained after more than 10 years of iterations and improvements of the material choices and conceptual designs due to the complexity of physical phenomena occurring inside the target material. The present report summarizes this process from the existing documents found in the literature as well as the inherent concerns which will have to be faced in the future design. Two major concerns which limit the target operation life were identified (i) shock wave effects and (ii) radiation damage. Therefore, a deep study of these phenomena and development of reliable models will be the way forward for the next steps in the re-design process.

  1. Computational Design of Proteins Targeting the Conserved Stem Region of Influenza Hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Fleishman, Sarel J.; Whitehead, Timothy A.; Ekiert, Damian C.; Dreyfus, Cyrille; Corn, Jacob E.; Strauch, Eva-Maria; Wilson, Ian A.; Baker, David (UWASH); (Scripps)

    2011-09-28

    We describe a general computational method for designing proteins that bind a surface patch of interest on a target macromolecule. Favorable interactions between disembodied amino acid residues and the target surface are identified and used to anchor de novo designed interfaces. The method was used to design proteins that bind a conserved surface patch on the stem of the influenza hemagglutinin (HA) from the 1918 H1N1 pandemic virus. After affinity maturation, two of the designed proteins, HB36 and HB80, bind H1 and H5 HAs with low nanomolar affinity. Further, HB80 inhibits the HA fusogenic conformational changes induced at low pH. The crystal structure of HB36 in complex with 1918/H1 HA revealed that the actual binding interface is nearly identical to that in the computational design model. Such designed binding proteins may be useful for both diagnostics and therapeutics.

  2. SRS analyses of direct-drive ICF experiments at the National Ignition Facility

    Science.gov (United States)

    Michel, P.; Rosenberg, M.; Myatt, J.; Solodov, A.; Seka, W.; Chapman, T.; Hohenberger, M.; Masse, L.; Goyon, C.; Turnbull, D.; Regan, S.; Moody, J. D.

    2016-10-01

    A series of planar target experiments was recently conducted at the National Ignition Facility (NIF) to study the laser-plasma interactions processes responsible for the production of suprathermal electrons, and their scaling from experiments at the Omega facility to full-scale ICF experiments at the MJ level on the NIF. We will present experimental analyses and simulations of Stimulated Raman Scattering (SRS) in these planar target experiments. Our work indicates the presence of purely backscattered SRS refracted off nearly one-dimensional density gradients, as well as more complicated features such as side-scatter and scattering from non-1D features (e.g. edges) in the target. Simulations using ray- and paraxial-wave- based simulation codes are used to extrapolate the hot electron fraction from the SRS measurements, and point to SRS being the primary mechanism for the generation of suprathermal electrons in these experiments. We will also present analyses of spherical implosions experiments and provide extrapolations and implications for future full-scale direct-drive experiments at NIF. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  3. Scattered and (n,2n) neutrons as a measure of areal density in ICF capsules

    CERN Document Server

    Wilson, D C; Disdier, L; Houry, M; Bourgade, J L; Murphy, T J

    2002-01-01

    The fraction of low-energy neutrons created from 14 MeV neutrons by elastic scattering and (n,2n) reactions on D and T has been proposed as a measure of the areal density (radial integral of density) of ICF targets. In simple situations the fraction of neutrons between 9.4 (the upper energy of T+T neutrons) and 13 MeV (below the Doppler broadened 14.1 MeV peak) is proportional to the at the time of neutron production. This ratio does not depend upon the temperature of the fuel, as does the number of reaction-in-flight neutrons. The ratio of neutrons elastically scattered at a specific energy (e.g. 13 MeV) to the total number of neutrons can be measured along different lines of sight. The ratio of two perpendicular measurements provides a quantitative measure of asymmetry. A detector can be placed inside the target chamber to measure these low-energy neutrons. If it is close enough to the target that measurements are made before the 14 MeV neutrons reach the chamber wall, gamma rays can be a negligible back...

  4. From laptop to benchtop to bedside: Structure-based Drug Design on Protein Targets

    OpenAIRE

    Chen, Lu; Morrow, John K.; Tran, Hoang T.; Phatak, Sharangdhar S.; Du-Cuny, Lei; Zhang, Shuxing

    2012-01-01

    As an important aspect of computer-aided drug design, structure-based drug design brought a new horizon to pharmaceutical development. This in silico method permeates all aspects of drug discovery today, including lead identification, lead optimization, ADMET prediction and drug repurposing. Structure-based drug design has resulted in fruitful successes drug discovery targeting protein-ligand and protein-protein interactions. Meanwhile, challenges, noted by low accuracy and combinatoric issue...

  5. Target Impact Detection Algorithm Using Computer-aided Design (CAD) Model Geometry

    Science.gov (United States)

    2014-09-01

    UNCLASSIFIED AD-E403 558 Technical Report ARMET-TR-13024 TARGET IMPACT DETECTION ALGORITHM USING COMPUTER-AIDED DESIGN ( CAD ...DETECTION ALGORITHM USING COMPUTER-AIDED DESIGN ( CAD ) MODEL GEOMETRY 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...This report documents a method and algorithm to export geometry from a three-dimensional, computer-aided design ( CAD ) model in a format that can be

  6. Analysis of Operating Strategies Using Different Target Designs For 238Pu Production

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Tomcy [University of Tennessee (UT); Sherman, Steven R [ORNL; Sawhney, Dr. Rapinder [University of Tennessee (UT)

    2017-01-01

    An engineering effort is underway to re-establish capability to produce 238Pu oxide at the kilogram scale in the United States. A multi-step batch process is being developed to produce this important material. Recently, a portion of this process was studied using discrete-event simulation tools to determine whether the conceptual process might achieve its yearly production goal. The study showed the conceptual process can meet the yearly production goal under some circumstances, but process improvements would be needed to ensure greater likelihood of success. This study extends the work performed previously by examining the effects of changing the reactor target design on the yearly process output. Two new reactor target configurations are considered an aluminum-clad reactor target containing 50% greater 237Np oxide content than the original target, and a zirconium alloy-clad target using no aluminum. The results indicate that use of the new aluminum-clad target configuration may allow the process to achieve the same yearly production goal in less time using fewer targets. If the zirconium alloy-clad target is used, then even fewer targets would be needed to reach the production goal, but some process changes would be required to handle the zirconium cladding. The number of days needed to process a target batch to completion, and the steady state 238Pu oxide production rate, for each configuration are compared to the results from the initial simulation study.

  7. Autonomous Rover Traverse and Precise Arm Placement on Remotely Designated Targets

    Science.gov (United States)

    Felder, Michael; Nesnas, Issa A.; Pivtoraiko, Mihail; Kelly, Alonzo; Volpe, Richard

    2011-01-01

    Exploring planetary surfaces typically involves traversing challenging and unknown terrain and acquiring in-situ measurements at designated locations using arm-mounted instruments. We present field results for a new implementation of an autonomous capability that enables a rover to traverse and precisely place an arm-mounted instrument on remote targets. Using point-and-click mouse commands, a scientist designates targets in the initial imagery acquired from the rover's mast cameras. The rover then autonomously traverse the rocky terrain for a distance of 10 - 15 m, tracks the target(s) of interest during the traverse, positions itself for approaching the target, and then precisely places an arm-mounted instrument within 2-3 cm from the originally designated target. The rover proceeds to acquire science measurements with the instrument. This work advances what has been previously developed and integrated on the Mars Exploration Rovers by using algorithms that are capable of traversing more rock-dense terrains, enabling tight thread-the-needle maneuvers. We integrated these algorithms on the newly refurbished Athena Mars research rover and fielded them in the JPL Mars Yard. We conducted 43 runs with targets at distances ranging from 5 m to 15 m and achieved a success rate of 93% for placement of the instrument within 2-3 cm.

  8. Analysis of the thermomechanical behavior of the IFMIF bayonet target assembly under design loading scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Bernardi, D., E-mail: davide.bernardi@enea.it [ENEA Brasimone, Camugnano, BO (Italy); Arena, P.; Bongiovì, G.; Di Maio, P.A. [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, Palermo (Italy); Frisoni, M. [ENEA Bologna, Via Martiri di Monte Sole 4, Bologna (Italy); Miccichè, G.; Serra, M. [ENEA Brasimone, Camugnano, BO (Italy)

    2015-10-15

    In the framework of the IFMIF Engineering Validation and Engineering Design Activities (IFMIF/EVEDA) phase, ENEA is responsible for the design of the European concept of the IFMIF lithium target system which foresees the possibility to periodically replace only the most irradiated and thus critical component (i.e., the backplate) while continuing to operate the rest of the target for a longer period (the so-called bayonet backplate concept). In this work, the results of the steady state thermomechanical analysis of the IFMIF bayonet target assembly under two different design loading scenarios (a “hot” scenario and a “cold” scenario) are briefly reported highlighting the relevant indications obtained with respect to the fulfillment of the design requirements. In particular, the analyses have shown that in the hot scenario the temperatures reached in the target assembly are within the material acceptable limits while in the cold scenario transition below the ductile to brittle transition temperature (DBTT) cannot be excluded. Moreover, results indicate that the contact between backplate and high flux test module is avoided and that the overall structural integrity of the system is assured in both scenarios. However, stress linearization analysis reveals that ITER Structural Design Criteria for In-vessel Components (SDC-IC) design rules are not always met along the selected paths at backplate middle plane section in the hot scenario, thus suggesting the need of a revision of the backplate design or a change of the operating conditions.

  9. Computational Design of High Efficiency Release Targets for Use at ISOL Facilities

    Energy Technology Data Exchange (ETDEWEB)

    Alton, G.D.; Liu, Y.; Middleton, J.W.

    1998-11-04

    This report describes efforts made at the Oak Ridge National Laboratory to design high-efficiency-release targets that simultaneously incorporate the short diffusion lengths, high permeabilities, controllable temperatures, and heat removal properties required for the generation of useful radioactive ion beam (RIB) intensities for nuclear physics and astrophysics research using the isotope separation on-line (ISOL) technique. Short diffusion lengths are achieved either by using thin fibrous target materials or by coating thin layers of selected target material onto low-density carbon fibers such as reticulated vitreous carbon fiber (RVCF) or carbon-bonded-carbon-fiber (CBCF) to form highly permeable composite target matrices. Computational studies which simulate the generation and removal of primary beam deposited heat from target materials have been conducted to optimize the design of target/heat-sink systems for generating RIBs. The results derived tlom diffusion release-rate simulation studies for selected targets and thermal analyses of temperature distributions within a prototype target/heat-sink system subjected to primary ion beam irradiation will be presented in this report.

  10. Content Validity of the Comprehensive ICF Core Set for Chronic Obstructive Pulmonary Diseases: An International Delphi Survey.

    Science.gov (United States)

    Jobst, Andrea; Kirchberger, Inge; Cieza, Alarcos; Stucki, Gerold; Stucki, Armin

    2013-01-01

    The "Comprehensive ICF Core Set for Chronic Obstructive Pulmonary Diseases (COPD)" is an application of the International Classification of Functioning, Disability and Health (ICF) and represents the typical spectrum of problems in functioning of patients with COPD. The objective of this study was to validate this ICF Core Set from the perspective of physicians. Physicians experienced in COPD treatment were asked about the patients' problems treated by physicians in patients with COPD in a three-round electronic mail survey using the Delphi technique. Responses were linked to the ICF. Seventy-six physicians in 44 countries gave a total of 1330 responses that were linked to 148 different ICF categories. Nine ICF categories were not represented in the Comprehensive ICF Core Set for COPD although at least 75% of the participants have rated them as important. Nineteen concepts were linked to the not yet developed ICF component personal factors and seventeen concepts were not covered by the ICF. The high percentage of ICF categories represented in the ICF Core Set for COPD indicates satisfactory content validity from the perspective of the physicians. However, some issues were raised that were not covered and need to be investigated further.

  11. Thermal hydraulic design and decay heat removal of a solid target for a spallation neutron source

    Energy Technology Data Exchange (ETDEWEB)

    Takenaka, N. [Department of Mechanical Engineering, Kobe University, Kobe (Japan)]. E-mail: takenaka@mech.kobe-u.ac.jp; Nio, D. [Hokkaido University, Sapporo (Japan); Kiyanagi, Y. [Hokkaido University, Sapporo (Japan); Mishima, K. [Kyoto University Research Reactor Institute, Kumatori (Japan); Kawai, M. [High Energy Accelerator Research Institute, Tsukuba (Japan); Furusaka, M. [High Energy Accelerator Research Institute, Tsukuba (Japan)

    2005-08-01

    Thermal hydraulic design and thermal stress calculations were conducted for a water-cooled solid target irradiated by a MW-class proton beam for a spallation neutron source. Plate type and rod bundle type targets were examined. The thickness of the plate and the diameter of the rod were determined based on the maximum and the wall surface temperature. The thermal stress distributions were calculated by a finite element method (FEM). The neutronics performance of the target is roughly proportional to its average density. The averaged densities of the designed targets were calculated for tungsten plates, tantalum-clad tungsten plates, tungsten rods sheathed by tantalum and Zircaloy and they were compared with mercury density. It was shown that the averaged density was highest for the tungsten plates and was high for the tantalum cladding tungsten plates, the tungsten rods sheathed by tantalum and Zircaloy in order. They were higher than or equal to that of mercury for the 1-2 MW proton beams. Tungsten target without the cladding or the sheath is not practical due to corrosion by water under irradiation condition. Therefore, the tantalum cladding tungsten plate already made successfully by HIP and the sheathed tungsten rod are the candidate of high performance solid targets. The decay heat of each target was calculated. It was low enough low compared to that of ISIS for the target without tantalum but was about four times as high as that of ISIS when the thickness of the tantalum cladding was 0.5 mm. Heat removal methods of the decay heat with tantalum were examined. It was shown that a special cooling system was required for the target exchange when tantalum was used for the target. It was concluded that the tungsten rod target sheathed with stainless steel or Zircaloy was the most reliable from the safety considerations and had similar neutronics performance to that of mercury.

  12. Thermal hydraulic design and decay heat removal of a solid target for a spallation neutron source

    Science.gov (United States)

    Takenaka, N.; Nio, D.; Kiyanagi, Y.; Mishima, K.; Kawai, M.; Furusaka, M.

    2005-08-01

    Thermal hydraulic design and thermal stress calculations were conducted for a water-cooled solid target irradiated by a MW-class proton beam for a spallation neutron source. Plate type and rod bundle type targets were examined. The thickness of the plate and the diameter of the rod were determined based on the maximum and the wall surface temperature. The thermal stress distributions were calculated by a finite element method (FEM). The neutronics performance of the target is roughly proportional to its average density. The averaged densities of the designed targets were calculated for tungsten plates, tantalum clad tungsten plates, tungsten rods sheathed by tantalum and Zircaloy and they were compared with mercury density. It was shown that the averaged density was highest for the tungsten plates and was high for the tantalum cladding tungsten plates, the tungsten rods sheathed by tantalum and Zircaloy in order. They were higher than or equal to that of mercury for the 1 2 MW proton beams. Tungsten target without the cladding or the sheath is not practical due to corrosion by water under irradiation condition. Therefore, the tantalum cladding tungsten plate already made successfully by HIP and the sheathed tungsten rod are the candidate of high performance solid targets. The decay heat of each target was calculated. It was low enough low compared to that of ISIS for the target without tantalum but was about four times as high as that of ISIS when the thickness of the tantalum cladding was 0.5 mm. Heat removal methods of the decay heat with tantalum were examined. It was shown that a special cooling system was required for the target exchange when tantalum was used for the target. It was concluded that the tungsten rod target sheathed with stainless steel or Zircaloy was the most reliable from the safety considerations and had similar neutronics performance to that of mercury.

  13. The ICF (International Classification of Functioning, Disability and Health) developed by the WHO for measuring function in hemophilia.

    Science.gov (United States)

    De la Corte-Rodriguez, H; Rodriguez-Merchan, E C

    2016-07-01

    Assessment of the disease in people with hemophilia (PWH) must include an analysis of functioning. Researchers have done a lot of work over the last two decades in developing disease specific assessment tools in hemophilia - some of them based on the ICF (International Classification of Functioning, Disability and Health). This article is a narrative review of the ICF developed by the World Health Organization (WHO) in the context of hemophilia. Expert commentary: The WFH has developed a website with a 'compendium of assessment tools' based on the ICF. The ICF developed by the WHO makes it possible to propose an approach that prioritizes capacities over difficulties. This article is intended to motivate physicians who treat PWH to incorporate the ICF into their assessments. A generalized use of the ICF will provide a common communication context. The ICF developed by the WHO should be used in hemophilia.

  14. Simplified bipartite concepts of functioning and disability recommended for interdisciplinary use of the ICF.

    Science.gov (United States)

    Thyberg, Mikael; Arvidsson, Patrik; Thyberg, Ingrid; Nordenfelt, Lennart

    2015-01-01

    To argue for and propose bipartite concepts of functioning and disability, to tally with the structure of the ICF classification list, concepts of social models and clinical needs. The ICF concepts are discussed in relation to the history of ideas regarding disability concepts and the needs for such concepts in interdisciplinary rehabilitation. Bipartite concepts are presented; they refer to actual functioning, simply body functions/structures and participation, including functioning in standardized environments. Participation refers to actually performed "activities", with "activities" simply denoting things that people may do. Bipartite concepts are congruent with the ICF classification and the structure of social models of disability, suitable for clinical and interdisciplinary use and easy to understand. The issue of standardized environments represents a methodological issue rather than the conceptual issue of defining functioning and disability. An individual perspective on activity and activity limitations, i.e. the middle part of the tripartite ICF concept, is somewhat similar to concepts of traditional language that were regarded as too generalizing already in 1912, when the interactional concept of "disability in a social sense" was introduced in rehabilitation practices. Bipartite concepts of functioning and disability are recommended for interdisciplinary use of the ICF. The ICF classification is useful, but the ICF concept of activities in an individual perspective is confusing. We suggest a use of the term "activities" simply to denote things that people may do and "participation" to denote actually performed activities. Estimations of ability should be explicit about how they are related to environmental factors.

  15. Development of consensus International Classification of Functioning, Disability and Health (ICF) core sets for lymphedema.

    Science.gov (United States)

    Viehoff, P B; Heerkens, Y F; Van Ravensberg, C D; Hidding, J; Damstra, R J; Ten Napel, H; Neumann, H A M

    2015-03-01

    To understand the challenges of patients with lymphedema it is important to describe functioning and to measure the effectiveness of treatment in changing functioning. The International Classification of Functioning, Disability and Health (ICF) offers an international framework to classify functioning of persons in their personal environment. ICF Core Sets are lists of selected ICF categories concerning those important aspects of functioning that are most likely to be affected by a specific health problem or disease. These Core Sets make it easier and faster to describe and communicate the patient's problems and to define treatment goals. Furthermore, they are available to health care providers of all professions, researchers, health insurance companies and policy-makers. The objective of this document is to present the outcomes of a consensus conference held to determine the first versions of the ICF Core Sets for lymphedema. Frequency rankings were made of the ICF categories derived from four preparatory studies, being: a) a systematic review; b) a qualitative study; c) an expert survey; and d) a cross-sectional study. By means of working group discussions and plenary sessions, a final consensus on ICF categories was achieved and Comprehensive and Brief Core Sets for lymphedema for the upper limb, lower limb, and midline lymphedema were defined. These ICF Core Sets contain different items in each region. Future validation of these Core Sets for health professions and for countries is needed.

  16. The feasibility and validity of the comprehensive ICF core set for stroke in Chinese clinical settings.

    Science.gov (United States)

    Wang, Pu; Li, Huagang; Guo, Yi; Xie, Yuxiao; Ge, Ruidong; Qiu, Zhuoying

    2014-02-01

    To inspect the feasibility and content validity of the comprehensive International Classification of Functioning, Disability and Health (ICF) core set for stroke by describing relevant aspects of functioning, disability and environmental factors affected in Chinese patients post stroke. Multicentre, cross-sectional study. Department of rehabilitation medicine. The content validity was evaluated using frequency and percentage of 208 patients with a mean age of 60 years post stroke in China. Aspects of body function and structure, activity and participation, and environmental factors in the comprehensive ICF core set for stroke. Six ICF categories of body function were identified as a problem in over 90% (n = 187) of the patients (functions of the cardiovascular system and neuromusculoskeletal and movement-related functions). Impairments of brain, upper and lower extremity were identified as a problem in over 50% (n = 104) of the patients. Four ICF categories of activities and participation were documented as a problem in 100% (n = 208) of the patients (domestic and civic life). In environmental factors, nine ICF categories were documented as barriers by more than 10% (n = 20) and fewer than 50% (n = 104) of the patients (products and technology, physical geography, societal attitudes, services, systems and polices). Six ICF categories were identified as facilitators in over 90% (n = 187) of the patients (support and relationships and attitudes). The findings suggest that it is feasible to apply the comprehensive ICF core set for stroke in the Chinese clinical setting, after the appropriate reduction of some categories according to Chinese patients' characteristics and culture.

  17. Forming Cryogenic Targets for Direct-Drive Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Harding, D.R.; Meyerhofer, D.D.; Loucks, S.J.; Lund, L.D.; Janezic, R.; Elasky, L.M.; Hinterman, T.H.; Edgell, D.H.; Seka, W.; Wittman, M.D.; Gram, R.Q.; Jacobs-Perkins, D.; Early, R.; Duffy, T.; Bonino, M.J.

    2006-06-09

    More than 100 spherical deuterium ice layers have been formed to make cryogenic targets for direct-drive inertial confinement fusion (ICF) implosion experiments on OMEGA. These ice layers have an inner surface roughness that ranges from 1.3- to 6-um rms, with the best layers having a value less than 2-um rms. These surface roughness values are averaged 2-D roughness measurements that cover the entire surface and includes all of the Fourier cosine modes. The ice thickness variation within the layer is predominately in the low spectral modes (mode 5 and lower) and is caused by the support used to hold the target. Changing the design of this support to minimize the thermal effect is constrained by the necessity of having a dynamically stable target for the implosion.

  18. Radar Constant-Modulus Waveform Design with Prior Information of the Extended Target and Clutter.

    Science.gov (United States)

    Yue, Wenzhen; Zhang, Yan; Liu, Yimin; Xie, Jingwen

    2016-06-17

    Radar waveform design is of great importance for radar system performances and has drawn considerable attention recently. Constant modulus is an important waveform design consideration, both from the point of view of hardware realization and to allow for full utilization of the transmitter's power. In this paper, we consider the problem of constant-modulus waveform design for extended target detection with prior information about the extended target and clutter. At first, we propose an arbitrary-phase unimodular waveform design method via joint transmitter-receiver optimization. We exploit a semi-definite relaxation technique to transform an intractable non-convex problem into a convex problem, which can then be efficiently solved. Furthermore, quadrature phase shift keying waveform is designed, which is easier to implement than arbitrary-phase waveforms. Numerical results demonstrate the effectiveness of the proposed methods.

  19. Refinements of the ICF Linking Rules to strengthen their potential for establishing comparability of health information.

    Science.gov (United States)

    Cieza, Alarcos; Fayed, Nora; Bickenbach, Jerome; Prodinger, Birgit

    2016-03-17

    Purpose The content of and methods for collecting health information often vary across settings and challenge the comparability of health information across time, individuals or populations. The International Classification of Functioning, Disability and Health (ICF) contains an exhaustive set of categories of information which constitutes a unified and consistent language of human functioning suitable as a reference for comparing health information. Methods and results In two earlier papers, we have proposed rules for linking existing health information to the ICF. Further refinements to these existing ICF Linking Rules are presented in this paper to enhance the transparency of the linking process. The refinements involve preparing information for linking, perspectives from which information is collected and the categorization of response options. Issues regarding the linking of information not covered or unspecified within the ICF are also revisited in this paper. The ICF Linking Rules are valuable for enhancing comparability of health information to ensure that information is available in a consistent manner to serve as a foundation for evidence-based decision-making across all levels of health systems. The refinements presented in this paper enhance transparency in, and ultimately reliability of the process of, linking health information to the ICF. Implications for Rehabilitation The International Classification of Functioning, Disability and Health (ICF) constitutes a unified and consistent language of human functioning suitable as a reference for comparing health information. Comparability of information is essential to ensure that the widest range of information is available in a consistent manner for any decision-maker at all levels of the health system. The refined ICF Linking Rules presented in this article outline the method to establish comparability of health information based on the ICF.

  20. ICF Based Comprehensive Evaluation for Post-Acute Spinal Cord Injury.

    Science.gov (United States)

    Nam, Hyung Seok; Kim, Kwang Dong; Shin, Hyung Ik

    2012-12-01

    To evaluate the feasibility of the ICF for initial comprehensive evaluation of early post-acute spinal cord injury. A comprehensive evaluation of 62 early post-acute spinal cord injury (SCI) patients was conducted by rehabilitation team members, such as physicians, physical therapists, occupational therapists, nutritionists, medical social-workers, and nurses. They recorded each of their evaluation according to the ICF first level classification. The contents of the comprehensive evaluation were linked to the ICF second level categories, retrospectively. The linked codes were analyzed descriptively and were also compared with the brief ICF core set for early post-acute SCI. In the evaluation of early post-acute SCI patients based on the ICF first level categories, 19 items from the body functions domain, such as muscle power functions (b730) and urination functions (b620), 15 items from the body structures domain, including spinal cord and related structures (s120), 11 items from the activities and participation domain, such as transferring oneself (d420) and walking (d450), and 9 items from the environmental factors domain, e.g., health professionals (e355), were linked to the ICF second level categories. In total, 82.4% of all contents were linked to the brief ICF core set. Prognosis insight, a personal factor not linkable to an ICF code, was mentioned in 29.0% of all patients. First level ICF categories can provide a structural base for a comprehensive evaluation in early post-acute spinal cord injury. However, frequently linked items, including the brief core set, as well as personal factors should be considered via a checklist in order to prevent the omission of significant contents.

  1. Do ICF core sets for low back pain include patients' self-reported activity limitations because of back problems?

    Science.gov (United States)

    Lygren, Hildegunn; Strand, Liv Inger; Anderson, Bodil; Magnussen, Liv Heide

    2014-06-01

    The aim of this study was to investigate content validity of the International Classification of Functioning, Disability and Health (ICF) Core Sets for low back pain (LBP), by examining whether common activities reported as difficult to perform are included in the Core Sets. A cross-sectional design was used. Ninety-eight patients with long-lasting back pain (>3 months) between 18 and 65 years of age were consecutively recruited from a Multidisciplinary Outpatient Spine Clinic. Difficulties with daily life and work task activities because of back pain were examined by asking the patients two questions: 1) can you specify activities that are difficult to perform because of your back pain? and 2) are there specific work tasks that you are unable to do because of your back pain? Two raters independently classified the written responses according to the ICF Core Sets' component Activities and Participation. Activities and work tasks were linked to 15 of 29 categories (52%) in the Comprehensive Core Set, and 9 of 12 (75%) in the Brief Core Set, and the initial agreement between the two raters in coding the answers according to the Core Sets was (83%, k = 0.80) and (93%, k = 0.9), respectively, before consensus was reached. The Comprehensive Core Set for LBP to a large degree contains daily life and work-related activities frequently reported as difficult to perform by patients with long-lasting LBP. The categories, however, are very broad and do not provide specified descriptions of the most frequently reported activity limitations such as sitting, standing and walking. The Brief Core Set does not include categories for frequently reported activities such as pulling/pushing and leisure/recreation activities. ICF Core Sets for LBP seem suitable for obtaining a gross overview of the patients' functional limitations, but do not give sufficient information from a therapeutic point of view. © 2013 John Wiley & Sons, Ltd.

  2. Eligibility, the ICF and the UN Convention: Australian perspectives

    Science.gov (United States)

    2011-01-01

    The UN Convention on the Rights of Persons with Disabilities, in Australia, acts as a philosophical and moral statement and framework guiding integrated and strategic policy across the nation. Broad policy agreement has been reached by governments, and both the government and non-government sectors are developing strategies for implementation or evaluation. There is however a need for a more integrated approach to disability policy and information, reflecting all three components of the Italian project: • legislation and a high level philosophical framework and policy guide; • a technical framework that can underpin specific policies and programs aiming to achieve the major goals; and , • a language and set of tools, relating to both the above, that provide infrastructure for assessment methods and information systems. The International Classification of Functioning, Disability and Health (ICF) is the ideal tool to support the latter two components, consistent with the UN Convention. While the ICF has been used as the basis for national data standards, in population surveys and in the national data collection on disability support services, there is considerable scope for greater use of it, including using all domains of the Activities and Participation and the Environmental Factors component for policy, information and service provision, to advance a disability-inclusive society. Information available from the income support system and from generic services could be enhanced by reference to the ICF components. It would be of significant national value in Australia, especially as a ‘continuum of care’ is desired, if consistency of concepts and information were expanded across health and social welfare sectors. It would then be possible to obtain consistent data from health, aged care, disability and community services systems about key aspects of health and functioning, building a consolidated picture of access and experience across these sectors. Without

  3. Designing nanoconjugates to effectively target pancreatic cancer cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Jameel Ahmad Khan

    Full Text Available BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer related deaths in America. Monoclonal antibodies are a viable treatment option for inhibiting cancer growth. Tumor specific drug delivery could be achieved utilizing these monoclonal antibodies as targeting agents. This type of designer therapeutic is evolving and with the use of gold nanoparticles it is a promising approach to selectively deliver chemotherapeutics to malignant cells. Gold nanoparticles (GNPs are showing extreme promise in current medicinal research. GNPs have been shown to non-invasively kill tumor cells by hyperthermia using radiofrequency. They have also been implemented as early detection agents due to their unique X-ray contrast properties; success was revealed with clear delineation of blood capillaries in a preclinical model by CT (computer tomography. The fundamental parameters for intelligent design of nanoconjugates are on the forefront. The goal of this study is to define the necessary design parameters to successfully target pancreatic cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The nanoconjugates described in this study were characterized with various physico-chemical techniques. We demonstrate that the number of cetuximab molecules (targeting agent on a GNP, the hydrodynamic size of the nanoconjugates, available reactive surface area and the ability of the nanoconjugates to sequester EGFR (epidermal growth factor receptor, all play critical roles in effectively targeting tumor cells in vitro and in vivo in an orthotopic model of pancreatic cancer. CONCLUSION: Our results suggest the specific targeting of tumor cells depends on a number of crucial components 1 targeting agent to nanoparticle ratio 2 availability of reactive surface area on the nanoparticle 3 ability of the nanoconjugate to bind the target and 4 hydrodynamic diameter of the nanoconjugate. We believe this study will help define the design parameters for formulating better strategies

  4. Design, Synthesis, and Some Aspects of the Biological Activity of Mitochondria-Targeted Antioxidants.

    Science.gov (United States)

    Korshunova, G A; Shishkina, A V; Skulachev, M V

    2017-07-01

    This review summarizes for the first time data on the design and synthesis of biologically active compounds of a new generation - mitochondria-targeted antioxidants, which are natural (or synthetic) p-benzoquinones conjugated via a lipophilic linker with (triphenyl)phosphonium or ammonium cations with delocalized charge. It also describes the synthesis of mitochondria-targeted antioxidants - uncouplers of oxidative phosphorylation - based on fluorescent dyes.

  5. Rational Design of Cancer-Targeted Benzoselenadiazole by RGD Peptide Functionalization for Cancer Theranostics.

    Science.gov (United States)

    Yang, Liye; Li, Wenying; Huang, Yanyu; Zhou, Yangliang; Chen, Tianfeng

    2015-09-01

    A cancer-targeted conjugate of the selenadiazole derivative BSeC (benzo[1,2,5] selenadiazole-5-carboxylic acid) with RGD peptide as targeting molecule and PEI (polyethylenimine) as a linker is rationally designed and synthesized in the present study. The results show that RGD-PEI-BSeC forms nanoparticles in aqueous solution with a core-shell nanostructure and high stability under physiological conditions. This rational design effectively enhances the selective cellular uptake and cellular retention of BSeC in human glioma cells, and increases its selectivity between cancer and normal cells. The nanoparticles enter the cells through receptor-mediated endocytosis via clathrin-mediated and nystatin-dependent lipid raft-mediated pathways. Internalized nanoparticles trigger glioma cell apoptosis by activation of ROS-mediated p53 phosphorylation. Therefore, this study provides a strategy for the rational design of selenium-containing cancer-targeted theranostics.

  6. Methods to enable the design of bioactive small molecules targeting RNA

    Science.gov (United States)

    Disney, Matthew D.; Yildirim, Ilyas; Childs-Disney, Jessica L.

    2014-01-01

    RNA is an immensely important target for small molecule therapeutics or chemical probes of function. However, methods that identify, annotate, and optimize RNA-small molecule interactions that could enable the design of compounds that modulate RNA function are in their infancies. This review describes recent approaches that have been developed to understand and optimize RNA motif-small molecule interactions, including Structure-Activity Relationships Through Sequencing (StARTS), quantitative structure-activity relationships (QSAR), chemical similarity searching, structure-based design and docking, and molecular dynamics (MD) simulations. Case studies described include the design of small molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and telomerase RNA. These approaches can be combined to afford a synergistic method to exploit the myriad of RNA targets in the transcriptome. PMID:24357181

  7. Customer Focused Product Design Using Integrated Model of Target Costing, Quality Function Deployment and Value Engineering

    Directory of Open Access Journals (Sweden)

    Hossein Rezaei Dolatabadi

    2013-01-01

    Full Text Available Target costing by integrating customer requirements, technical attributes and cost information into the product design phase and eliminating the non-value added functions, plays a vital role in different phases of the product life cycle. Quality Function Deployment (QFD and Value Engineering (VE are two techniques which can be used for applying target costing, successfully. The purpose of this paper is to propose an integrated model of target costing, QFD and VE to explore the role of target costing in managing product costs while promoting quality specifications meeting customers’ needs. F indings indicate that the integration of target costing, QFD and VE is an essential technique in managing the costs of production process. Findings also imply that integration of the three techniques provides a competitive cost advantage to companies.

  8. TARGET:?

    National Research Council Canada - National Science Library

    James M Acton

    2014-01-01

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

  9. CFD Analysis and Design of Detailed Target Configurations for an Accelerator-Driven Subcritical System

    Energy Technology Data Exchange (ETDEWEB)

    Kraus, Adam; Merzari, Elia; Sofu, Tanju; Zhong, Zhaopeng; Gohar, Yousry

    2016-08-01

    High-fidelity analysis has been utilized in the design of beam target options for an accelerator driven subcritical system. Designs featuring stacks of plates with square cross section have been investigated for both tungsten and uranium target materials. The presented work includes the first thermal-hydraulic simulations of the full, detailed target geometry. The innovative target cooling manifold design features many regions with complex flow features, including 90 bends and merging jets, which necessitate three-dimensional fluid simulations. These were performed using the commercial computational fluid dynamics code STAR-CCM+. Conjugate heat transfer was modeled between the plates, cladding, manifold structure, and fluid. Steady-state simulations were performed but lacked good residual convergence. Unsteady simulations were then performed, which converged well and demonstrated that flow instability existed in the lower portion of the manifold. It was established that the flow instability had little effect on the peak plate temperatures, which were well below the melting point. The estimated plate surface temperatures and target region pressure were shown to provide sufficient margin to subcooled boiling for standard operating conditions. This demonstrated the safety of both potential target configurations during normal operation.

  10. Signal waveform design to detect an underwater high-speed small target

    Institute of Scientific and Technical Information of China (English)

    YANG Chonglin; YAO Lan

    2002-01-01

    The problem of sonar signal waveform design to detect a high-speed small target in an underwater environment is discussed. From theoretical analysis, time-frequency hop signal is regarded as the most suitable signal waveform in this application. To get precise target parameter estimation ability, the signal should have high range-Doppler resolution performance.The results of signal analysis show that hop signal with frequency serial coding as Costas array has sharp ambiguity characteristic, so it can be used in an active sonar system to detect a high speed small target. A scheme of frequency coding is also presented.

  11. Design techniques and analysis of high-resolution neural recording systems targeting epilepsy focus localization.

    Science.gov (United States)

    Shoaran, Mahsa; Pollo, Claudio; Leblebici, Yusuf; Schmid, Alexandre

    2012-01-01

    The design of a high-density neural recording system targeting epilepsy monitoring is presented. Circuit challenges and techniques are discussed to optimize the amplifier topology and the included OTA. A new platform supporting active recording devices targeting wireless and high-resolution focus localization in epilepsy diagnosis is also proposed. The post-layout simulation results of an amplifier dedicated to this application are presented. The amplifier is designed in a UMC 0.18µm CMOS technology, has an NEF of 2.19 and occupies a silicon area of 0.038 mm(2), while consuming 5.8 µW from a 1.8-V supply.

  12. ICStatus and progress of the National Ignition Facility as ICF and HED user facility

    Science.gov (United States)

    Van Wonterghem, B. M.; Kauffman, R. L.; Larson, D. W.; Herrmann, M. C.

    2016-05-01

    Since its completion in 2009, the National Ignition Facility has been operated in support of NNSA's Stockpile Stewardship mission, providing unique experimental data in the high energy density regime. We will describe the progress made by the National Ignition facility in the user office and management, facility capabilities, target diagnostics and diagnostics development. We will also discuss the results of a major effort to increase the shot rate on NIF. An extensive set of projects, developed in conjunction with the HED community and drawing on best practices at other facilities, improved shot rate by over 80% and recently enabled us to deliver 356 target experiments in FY15 in support of the users. Through an updated experimental set-up and review process, computer controlled set-up of the laser and diagnostics and disciplined operations, NIF also continued to deliver experimental reliability, precision and repeatability. New and complex platforms are introduced with a high success rate. Finally we discuss how new capabilities and further efficiency improvements will enable the successful execution of ICF and HED experimental programs required to support the quest for Ignition and the broader Science Based Stockpile Stewardship mission

  13. Strategie didattiche inclusive: le nuove tecnologie nell’ICF-CY

    Directory of Open Access Journals (Sweden)

    Marina Chiaro

    2013-12-01

    Full Text Available Questa nota illustra i presupposti teorici e la metodologia definita per il progetto di ricerca relativo alla Scuola Dottorale in Pedagogia e Servizio Sociale dell’Università di Roma Tre. La ricerca riguarda la possibilità di valutare quanto la formazione di insegnanti in servizio erogata con modalità blended, ovvero con parziale utilizzo delle nuove tecnologie, su tematiche relative ai Disturbi Specifici di Apprendimento (DSA, possa facilitare la progettazione di strategie didattiche inclusive. Il tema di ricerca ha come quadro concettuale di riferimento il modello dell’International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY con il capitolo “Prodotti e Tecnologie” inserito nella componente “Fattori Ambientali” della classificazione. L’aspetto della formazione degli insegnanti è stato affrontato riflettendo anche sulla possibilità di costituire e favorire la costituzione delle Comunità di Pratica (CdP.

  14. Numerical analysis of anisotropic diffusion effect on ICF hydrodynamic instabilities

    Directory of Open Access Journals (Sweden)

    Olazabal-Loumé M.

    2013-11-01

    Full Text Available The effect of anisotropic diffusion on hydrodynamic instabilities in the context of Inertial Confinement Fusion (ICF flows is numerically assessed. This anisotropy occurs in indirect-drive when laminated ablators are used to modify the lateral transport [1,2]. In direct-drive, non-local transport mechanisms and magnetic fields may modify the lateral conduction [3]. In this work, numerical simulations obtained with the code PERLE [4], dedicated to linear stability analysis, are compared with previous theoretical results [5]. In these approaches, the diffusion anisotropy can be controlled by a characteristic coefficient which enables a comprehensive study. This work provides new results on the ablative Rayleigh-Taylor (RT, ablative Richtmyer-Meshkov (RM and Darrieus-Landau (DL instabilities.

  15. Flux-limitation of the Nernst effect in magnetized ICF

    Science.gov (United States)

    Ridgers, Christopher; Barrois, Rion; Wengraf, Joshua; Bissell, John; Brodrick, Jonathan; Kingham, Robert; Read, Martin

    2016-10-01

    Magnetized ICF is a promising scheme which combines the advantages of magnetic and inertial confinement fusion. In the relevant high-energy density plasmas magnetic field evolution is often controlled by the Nernst effect where the magnetic field advects with the electron heat flow. It is well known that non-local thermal transport necessitates a flux-limiter on the heat flow. This suggests that a flux-limiter should also be applied to the Nernst effect. We have shown that this is the case using Vlasov-Fokker-Planck simulations and that the flux-limter is not the same as that required for the heat flow itself, for example when a NIF-relevant flux-limiter of 0.15 is required to limit the heat flow a Nernst flux limiter of 0.08 is required. We acknowledge support from EPSRC Grant No. EPM011372/1.

  16. Thermodynamic and dynamical properties of dense ICF plasma

    Directory of Open Access Journals (Sweden)

    Gabdullin Maratbek T.

    2016-06-01

    Full Text Available In present work, thermodynamic expressions were obtained through potentials that took into consideration long-range many-particle screening effects as well as short-range quantum-mechanical effects and radial distribution functions (RDFs. Stopping power of the projectile ions in dense, non-isothermal plasma was considered. One of the important values that describe the stopping power of the ions in plasma is the Coulomb logarithm. We investigated the stopping power of ions in inertial confinement fusion (ICF plasma and other energetic characteristics of fuel. Calculations of ions energy losses in the plasma for different values of the temperature and plasma density were carried out. A comparison of the calculated data of ion stopping power and energy deposition with experimental and theoretical results of other authors was also performed.

  17. Rational design of antibodies targeting specific epitopes within intrinsically disordered proteins

    Science.gov (United States)

    Sormanni, Pietro; Aprile, Francesco A.; Vendruscolo, Michele

    2015-01-01

    Antibodies are powerful tools in life sciences research, as well as in diagnostic and therapeutic applications, because of their ability to bind given molecules with high affinity and specificity. Using current methods, however, it is laborious and sometimes difficult to generate antibodies to target specific epitopes within a protein, in particular if these epitopes are not effective antigens. Here we present a method to rationally design antibodies to enable them to bind virtually any chosen disordered epitope in a protein. The procedure consists in the sequence-based design of one or more complementary peptides targeting a selected disordered epitope and the subsequent grafting of such peptides on an antibody scaffold. We illustrate the method by designing six single-domain antibodies to bind different epitopes within three disease-related intrinsically disordered proteins and peptides (α-synuclein, Aβ42, and IAPP). Our results show that all these designed antibodies bind their targets with good affinity and specificity. As an example of an application, we show that one of these antibodies inhibits the aggregation of α-synuclein at substoichiometric concentrations and that binding occurs at the selected epitope. Taken together, these results indicate that the design strategy that we propose makes it possible to obtain antibodies targeting given epitopes in disordered proteins or protein regions. PMID:26216991

  18. Rational design of antibodies targeting specific epitopes within intrinsically disordered proteins.

    Science.gov (United States)

    Sormanni, Pietro; Aprile, Francesco A; Vendruscolo, Michele

    2015-08-11

    Antibodies are powerful tools in life sciences research, as well as in diagnostic and therapeutic applications, because of their ability to bind given molecules with high affinity and specificity. Using current methods, however, it is laborious and sometimes difficult to generate antibodies to target specific epitopes within a protein, in particular if these epitopes are not effective antigens. Here we present a method to rationally design antibodies to enable them to bind virtually any chosen disordered epitope in a protein. The procedure consists in the sequence-based design of one or more complementary peptides targeting a selected disordered epitope and the subsequent grafting of such peptides on an antibody scaffold. We illustrate the method by designing six single-domain antibodies to bind different epitopes within three disease-related intrinsically disordered proteins and peptides (α-synuclein, Aβ42, and IAPP). Our results show that all these designed antibodies bind their targets with good affinity and specificity. As an example of an application, we show that one of these antibodies inhibits the aggregation of α-synuclein at substoichiometric concentrations and that binding occurs at the selected epitope. Taken together, these results indicate that the design strategy that we propose makes it possible to obtain antibodies targeting given epitopes in disordered proteins or protein regions.

  19. Secondary structure in the target as a confounding factor in synthetic oligomer microarray design

    Directory of Open Access Journals (Sweden)

    Gibas Cynthia J

    2005-03-01

    Full Text Available Abstract Background Secondary structure in the target is a property not usually considered in software applications for design of optimal custom oligonucleotide probes. It is frequently assumed that eliminating self-complementarity, or screening for secondary structure in the probe, is sufficient to avoid interference with hybridization by stable secondary structures in the probe binding site. Prediction and thermodynamic analysis of secondary structure formation in a genome-wide set of transcripts from Brucella suis 1330 demonstrates that the properties of the target molecule have the potential to strongly influence the rate and extent of hybridization between transcript and tethered oligonucleotide probe in a microarray experiment. Results Despite the relatively high hybridization temperatures and 1M monovalent salt imposed in the modeling process to approximate hybridization conditions used in the laboratory, we find that parts of the target molecules are likely to be inaccessible to intermolecular hybridization due to the formation of stable intramolecular secondary structure. For example, at 65°C, 28 ± 7% of the average cDNA target sequence is predicted to be inaccessible to hybridization. We also analyzed the specific binding sites of a set of 70mer probes previously designed for Brucella using a freely available oligo design software package. 21 ± 13% of the nucleotides in each probe binding site are within a double-stranded structure in over half of the folds predicted for the cDNA target at 65°C. The intramolecular structures formed are more stable and extensive when an RNA target is modeled rather than cDNA. When random shearing of the target is modeled for fragments of 200, 100 and 50 nt, an overall destabilization of secondary structure is predicted, but shearing does not eliminate secondary structure. Conclusion Secondary structure in the target is pervasive, and a significant fraction of the target is found in double stranded

  20. Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction.

    Science.gov (United States)

    Ye, Jian; Coulouris, George; Zaretskaya, Irena; Cutcutache, Ioana; Rozen, Steve; Madden, Thomas L

    2012-06-18

    Choosing appropriate primers is probably the single most important factor affecting the polymerase chain reaction (PCR). Specific amplification of the intended target requires that primers do not have matches to other targets in certain orientations and within certain distances that allow undesired amplification. The process of designing specific primers typically involves two stages. First, the primers flanking regions of interest are generated either manually or using software tools; then they are searched against an appropriate nucleotide sequence database using tools such as BLAST to examine the potential targets. However, the latter is not an easy process as one needs to examine many details between primers and targets, such as the number and the positions of matched bases, the primer orientations and distance between forward and reverse primers. The complexity of such analysis usually makes this a time-consuming and very difficult task for users, especially when the primers have a large number of hits. Furthermore, although the BLAST program has been widely used for primer target detection, it is in fact not an ideal tool for this purpose as BLAST is a local alignment algorithm and does not necessarily return complete match information over the entire primer range. We present a new software tool called Primer-BLAST to alleviate the difficulty in designing target-specific primers. This tool combines BLAST with a global alignment algorithm to ensure a full primer-target alignment and is sensitive enough to detect targets that have a significant number of mismatches to primers. Primer-BLAST allows users to design new target-specific primers in one step as well as to check the specificity of pre-existing primers. Primer-BLAST also supports placing primers based on exon/intron locations and excluding single nucleotide polymorphism (SNP) sites in primers. We describe a robust and fully implemented general purpose primer design tool that designs target-specific PCR

  1. 1-MJ, Wetted-Foam Target-Design Performance for the NIF

    Science.gov (United States)

    Collins, T. J. B.

    2006-10-01

    Wetted-foam, direct-drive target designs are a path to high-gain experiments on the National Ignition Facility (NIF). Wetted-foam designs take advantage of the increased laser absorption provided by the higher-atomic-number elements in the mixture of plastic foam and deuterium--tritium (DT). The fractional absorption is expected to increase by as much as 30% relative to an ``all-DT'' target for a ˜1-MJ design, depending on the density of the foam and the specific target design. With the increased laser coupling, more fuel can be driven with the same incident laser energy, resulting in increased target gain and/or increased hydrodynamic stability. A stability analysis of a 1-MJ design performed using two-dimensional hydrodynamic simulations in the presence of expected levels of laser and target nonuniformities will be shown. For this design, the sources of nonuniformity from the laser include power imbalance between laser beams and the imprint of single-beam nonuniformities on the target. Target nonuniformities include surface finish and inner-surface DT-ice roughness. The relative impact of these sources of nonuniformity on target performance will be examined. Particular emphasis will be placed on identifying the required levels of beam smoothing with regard to smoothing by spectral dispersion. While this emphasizes symmetric illumination, the results are relevant to polar direct drive, where a direct-drive target is driven on the NIF while it is in its indirect-drive configuration. S. Skupsky et al., in Inertial Fusion Sciences and Applications 2001, edited by K. Tanaka, D. D. Meyerhofer, and J. Meyer-ter-Vehn (Elsevier, Paris, 2002), p. 240. D.G. Colombant et al., Phys. Plasmas 7, 2046 (2000). P. W. McKenty et al., Phys. Plasmas 8, 2315 (2001). S. Skupsky et al., Phys. Plasmas 11, 2763 (2004). This work was supported by U. S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC52-92SF19460. Contributors: S. Skupsky, R

  2. Can the ICF be used as a rehabilitation outcome measure? A study looking at the inter- and intra-rater reliability of ICF categories derived from an ADL assessment tool.

    Science.gov (United States)

    Kohler, Friedbert; Connolly, Carol; Sakaria, Aroha; Stendara, Kimberly; Buhagiar, Mark; Mojaddidi, Mohammad

    2013-09-01

    The categories of the International Classification of Functioning , Disability and Health (ICF) could potentially be used as components of outcome measures. Literature demonstrating the psychometric properties of ICF categories is limited. Determine the agreement and reliability of ICF activities of daily living category scores and compare these to agreement and reliability of the Functional Independence Measure (FIM) item scores. Two investigators independently reviewed the clinical notes to score the ICF activities of daily living cate-gories, of 100 patients using ICF qualifiers with additional scoring guidelines. The percentage agreement, interrater and intrarater reliability were compared with the matched FIM items scored by a separate set of two investigators using the same methodology. Kappa Statistic was calculated using Med Calc. ICF interrater reliability as indicated by Kappa values ranging from 0.42 to 0.81 was moderate or better for the eleven self care and mobility categories. The language ICF categories and problem solving generally have fair agreement, with Kappa values ranging from 0.21 for receiving verbal messages to 0.44 for basic social interactions. Absolute agreement was above 72% for all categories. Reliability and agreement of the FIM items was generally lower than the corresponding ICF categories. The inter-rater and intra-rater reliability and agreement of the ICF activities of daily living categories were comparable or better than the corresponding FIM items. The results of this study provide an indication that the ICF categories could be used as components of rehabilitation outcome measures.

  3. Network Pharmacology Strategies Toward Multi-Target Anticancer Therapies: From Computational Models to Experimental Design Principles

    Science.gov (United States)

    Tang, Jing; Aittokallio, Tero

    2014-01-01

    Polypharmacology has emerged as novel means in drug discovery for improving treatment response in clinical use. However, to really capitalize on the polypharmacological effects of drugs, there is a critical need to better model and understand how the complex interactions between drugs and their cellular targets contribute to drug efficacy and possible side effects. Network graphs provide a convenient modeling framework for dealing with the fact that most drugs act on cellular systems through targeting multiple proteins both through on-target and off-target binding. Network pharmacology models aim at addressing questions such as how and where in the disease network should one target to inhibit disease phenotypes, such as cancer growth, ideally leading to therapies that are less vulnerable to drug resistance and side effects by means of attacking the disease network at the systems level through synergistic and synthetic lethal interactions. Since the exponentially increasing number of potential drug target combinations makes pure experimental approach quickly unfeasible, this review depicts a number of computational models and algorithms that can effectively reduce the search space for determining the most promising combinations for experimental evaluation. Such computational-experimental strategies are geared toward realizing the full potential of multi-target treatments in different disease phenotypes. Our specific focus is on system-level network approaches to polypharmacology designs in anticancer drug discovery, where we give representative examples of how network-centric modeling may offer systematic strategies toward better understanding and even predicting the phenotypic responses to multi-target therapies.

  4. Reduced cost design of liquid lithium target for international fusion material irradiation facility (IFMIF)

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Hiroo; Ida, Mizuho; Sugimoto, Masayoshi; Takeuchi, Hiroshi [Department of Fussion Engineering Research, Naka Fusion Research Establishment, Japan Atomic Energy Research Institute, Tokai, Ibaraki (Japan); Yutani, Toshiaki [Toshiba Corp., Tokyo (Japan)

    2001-01-01

    The International Fusion Materials Irradiation Facility (IFMIF) is being jointly planned to provide an accelerator-based D-Li neutron source to produce intense high energy neutrons (2 MW/m{sup 2}) up to 200 dpa and a sufficient irradiation volume (500 cm{sup 3}) for testing the candidate materials and components up to about a full lifetime of their anticipated use in ITER and DEMO. To realize such a condition, 40 MeV deuteron beam with a current of 250 mA is injected into high speed liquid lithium flow with a speed of 20 m/s. Following Conceptual Design Activity (1995-1998), a design study with focus on cost reduction without changing its original mission has been done in 1999. The following major changes to the CAD target design have been considered in the study and included in the new design: i) number of the Li target has been changed from 2 to 1, ii) spare of impurity traps of the Li loop was removed although the spare will be stored in a laboratory for quick exchange, iii) building volume was reduced via design changes in lithium loop length. This paper describes the reduced cost design of the lithium target system and recent status of Key Element Technology activities. (author)

  5. An investigative approach to explore optimum assembly process design for annular targets carrying LEU foil

    Science.gov (United States)

    Hoyer, Annemarie

    Technetium-99m is the most widely used nuclear isotope in the medical field, with nearly 80 to 85% of all diagnostic imaging procedures. The daughter isotope of molybdenum-99 is currently produced using weapons-grade uranium. A suggested design for aluminum targets carrying low-enriched uranium (LEU) foil is presented for the fulfillment of eliminating highly enriched uranium (HEU) for medical isotope production. The assembly process that this research focuses on is the conventional draw-plug process which is currently used and lastly the sealing process. The research is unique in that it is a systematic approach to explore the optimal target assembly process to produce those targets with the required quality and integrity. Conducting 9 parametric experiments, aluminum tubes with a nickel foil fission-barrier and a surrogate stainless steel foil are assembled, welded and then examined to find defects, to determine residual stresses, and to find the best cost-effective target dimensions. The experimental design consists of 9 assembly combinations that were found through orthogonal arrays in order to explore the significance of each factor. Using probabilistic modeling, the parametric study is investigated using the Taguchi method of robust analysis. Depending on the situation, optimal conditions may be a nominal, a minimized or occasionally a maximized condition. The results will provide the best target design and will give optimal quality with little or no assembly defects.

  6. Development of consensus International Classification of Functioning, Disability and Health (ICF) core sets for lymphedema

    NARCIS (Netherlands)

    Viehoff, P.B.; Heerkens, Y.F.; Ravensberg, C.D. van; Hidding, J.; Damstra, R.J.; Napel, H. ten; Neumann, H.A.

    2015-01-01

    To understand the challenges of patients with lymphedema it is important to describe functioning and to measure the effectiveness of treatment in changing functioning. The International Classification of Functioning, Disability and Health (ICF) offers an international framework to classify functioni

  7. Coding of meaningful concepts in lymphedema-specific questionnaires with the ICF

    NARCIS (Netherlands)

    Viehoff, P.B.; Hidding, J.T.; Heerkens, Y.F.; Ravensberg, C.D. van; Neumann, H.A.

    2013-01-01

    Abstract Purpose: To identify and quantify the meaningful concepts within questionnaires focusing on lymphedema using the International Classification of Functioning, Disability and Health (ICF). Methods: Electronic searches of Medline, EMBASE, CINAHL, CENtral and Pedro (2005-2010) were conducted. T

  8. Applying the ICF to identify requirements for students with Asperger syndrome in higher education.

    Science.gov (United States)

    Adolfsson, Margareta; Simmeborn Fleischer, Ann

    2015-06-01

    Higher education requires more than academic skills and everyday student-life can be stressful. Students with Asperger syndrome (AS) may need support to manage their education due to difficulties in social functioning. As preparation for the development of a structured tool to guide student and coordinator dialogues at Swedish universities, this study aimed to identify ICF categories that reflect requirements in everyday student-life for students with AS. Using descriptive qualitative approach, information in documents reflecting the perspectives of university students, international classifications, user/health organisations and education authorities were linked to ICF codes. In total, 114 ICF categories were identified, most of which related to learning, tasks and demands, communication and interactions. Students with AS need varying accommodations to be successful in higher education. In the future, ICF-based code sets, including demands on student roles, can be used as checklists to describe functioning and needs for support.

  9. Coding of meaningful concepts in lymphedema-specific questionnaires with the ICF

    NARCIS (Netherlands)

    Viehoff, P.B.; Hidding, J.T.; Heerkens, Y.F.; Ravensberg, C.D. van; Neumann, H.A.

    2013-01-01

    Abstract Purpose: To identify and quantify the meaningful concepts within questionnaires focusing on lymphedema using the International Classification of Functioning, Disability and Health (ICF). Methods: Electronic searches of Medline, EMBASE, CINAHL, CENtral and Pedro (2005-2010) were conducted.

  10. Development of consensus International Classification of Functioning, Disability and Health (ICF) core sets for lymphedema

    NARCIS (Netherlands)

    Viehoff, P.B.; Heerkens, Y.F.; Ravensberg, C.D. van; Hidding, J.; Damstra, R.J.; Napel, H. ten; Neumann, H.A.

    2015-01-01

    To understand the challenges of patients with lymphedema it is important to describe functioning and to measure the effectiveness of treatment in changing functioning. The International Classification of Functioning, Disability and Health (ICF) offers an international framework to classify

  11. A Conceptual Definition of Vocational Rehabilitation Based on the ICF : building a shared global model

    NARCIS (Netherlands)

    Escorpizo, Reuben; Reneman, Michiel F.; Ekholm, Jan; Fritz, Julie; Krupa, Terry; Marnetoft, Sven-Uno; Maroun, Claude E.; Guzman, Julietta Rodriguez; Suzuki, Yoshiko; Stucki, Gerold; Chan, Chetwyn C. H.

    Background The International Classification of Functioning, Disability and Health (ICF) is a conceptual framework and classification system by the World Health Organization (WHO) to understand functioning. The objective of this discussion paper is to offer a conceptual definition for vocational

  12. Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).

    NARCIS (Netherlands)

    Hagleitner, M.M.; Lankester, A.; Maraschio, P.; Hulten, M.; Fryns, J.P.; Schuetz, C.; Gimelli, G.; Davies, E.G.; Gennery, A.; Belohradsky, B.H.; Groot, R. de; Gerritsen, E.J.; Mattina, T.; Howard, P.J.; Fasth, A.; Reisli, I.; Furthner, D.; Slatter, M.A.; Cant, A.J.; Cazzola, G.; Dijken, P.J. van; Deuren, M. van; Greef, J.C. de; Maarel, S.M. van der; Weemaes, C.M.R.

    2008-01-01

    BACKGROUND: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a

  13. Modifications to risk-targeted seismic design maps for subduction and near-fault hazards

    Science.gov (United States)

    Liel, Abbie B.; Luco, Nicolas; Raghunandan, Meera; Champion, C.; Haukaas, Terje

    2015-01-01

    ASCE 7-10 introduced new seismic design maps that define risk-targeted ground motions such that buildings designed according to these maps will have 1% chance of collapse in 50 years. These maps were developed by iterative risk calculation, wherein a generic building collapse fragility curve is convolved with the U.S. Geological Survey hazard curve until target risk criteria are met. Recent research shows that this current approach may be unconservative at locations where the tectonic environment is much different than that used to develop the generic fragility curve. This study illustrates how risk-targeted ground motions at selected sites would change if generic building fragility curve and hazard assessment were modified to account for seismic risk from subduction earthquakes and near-fault pulses. The paper also explores the difficulties in implementing these changes.

  14. Multi-target drug design approaches for multifactorial diseases: from neurodegenerative to cardiovascular applications.

    Science.gov (United States)

    Katselou, M G; Matralis, A N; Kourounakis, A P

    2014-01-01

    In multi-target drug design (MTD) medicinal chemistry aims to integrate multiple pharmacophores into a single drug molecule in order to make it active on several molecular biological mechanisms simultaneously. Given the fact that most diseases are multifactorial in nature, MTD is being pursued with increasing intensity, which has resulted in improved outcomes in disease models and several compounds have entered clinical trials. In a wide range of examples we illustrate how various functionalities have been combined within single structures and how this has affected their (pre)clinical outcome. This review describes the successful application of MTD for disorders such as neurodegenerative, cardiovascular, diabetes, metabolic and inflammatory diseases, especially focusing on the field of atherosclerosis where multi-target strategies are a promising alternative to the classical "one target-one drug" design approach.

  15. Design of block-copolymer-based micelles for active and passive targeting

    NARCIS (Netherlands)

    Lebouille, Jérôme G.J.L.; Leermakers, Frans A.M.; Cohen Stuart, Martien A.; Tuinier, Remco

    2016-01-01

    A self-consistent field study is presented on the design of active and passive targeting block-copolymeric micelles. These micelles form in water by self-assembly of triblock copolymers with a hydrophilic middle block and two hydrophobic outer blocks. A minority amount of diblock copolymers with the

  16. Optimal drug cocktail design: methods for targeting molecular ensembles and insights from theoretical model systems.

    Science.gov (United States)

    Radhakrishnan, Mala L; Tidor, Bruce

    2008-05-01

    Drug resistance is a significant obstacle in the effective treatment of diseases with rapidly mutating targets, such as AIDS, malaria, and certain forms of cancer. Such targets are remarkably efficient at exploring the space of functional mutants and at evolving to evade drug binding while still maintaining their biological role. To overcome this challenge, drug regimens must be active against potential target variants. Such a goal may be accomplished by one drug molecule that recognizes multiple variants or by a drug "cocktail"--a small collection of drug molecules that collectively binds all desired variants. Ideally, one wants the smallest cocktail possible due to the potential for increased toxicity with each additional drug. Therefore, the task of designing a regimen for multiple target variants can be framed as an optimization problem--find the smallest collection of molecules that together "covers" the relevant target variants. In this work, we formulate and apply this optimization framework to theoretical model target ensembles. These results are analyzed to develop an understanding of how the physical properties of a target ensemble relate to the properties of the optimal cocktail. We focus on electrostatic variation within target ensembles, as it is one important mechanism by which drug resistance is achieved. Using integer programming, we systematically designed optimal cocktails to cover model target ensembles. We found that certain drug molecules covered much larger regions of target space than others, a phenomenon explained by theory grounded in continuum electrostatics. Molecules within optimal cocktails were often dissimilar, such that each drug was responsible for binding variants with a certain electrostatic property in common. On average, the number of molecules in the optimal cocktails correlated with the number of variants, the differences in the variants' electrostatic properties at the binding interface, and the level of binding affinity

  17. BaitFisher: A Software Package for Multispecies Target DNA Enrichment Probe Design.

    Science.gov (United States)

    Mayer, Christoph; Sann, Manuela; Donath, Alexander; Meixner, Martin; Podsiadlowski, Lars; Peters, Ralph S; Petersen, Malte; Meusemann, Karen; Liere, Karsten; Wägele, Johann-Wolfgang; Misof, Bernhard; Bleidorn, Christoph; Ohl, Michael; Niehuis, Oliver

    2016-07-01

    Target DNA enrichment combined with high-throughput sequencing technologies is a powerful approach to probing a large number of loci in genomes of interest. However, software algorithms that explicitly consider nucleotide sequence information of target loci in multiple reference species for optimizing design of target enrichment baits to be applicable across a wide range of species have not been developed. Here we present an algorithm that infers target DNA enrichment baits from multiple nucleotide sequence alignments. By applying clustering methods and the combinatorial 1-center sequence optimization to bait design, we are able to minimize the total number of baits required to efficiently probe target loci in multiple species. Consequently, more loci can be probed across species with a given number of baits. Using transcript sequences of 24 apoid wasps (Hymenoptera: Crabronidae, Sphecidae) from the 1KITE project and the gene models of Nasonia vitripennis, we inferred 57,650, 120-bp-long baits for capturing 378 coding sequence sections of 282 genes in apoid wasps. Illumina reduced-representation library sequencing confirmed successful enrichment of the target DNA when applying these baits to DNA of various apoid wasps. The designed baits furthermore enriched a major fraction of the target DNA in distantly related Hymenoptera, such as Formicidae and Chalcidoidea, highlighting the baits' broad taxonomic applicability. The availability of baits with broad taxonomic applicability is of major interest in numerous disciplines, ranging from phylogenetics to biodiversity monitoring. We implemented our new approach in a software package, called BaitFisher, which is open source and freely available at https://github.com/cmayer/BaitFisher-package.git. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Pharmacological Targeting of AMP-Activated Protein Kinase and Opportunities for Computer-Aided Drug Design.

    Science.gov (United States)

    Miglianico, Marie; Nicolaes, Gerry A F; Neumann, Dietbert

    2016-04-14

    As a central regulator of metabolism, the AMP-activated protein kinase (AMPK) is an established therapeutic target for metabolic diseases. Beyond the metabolic area, the number of medical fields that involve AMPK grows continuously, expanding the potential applications for AMPK modulators. Even though indirect AMPK activators are used in the clinics for their beneficial metabolic outcome, the few described direct agonists all failed to reach the market to date, which leaves options open for novel targeting methods. As AMPK is not actually a single molecule and has different roles depending on its isoform composition, the opportunity for isoform-specific targeting has notably come forward, but the currently available modulators fall short of expectations. In this review, we argue that with the amount of available structural and ligand data, computer-based drug design offers a number of opportunities to undertake novel and isoform-specific targeting of AMPK.

  19. Induced pluripotent stem cells as a model for telomeric abnormalities in ICF type I syndrome.

    Science.gov (United States)

    Sagie, Shira; Ellran, Erika; Katzir, Hagar; Shaked, Rony; Yehezkel, Shiran; Laevsky, Ilana; Ghanayim, Alaa; Geiger, Dan; Tzukerman, Maty; Selig, Sara

    2014-07-15

    Human telomeric regions are packaged as constitutive heterochromatin, characterized by extensive subtelomeric DNA methylation and specific histone modifications. ICF (immunodeficiency, centromeric instability, facial anomalies) type I patients carry mutations in DNA methyltransferase 3B (DNMT3B) that methylates de novo repetitive sequences during early embryonic development. ICF type I patient fibroblasts display hypomethylated subtelomeres, abnormally short telomeres and premature senescence. In order to study the molecular mechanism by which the failure to de novo methylate subtelomeres results in accelerated telomere shortening, we generated induced pluripotent stem cells (iPSCs) from 3 ICF type I patients. Telomeres were elongated in ICF-iPSCs during reprogramming, and the senescence phenotype was abolished despite sustained subtelomeric hypomethylation and high TERRA levels. Fibroblast-like cells (FLs) isolated from differentiated ICF-iPSCs maintained abnormally high TERRA levels, and telomeres in these cells shortened at an accelerated rate, leading to early senescence, thus recapitulating the telomeric phenotype of the parental fibroblasts. These findings demonstrate that the abnormal telomere phenotype associated with subtelomeric hypomethylation is overridden in cells expressing telomerase, therefore excluding telomerase inhibition by TERRA as a central mechanism responsible for telomere shortening in ICF syndrome. The data in the current study lend support to the use of ICF-iPSCs for modeling of phenotypic and molecular defects in ICF syndrome and for unraveling the mechanism whereby subtelomeric hypomethylation is linked to accelerated telomeric loss in this syndrome. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. ICF profiling of patients with traumatic brain injury: an international professional survey.

    Science.gov (United States)

    Laxe, Sara; Zasler, Nathan; Robles, Verónica; López-Blázquez, Raquel; Tormos, Jose María; Bernabeu, Montserrat

    2014-01-01

    A worldwide internet survey was conducted (1) to identify problems of individuals with traumatic brain injury (TBI) addressed by health professionals and (2) to summarize these problems using the International Classification of Functioning, Disability and Health (ICF). A pool of professionals involved in the TBI rehabilitation process that included physicians, nurses, physical therapists, occupational therapists, social workers and psychologists were surveyed to identify problems in functioning and contextual factors of individuals with TBI using open-ended questions. All answers were translated ("linked") to the ICF based on established rules. The frequencies of the linked ICF categories were reported stratified based on context. One-hundred thirty seven professionals from the six World Health Organization regions identified 5656 concepts. 92.66% could be linked to the ICF; 33.03% were related to the domain of body functions, 27.28% to activities and participation, 10.98% to structures and 21.38% to environmental factors. The complexity of TBI was described through the identification of a wide variety of ICF categories. ICF language proved to be a neutral framework allowing the comparison of answers between different professionals in different world regions. People that suffered a traumatic brain injury (TBI) may have a variety of sequelae that impair functioning. The International Classification of Functioning, Disability and Health (ICF) can help in providing information regarding the identification of patients problems and needs as well as planning, implementing and coordinating the rehabilitation process. The ICF provides a frame of reference process illustrated as the rehabilitation cycle that can help during the rehabilitation process in goal setting bringing together the clinicians' and patient's perspectives in a patient oriented biopsychosocial approach. In the field of TBI rehabilitation, activity limitations and participation restrictions are broadly

  1. Management a marketing sportovní akce: ICF Slalom World Ranking Race Prague 2009

    OpenAIRE

    Kubričan, Lukáš

    2009-01-01

    Title: Management and marketing of sport's event: ICF Slalom World Ranking Race Prague 2009 Objectives: Present strengths and weaknesses of ICF Slalom World Ranking Race Prague 2009 based on analyse of recent years and present ideas for its improvement. Methods: Descriptive analysis, SWOT analysis and interview with expert. Results: Conclusion and advices for organizers of sport's events. Key words: Management, marketing, SWOT analysis, descriptive analysis, sport's event, canoe slalom compet...

  2. A New 3He-Target Design for Compton Scattering Experiment

    Science.gov (United States)

    Mahalchick, S.; Gao, H.; Laskaris, G.; Weir, W.; Ye, Q.; Ye, Q. J.

    2011-10-01

    The neutron spin polarizabilities describe the stiffness of the neutron spin to external electric and magnetic fields. A double-polarized elastic Compton Scattering experiment will try to determine the neutron spin polarizabilities using a new polarized 3He target and the circularly polarized γ-beam of HI γS facility at the Duke Free Electron Laser Laboratory (DFELL). To polarize the 3He target, a newly constructed solenoid is being used which can provide a very uniform magnetic field around the target area and allows to place High Intensity Gamma Source NaI Detector Arrays (HINDA) closer to the target. The ideal target polarization is 40-60% and will be measured using the nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) techniques. A prototype of the polarized 3He target is being constructed in the Medium Energy Physics Group laboratories at Duke and is currently being tested. The experiment is expected to take place in 2013 after the DFELL upgrade. I will be presenting details of the construction process, including design specifications and data from the magnetic field mapping, as well as preliminary target polarization results. This work is supported by the US Department of Energy, under contract number DE-FG02-03ER41231, and by the National Science Foundation, grant number NSF-PHY-08-51813.

  3. Using the uncertainty principle to design simple interactions for targeted self-assembly.

    Science.gov (United States)

    Edlund, E; Lindgren, O; Jacobi, M Nilsson

    2013-07-14

    We present a method that systematically simplifies isotropic interactions designed for targeted self-assembly. The uncertainty principle is used to show that an optimal simplification is achieved by a combination of heat kernel smoothing and Gaussian screening of the interaction potential in real and reciprocal space. We use this method to analytically design isotropic interactions for self-assembly of complex lattices and of materials with functional properties. The derived interactions are simple enough to narrow the gap between theory and experimental implementation of theory based designed self-assembling materials.

  4. Design and modeling of ignition targets for the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Haan, S.W.; Pollaine, S.M.; Lindl, J.D.; Suter, L.J.; Berger, R.L.; Powers, L.V.; Alley, W.E.; Amendt, P.A.; Futterman, J.A.; Levedahl, W.K.; Rosen, M.D.; Rowley, D.P.; Sacks, R.A.; Shestakov, A.I.; Strobel, G.L.; Tabak, M.; Weber, S.V.; Zimmerman, G.B. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); Krauser, W.J.; Wilson, D.C.; Coggeshall, S.V.; Harris, D.B.; Hoffman, N.M.; Wilde, B.H. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    1995-06-01

    Several targets are described that in simulations give yields of 1--30 MJ when indirectly driven by 0.9--2 MJ of 0.35 {mu}m laser light. The article describes the targets, the modeling that was used to design them, and the modeling done to set specifications for the laser system in the proposed National Ignition Facility. Capsules with beryllium or polystyrene ablators are enclosed in gold hohlraums. All the designs utilize a cryogenic fuel layer; it is very difficult to achieve ignition at this scale with a noncryogenic capsule. It is necessary to use multiple bands of illumination in the hohlraum to achieve sufficiently uniform x-ray irradiation, and to use a low-{ital Z} gas fill in the hohlraum to reduce filling of the hohlraum with gold plasma. Critical issues are hohlraum design and optimization, Rayleigh--Taylor instability modeling, and laser--plasma interactions.

  5. Elaboration of the contextual factors of the ICF for Occupational Health Care.

    Science.gov (United States)

    Heerkens, Yvonne F; de Brouwer, Carin P M; Engels, Josephine A; van der Gulden, Joost W J; Kant, IJmert

    2017-01-01

    Many work-related items are not included in the current classification of environmental factors from the International Classification of Functioning, Disability and Health (ICF). Furthermore, personal factors are not classified and the ICF only provides a very limited list of examples. These facts make the ICF less useful for occupational health care and for research in the field of occupation and health. The objective of this discussion paper is to introduce an elaboration of contextual factors, focussing on factors that influence work participation. During the last 12 years, we developed two concept lists from the bottom up. These lists are based on our experiences in teaching and research, suggestions from students and other researchers, and factors found in the literature. In the fall of 2015 a scoping literature review was done to check for missing factors in these two concept lists. An elaboration of contextual factors, consisting of a list of work-related environmental factors and a list of personal factors. Important contextual factors that influence work participation are identified. Researchers, teachers, students, occupational and insurance physicians, allied health care professionals, employers, employees, and policy makers are invited to use the elaboration and to make suggestions for improvement. The elaboration and the suggestions received can be used in the ICF revision process. The development of an ICF ontology must be given priority, to give room to this elaboration, which will increase the applicability of the ICF and enable mapping with other terminologies and classifications.

  6. Child oral health from the professional perspective - a global ICF-CY survey.

    Science.gov (United States)

    Faulks, Denise; Molina, Gustavo; Eschevins, Caroline; Dougall, Alison

    2016-07-01

    The International Classification of Functioning, Disability and Health Children and Youth version (ICF-CY) (WHO) may serve as a tool for the application of holistic models of oral health. The ICF-CY Global Oral Health Survey explored international professional opinion regarding factors relating to child oral health, including social environment, functioning, activity, and participation. Networking resulted in 514 professionals from 81 countries registering for a two-round Delphi survey online. Participants were pooled into 18 groups according to six WHO world regions and three professional groups. In a randomized stratification process, eight from each pool (n = 144) completed the survey. The first round consisted of eight open-ended questions. Open-expression replies were analysed for meaningful concepts and linked using established rules to the ICF-CY. In the second round, items were rated for their relevance to oral health (86% response rate). A total of 86 ICF-CY items and 31 other factors were considered relevant to child oral health and function by at least 80% of professionals. The ICF-CY can describe the holistic experience of oral health in children from the professional perspective. The data from this study will contribute to the development of an ICF-CY Core Set in Oral Health. © 2015 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Agenesis of the corpus callosum: classifying functional manifestations with the ICF-CY.

    Science.gov (United States)

    Kovac, Megan L; Simeonsson, Rune J

    2014-01-01

    Agenesis of the corpus callosum (ACC) is a congenital condition in which the corpus callosum fails to develop fully. In the literature, ACC has been broadly conceptualized and inconsistently described. This article demonstrates how the universal language of the International Classification of Functioning, Disability and Health-Children and Youth can increase the specificity with which researchers and clinicians describe the variable manifestations of ACC. The database for this article was based on a review of 83 studies on developmental and neuropsychological manifestations of congenital ACC in children and adolescents. First, the extent to which the findings on ACC could be documented using the taxonomic codes in the ICF-CY was examined. Next, the findings from each study were mapped onto the ICF-CY to summarize the distribution of clinical features reported in the literature. There was a high degree of correspondence between the reported findings and the taxonomic codes of the ICF-CY. The distribution of clinical features was discussed. This taxonomic application advances the ICF-CY as a common language for researchers and clinicians who work with children who have ACC. Implications for Rehabilitation Agenesis of the corpus callosum (ACC) is a condition that has been broadly conceptualized and inconsistently described in research and practice. The variable clinical manifestations of children with ACC can be most effectively described using the ICF-CY. The application of the ICF-CY to conditions with highly variable clinical manifestations, like ACC, positively impacts research and practice.

  8. Looking at the ICF and human communication through the lens of classification theory.

    Science.gov (United States)

    Walsh, Regina

    2011-08-01

    This paper explores the insights that classification theory can provide about the application of the International Classification of Functioning, Disability and Health (ICF) to communication. It first considers the relationship between conceptual models and classification systems, highlighting that classification systems in speech-language pathology (SLP) have not historically been based on conceptual models of human communication. It then overviews the key concepts and criteria of classification theory. Applying classification theory to the ICF and communication raises a number of issues, some previously highlighted through clinical application. Six focus questions from classification theory are used to explore these issues, and to propose the creation of an ICF-related conceptual model of communicating for the field of communication disability, which would address some of the issues raised. Developing a conceptual model of communication for SLP purposes closely articulated with the ICF would foster productive intra-professional discourse, while at the same time allow the profession to continue to use the ICF for purposes in inter-disciplinary discourse. The paper concludes by suggesting the insights of classification theory can assist professionals to apply the ICF to communication with the necessary rigour, and to work further in developing a conceptual model of human communication.

  9. International Classification of Functioning, Disability and Health: development of an assessment set to evaluate functioning based on the Brief ICF Core Set for Hand Conditions - ICF HandA.

    Science.gov (United States)

    Kus, S; Dereskewitz, C; Coenen, M; Rauch, A; Rudolf, K-D

    2017-09-01

    Timely identification of patients' problems after disorder or injury of the hand requires a thorough functional assessment. However, the variety of outcome measures available makes it difficult to choose the appropriate instrument. The brief International Classification of Functioning, Disability and Health (Brief ICF Core Set for Hand Conditions) provides a standard for what aspects need to be measured in hand injuries and disorders without specifying how to make the assessment. We developed the ICF-based Assessment Hand (ICF HandA), an assessment set for functioning based on the Brief ICF Core Set for Hand Conditions. First, we performed a literature review and an expert survey to pool outcome measures appropriate to assess functioning in clinical practice. At an interdisciplinary consensus conference experts decided on the outcome measures to be included in the ICF HandA. The ICF HandA provides a consensus on outcome measures and instruments to systematically assess function in patients with hand injuries and disorders.

  10. The development of an ICF-based clinical guideline and screening tool for the standardized assessment and evaluation of functioning after head and neck cancer treatment.

    Science.gov (United States)

    Kisser, Ulrich; Adderson-Kisser, Christine; Coenen, Michaela; Stier-Jarmer, Marita; Becker, Sven; Sabariego, Carla; Harréus, Ulrich

    2017-02-01

    The assessment and evaluation of functioning and quality of life after tumor treatment in head and neck cancer (HNC) are considered as essential aspects of clinical routine and studies. A huge number of instruments are available that have been designed to evaluate functioning and quality of life after HNC treatment. The diversity of these instruments in terms of content, response options and administration hinders the comparability of available studies and the performance of meta-analyses. The objective of this paper is to inform about the development of a screening tool for the standardized assessment and evaluation of functioning based on the International Classification of Functioning, Disability and Health (ICF) Core Set for HNC. We followed a multi-step approach including (1) preparatory studies to identify and preselect suitable instruments for the assessment of functioning, (2) a decision-making process to agree on an ICF-based clinical guideline including instruments assessing functioning and (3) the development of a computer-based standardized screening tool to assess and evaluate functioning based on this guideline in clinical routine. Twenty-one experts participated in a consensus meeting and decided on instruments to be included in an ICF-based clinical guideline and screening tool for the assessment and evaluation of functioning in HNC patients in cancer treatment. The chosen instruments cover all aspects of the ICF Core Set for HNC addressing therapy control, pain, food intake/swallowing, voice/speech/breathing, other somatic complaints and psychosocial aspects. The screening tool contains patient-reported outcome measures and a clinician's checklist. It has to be further tested in clinical practice.

  11. Statistical inference on censored data for targeted clinical trials under enrichment design.

    Science.gov (United States)

    Chen, Chen-Fang; Lin, Jr-Rung; Liu, Jen-Pei

    2013-01-01

    For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures.

  12. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

    Science.gov (United States)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

    2016-05-05

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

  13. Pentameric models as alternative molecular targets for the design of new antiaggregant agents.

    Science.gov (United States)

    Barrera Guisasola, Exequiel E; Gutierrez, Lucas J; Andujar, Sebastián A; Angelina, Emilio; Rodríguez, Ana M; Enriz, Ricardo D

    2016-01-01

    The structure-based drug design has been an extremely useful technique used for searching and developing of new therapeutic agents in various biological systems. In the case of AD, this approach has been difficult to implement. Among other several causes, the main problem might be the lack of a specific stable and reliable molecular target. In this paper the results obtained using a pentameric amyloid beta (Aβ) model as a molecular target are discussed. Our MD simulations have shown that this system is relatively structured and stable, displaying a lightly conformational flexibility during 2.0 μs of simulation time. This study allowed us to distinguish characteristic structural features in specific regions of the pentamer which should be taken into account when choosing this model as a molecular target. This represents a clear advantage compared to the monomer or dimer models which are highly flexible structures with large numbers of possible conformers. Using this pentameric model we performed two types of studies usually carried out on a molecular target: a virtual screening and the design on structural basis of new mimetic peptides with antiaggregant properties. Our results indicate that this pentameric model might be a good molecular target for these particular studies of molecular modeling. Details about the predictive power of our virtual screening as well as about the molecular interactions that stabilize the mimetic peptide-pentamer Aβ complexes are discussed in this paper.

  14. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design

    Science.gov (United States)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M.

    2016-05-01

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

  15. A novel target detection approach based on adaptive radar waveform design

    Institute of Scientific and Technical Information of China (English)

    Wang Haitao; Shi Lei; Wang Youlin; Ben De

    2013-01-01

    To resolve problems of complicated clutter,fast-varying scenes,and low signal-clutterratio (SCR) in application of target detection on sea for space-based radar (SBR),a target detection approach based on adaptive waveform design is proposed in this paper.Firstly,complicated sea clutter is modeled as compound Gaussian process,and a target is modeled as some scatterers with Gaussian reflectivity.Secondly,every dwell duration of radar is divided into several sub-dwells.Regular linear frequency modulated pulses are transmitted at Sub-dwell 1,and the received signal at this sub-dwell is used to estimate clutter covariance matrices and pre-detection.Estimated matrices are updated at every following sub-dwell by multiple particle filtering to cope with fast-varying clutter scenes of SBR.Furthermore,waveform of every following sub-dwell is designed adaptively according to mean square optimization technique.Finally,principal component analysis and generalized likelihood ratio test is used for mitigation of colored interference and property of constant false alarm rate,respectively.Simulation results show that,considering configuration of SBR and condition of complicated clutter,9 dB is reduced for SCR which reliable detection requires by this target detection approach.Therefore,the work in this paper can markedly improve radar detection performance for weak targets.

  16. Design and development of a tantalum foil target for the production of high intensity radioactive beams

    CERN Document Server

    Densham, Cristopher John

    2000-01-01

    The design and development of a high power target and ion source for the production of Radioactive Beams at intensities approaching two orders of magnitude greater than currently possible is presented. This was a key aim of the RIST experiment, designed to utilise the proton synchrotron of the ISIS facility at Rutherford Appleton laboratory, Chilton, Oxfordshire, where an 800 MeV proton beam is available at currents of up to 200 mu A. A number of different target designs were considered and analysed, and high temperature power dissipation tests were conducted. This culminated in the manufacture of a diffusion bonded structure comprising 6000 separate tantalum foil discs and spacer washers. The target was installed in the RIST facility, and thermal tests using electron beam heating demonstrated that the target was capable of dissipating 24 kW by thermal radiation, at the desired temperature of 2000 deg C. This is equivalent to running with the 800 MeV ISIS proton beam at a current of 100 mu A. A smaller diamet...

  17. Adaptable setups for magnetic drug targeting in human muscular arteries: Design and implementation

    Science.gov (United States)

    Hajiaghajani, Amirhossein; Hashemi, Soheil; Abdolali, Ali

    2017-09-01

    Magnetic drug targeting has been used to steer magnetic therapeutic agents and has received much attention for capillaries and human brain arteries. In this paper, we focus on noninvasive targeting of nanoparticles in muscular arteries, in where the vessel diameter and blood flow are much challengingly higher than brain capillaries. We aim to design a low intensity magnetic field which avoids potential side effects on blood cells while steers particles with high targeting rate. The setup design procedure is considerably flexible to be used in a wide variety of large vessels. Using particle tracing, a new method is proposed to connect the geometry of the vessel under the action of targeting to the required magnetic force. Specifications of the coil which is placed outside the body are derived based on this required force. Mutual effects of coil dimensions on the produced magnetic force are elaborated and summarized in a design flowchart to be used for arbitrary muscular vessel sizes. The performance of the optimized coil is validated by in vitro experiments and it is shown that particles are steered with the average efficiency of 80.2% for various conditions.

  18. Laser glass process development for the next generation of ICF lasers

    Science.gov (United States)

    Thorne, Alfred J.; Hayden, Joseph S.

    1997-12-01

    The next generation of high energy laser systems for ICF research demands an unprecedented volume of laser glass to be produced over a limited manufacturing period while still meeting ambitious targets of internal quality and overall cost. To meet this challenge, Schott has conceived a continuous manufacturing unit capable of producing 5,000 meter class PH 4 slabs of platinum particle-free phosphate laser glass within a three-year time period. This manufacturing unit concept draws on years of prior production experience with phosphate laser glass and other high quality optical materials but still represents a significant departure from the proven discontinuous manufacturing technology successfully employed over the last ten years for platinum-free phosphate laser glass. In addition, Schott has developed a new phosphate laser glass that simultaneously offers improvements in properties that relate to both laser performance and to characteristics related to forming the glass into large, high quality slabs. In this paper we will describe the key technology issues addressed in the manufacturing development and present a brief description of the planned manufacturing method to be employed. Lastly, the status of the development will be reviewed including characterization of pilot production melts of the new laser glass and the schedule for completion of the development program.

  19. Inference of ICF implosion core mix using experimental data and theoretical mix modeling

    Energy Technology Data Exchange (ETDEWEB)

    Sherrill, Leslie Welser [Los Alamos National Laboratory; Haynes, Donald A [Los Alamos National Laboratory; Cooley, James H [Los Alamos National Laboratory; Sherrill, Manolo E [Los Alamos National Laboratory; Mancini, Roberto C [UNR; Tommasini, Riccardo [LLNL; Golovkin, Igor E [PRISM COMP. SCIENCES; Haan, Steven W [LLNL

    2009-01-01

    The mixing between fuel and shell materials in Inertial Confinement Fusion (lCF) implosion cores is a current topic of interest. The goal of this work was to design direct-drive ICF experiments which have varying levels of mix, and subsequently to extract information on mixing directly from the experimental data using spectroscopic techniques. The experimental design was accomplished using hydrodynamic simulations in conjunction with Haan's saturation model, which was used to predict the mix levels of candidate experimental configurations. These theoretical predictions were then compared to the mixing information which was extracted from the experimental data, and it was found that Haan's mix model predicted trends in the width of the mix layer as a function of initial shell thickness. These results contribute to an assessment of the range of validity and predictive capability of the Haan saturation model, as well as increasing confidence in the methods used to extract mixing information from experimental data.

  20. Target enrichment sequencing in cultivated peanut (Arachis hypogaea L.) using probes designed from transcript sequences.

    Science.gov (United States)

    Peng, Ze; Fan, Wen; Wang, Liping; Paudel, Dev; Leventini, Dante; Tillman, Barry L; Wang, Jianping

    2017-05-10

    Enabled by the next generation sequencing, target enrichment sequencing (TES) is a powerful method to enrich genomic regions of interest and to identify sequence variations. The objective of this study was to explore the feasibility of probe design from transcript sequences for TES application in calling sequence variants in peanut, an important allotetraploid crop with a large genome size. In this study, we applied an in-solution hybridization method to enrich DNA sequences of seven peanut genotypes. Our results showed that it is feasible to apply TES with probes designed from transcript sequences in polyploid peanut. Using a set of 31,123 probes, a total of 5131 and 7521 genes were targeted in peanut A and B genomes, respectively. For each genotype used in this study, the probe target capture regions were efficiently covered with high depth. The average on-target rate of sequencing reads was 42.47%, with a significant amount of off-target reads coming from genomic regions homologous to target regions. In this study, when given predefined genomic regions of interest and the same amount of sequencing data, TES provided the highest coverage of target regions when compared to whole genome sequencing, RNA sequencing, and genotyping by sequencing. Single nucleotide polymorphism (SNP) calling and subsequent validation revealed a high validation rate (85.71%) of homozygous SNPs, providing valuable markers for peanut genotyping. This study demonstrated the success of applying TES for SNP identification in peanut, which shall provide valuable suggestions for TES application in other non-model species without a genome reference available.

  1. Design of the Fifth-Generation Target-Moderator-Reflector-Shield Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Nowicki, Suzanne Florence [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mocko, Michal [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-11-16

    The facilities at the Los Alamos Neutron Science Center are described first. The target is being redesigned so that the Flight Paths (FP) in the upper tier provide a higher intensity in the epithermal and medium energy range. It is found that a 3-piece design looks promising: intensity in epithermal and medium energy range in upper tier is an order of magnitude higher than current Mark III, and intensity in the thermal energy range is higher in the lower tier than current Mark III. Time emission spectra show a bump due to the scattering of fast neutrons. Other investigations such as the addition of wings around the upper target will be conducted.

  2. Progress in antiandrogen design targeting hormone binding pocket to circumvent mutation based resistance

    Directory of Open Access Journals (Sweden)

    Xiaohong eTian

    2015-03-01

    Full Text Available Androgen receptor (AR plays a critical role in the development and progression of prostate cancer (PCa. Current clinically used antiandrogens such as flutamide, bicalutamide, and newly approved enzalutamide mainly target the hormone binding pocket (HBP of AR. However, over time, drug resistance invariably develops and switches these antiandrogens from antagonist to agonist of the AR. Accumulated evidence indicates that AR mutation is an important cause for the drug resistance. This review will give an overview of the mutation based resistance of the current clinically used antiandrogens and the rational drug design to overcome the resistance, provides a promising strategy for the development of the new generation of antiandrogens targeting HBP.

  3. Systematic Literature Review on ICF From 2001 to 2013 in the Nordic Countries Focusing on Clinical and Rehabilitation Context

    DEFF Research Database (Denmark)

    Maribo, Thomas; Petersen, Kirsten Schultz; Handberg, Charlotte

    2016-01-01

    We present a systematic review on International Classification of Functioning, Disability and Health (ICF) used in the Nordic countries from 2001 through 2013, describing and quantifying the development in utilization of ICF, and describe the extent to which the different components of the ICF have...... been used. A search was conducted in EMBASE, MEDLINE and PsycInfo. Papers from Nordic countries were included if ICF was mentioned in title or abstract. Papers were assigned to one of eight categories covering the wide rehabilitation area; furthermore, area of focus was assigned. Use of ICF components...... included papers were published in the period 2011 - 2013. There was an increase in ICF-relevant papers from 2001 to 2013, especially in the categories "clinical and/or rehabilitation contexts" and "non-clinical contexts". The most represented focus areas were neurology, musculoskeletal, and work...

  4. Validation of a new design of tellurium dioide-irradiated target

    Energy Technology Data Exchange (ETDEWEB)

    Fllaoui, Aziz; Ghamad, Younes; Zoubir, Brahim; Ayaz, Zinel Abidine; El Morabiti, Aissam; Amayoud, Hafid [Centre National de l' Energie des Sciences et des Techniques Nucleaires, Rabat (Morocco); Chakir, El Mahjoub [Nuclear Physics Department, University Ibn Toufail, Kenitra (Morocco)

    2016-10-15

    Production of iodine-131 by neutron activation of tellurium in tellurium dioxide (TeO{sub 2}) material requires a target that meets the safety requirements. In a radiopharmaceutical production unit, a new lid for a can was designed, which permits tight sealing of the target by using tungsten inert gas welding. The leakage rate of all prepared targets was assessed using a helium mass spectrometer. The accepted leakage rate is ≤ 10 - 4 mbr.L/s, according to the approved safety report related to iodine-131 production in the TRIGA Mark II research reactor (TRIGA: Training, Research, Isotopes, General Atomics). To confirm the resistance of the new design to the irradiation conditions in the TRIGA Mark II research reactor's central thimble, a study of heat effect on the sealed targets for 7 hours in an oven was conducted and the leakage rates were evaluated. The results show that the tightness of the targets is ensured up to 600 .deg. C with the appearance of deformations on lids beyond 450 .deg. C. The study of heat transfer through the target was conducted by adopting a one-dimensional approximation, under consideration of the three transfer modes-convection, conduction, and radiation. The quantities of heat generated by gamma and neutron heating were calculated by a validated computational model for the neutronic simulation of the TRIGA Mark II research reactor using the Monte Carlo N-Particle transport code. Using the heat transfer equations according to the three modes of heat transfer, the thermal study of I-131 production by irradiation of the target in the central thimble showed that the temperatures of materials do not exceed the corresponding melting points. To validate this new design, several targets have been irradiated in the central thimble according to a preplanned irradiation program, going from 4 hours of irradiation at a power level of 0.5 MW up to 35 hours (7 h/d for 5 days a week) at 1.5 MW. The results show that the irradiated targets are

  5. Validation of a New Design of Tellurium Dioxide-Irradiated Target

    Directory of Open Access Journals (Sweden)

    Aziz Fllaoui

    2016-10-01

    Full Text Available Production of iodine-131 by neutron activation of tellurium in tellurium dioxide (TeO2 material requires a target that meets the safety requirements. In a radiopharmaceutical production unit, a new lid for a can was designed, which permits tight sealing of the target by using tungsten inert gas welding. The leakage rate of all prepared targets was assessed using a helium mass spectrometer. The accepted leakage rate is ≤ 10−4 mbr.L/s, according to the approved safety report related to iodine-131 production in the TRIGA Mark II research reactor (TRIGA: Training, Research, Isotopes, General Atomics. To confirm the resistance of the new design to the irradiation conditions in the TRIGA Mark II research reactor's central thimble, a study of heat effect on the sealed targets for 7 hours in an oven was conducted and the leakage rates were evaluated. The results show that the tightness of the targets is ensured up to 600°C with the appearance of deformations on lids beyond 450°C. The study of heat transfer through the target was conducted by adopting a one-dimensional approximation, under consideration of the three transfer modes—convection, conduction, and radiation. The quantities of heat generated by gamma and neutron heating were calculated by a validated computational model for the neutronic simulation of the TRIGA Mark II research reactor using the Monte Carlo N-Particle transport code. Using the heat transfer equations according to the three modes of heat transfer, the thermal study of I-131 production by irradiation of the target in the central thimble showed that the temperatures of materials do not exceed the corresponding melting points. To validate this new design, several targets have been irradiated in the central thimble according to a preplanned irradiation program, going from 4 hours of irradiation at a power level of 0.5 MW up to 35 hours (7 h/d for 5 days a week at 1.5 MW. The results show that the irradiated targets are

  6. Design of a bioactive small molecule that targets r(AUUCU) repeats in spinocerebellar ataxia 10.

    Science.gov (United States)

    Yang, Wang-Yong; Gao, Rui; Southern, Mark; Sarkar, Partha S; Disney, Matthew D

    2016-06-01

    RNA is an important target for chemical probes of function and lead therapeutics; however, it is difficult to target with small molecules. One approach to tackle this problem is to identify compounds that target RNA structures and utilize them to multivalently target RNA. Here we show that small molecules can be identified to selectively bind RNA base pairs by probing a library of RNA-focused small molecules. A small molecule that selectively binds AU base pairs informed design of a dimeric compound (2AU-2) that targets the pathogenic RNA, expanded r(AUUCU) repeats, that causes spinocerebellar ataxia type 10 (SCA10) in patient-derived cells. Indeed, 2AU-2 (50 nM) ameliorates various aspects of SCA10 pathology including improvement of mitochondrial dysfunction, reduced activation of caspase 3, and reduction of nuclear foci. These studies provide a first-in-class chemical probe to study SCA10 RNA toxicity and potentially define broadly applicable compounds targeting RNA AU base pairs in cells.

  7. Package design and nutritional profile of foods targeted at children in supermarkets in Montevideo, Uruguay.

    Science.gov (United States)

    Giménez, Ana; Saldamando, Luis de; Curutchet, María Rosa; Ares, Gastón

    2017-06-12

    Marketing of unhealthy products has been identified as one of the main characteristics of the food environment that negatively affects children's eating patterns. Restrictions on advertising of unhealthy foods to children have already been imposed in different countries. However, marketing strategies are not limited to broadcast and digital advertising, but also include package design. In this context, the current study aimed to describe the food products targeted at children and sold in supermarkets in Montevideo, Uruguay, in terms of package design and nutrient profile. Two supermarkets in Montevideo were selected for data collection. In each supermarket, all products targeted at children were identified. Products were analyzed in terms of package design and nutritional profile, considering the Pan American Health Organization Nutrient Profile Model. A total of 180 unique products were identified, which included a wide range of product categories. The great majority of the products corresponded to ultra-processed products with excessive amounts of sodium, free sugars, total fat, saturated fat, and/or trans fat, which are not recommended for frequent consumption. Several marketing strategies were identified in the design of packages to attract children's attention and drive their preferences. The most common strategies were the inclusion of cartoon characters, bright colors, childish lettering, and a wide range of claims related to health and nutrition, as well as the products' sensory and hedonic characteristics. The study's findings provide additional evidence on the need to regulate packaging of products targeted at children.

  8. Designing Multi-Targeted Therapeutics for the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Orhan, Ilkay Erdogan; Senol, F Sezer

    2016-01-01

    Due to multi-faceted pathology of AD; no drug can seize the progress of the disease, whereas only the symptomatic treatment is available at the moment. Several drug classes to treat AD are available in clinical use, AChEIs being the most prescribed. In addition to AChEIs, secretase enzymes and iron chelators have turned out to be the focus of research and the popular targets in drug discovery against AD. The latest approaches such as immunotherapy, multi-targeted drug ligand design, AChE inhibitors, antioxidants, metal chelators, monoamine oxidase (MAO) inhibitors, antiinflammatory drugs, and N-methyl-D-aspartate (NMDA) inhibitors are currently in use to cure this disease to some extent. But, there is a certain need to develop new drugs to fight with AD, particularly acting on multi-targets or with dual mechanisms of action. In this review, a particular emphasis will be focused on multitargets aiming at AD to design new drug molecules with respect to treatment strategies and preventive measures. Since the underlying pathogenesis of AD is complicated and still under investigation, the attempts to design highly selective and potent agents to treat AD are quite intensively continuing. In this respect, designing novel drugs with dual/multi-acting mechanisms seems to be more rational.

  9. Path To Ignition: US Indirect Target Physics (LIRPP Vol. 12)

    Science.gov (United States)

    Cray, M.; Campbell, E. M.

    2016-10-01

    The United States ICF Program has been pursuing an aggressive research program in preparation for an ignition demonstration on the National Ignition Facility. Los Alamos and Livermore laboratories have collaborated on resolving indirect drive target physics issues on the Nova laser at Livermore National Laboratory. This combined with detailed modeling of laser heated indirectly driven targets likely to achieve ignition, has provided the basis for planning for the NIF. A detailed understanding of target physics, laser performance, and target fabrication is required for developing robust ignition targets. We have developed large-scale computational models to simulate complex physics which occurs in an indirectly driven target. For ignition, detailed understanding of hohlraum and implosion physics is required in order to control competing processes at the few percent level. From crucial experiments performed by Los Alamos and Livermore on the Nova laser, a comprehensive indirect drive database has been assembled. Time integrated and time dependent measurements of radiation drive and symmetry coupled with a detailed set of plasma instability measurements have confirmed our ability to predict hohlraum energetics. Implosion physics campaigns are focused on underdstanding detailed capsule hydrodynamics and instability growth. Target fabrication technology is also an active area of research at Los Alamos, Livermore, and General Atomics for NIF. NIF targets require developing technology in cryogenics and manufacturing in such areas as beryllium shell manufacture. Descriptions of our NIF target designs, experimental results, and fabrication technology supporting NIF target performance predictions will be given.

  10. Rotational spectra and properties of complexes B···ICF3 (B = Kr or CO) and a comparison of the efficacy of ICl and ICF3 as iodine donors in halogen bond formation.

    Science.gov (United States)

    Stephens, Susanna L; Walker, Nicholas R; Legon, Anthony C

    2011-12-14

    The ground-state rotational spectra of two weakly bound complexes B···ICF(3) (B = Kr or CO) formed by trifluoroiodomethane have been observed in pulsed jets by using two types of Fourier-transform microwave spectroscopy (chirped-pulse and Fabry-Perot cavity). Both complexes exhibit symmetric-top type spectra, thus indicating that the Kr atom in Kr···ICF(3) and both the C and O atoms in OC···ICF(3) lie along the C(3) axis of ICF(3). The rotational constant B(0), the centrifugal distortion constants D(J) and D(JK), and the iodine nuclear quadrupole coupling constant χ(aa)(I) were determined for each of the isotopologues (84)Kr···ICF(3), (86)Kr···ICF(3), (16)O(12)C···ICF(3), (16)O(13)C···ICF(3), and (18)O(12)C···ICF(3). Interpretation of the spectroscopic constants reveals that the carbon atom of CO is adjacent to I and participates in the weak bond in OC···ICF(3). Simple models based on unperturbed component geometries lead to the distances r(Kr···I) = 3.830(1) Å and r(C···I) = 3.428(1) Å in Kr···ICF(3) and OC···ICF(3), respectively, and to the quadratic force constants for stretching of the weak bond k(σ) = 2.80 N m(-1) and 3.96 N m(-1), respectively. The distances r(Z···I) (Z is the acceptor atom in B), the k(σ) values, and the angular geometries of the pair of complexes B···ICF(3) and B···ICl for a given B are compared when B = Kr, CO, H(2)O, H(2)S, or NH(3). The comparison reveals that the iodine bond in B···ICF(3) is systematically longer and weaker than that of B···ICl, while the angular geometry of the B···I moiety is isomorphic in B···ICF(3) and B···ICl for a given B. It is concluded that -CF(3) is less effective than -Cl as an electron-withdrawing group when attached to an I atom and that the angular geometries of the B···ICF(3) can be predicted by means of a simple rule that holds for many hydrogen- and halogen-bonded complexes.

  11. A multiple-alignment based primer design algorithm for genetically highly variable DNA targets.

    Science.gov (United States)

    Brodin, Johanna; Krishnamoorthy, Mohan; Athreya, Gayathri; Fischer, Will; Hraber, Peter; Gleasner, Cheryl; Green, Lance; Korber, Bette; Leitner, Thomas

    2013-08-21

    Primer design for highly variable DNA sequences is difficult, and experimental success requires attention to many interacting constraints. The advent of next-generation sequencing methods allows the investigation of rare variants otherwise hidden deep in large populations, but requires attention to population diversity and primer localization in relatively conserved regions, in addition to recognized constraints typically considered in primer design. Design constraints include degenerate sites to maximize population coverage, matching of melting temperatures, optimizing de novo sequence length, finding optimal bio-barcodes to allow efficient downstream analyses, and minimizing risk of dimerization. To facilitate primer design addressing these and other constraints, we created a novel computer program (PrimerDesign) that automates this complex procedure. We show its powers and limitations and give examples of successful designs for the analysis of HIV-1 populations. PrimerDesign is useful for researchers who want to design DNA primers and probes for analyzing highly variable DNA populations. It can be used to design primers for PCR, RT-PCR, Sanger sequencing, next-generation sequencing, and other experimental protocols targeting highly variable DNA samples.

  12. Generation of an ICF Syndrome Model by Efficient Genome Editing of Human Induced Pluripotent Stem Cells Using the CRISPR System

    Directory of Open Access Journals (Sweden)

    Izuho Hatada

    2013-09-01

    Full Text Available Genome manipulation of human induced pluripotent stem (iPS cells is essential to achieve their full potential as tools for regenerative medicine. To date, however, gene targeting in human pluripotent stem cells (hPSCs has proven to be extremely difficult. Recently, an efficient genome manipulation technology using the RNA-guided DNase Cas9, the clustered regularly interspaced short palindromic repeats (CRISPR system, has been developed. Here we report the efficient generation of an iPS cell model for immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF syndrome using the CRISPR system. We obtained iPS cells with mutations in both alleles of DNA methyltransferase 3B (DNMT3B in 63% of transfected clones. Our data suggest that the CRISPR system is highly efficient and useful for genome engineering of human iPS cells.

  13. Generation of an ICF syndrome model by efficient genome editing of human induced pluripotent stem cells using the CRISPR system.

    Science.gov (United States)

    Horii, Takuro; Tamura, Daiki; Morita, Sumiyo; Kimura, Mika; Hatada, Izuho

    2013-09-30

    Genome manipulation of human induced pluripotent stem (iPS) cells is essential to achieve their full potential as tools for regenerative medicine. To date, however, gene targeting in human pluripotent stem cells (hPSCs) has proven to be extremely difficult. Recently, an efficient genome manipulation technology using the RNA-guided DNase Cas9, the clustered regularly interspaced short palindromic repeats (CRISPR) system, has been developed. Here we report the efficient generation of an iPS cell model for immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF) syndrome using the CRISPR system. We obtained iPS cells with mutations in both alleles of DNA methyltransferase 3B (DNMT3B) in 63% of transfected clones. Our data suggest that the CRISPR system is highly efficient and useful for genome engineering of human iPS cells.

  14. XT-ADS Windowless spallation target thermohydraulic design and experimental setup

    Energy Technology Data Exchange (ETDEWEB)

    Class, A.G., E-mail: andreas.class@kit.edu [KIT, Kaiserstrasse 12, D-76131 Karlsruhe (Germany); Angeli, D. [AAA, Advanced Accelerator Applications, 20 Rue Diesel, 06130 Saint-Genis-Poully (France); Batta, A. [KIT, Kaiserstrasse 12, D-76131 Karlsruhe (Germany); Dierckx, M. [SCK-CEN, Boeretang 200, B-2400 Mol (Belgium); Fellmoser, F. [KIT, Kaiserstrasse 12, D-76131 Karlsruhe (Germany); Moreau, V. [CRS4, Polaris Edificio 1, 09010 Pula, CA (Italy); Roelofs, F. [NRG Petten, Westerduinweg 3, P.O. Box 25, NL-1755 ZG Petten (Netherlands); Schuurmans, P.; Van Tichelen, K. [SCK-CEN, Boeretang 200, B-2400 Mol (Belgium); Wetzel, T. [KIT, Kaiserstrasse 12, D-76131 Karlsruhe (Germany)

    2011-08-31

    The objective of the European 6th framework Integrated Project (IP) EUROTRANS (EUROpean Research Programme for the TRANSmutation of High Level Nuclear Waste in an Accelerator Driven System) is to demonstrate the feasibility of transmutation of high level nuclear waste using subcritical Accelerator Driven Systems (ADS). The spallation target represents the most challenging new component in an ADS since it is the component coupling the accelerator and the nuclear core and is subjected to very high thermal load in a high radiation field. In this document the thermal hydraulic activities which led to reliable design rules for a windowless target are presented and the status of the heavy liquid metal target mock-up experiment at the KArlsruhe Liquid metal LAboratory (KALLA) are reported.

  15. Critical Density Target Design for Ion Acceleration on the T-Cubed Laser

    Science.gov (United States)

    Kordell, Peter; Campbell, Paul; Maksimchuk, Anatoly; Willingale, Louise; Krushelnick, Karl

    2016-10-01

    The interaction of an intense laser pulse with a critical density target can form a high Mach number electrostatic shock. Recent experiments on CO2 lasers have demonstrated that such shocks can be used to produce directional, quasi-monoenergetic proton beams. PIC simulations indicate that the our single pulse system, the T-Cubed laser (1.053 μm, 6J in 400fs), is both capable of both producing these shocks and accelerating protons to MeV energies. Shock formation and propagation with our system has challenging target peak density and density gradient requirements. We present our target design, an interferometric characterization of its density profile and preliminary experiments on T-Cubed.

  16. Developing an integrated biomedical and behavioural theory of functioning and disability: adding models of behaviour to the ICF framework.

    Science.gov (United States)

    Johnston, Marie; Dixon, Diane

    2014-01-01

    The International Classification of Functioning Disability and Health (ICF) offers an agreed language on which a scientific model of functional outcomes can be built. The ICF defines functional outcomes as activity and activity limitations (AL) and defines both in behavioural terms. The ICF, therefore, appears to invite explanations of AL as behaviours. Studies of AL find that psychological variables, especially perceptions of control, add to biomedical variables in predicting AL. Therefore, two improved models are proposed, which integrate the ICF with two psychological theories, the theory of planned behaviour (TPB) and social cognitive theory (SCT). These models have a sound evidence base as good predictors of behaviour, include perceived control constructs and are compatible with existing evidence about AL. When directly tested in studies of community and clinic-based populations, both integrated models (ICF/TPB and ICF/SCT) outperform each of the three basic models (ICF, TPB and SCT). However, when predicting activity rather than AL, the biomedical model of the ICF does not improve prediction of activity by TPB and SCT on their own. It is concluded that these models offer a better explanation of functional outcomes than the ICF alone and could form the basis for the development of improved models.

  17. Computational and Pharmacological Target of Neurovascular Unit for Drug Design and Delivery

    Directory of Open Access Journals (Sweden)

    Md. Mirazul Islam

    2015-01-01

    Full Text Available The blood-brain barrier (BBB is a dynamic and highly selective permeable interface between central nervous system (CNS and periphery that regulates the brain homeostasis. Increasing evidences of neurological disorders and restricted drug delivery process in brain make BBB as special target for further study. At present, neurovascular unit (NVU is a great interest and highlighted topic of pharmaceutical companies for CNS drug design and delivery approaches. Some recent advancement of pharmacology and computational biology makes it convenient to develop drugs within limited time and affordable cost. In this review, we briefly introduce current understanding of the NVU, including molecular and cellular composition, physiology, and regulatory function. We also discuss the recent technology and interaction of pharmacogenomics and bioinformatics for drug design and step towards personalized medicine. Additionally, we develop gene network due to understand NVU associated transporter proteins interactions that might be effective for understanding aetiology of neurological disorders and new target base protective therapies development and delivery.

  18. Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site.

    Science.gov (United States)

    Kanekiyo, Masaru; Bu, Wei; Joyce, M Gordon; Meng, Geng; Whittle, James R R; Baxa, Ulrich; Yamamoto, Takuya; Narpala, Sandeep; Todd, John-Paul; Rao, Srinivas S; McDermott, Adrian B; Koup, Richard A; Rossmann, Michael G; Mascola, John R; Graham, Barney S; Cohen, Jeffrey I; Nabel, Gary J

    2015-08-27

    Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and ∼200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The structurally designed nanoparticle vaccine increased neutralization 10- to 100-fold compared to soluble gp350 by targeting a functionally conserved site of vulnerability, improving vaccine-induced protection in a mouse model. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by arrayed presentation of a conserved viral entry domain, a strategy that can be applied to other viruses.

  19. Computational and Pharmacological Target of Neurovascular Unit for Drug Design and Delivery.

    Science.gov (United States)

    Islam, Md Mirazul; Mohamed, Zahurin

    2015-01-01

    The blood-brain barrier (BBB) is a dynamic and highly selective permeable interface between central nervous system (CNS) and periphery that regulates the brain homeostasis. Increasing evidences of neurological disorders and restricted drug delivery process in brain make BBB as special target for further study. At present, neurovascular unit (NVU) is a great interest and highlighted topic of pharmaceutical companies for CNS drug design and delivery approaches. Some recent advancement of pharmacology and computational biology makes it convenient to develop drugs within limited time and affordable cost. In this review, we briefly introduce current understanding of the NVU, including molecular and cellular composition, physiology, and regulatory function. We also discuss the recent technology and interaction of pharmacogenomics and bioinformatics for drug design and step towards personalized medicine. Additionally, we develop gene network due to understand NVU associated transporter proteins interactions that might be effective for understanding aetiology of neurological disorders and new target base protective therapies development and delivery.

  20. Design, manufacture and testing of the IFMIF lithium target bayonet concept

    Energy Technology Data Exchange (ETDEWEB)

    Micciche, G. [ENEA CR Brasimone, via bacino del Brasimone, I-40035 Camugnano, Bo (Italy)]. E-mail: gioacchino.micciche@brasimone.enea.it; Riccardi, B. [Associazione EURATOM ENEA sulla Fusione, I-00044 Frascati, Rome (Italy)

    2005-11-15

    In the frame of the IFMIF R and D activities program a prototype of a replaceable backplate, based on the so called ' bayonet concept', has been developed, manufactured and tested. This concept allows the backplate replacement inside the target assembly while working laterally to the target, using a set of dedicated devices. The prototype design utilises an innovative closing and tightening system. The feasibility of the bayonet concept has been assessed and the remote handling trials carried out during 2003 have successfully demonstrated the maintainability requirements and procedures specification. This paper focuses on the design and manufacturing of the bayonet concept prototype and on the related remote handling trials carried out. The overall results of the activities are also reported.

  1. Generalization of a targeted library design protocol: application to 5-HT7 receptor ligands.

    Science.gov (United States)

    Nordling, Erik; Homan, Evert

    2004-01-01

    Herein a general concept for the design of targeted libraries for proteins with binding sites that are divided into subsites is laid out, including several practical aspects and their solutions. The design is based on a chemogenomic classification of the subsites followed by collection of bioactive molecular fragments and virtual library generation. The general process is outlined and applied to the assembly of a library of 500 molecules targeting the serotonin type 7 (5-HT7) receptor, a class A G-Protein Coupled Receptor (GPCR). Utilizing commercially available building blocks of similar size and composition, a reference library was created. Control sets of known ligands for the 5-HT7 receptor, other GPCRs, and nuclear receptors were collected from literature sources. Principal component analysis of molecular descriptors for the two libraries and the literature sets, displayed a focusing of the targeted library to the region in the chemical space defined by the literature actives, suggesting a denser coverage of the bioactive region than for the more diverse reference library. Additional computational validations, including PCA class predictions, 3D pharmacophore modeling, and docking calculations all indicated an enrichment factor of 5-HT7 ligand-like molecules in the range of 2-4 for the targeted library compared to the reference library.

  2. Recent Developments in the VISRAD 3-D Target Design and Radiation Simulation Code

    Science.gov (United States)

    Macfarlane, Joseph; Woodruff, P.; Golovkin, I.

    2011-10-01

    The 3-D view factor code VISRAD is widely used in designing HEDP experiments at major laser and pulsed-power facilities, including NIF, OMEGA, OMEGA-EP, ORION, Z, and PLX. It simulates target designs by generating a 3-D grid of surface elements, utilizing a variety of 3-D primitives and surface removal algorithms, and can be used to compute the radiation flux throughout the surface element grid by computing element-to-element view factors and solving power balance equations. Target set-up and beam pointing are facilitated by allowing users to specify positions and angular orientations using a variety of coordinates systems (e . g . , that of any laser beam, target component, or diagnostic port). Analytic modeling for laser beam spatial profiles for OMEGA DPPs and NIF CPPs is used to compute laser intensity profiles throughout the grid of surface elements. VISRAD includes a variety of user-friendly graphics for setting up targets and displaying results, can readily display views from any point in space, and can be used to generate image sequences for animations. We will discuss recent improvements to the software package and plans for future developments.

  3. Design of Student Information Management Database Application System for Office and Departmental Target Responsibility System

    Science.gov (United States)

    Zhou, Hui

    It is the inevitable outcome of higher education reform to carry out office and departmental target responsibility system, in which statistical processing of student's information is an important part of student's performance review. On the basis of the analysis of the student's evaluation, the student information management database application system is designed by using relational database management system software in this paper. In order to implement the function of student information management, the functional requirement, overall structure, data sheets and fields, data sheet Association and software codes are designed in details.

  4. New tuberculostatic agents targeting nucleic acid biosynthesis: drug design using QSAR approaches.

    Science.gov (United States)

    Bueno, Renata V; Braga, Rodolpho C; Segretti, Natanael D; Ferreira, Elizabeth I; Trossini, Gustavo H G; Andrade, Carolina H

    2014-01-01

    Worldwide, tuberculosis (TB) is the leading cause of death among curable infectious diseases. The emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) TB is a growing global health concern and there is an urgent need for new anti-TB drugs. Enzymes involved in DNA and ATP biosynthesis are potential targets for tuberculostatic drug design, since these enzymes are essential for Mycobacterium tuberculosis growth. This review presents the current progress and applications of structure-activity relationship analysis for the discovery of innovative tuberculostatic agents as inhibitors of ribonucleotide reductase, DNA gyrase, ATP synthase, and thymidylate kinase enzymes, highlighting present challenges and new opportunities in TB drug design.

  5. Optimal marker-strategy clinical trial design to detect predictive markers for targeted therapy.

    Science.gov (United States)

    Zang, Yong; Liu, Suyu; Yuan, Ying

    2016-07-01

    In developing targeted therapy, the marker-strategy design (MSD) provides an important approach to evaluate the predictive marker effect. This design first randomizes patients into non-marker-based or marker-based strategies. Patients allocated to the non-marker-based strategy are then further randomized to receive either the standard or targeted treatments, while patients allocated to the marker-based strategy receive treatments based on their marker statuses. Little research has been done on the statistical properties of the MSD, which has led to some widespread misconceptions and placed clinical researchers at high risk of using inefficient designs. In this article, we show that the commonly used between-strategy comparison has low power to detect the predictive effect and is valid only under a restrictive condition that the randomization ratio within the non-marker-based strategy matches the marker prevalence. We propose a Wald test that is generally valid and also uniformly more powerful than the between-strategy comparison. Based on that, we derive an optimal MSD that maximizes the power to detect the predictive marker effect by choosing the optimal randomization ratios between the two strategies and treatments. Our numerical study shows that using the proposed optimal designs can substantially improve the power of the MSD to detect the predictive marker effect. We use a lung cancer trial to illustrate the proposed optimal designs.

  6. Inverse Design of Low-Boom Supersonic Concepts Using Reversed Equivalent-Area Targets

    Science.gov (United States)

    Li, Wu; Rallabhand, Sriam

    2011-01-01

    A promising path for developing a low-boom configuration is a multifidelity approach that (1) starts from a low-fidelity low-boom design, (2) refines the low-fidelity design with computational fluid dynamics (CFD) equivalent-area (Ae) analysis, and (3) improves the design with sonic-boom analysis by using CFD off-body pressure distributions. The focus of this paper is on the third step of this approach, in which the design is improved with sonic-boom analysis through the use of CFD calculations. A new inverse design process for off-body pressure tailoring is formulated and demonstrated with a low-boom supersonic configuration that was developed by using the mixed-fidelity design method with CFD Ae analysis. The new inverse design process uses the reverse propagation of the pressure distribution (dp/p) from a mid-field location to a near-field location, converts the near-field dp/p into an equivalent-area distribution, generates a low-boom target for the reversed equivalent area (Ae,r) of the configuration, and modifies the configuration to minimize the differences between the configuration s Ae,r and the low-boom target. The new inverse design process is used to modify a supersonic demonstrator concept for a cruise Mach number of 1.6 and a cruise weight of 30,000 lb. The modified configuration has a fully shaped ground signature that has a perceived loudness (PLdB) value of 78.5, while the original configuration has a partially shaped aft signature with a PLdB of 82.3.

  7. Fuel Cavity Asymmetry at the Onset of Deceleration in ICF

    Science.gov (United States)

    Shah, Rahul C.; Wysocki, F. J.; Glebov, V.; Hakel, P.; Joshi, T.; Kagan, G.; Mancini, R. C.; Murphy, T. J.; Stoeckl, C.; Yaakobi, B.; Benage, J. F.

    2014-10-01

    In ICF, the impact on symmetry of low mode drive non-uniformity is amplified by high convergence. Measurements have shown low mode areal density variation, however, direct impact of low modes on fuel volume has remained undemonstrated. We suggest our images provide first evidence of symmetry loss at the fuel-shell interface. The experiments use direct-drive spherical implosions (Omega). The inner 100 nm layer of the plastic shell is doped with diagnostic Ti to obtain information about interface position, temperature and density. Measurement is made at onset of deceleration at which time nuclear yield rate (NTD) and time resolved (SSCA) spectrum both are in agreement with 1-D prediction. Spectrally resolved images are obtained using the Multiple Monochromatic Imager, which combines a pinhole array with x-ray dispersive mirror and gated detector. Angle averaging of the limb-brightened image data also shows agreement with the 1D calculation. However, the 2D image shows ~20% brightness variations over modes 2-10. These modulations are discussed in context of predicted variations of interface position.

  8. 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

  9. Standardized reporting of functioning information on ICF--based common metrics.

    Science.gov (United States)

    Prodinger, Birgit; Tennant, Alan; Stucki, Gerold

    2017-05-23

    In clinical practice and research a variety of clinical data collection tools are used to collect information on people's functioning for clinical practise and research and National Health Information Systems. Reporting on ICF-based common metrics enables standardized documentation of functioning information in national health information systems. The objective of this methodological note on applying the ICF in rehabilitation is to demonstrate how to report functioning information collected with a data collection tool on ICF-based common metrics. We first specify the requirements for the standardized reporting of functioning information. Secondly, we introduce the methods needed for transforming functioning data to ICF-based common metrics. Finally, we provide an example. The requirements for standardized reporting are as follows: 1) having a common conceptual framework to enable content comparability between any health information; and 2) a measurement framework so that scores between two or more clinical data collection tools can be directly compared. The methods needed to achieve these requirements are the ICF Linking Rules and the Rasch Measurement Model. Using data collected incorporating the 36- item Short Form Health Survey (SF-36), the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0), and the Stroke Impact Scale 3.0 (SIS 3.0), the application of the standardized reporting based on common metrics is demonstrated. A subset of items from the three tools linked to common chapters of the ICF (d4 Mobility, d5 Self-care and d6 Domestic life), were entered as 'super items' into the Rasch model. Good fit was achieved with no residual local dependency and a unidimensional metric. A transformation table allows for comparison between scales, and between a scale and the reporting common metric. Being able to report functioning information collected with commonly used clinical data collection tools with ICF-based common metrics enables clinicians

  10. ICF-based approach to evaluating functionality in cardiac rehabilitation patients after heart surgery.

    Science.gov (United States)

    Racca, V; Di Rienzo, M; Mazzini, P; Ripamonti, V; Gasti, G; Spezzaferri, R; Modica, M; Ferratini, M

    2015-08-01

    Heart surgery is a frequent reason for admission to in-patient cardiac rehabilitation programmes. ICF approach has never been used to evaluate cardiac patients after major heart surgery. The aim was to evaluate and measure functionality in cardiac patients who have undergone heart surgery, using for the first time the ICF-based approach and to assess whether such approach can be feasible and useful in cardiac rehabilitation. Observational study. In-patients cardiac Rehabilitation Unit in Milan. Fifty consecutively admitted patients who had undergone heart surgery (34 males, 16 females; mean age 65.7±12.5 years). We prepared a ICF-core set short enough to be feasible and practical. Patients were individually interviewed by different healthcare professionals (randomly selected from a group of two physicians, two physiotherapists and two psychologists) at the beginning (T1) and end of cardiac rehabilitation (T2) RESULTS: The sum of the scores of each ICF body function, body structure, activity and participation code significantly decreased between T1 and T2 (PICF body function scores and Barthel's index (ρ=0.381; P=0.006), NYHA class (ρ=0.404; P=0.004) and plasma Cr-P levels (r=0.31; P=0.03), between the ICF body structure codes and the Conley scale (ρ=0.306; P=0.02), and between the activity/participation codes and SpO2 (ρ=0.319; P=0.04). There were no correlations between the ICF environmental codes and clinical parameters. The ICF-based data provided functional information that was consistent with the patients' clinical course. The core set used allowed to quantify important body functions and activities, including some areas that are generally insufficiently considered by healthcare professionals during cardiac rehabilitation, and document their improvement.

  11. Contribution to modelization and simulation of the ablative-like Rayleigh-Taylor instabilities for ICF; Contribution a la modelisation et a la simulation des instabilites de type Rayleigh-Taylor ablatif pour la FCI

    Energy Technology Data Exchange (ETDEWEB)

    Egly, H

    2007-10-15

    This thesis deals with the dynamics of accelerated ablative front spreading in Inertial Confinement Fusion experiments. ICF is designed for the implosion of a deuterium-tritium spherical target. The outer shell, the ablator, is irradiated providing a high level pressure inside the target. During this first stage, the ablation front propagating inwards is perturbed by hydrodynamics instabilities, which can prevent the fusion reaction in the decelerated stage. We propose here a study on Rayleigh-Taylor instabilities during ablation process, in the two dimensional case. In order to obtain a numerical solution, we perform an asymptotic analysis in the limit of a high temperature ratio, between the remaining cold ablator and the hot ablated plasma. This study is divided in two steps. First, the thermo-diffusive part of the set of equations is approximated by a Hele-Shaw model, which is then perturbed by the hydrodynamics part. Using a vortex method, we have to solve the advection of a vortical sheet moving with the ablation front. We compute the numerical solution on an Eulerian mesh coupled with a marker method. The thermal part is computed by implementing the Fat Boundary Method, recently developed. The hydrodynamic part is obtained from a Finite Volume scheme. (author)

  12. Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma.

    Science.gov (United States)

    Cardenas, Mariano G; Yu, Wenbo; Beguelin, Wendy; Teater, Matthew R; Geng, Huimin; Goldstein, Rebecca L; Oswald, Erin; Hatzi, Katerina; Yang, Shao-Ning; Cohen, Joanna; Shaknovich, Rita; Vanommeslaeghe, Kenno; Cheng, Huimin; Liang, Dongdong; Cho, Hyo Je; Abbott, Joshua; Tam, Wayne; Du, Wei; Leonard, John P; Elemento, Olivier; Cerchietti, Leandro; Cierpicki, Tomasz; Xue, Fengtian; MacKerell, Alexander D; Melnick, Ari M

    2016-09-01

    Diffuse large B cell lymphomas (DLBCLs) arise from proliferating B cells transiting different stages of the germinal center reaction. In activated B cell DLBCLs (ABC-DLBCLs), a class of DLBCLs that respond poorly to current therapies, chromosomal translocations and amplification lead to constitutive expression of the B cell lymphoma 6 (BCL6) oncogene. The role of BCL6 in maintaining these lymphomas has not been investigated. Here, we designed small-molecule inhibitors that display higher affinity for BCL6 than its endogenous corepressor ligands to evaluate their therapeutic efficacy for targeting ABC-DLBCL. We used an in silico drug design functional-group mapping approach called SILCS to create a specific BCL6 inhibitor called FX1 that has 10-fold greater potency than endogenous corepressors and binds an essential region of the BCL6 lateral groove. FX1 disrupted formation of the BCL6 repression complex, reactivated BCL6 target genes, and mimicked the phenotype of mice engineered to express BCL6 with corepressor binding site mutations. Low doses of FX1 induced regression of established tumors in mice bearing DLBCL xenografts. Furthermore, FX1 suppressed ABC-DLBCL cells in vitro and in vivo, as well as primary human ABC-DLBCL specimens ex vivo. These findings indicate that ABC-DLBCL is a BCL6-dependent disease that can be targeted by rationally designed inhibitors that exceed the binding affinity of natural BCL6 ligands.

  13. Design and Implementation of a Fibre Channel Target Driver Supporting SCSI

    Institute of Scientific and Technical Information of China (English)

    WU Hao; SHU Jiwu; WEN Dongchan; ZHENG Weimin

    2005-01-01

    Fibre channel storage area networks (FC-SAN) are effective solutions to address storage management problems caused by very large volumes of data. But the expense of fibre channel devices limits FC-SAN applications. The use of IP networks instead of fibre channel networks will reduce SAN cost, but will also reduce the performance. Therefore, small computer system interface (SCSI) devices were considered to replace FC disks to reduce the SAN cost. A driver for the FC network adapter and the FC target, designed and implemented to support this structure, obeys the SCSI protocol and works in target mode with 200 MB/s bandwidth. The FC target architecture and implementation were compared with the FC initiator. The SCSI command transfer process in the FC layer was described. The performance test results show that the maximum I/O throughput reachs 167 MB/s for read requests and 196 MB/s for write requests (FC bandwidth is 200 MB/s), verifying that the FC target is very efficient. The modularization, efficiency, and low cost of the FC target will enable SAN and fibre channel to be more widely used in applications.

  14. Design of the EURISOL multi-MW target assembly radiation and safety issues

    CERN Document Server

    Felcini, Marta; Kadi, Yacine; Otto, Thomas; Tecchio, L

    2006-01-01

    The multi-MW target proposed for the EURISOL facility will be based on fission of uranium (or thorium) compounds to produce rare isotopes far from stability. A two-step process is used for the isotope production. First, neutrons are generated in a liquid mercury target, irradiated by the 1 GeV proton or deuteron beam, provided by the EURISOL linac driver. Then, the neutrons induce fission in a surrounding assembly of uranium carbide. R&D projects on several aspects of the target assembly are ongoing. Key criteria for the target design are a maximum beam power capability of 4 MW, a remote handling system with minimum downtime and maximum reliability, as well as radiation safety, minimization of hazards and the classification of the facility. In the framework of the ongoing radiation characterization and safety studies, radiation transport simulations have been performed to calculate the prompt radiation dose in the target and surrounding materials, as well as to determine shielding material and angle-depen...

  15. Design of the EURISOL multi-MW target assembly: radiation and safety issues

    CERN Document Server

    Felcini, M; Kadi, Y; Otto, T; Tecchio, L; Otto, Th.

    2006-01-01

    The multi-MW target proposed for the EURISOL facility will be based on fission of uranium (or thorium) compounds to produce rare isotopes far from stability. A two-step process is used for the isotope production. First, neutrons are generated in a liquid mercury target, irradiated by the 1 GeV proton or deuteron beam, provided by the EURISOL linac driver. Then, the neutrons induce fission in a surrounding assembly of uranium carbide. R&D projects on several aspects of the target assembly are ongoing. Key criteria for the target design are a maximum beam power capability of 4 MW, a remote handling system with minimum downtime and maximum reliability, as well as radiation safety, minimization of hazards and the classification of the facility. In the framework of the ongoing radiation characterization and safety studies, radiation transport simulations have been performed to calculate the prompt radiation dose in the target and surrounding materials, as well as to determine shielding material and angle-depen...

  16. Surrogate models for identifying robust, high yield regions of parameter space for ICF implosion simulations

    Science.gov (United States)

    Humbird, Kelli; Peterson, J. Luc; Brandon, Scott; Field, John; Nora, Ryan; Spears, Brian

    2016-10-01

    Next-generation supercomputer architecture and in-transit data analysis have been used to create a large collection of 2-D ICF capsule implosion simulations. The database includes metrics for approximately 60,000 implosions, with x-ray images and detailed physics parameters available for over 20,000 simulations. To map and explore this large database, surrogate models for numerous quantities of interest are built using supervised machine learning algorithms. Response surfaces constructed using the predictive capabilities of the surrogates allow for continuous exploration of parameter space without requiring additional simulations. High performing regions of the input space are identified to guide the design of future experiments. In particular, a model for the yield built using a random forest regression algorithm has a cross validation score of 94.3% and is consistently conservative for high yield predictions. The model is used to search for robust volumes of parameter space where high yields are expected, even given variations in other input parameters. Surrogates for additional quantities of interest relevant to ignition are used to further characterize the high yield regions. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344, Lawrence Livermore National Security, LLC. LLNL-ABS-697277.

  17. Risk-Targeted versus Current Seismic Design Maps for the Conterminous United States

    Science.gov (United States)

    Luco, Nicolas; Ellingwood, Bruce R.; Hamburger, Ronald O.; Hooper, John D.; Kimball, Jeffrey K.; Kircher, Charles A.

    2007-01-01

    The probabilistic portions of the seismic design maps in the NEHRP Provisions (FEMA, 2003/2000/1997), and in the International Building Code (ICC, 2006/2003/2000) and ASCE Standard 7-05 (ASCE, 2005a), provide ground motion values from the USGS that have a 2% probability of being exceeded in 50 years. Under the assumption that the capacity against collapse of structures designed for these "uniformhazard" ground motions is equal to, without uncertainty, the corresponding mapped value at the location of the structure, the probability of its collapse in 50 years is also uniform. This is not the case however, when it is recognized that there is, in fact, uncertainty in the structural capacity. In that case, siteto-site variability in the shape of ground motion hazard curves results in a lack of uniformity. This paper explains the basis for proposed adjustments to the uniform-hazard portions of the seismic design maps currently in the NEHRP Provisions that result in uniform estimated collapse probability. For seismic design of nuclear facilities, analogous but specialized adjustments have recently been defined in ASCE Standard 43-05 (ASCE, 2005b). In support of the 2009 update of the NEHRP Provisions currently being conducted by the Building Seismic Safety Council (BSSC), herein we provide examples of the adjusted ground motions for a selected target collapse probability (or target risk). Relative to the probabilistic MCE ground motions currently in the NEHRP Provisions, the risk-targeted ground motions for design are smaller (by as much as about 30%) in the New Madrid Seismic Zone, near Charleston, South Carolina, and in the coastal region of Oregon, with relatively little (<15%) change almost everywhere else in the conterminous U.S.

  18. Rationally designed small molecules targeting the RNA that causes myotonic dystrophy type 1 are potently bioactive.

    Science.gov (United States)

    Childs-Disney, Jessica L; Hoskins, Jason; Rzuczek, Suzanne G; Thornton, Charles A; Disney, Matthew D

    2012-05-18

    RNA is an important drug target, but it is difficult to design or discover small molecules that modulate RNA function. In the present study, we report that rationally designed, modularly assembled small molecules that bind the RNA that causes myotonic dystrophy type 1 (DM1) are potently bioactive in cell culture models. DM1 is caused when an expansion of r(CUG) repeats, or r(CUG)(exp), is present in the 3' untranslated region (UTR) of the dystrophia myotonica protein kinase (DMPK) mRNA. r(CUG)(exp) folds into a hairpin with regularly repeating 5'CUG/3'GUC motifs and sequesters muscleblind-like 1 protein (MBNL1). A variety of defects are associated with DM1, including (i) formation of nuclear foci, (ii) decreased translation of DMPK mRNA due to its nuclear retention, and (iii) pre-mRNA splicing defects due to inactivation of MBNL1, which controls the alternative splicing of various pre-mRNAs. Previously, modularly assembled ligands targeting r(CUG)(exp) were designed using information in an RNA motif-ligand database. These studies showed that a bis-benzimidazole (H) binds the 5'CUG/3'GUC motif in r(CUG)(exp.) Therefore, we designed multivalent ligands to bind simultaneously multiple copies of this motif in r(CUG)(exp). Herein, we report that the designed compounds improve DM1-associated defects including improvement of translational and pre-mRNA splicing defects and the disruption of nuclear foci. These studies may establish a foundation to exploit other RNA targets in genomic sequence.

  19. Inertial confinement fusion target component fabrication and technology development support: Annual report, October 1, 1997--September 30, 1998

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, J. [ed.

    1998-12-01

    During this period, General Atomics (GA) and their partner Schafer Corporation were assigned 17 formal tasks in support of the Inertial Confinement Fusion (ICF) program and its five laboratories. A portion of the effort on these tasks included providing direct ``On-site Support`` at Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), and Sandia National Laboratory Albuquerque (SNLA). They fabricated and delivered over 1,200 hohlraum mandrels and numerous other micromachined components to LLNL, LANL, and SNLA. They produced more than 1,300 glass and plastic target capsules for LLNL, LANL, SNLA, and the University of Rochester/Laboratory for Laser Energetics (UR/LLE). They also delivered nearly 2,000 various target foils and films for Naval Research Lab (NRL) and UR/LLE in FY98. This report describes these target fabrication activities and the target fabrication and characterization development activities that made the deliveries possible. During FY98, great progress was made by the GA/Schafer-UR/LLE-LANL team in the design, procurement, installation, and testing of the OMEGA Cryogenic Target System (OCTS) that will field cryogenic targets on OMEGA. The design phase was concluded for all components of the OCTS and all major components were procured and nearly all were fabricated. Many of the components were assembled and tested, and some have been shipped to UR/LLE. The ICF program is anticipating experiments at the OMEGA laser and the National Ignition Facility (NIF) which will require targets containing cryogenic layered D{sub 2} or deuterium-tritium (DT) fuel. They are part of the National Cryogenic Target Program and support experiments at LLNL and LANL to generate and characterize cryogenic layers for these targets. They also contributed cryogenic support and developed concepts for NIF cryogenic targets. This report summarizes and documents the technical progress made on these tasks.

  20. Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets

    Science.gov (United States)

    Clinton, Tracy R; Weinstock, Matthew T; Jacobsen, Michael T; Szabo-Fresnais, Nicolas; Pandya, Maya J; Whitby, Frank G; Herbert, Andrew S; Prugar, Laura I; McKinnon, Rena; Hill, Christopher P; Welch, Brett D; Dye, John M; Eckert, Debra M; Kay, Michael S

    2015-01-01

    Ebolaviruses are highly lethal filoviruses that cause hemorrhagic fever in humans and nonhuman primates. With no approved treatments or preventatives, the development of an anti-ebolavirus therapy to protect against natural infections and potential weaponization is an urgent global health need. Here, we describe the design, biophysical characterization, and validation of peptide mimics of the ebolavirus N-trimer, a highly conserved region of the GP2 fusion protein, to be used as targets to develop broad-spectrum inhibitors of ebolavirus entry. The N-trimer region of GP2 is 90% identical across all ebolavirus species and forms a critical part of the prehairpin intermediate that is exposed during viral entry. Specifically, we fused designed coiled coils to the N-trimer to present it as a soluble trimeric coiled coil as it appears during membrane fusion. Circular dichroism, sedimentation equilibrium, and X-ray crystallography analyses reveal the helical, trimeric structure of the designed N-trimer mimic targets. Surface plasmon resonance studies validate that the N-trimer mimic binds its native ligand, the C-peptide region of GP2. The longest N-trimer mimic also inhibits virus entry, thereby confirming binding of the C-peptide region during viral entry and the presence of a vulnerable prehairpin intermediate. Using phage display as a model system, we validate the suitability of the N-trimer mimics as drug screening targets. Finally, we describe the foundational work to use the N-trimer mimics as targets in mirror-image phage display, which will be used to identify d-peptide inhibitors of ebolavirus entry. PMID:25287718

  1. One-megajoule, wetted-foam target-design performance for the National Ignition Facilitya)

    Science.gov (United States)

    Collins, T. J. B.; Marozas, J. A.; Betti, R.; Harding, D. R.; McKenty, P. W.; Radha, P. B.; Skupsky, S.; Goncharov, V. N.; Knauer, J. P.; McCrory, R. L.

    2007-05-01

    Wetted-foam, direct-drive target designs are a path to high-gain experiments on the National Ignition Facility (NIF) [J. Paisner et al., Laser Focus World 30, 75 (1994)]. Wetted-foam designs [S. Skupsky et al., in Inertial Fusion Sciences and Applications 2001, edited by K. Tanaka, D. D. Meyerhofer, and J. Meyer-ter-Vehn (Elsevier, Paris, 2002)] take advantage of the increased laser absorption provided by the higher-atomic-number elements in a target ablator composed of plastic foam saturated with deuterium-tritium (DT). The increased laser coupling allows more fuel to be driven with the same incident laser energy, resulting in increased hydrodynamic stability and target gain. A stability analysis of a 1-MJ design was performed using the two-dimensional hydrodynamic code DRACO [P. B. Radha et al., Phys. Plasmas 12, 032702 (2005)]. Simulations examining the effect of the expected levels of laser nonuniformities (single-beam and multiple-beam) and target nonuniformities (surface and ice roughness) have been performed. A nonuniformity-budget analysis has been constructed and suggests that two-dimensional (2D) smoothing by spectral dispersion (SSD) [S. Skupsky et al., J. Appl. Phys. 66, 3456 (1989)] is needed to reduce single-beam nonuniformities to levels sufficient for ignition to proceed. Two integrated 2D simulations with 0.75-μm initial ice roughness, multiple-beam nonuniformity, surface roughness, and imprint were completed, one with 2D SSD smoothing and one with 1D SSD. The former ignited and produced a gain of 32, while the latter failed to ignite. A third integrated 2D simulation with 1-μm initial ice roughness and an ice power-law spectral index of 1 was also completed and produced a gain of 27.

  2. Validation of the Comprehensive ICF Core Set for Vocational Rehabilitation From the Perspective of Physical Therapists: International Delphi Survey.

    Science.gov (United States)

    Kaech Moll, Veronika M; Escorpizo, Reuben; Portmann Bergamaschi, Ruth; Finger, Monika E

    2016-08-01

    The Comprehensive ICF Core Set for vocational rehabilitation (VR) is a list of essential categories on functioning based on the World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF), which describes a standard for interdisciplinary assessment, documentation, and communication in VR. The aim of this study was to examine the content validity of the Comprehensive ICF Core Set for VR from the perspective of physical therapists. A 3-round email survey was performed using the Delphi method. A convenience sample of international physical therapists working in VR with work experience of ≥2 years were asked to identify aspects they consider as relevant when evaluating or treating clients in VR. Responses were linked to the ICF categories and compared with the Comprehensive ICF Core Set for VR. Sixty-two physical therapists from all 6 WHO world regions responded with 3,917 statements that were subsequently linked to 338 ICF categories. Fifteen (17%) of the 90 categories in the Comprehensive ICF Core Set for VR were confirmed by the physical therapists in the sample. Twenty-two additional ICF categories were identified that were not included in the Comprehensive ICF Core Set for VR. Vocational rehabilitation in physical therapy is not well defined in every country and might have resulted in the small sample size. Therefore, the results cannot be generalized to all physical therapists practicing in VR. The content validity of the ICF Core Set for VR is insufficient from solely a physical therapist perspective. The results of this study could be used to define a physical therapy-specific set of ICF categories to develop and guide physical therapist clinical practice in VR. © 2016 American Physical Therapy Association.

  3. The Parameter Space of Magnetized Target Fusion (aka Magneto-Inertial Fusion)

    Science.gov (United States)

    Lindemuth, Irvin

    2016-10-01

    Magnetized Target Fusion (MTF), aka Magneto-Inertial Fusion (MIF), is an approach to fusion that compresses a preformed, magnetized (but not necessarily magnetically confined) plasma with an imploding liner or pusher. MTF/MIF operates in a density regime in between the eleven orders of magnitude (1011) in density that separate inertial confinement fusion (ICF) from magnetic confinement fusion MCF. Compared to MCF, the higher density, shorter confinement times, and compressional heating as the dominant heating mechanism potentially reduce the impact of magnetic instabilities. Compared to ICF, the magnetically reduced thermal transport and lower density leads to orders-of-magnitude reduction in the difficult-to-achieve areal-density parameter and a significant reduction in required implosion velocity and radial convergence, potentially reducing the deleterious effects of implosion hydrodynamic instabilities. This tutorial presents fundamental analysis and simple time-dependent modeling to show where significant fusion gain might be achieved in the intermediate-density regime. The analysis shows that the fusion design space is potentially a continuum between ICF and MCF but practical considerations limit the space in which ignition might be obtained. Generic time-dependent modeling addresses the key physics requirements and defines ``ball-park'' values needed for target-plasma initial density, temperature, and magnetic field and implosion system size, energy, and velocity. The modeling shows energy gains greater than 30 can potentially be achieved and that high gain may be obtained at low convergence ratios, e.g., less than 15. A non-exhaustive review of past and present MTF/MIF efforts is presented and the renewed interest in MTF/MIF within the US (e.g., ARPA-E's ALPHA program) and abroad is noted.

  4. Preconceptual engineering design for the APT {sup 3}He target/blanket concept

    Energy Technology Data Exchange (ETDEWEB)

    Mensink, D.L. [Babcock & Wilcox Co., Naval Nuclear Fuel Division, P.O. Box 785, Mt. Athos Rd., Lynchburg, Virginia 24505-0785 (United States); Rose, S.C. Jr. [Reactor Design and Analysis, Los Alamos National Laboratory, Los Alamos, New Mexico 87544 (United States)

    1995-01-20

    A preconceptual engineering design has been developed for the {sup 3}He Target/Blanket (T/B) System for the Accelerator Production of Tritium Project. This concept uses an array of pressure tubes containing tungsten rods for the neutron spallation source and {sup 3}He gas contained in a metal tank and blanket tubes as the tritium production material. The engineering design is based on a physics model optimized for efficient tritium production. Principle engineering consideration were: provisions for cooling all materials including the {sup 3}He gas; containment of the gas and radionuclides; remote handling; material compatibility; minimization of {sup 3}He, D{sub 2}O, and activated waste; modularity; and manufacturability. The design provides a basis for estimating the cost to implement the system.

  5. Metabolic engineering of an industrial polyoxin producer for the targeted overproduction of designer nucleoside antibiotics.

    Science.gov (United States)

    Qi, Jianzhao; Liu, Jin; Wan, Dan; Cai, You-Sheng; Wang, Yinghu; Li, Shunying; Wu, Pan; Feng, Xuan; Qiu, Guofu; Yang, Sheng-Ping; Chen, Wenqing; Deng, Zixin

    2015-09-01

    Polyoxin and nikkomycin are naturally occurring peptidyl nucleoside antibiotics with potent antifungal bioactivity. Both exhibit similar structural features, having a nucleoside skeleton and one or two peptidyl moieties. Combining the refactoring of the polyoxin producer Streptomyces aureochromogenes with import of the hydroxypyridylhomothreonine pathway of nikkomycin allows the targeted production of three designer nucleoside antibiotics designated as nikkoxin E, F, and G. These structures were determined by NMR and/or high resolution mass spectrometry. Remarkably, the introduction of an extra copy of the nikS gene encoding an ATP-dependent ligase significantly enhanced the production of the designer antibiotics. Moreover, all three nikkoxins displayed improved bioactivity against several pathogenic fungi as compared with the naturally-occurring antibiotics. These data provide a feasible model for high efficiency generation of nucleoside antibiotics related to polyoxins and nikkomycins in a polyoxin cell factory via synthetic biology strategy.

  6. Rationally designed small molecules that target both the DNA and RNA causing myotonic dystrophy type 1.

    Science.gov (United States)

    Nguyen, Lien; Luu, Long M; Peng, Shaohong; Serrano, Julio F; Chan, H Y Edwin; Zimmerman, Steven C

    2015-11-11

    Single-agent, single-target therapeutic approaches are often limited by a complex disease pathobiology. We report rationally designed, multi-target agents for myotonic dystrophy type 1 (DM1). DM1 originates in an abnormal expansion of CTG repeats (CTG(exp)) in the DMPK gene. The resultant expanded CUG transcript (CUG(exp)) identified as a toxic agent sequesters important proteins, such as muscleblind-like proteins (MBNL), undergoes repeat-associated non-ATG (RAN) translation, and potentially causes microRNA dysregulation. We report rationally designed small molecules that target the DM1 pathobiology in vitro in three distinct ways by acting simultaneously as transcription inhibitors, by inhibiting aberrant protein binding to the toxic RNA, and by acting as RNase mimics to degrade the toxic RNA. In vitro, the agents are shown to (1) bind CTG(exp) and inhibit formation of the CUG(exp) transcript, (2) bind CUG(exp) and inhibit sequestration of MBNL1, and (3) cleave CUG(exp) in an RNase-like manner. The most potent compounds are capable of reducing the levels of CUG(exp) in DM1 model cells, and one reverses two separate CUG(exp)-induced phenotypes in a DM1 Drosophila model.

  7. The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors

    Directory of Open Access Journals (Sweden)

    Wei Lu

    2013-06-01

    Full Text Available Over the years, the development of targeted medicines has made significant achievements. As a typical example, receptor tyrosine kinases (RTK inhibitors have become important chemotherapy drugs for a variety of cancers. However, the effectiveness of these agents is always hindered by poor response rates and acquired drug resistance. In order to overcome these limitations, several dual-targeted inhibitors with quinazoline core were designed and synthesized. Though these compounds can simultaneously inhibit histone deacetylases (HDAC as well as RTK, the structure-activity relationship (SAR is still not clear enough. To further explore this type of dual-targeted inhibitors, a new class of quinazoline derivatives were designed and synthesized. Their activity evaluations include in vitro inhibitory activity of HDAC, epidermal growth factor receptor (EGFR and human epidermal growth factor receptor 2 (HER2. The SAR study indicated that the introduction of polar group such as hydroxamate on the 4-position of the quinazoline core is more likely to provide a potent HDACi/HER2i hybrid rather than HDACi/EGFRi molecule.

  8. Design Optimisation of a High Intensity Beam Facility and Feasibility Experiment of a Solid Fragmented Target

    CERN Document Server

    Charitonidis, Nikolaos; Rivkin, Leonid

    2014-06-13

    The present PhD thesis describes the design, execution and results of the HRMT-10 experiment performed at the HiRadMat facility of the CERN/SPS complex. The first part of the thesis covers the design optimization studies of the HiRadMat facility, focusing in particular on the radiation protection issues. A detailed Monte-Carlo model of the facility has been developed and validated through comparison with measurements. A very satisfactory agreement between the simulation and the experimental data is observed. In the second part of this thesis, a novel feasibility experiment of a fragmented solid target for a future Neutrino Factory or a Super Beam facility, able to support high beam powers ( 1 MW) is presented in detail. A solid granular target has been proposed as an interesting alternative to an open Hg jet target, presently considered as the baseline for such facilities, but posing considerable technical challenges. The HRMT-10 experiment seeks to address the lack of experimental data of the feasibility of...

  9. A Rapid Python-Based Methodology for Target-Focused Combinatorial Library Design.

    Science.gov (United States)

    Li, Shiliang; Song, Yuwei; Liu, Xiaofeng; Li, Honglin

    2016-01-01

    The chemical space is so vast that only a small portion of it has been examined. As a complementary approach to systematically probe the chemical space, virtual combinatorial library design has extended enormous impacts on generating novel and diverse structures for drug discovery. Despite the favorable contributions, high attrition rates in drug development that mainly resulted from lack of efficacy and side effects make it increasingly challenging to discover good chemical starting points. In most cases, focused libraries, which are restricted to particular regions of the chemical space, are deftly exploited to maximize hit rate and improve efficiency at the beginning of the drug discovery and drug development pipeline. This paper presented a valid methodology for fast target-focused combinatorial library design in both reaction-based and production-based ways with the library creating rates of approximately 70,000 molecules per second. Simple, quick and convenient operating procedures are the specific features of the method. SHAFTS, a hybrid 3D similarity calculation software, was embedded to help refine the size of the libraries and improve hit rates. Two target-focused (p38-focused and COX2-focused) libraries were constructed efficiently in this study. This rapid library enumeration method is portable and applicable to any other targets for good chemical starting points identification collaborated with either structure-based or ligand-based virtual screening.

  10. Heritable Targeted Gene Disruption in Zebrafish Using Designed Zinc Finger Nucleases

    Science.gov (United States)

    Doyon, Yannick; McCammon, Jasmine M; Miller, Jeffrey C; Faraji, Farhoud; Ngo, Catherine; Katibah, George E; Amora, Rainier; Hocking, Toby D; Zhang, Lei; Rebar, Edward J; Gregory, Philip D; Urnov, Fyodor D; Amacher, Sharon L

    2009-01-01

    We describe here the use of zinc finger nucleases (ZFNs) for somatic and germline disruption of genes in zebrafish (Danio rerio), where targeted mutagenesis was previously intractable. ZFNs induce a targeted double-strand break in the genome that is repaired to generate small insertions and deletions. We designed ZFNs targeting the zebrafish golden and no tail/Brachyury genes. In both cases, injection of ZFN-encoding mRNA into 1-cell embryos yielded a high percentage of animals carrying distinct mutations at the ZFN-specified position and exhibiting expected loss-of-function phenotypes. Disrupted ntl alleles were transmitted from ZFN mRNA-injected founder animals in over half the adults tested at frequencies averaging 20%. The frequency and precision of gene disruption events observed, in combination with the ability to design ZFNs against any locus, open fundamentally novel avenues of experimentation, and suggest that ZFN technology may be widely applied to many organisms that allow mRNA delivery into the fertilized egg. PMID:18500334

  11. Development of TMTP-1 targeted designer biopolymers for gene delivery to prostate cancer.

    Science.gov (United States)

    McBride, John W; Massey, Ashley S; McCaffrey, J; McCrudden, Cian M; Coulter, Jonathan A; Dunne, Nicholas J; Robson, Tracy; McCarthy, Helen O

    2016-03-16

    Designer biopolymers (DBPs) represent state of the art genetically engineered biomacromolecules designed to condense plasmid DNA, and overcome intra- and extra- cellular barriers to gene delivery. Three DBPs were synthesized, each with the tumor molecular targeting peptide-1 (TMTP-1) motif to specifically target metastases. Each DBP was complexed with a pEGFP-N1 reporter plasmid to permit physiochemical and biological assay analysis. Results indicated that two of the biopolymers (RMHT and RM3GT) effectively condensed pEGFP-N1 into cationic nanoparticles prostate cancer cells. Conversely the anionic RMGT DBP nanoparticles could not transfect PC-3 cells. RMHT and RM3GT nanoparticles were stable in the presence of serum and protected the cargo from degradation. Additionally it was concluded that cell viability could recover post-transfection with these DBPs, which were less toxic than the commercially available transfection reagent Lipofectamine(®) 2000. With both DBPs, a higher transfection efficacy was observed in PC-3 cells than in the moderately metastatic, DU145, and normal, PNT2-C2, cell lines. Blocking of the TMTP-1 receptors inhibited gene transfer indicating internalization via this receptor. In conclusion RMHT and RM3GT are fully functional DBPs that address major obstacles to gene delivery and target metastatic cells expressing the TMTP-1 receptor.

  12. Customizable de novo design strategies for DOCK: Application to HIVgp41 and other therapeutic targets.

    Science.gov (United States)

    Allen, William J; Fochtman, Brian C; Balius, Trent E; Rizzo, Robert C

    2017-09-22

    De novo design can be used to explore vast areas of chemical space in computational lead discovery. As a complement to virtual screening, from-scratch construction of molecules is not limited to compounds in pre-existing vendor catalogs. Here, we present an iterative fragment growth method, integrated into the program DOCK, in which new molecules are built using rules for allowable connections based on known molecules. The method leverages DOCK's advanced scoring and pruning approaches and users can define very specific criteria in terms of properties or features to customize growth toward a particular region of chemical space. The code was validated using three increasingly difficult classes of calculations: (1) Rebuilding known X-ray ligands taken from 663 complexes using only their component parts (focused libraries), (2) construction of new ligands in 57 drug target sites using a library derived from ∼13M drug-like compounds (generic libraries), and (3) application to a challenging protein-protein interface on the viral drug target HIVgp41. The computational testing confirms that the de novo DOCK routines are robust and working as envisioned, and the compelling results highlight the potential utility for designing new molecules against a wide variety of important protein targets. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Conceptual design of the beryllium rotating target for the ESS-Bilbao facility

    Energy Technology Data Exchange (ETDEWEB)

    Terrón, S., E-mail: santiago.terron@essbilbao.org [ESS-Bilbao, Parque Tecnológico Bizkaia, Laida Bidea, Edificio 207 B Planta Baja. 48160 Derio (Spain); Instituto de Fusión Nuclear - UPM, ETS Ingenieros Industriales, C José Gutiérrez Abascal, 2, 28006 Madrid (Spain); Sordo, F.; Magán, M.; Ghiglino, A.; Martínez, F.; Vicente, P.J. de; Vivanco, R. [ESS-Bilbao, Parque Tecnológico Bizkaia, Laida Bidea, Edificio 207 B Planta Baja. 48160 Derio (Spain); Instituto de Fusión Nuclear - UPM, ETS Ingenieros Industriales, C José Gutiérrez Abascal, 2, 28006 Madrid (Spain); Thomsen, K. [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Perlado, J.M. [Instituto de Fusión Nuclear - UPM, ETS Ingenieros Industriales, C José Gutiérrez Abascal, 2, 28006 Madrid (Spain); Bermejo, F.J. [Instituto de Estructura de la Materia, IEM-CSIC, Consejo Superior de Investigaciones Científicas, Serrano 123, 28006 Madrid (Spain); ESS-Bilbao, Parque Tecnológico Bizkaia, Laida Bidea, Edificio 207 B Planta Baja. 48160 Derio (Spain); Abánades, A. [Instituto de Fusión Nuclear - UPM, ETS Ingenieros Industriales, C José Gutiérrez Abascal, 2, 28006 Madrid (Spain)

    2013-10-01

    The ESS-Bilbao facility, hosted by the University of the Basque Country (UPV/EHU), envisages the operation of a high-current proton accelerator delivering beams with energies up to 50 MeV. The time-averaged proton current will be 2.25 mA, delivered by 1.5 ms proton pulses with a repetition rate of 20 Hz. This beam will feed a neutron source based upon the Be (p,n) reaction, which will enable the provision of relevant neutron experimentation capabilities. The neutron source baseline concept consists in a rotating beryllium target cooled by water. The target structure will comprise a rotatable disk made of 6061-T6 aluminium alloy holding 20 beryllium plates. Heat dissipation from the target relies upon a distribution of coolant-flow channels. The practical implementation of such a concept is here described with emphasis put on the beryllium plates thermo-mechanical optimization, the chosen coolant distribution system as well as the mechanical behavior of the assembly. -- Highlights: • The conceptual design of ESS-Bilbao neutron production target has been carried out. • This device is a rotating disk holding Be elements cooled by water. • Thermo-mechanical and lifespan behavior of the Be elements have been analyzed. • Disk structure ensures coolability and a proper mechanical behavior of the assembly.

  14. [siRNAs with high specificity to the target: a systematic design by CRM algorithm].

    Science.gov (United States)

    Alsheddi, T; Vasin, L; Meduri, R; Randhawa, M; Glazko, G; Baranova, A

    2008-01-01

    'Off-target' silencing effect hinders the development of siRNA-based therapeutic and research applications. Common solution to this problem is an employment of the BLAST that may miss significant alignments or an exhaustive Smith-Waterman algorithm that is very time-consuming. We have developed a Comprehensive Redundancy Minimizer (CRM) approach for mapping all unique sequences ("targets") 9-to-15 nt in size within large sets of sequences (e.g. transcriptomes). CRM outputs a list of potential siRNA candidates for every transcript of the particular species. These candidates could be further analyzed by traditional "set-of-rules" types of siRNA designing tools. For human, 91% of transcripts are covered by candidate siRNAs with kernel targets of N = 15. We tested our approach on the collection of previously described experimentally assessed siRNAs and found that the correlation between efficacy and presence in CRM-approved set is significant (r = 0.215, p-value = 0.0001). An interactive database that contains a precompiled set of all human siRNA candidates with minimized redundancy is available at http://129.174.194.243. Application of the CRM-based filtering minimizes potential "off-target" silencing effects and could improve routine siRNA applications.

  15. Ionic Channels as Targets for Drug Design: A Review on Computational Methods

    Directory of Open Access Journals (Sweden)

    José Manuel González-Ros

    2011-12-01

    Full Text Available Ion channels are involved in a broad range of physiological and pathological processes. The implications of ion channels in a variety of diseases, including diabetes, epilepsy, hypertension, cancer and even chronic pain, have signaled them as pivotal drug targets. Thus far, drugs targeting ion channels were developed without detailed knowledge of the molecular interactions between the lead compounds and the target channels. In recent years, however, the emergence of high-resolution structures for a plethora of ion channels paves the way for computer-assisted drug design. Currently, available functional and structural data provide an attractive platform to generate models that combine substrate-based and protein-based approaches. In silico approaches include homology modeling, quantitative structure-activity relationships, virtual ligand screening, similarity and pharmacophore searching, data mining, and data analysis tools. These strategies have been frequently used in the discovery and optimization of novel molecules with enhanced affinity and specificity for the selected therapeutic targets. In this review we summarize recent applications of in silico methods that are being used for the development of ion channel drugs.

  16. Design of functional small interfering RNAs targeting amyotrophic lateral sclerosis-associated mutant alleles

    Institute of Scientific and Technical Information of China (English)

    GENG Chang-ming; DING Hong-liu

    2011-01-01

    Background RNA interference (RNAi) is a potential cure for amyotrophic lateral sclerosis (ALS) caused by dominant,gain-of-function superoxide dismutase 1 (SOD1) mutations. The success of such therapy relies on the functional small interfering RNAs (siRNAs) that can effectively deliver RNAi. This study aimed to design the functional siRNAs targeting ALS-associated mutant alleles.Methods A modified dual luciferase system containing human SOD1 mRNA target was established to quantify siRNA efficacy. Coupled with validated siRNAs identified in the literature, we analyzed the rationale of siRNA design and subsequently developed an asymmetry rule-based strategy for designing siRNA. We then further tested the effectiveness of this design strategy in converting a naturally symmetric siRNA into functional siRNAs with favorable asymmetry for gene silencing of SOD1 alleles.Results The efficacies of siRNAs could vary tremendously by one base-pair position change. Functional siRNAs could target the whole span of SOD1 mRNA coding sequence as well as non-coding region. While there is no distinguishable pattern of the distribution of nucleobases in these validated siRNAs, the high percent of GC count at the last two positions of siRNAs (P18 and P19) indicated a strong effect of asymmetry rule. Introducing a mismatch at position 1 of the 5' of antisense strand of siRNA successfully converted the inactive siRNA into functional siRNAs that silence SOD1 with desired efficacy.Conclusions Asymmetry rule-based strategy that incorporates a mismatch into siRNA most consistently enhances RNAi efficacy and guarantees producing functional siRNAs that successfully silence ALS-associated SOD1 mutant alleles regardless target positions. This strategy could also be useful to design siRNAs for silencing other disease-associated dominant, gain-of-function mutant genes.

  17. Feasibility of the Dutch ICF Activity Inventory: a pilot study

    Directory of Open Access Journals (Sweden)

    van Nispen Ruth MA

    2010-11-01

    Full Text Available Abstract Background Demographic ageing will lead to increasing pressure on visual rehabilitation services, which need to be efficiently organised in the near future. The Dutch ICF Activity Inventory (D-AI was developed to assess the rehabilitation needs of visually impaired persons. This pilot study tests the feasibility of the D-AI using a computer-assisted telephone interview. Methods In addition to the regular intake, the first version of the D-AI was assessed in 20 patients. Subsequently, patients and intake assessors were asked to fill in an evaluation form. Based on these evaluations, a new version of the D-AI was developed. Results Mean administration time of the D-AI was 88.8 (± 41.0 minutes. Overall, patients and assessors were positive about the D-AI assessment. However, professionals and 60% of the patients found the administration time to be too long. All included items were considered relevant and only minor adjustments were recommended. Conclusion The systematic character of the revised D-AI will prevent topics from being overlooked and indicate which needs have the highest priority from a patient-centred perspective. Moreover, ongoing assessment of the D-AI will enhance evaluation of the rehabilitation process. To decrease administration time, in the revised D-AI only the top priority goals will be fully assessed. Using the D-AI, a rehabilitation plan based on individual needs can be developed for each patient. Moreover, it enables better evaluation of the effects of rehabilitation. A larger validation study is planned.

  18. Parametric expressions of tritium flow rates and inventories in a target factory

    Energy Technology Data Exchange (ETDEWEB)

    Sherohman, J.W.

    1980-12-29

    Parametric expressions have been derived for tritium flow rates and inventories in a target factory. The expressions are based on a tritium system that interfaces with a generalized target production process. The relationship of flow rates and inventories to target production form a basis for parametric study to determine the amount of tritium involved in the target factory of an ICF power plant.

  19. Design of a modular protein-based MRI contrast agent for targeted application.

    Directory of Open Access Journals (Sweden)

    Daniel Grum

    Full Text Available Magnetic resonance imaging (MRI offers a non-radioactive alternative for the non-invasive detection of tumours. Low molecular weight MRI contrast agents currently in clinical use suffer either from a lack of specificity for tumour tissue or from low relaxivity and thus low contrast amplification. In this study, we present the newly designed two domain fusion protein Zarvin, which is able to bind to therapeutic IgG antibodies suitable for targeting, while facilitating contrast enhancement through high affinity binding sites for Gd(3+. We show that the Zarvin fold is stable under serum conditions, specifically targets a cancer cell-line when bound to the Cetuximab IgG, and allows for imaging with high relaxivity, a property that would be advantageous for the detection of small tumours and metastases at 1.5 or 3 T.

  20. Design of miniature hybrid target recognition system with combination of FPGA+DSP

    Science.gov (United States)

    Luo, Shishang; Li, Xiujian; Jia, Hui; Hu, Wenhua; Nie, Yongming; Chang, Shengli

    2010-10-01

    With advantages of flexibility, high bandwidth, high spatial resolution and high-speed parallel operation, the opto-electronic hybrid target recognition system can be applied in many civil and military areas, such as video surveillance, intelligent navigation and robot vision. A miniature opto-electronic hybrid target recognition system based on FPGA+DSP is designed, which only employs single Fourier lens and with a focal length. With the precise timing control of the FPGA and images pretreatment of the DSP, the system performs both Fourier transform and inverse Fourier transform with all optical process, which can improve recognition speed and reduce the system volume remarkably. We analyzed the system performance, and a method to achieve scale invariant pattern recognition was proposed on the basis of lots of experiments.

  1. Target Channel Visiting Order Design Using Particle Swarm Optimization for Spectrum Handoff in Cognitive Radio Networks

    Directory of Open Access Journals (Sweden)

    Shilian Zheng

    2014-08-01

    Full Text Available In a dynamic spectrum access network, when a primary user (licensed user reappears on the current channel, cognitive radios (CRs need to vacate the channel and reestablish a communications link on some other channel to avoid interference to primary users, resulting in spectrum handoff. This paper studies the problem of designing target channel visiting order for spectrum handoff to minimize expected spectrum handoff delay. A particle swarm optimization (PSO based algorithm is proposed to solve the problem. Simulation results show that the proposed algorithm performs far better than random target channel visiting scheme. The solutions obtained by PSO are very close to the optimal solution which further validates the effectiveness of the proposed method.

  2. Inertial confinement fusion target component fabrication and technology development support. Annual report, October 1, 1996--September 30, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, J. [ed.

    1998-03-01

    This report documents the technical activities of the period October 1, 1996 through September 30, 1997. During this period, GA and their partner Schafer Corporation were assigned 13 formal tasks in support of the ICF program and its five laboratories. A portion of the effort on these tasks included providing direct {open_quotes}Onsite Support{close_quotes} at Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), and Sandia National Laboratory Albuquerque (SNLA). Over 700 gold-plated hohlraum mandrels were fabricated and delivered to LLNL, LANL and SNLA. More than 1600 glass and plastic target capsules were produced for LLNL, LANL, SNLA and University of Rochester/Laboratory for Laser Energetics (UR/LLE). Nearly 2000 various target foils and films were delivered for Naval Research Lab (NRL) and UR/LLE in FY97. This report describes these target fabrication activities and the target fabrication and characterization development activities that made the deliveries possible. The ICF program is anticipating experiments at the OMEGA laser and the National Ignition Facility (NIF) which will require targets containing cryogenic layered D{sub 2} or deuterium-tritium (DT) fuel. This project is part of the National Cryogenic Target Program and support experiments at LLNL and LANL to generate and characterize cryogenic layers for these targets. During FY97, significant progress was made in the design and component testing of the OMEGA Cryogenic Target System that will field cryogenic targets on OMEGA. This included major design changes, reduction in equipment, and process simplifications. This report summarizes and documents the technical progress made on these tasks.

  3. Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes

    Directory of Open Access Journals (Sweden)

    Shea N. Gardner

    2014-01-01

    Full Text Available Background. Targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. Degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. Results. A tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. The new script, run_tiled_primers, is part of the PriMux software. Primers were designed for each segment of South American hemorrhagic fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus. Each group is highly diverse with as little as 5% genome consensus. Primer sets were computationally checked for nontarget cross reactions against the NCBI nucleotide sequence database. Primers for murine hepatitis virus were demonstrated in the lab to specifically amplify selected genes from a laboratory cultured strain that had undergone extensive passage in vitro and in vivo. Conclusions. This software should help researchers design multiplex sets of primers for targeted whole genome enrichment prior to sequencing to obtain better coverage of low titer, divergent viruses. Applications include viral discovery from a complex background and improved sensitivity and coverage of rapidly evolving strains or variants in a gene family.

  4. Image-based overlay (IBO) target segment design on self-aligned patterning process

    Science.gov (United States)

    Ye, Lei; Hu, Huayong; He, Weiming

    2016-03-01

    Self-Aligned Double Patterning (SADP) is widely applied in advanced sub-4X patterning technology, especially for the 1D resolution shrinkage of memory technology. As the application of SADP makes lithography minimum pitch down to half of design pitch with the remaining spacer aside core, its alignment mark and overlay (OVL) mark have to be well-segmented to ensure enough mark contrast. In this paper, we designed two types of image-based overlay (IBO) bar in bar (BIB) OVL target: bar-segmentation and background-segmentation with different duty ratio. Based on these two designed types of marks, we focus on the OVL of 2nd photo layer to 1st SADP layer with the core removed (which means spacer grating structure remained). We studied the effect of the overlay target segmentation on the precision and robustness of wafer-level overlay performance. Different lithography processes were also studied, including single layer lithography and tri-layer lithography with planarized spacer grating structures. We found there are strong correlations between overlay measurement accuracy and background segmentation rules. The results of our study will be presented and discussed in this paper.

  5. Size Matters: Developing Design Rules to Engineer Nanoparticles for Solid Tumour Targeting

    Science.gov (United States)

    Sykes, Edward Alexander

    Nanotechnology enables the design of highly customizable platforms for producing minimally invasive and programmable strategies for cancer diagnosis and treatment. Advances in this field have demonstrated that nanoparticles can enhance specificity of anti-cancer agents, respond to tumour-specific cues, and direct the visualization of biological targets in vivo. . Nanoparticles can be synthesized within the 1 to 100 nm range to achieve different electromagnetic properties and specifically interact with biological tissues by tuning their size, shape, and surface chemistry. However, it remains unclear which physicochemical parameters are critical for delivering nanomaterials to the tumour site. With less than 5% of administered nanoparticles reaching the tumour, engineering of nanoparticles for effective delivery to solid tumours remains a critical challenge to cancer nanomedicine. A more comprehensive understanding of the interplay between the nanomaterial physicochemical properties and biological systems is necessary to enhance the efficacy of nanoparticle tumour targeting. This thesis explores how nanoparticle size and functionalization with cancer cell specific agents impact nanoparticle delivery to tumours. Furthermore, this doctoral work (i) discusses how tumour structure evolves with growth, (ii) elucidates how such changes modulate nanoparticle accumulation, and (iii) identifies how the skin serves as a significant off-target site for nanoparticle uptake. This thesis also demonstrates the utility of empirically-derived parametric models, Monte Carlo simulations, and decision matrices for mechanistically understanding and predicting the impact of nanomaterial features and tumour biology on nanoparticle fate in vivo. These topics establish key design considerations to tailor nanoparticles for enhanced tumour targeting. Collectively, the concepts presented herein form a fundamental framework for the development of personalized nanomedicine and nano

  6. Design upgrade of the ISOLDE target unit for HIE-ISOLDE

    Energy Technology Data Exchange (ETDEWEB)

    Montaño, J., E-mail: Jacobo.Montano@cern.ch [CERN, ISOLDE, CH-1211 Geneva 23 (Switzerland); Giles, T. [CERN, ISOLDE, CH-1211 Geneva 23 (Switzerland); Gottberg, A. [CERN, ISOLDE, CH-1211 Geneva 23 (Switzerland); Instituto de Estructura de la Materia, CSIC, 28006 Madrid (Spain)

    2013-12-15

    Highlights: • Requirements for a new target-source system for the radioactive facility HIE-ISOLDE. • For the upgraded facility a higher radiation field will be present. • The new design has to take into account the radiation field of the upgraded facility. -- Abstract: The High Intensity and Energy HIE-ISOLDE project is a major upgrade of the existing ISOLDE and REX-ISOLDE facilities with the objective of increasing the energy and the intensity of the delivered radioactive ion beams (RIB) [1]. In order to accommodate the future increase of primary beam intensity delivered by the new LINAC4 H{sup −} driver to the Proton Synchrotron Booster (PSB) [2] and from this to ISOLDE, a major study is being carried out to upgrade the existing designs of the ISOLDE target and its supporting infrastructure. In particular, the extraction optics plays an important role in the initial beam transport and the quality of the beam supplied to the mass separators. Important factors include the emittance of the beam and the beam profile to avoid beam losses. A new double electrode extraction system has been developed for simplifying and improving the interface between the target unit and the frontend (target coupling table). Numerical and experimental studies have been performed in order to define the new extraction geometry, and the coupling table has been adapted to keep the compatibility. An alternative heating system is under study. An electron bombardment heating system is being developed as an option for avoiding the employment of big cross section cables. The results of these studies and the mechanical models developed are presented and discussed.

  7. Identification of relevant ICF (International Classification of Functioning, Disability and Health) categories in lymphedema patients: A cross-sectional study

    NARCIS (Netherlands)

    Viehoff, P.B.; Potijk, F.; Damstra, R.J.; Heerkens, Y.F.; Ravensberg, C.D. van; Berkel, D.M. van; Neumann, H.A.

    2015-01-01

    BACKGROUND: To describe functioning and health of lymphedema patients and to identify their most common problems using the International Classification of Functioning, Disability and Health (ICF) as part of the preparatory studies for the development of ICF Core Sets for lymphedema. METHODS: Cross-s

  8. Identification of relevant ICF (International Classification of Functioning, Disability and Health) categories in lymphedema patients: A cross-sectional study

    NARCIS (Netherlands)

    P.B. Viehoff (Peter); F. Potijk; R.J. Damstra (Robert); Y.F. Heerkens (Yvonne); C.D. van Ravensberg (Dorine); D.M. Van Berkel; H.A.M. Neumann (Martino)

    2015-01-01

    textabstractBackground. To describe functioning and health of lymphedema patients and to identify their most common problems using the International Classification of Functioning, Disability and Health (ICF) as part of the preparatory studies for the development of ICF Core Sets for lymphedema.Metho

  9. Identification of relevant ICF (International Classification of Functioning, Disability and Health) categories in lymphedema patients: A cross-sectional study

    NARCIS (Netherlands)

    Viehoff, P.B.; Potijk, F.; Damstra, R.J.; Heerkens, Y.F.; Ravensberg, C.D. van; Berkel, D.M. van; Neumann, H.A.

    2015-01-01

    BACKGROUND: To describe functioning and health of lymphedema patients and to identify their most common problems using the International Classification of Functioning, Disability and Health (ICF) as part of the preparatory studies for the development of ICF Core Sets for lymphedema. METHODS:

  10. Identification of relevant ICF (International Classification of Functioning, Disability and Health) categories in lymphedema patients: A cross-sectional study

    NARCIS (Netherlands)

    P.B. Viehoff (Peter); F. Potijk; R.J. Damstra (Robert); Y.F. Heerkens (Yvonne); C.D. van Ravensberg (Dorine); D.M. Van Berkel; H.A.M. Neumann (Martino)

    2015-01-01

    textabstractBackground. To describe functioning and health of lymphedema patients and to identify their most common problems using the International Classification of Functioning, Disability and Health (ICF) as part of the preparatory studies for the development of ICF Core Sets for

  11. Development of ICF Core Sets to standardize assessment of functioning and impairment in ADHD: the path ahead.

    Science.gov (United States)

    Bölte, Sven; de Schipper, Elles; Holtmann, Martin; Karande, Sunil; de Vries, Petrus J; Selb, Melissa; Tannock, Rosemary

    2014-12-01

    In the study of health and quality of life in attention deficit/hyperactivity disorder (ADHD), it is of paramount importance to include assessment of functioning. The International Classification of Functioning, Disability and Health (ICF) provides a comprehensive, universally accepted framework for the description of functioning in relation to health conditions. In this paper, the authors outline the process to develop ICF Core Sets for ADHD. ICF Core Sets are subgroups of ICF categories selected to capture the aspects of functioning that are most likely to be affected in specific disorders. The ICF categories that will be included in the ICF Core Sets for ADHD will be determined at an ICF Core Set Consensus Conference, wherein evidence from four preliminary studies (a systematic review, an expert survey, a patient and caregiver qualitative study, and a clinical cross-sectional study) will be integrated. Comprehensive and Brief ICF Core Sets for ADHD will be developed with the goal of providing useful standards for research and clinical practice, and to generate a common language for the description of functioning in ADHD in different areas of life and across the lifespan.

  12. 42 CFR 442.119 - Duration of denial of payments and subsequent termination of an ICF/MR.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Duration of denial of payments and subsequent termination of an ICF/MR. 442.119 Section 442.119 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... § 442.119 Duration of denial of payments and subsequent termination of an ICF/MR. (a) Period of denial...

  13. Utility of the International Classification of Functioning, Disability and Health (ICF) for educational psychologists’ work

    Science.gov (United States)

    Aljunied, Mariam; Frederickson, Norah

    2014-01-01

    Despite embracing a bio-psycho-social perspective, the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) assessment framework has had limited application to date with children who have special educational needs (SEN). This study examines its utility for educational psychologists’ work with children who have Autism Spectrum Disorders (ASD). Mothers of 40 children with ASD aged eight to 12 years were interviewed using a structured protocol based on the ICF framework. The Diagnostic Interview for Social and Communication Disorder (DISCO) was completed with a subset of 19 mothers. Internal consistency and inter-rater reliability of the interview assessments were found to be acceptable and there was evidence for concurrent and discriminant validity. Despite some limitations, initial support for the utility of the ICF model suggests its potential value across educational, health and care fields. Further consideration of its relevance to educational psychologists in new areas of multi-agency working is warranted. PMID:26157197

  14. [Relevance of personal contextual factors of the ICF for use in practical social medicine and rehabilitation].

    Science.gov (United States)

    Grotkamp, S; Cibis, W; Bahemann, A; Baldus, A; Behrens, J; Nyffeler, I D; Echterhoff, W; Fialka-Moser, V; Fries, W; Fuchs, H; Gmünder, H P; Gutenbrunner, C; Keller, K; Nüchtern, E; Pöthig, D; Queri, S; Rentsch, H P; Rink, M; Schian, H-M; Schian, M; Schmitt, K; Schwarze, M; Ulrich, P; von Mittelstaedt, G; Seger, W

    2014-03-01

    Personal contextual factors play an essential part in the model of the International Classification of Functioning, Disability and Health (ICF). The WHO has not yet classified personal factors for global use although they impact on the functioning of persons positively or negatively. In 2010, the ICF working group of the German Society of Social Medicine and Prevention (DGSMP) presented a proposal for the classification of personal factors into 72 categories previously arranged in 6 chapters. Now a positioning paper has been added in order to stimulate a discussion about the fourth component of the ICF, to contribute towards a broader and common understanding about the nature of personal factors and to incite a dialogue among all those involved in health care as well as those people with or with-out health problems in order to gain a comprehensive perspective about a person's condition.

  15. Towards an optimal design of target for tsetse control: comparisons of novel targets for the control of Palpalis group tsetse in West Africa.

    Directory of Open Access Journals (Sweden)

    Jean Baptiste Rayaisse

    2011-09-01

    Full Text Available BACKGROUND: Tsetse flies of the Palpalis group are the main vectors of sleeping sickness in Africa. Insecticide impregnated targets are one of the most effective tools for control. However, the cost of these devices still represents a constraint to their wider use. The objective was therefore to improve the cost effectiveness of currently used devices. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed on three tsetse species, namely Glossina palpalis gambiensis and G. tachinoides in Burkina Faso and G. p. palpalis in Côte d'Ivoire. The 1 × 1 m(2 black blue black target commonly used in W. Africa was used as the standard, and effects of changes in target size, shape, and the use of netting instead of black cloth were measured. Regarding overall target shape, we observed that horizontal targets (i.e. wider than they were high killed 1.6-5x more G. p. gambiensis and G. tachinoides than vertical ones (i.e. higher than they were wide (P < 0.001. For the three tsetse species including G. p. palpalis, catches were highly correlated with the size of the target. However, beyond the size of 0.75 m, there was no increase in catches. Replacing the black cloth of the target by netting was the most cost efficient for all three species. CONCLUSION/SIGNIFICANCE: Reducing the size of the current 1*1 m black-blue-black target to horizontal designs of around 50 cm and replacing black cloth by netting will improve cost effectiveness six-fold for both G. p. gambiensis and G. tachinoides. Studying the visual responses of tsetse to different designs of target has allowed us to design more cost-effective devices for the effective control of sleeping sickness and animal trypanosomiasis in Africa.

  16. Optimal design and validation of antiviral siRNA for targeting hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Jie FU; Zhong-ming TANG; Xin GAO; Fan ZHAO; Hui ZHONG; Mao-rong WEN; Xiao SUN; Hai-feng SONG; Xiao-hong QIAN

    2008-01-01

    Aim: Optimal design of antiviral short-interfering RNA (siRNA) targeting highly divergent hepatitis B virus (HBV) was validated by quantitative structure-activity relationship (QSAR) analysis. Methods: The potency of 23 synthetic siRNAs targeting 23 sites throughout HBV pregenomic RNA were evaluated at 10 nmol/L by determining the inhibition on the expression of S/P/pregenomic mRNA and hepatitis B surface antigen (HBsAg) quantitatively in HepG2.2.15 cells. Genotype homology within HBV genomes was identified through plentiful computational analysis and the multiple linear regression analysis was made to validate the relationship between the functional siRNAs and primary characteristics. Based on the preliminary results, relationships between different determined endpoints [S/P mRNA, HBsAg, C/P mRNA, hepatitis B e antigen (HBeAg) and viral DNA load] and siRNA efficacy evaluation were investigated. Results: Genotype homology, open reading frame (ORF) S/E X and C had tight correlation with the ability of siRNAs on inhibiting the expression of S/P/Pregenomic mRNA and HBsAg (P<0.01), of which, ORF C was negatively correlated with the siRNA potency (P<0.05). Further study showed that siRNA potency evaluation was influenced by different determined endpoints. P-target siRNAs showed significant inhibition on the S mRNA and HBsAg expression. S-target siRNAs inhibited the expression of S mRNA and HBsAg strongly. X-target siRNAs played active roles in inhibiting all 5 determined endpoints. C-target siRNAs blocked the expression of C mRNA, HBeAg and viral DNA load significantly. Conclusion: The antiviral potency of siRNA was relevant to its primary characteristics and determined endpoints were important for siRNA efficacy evaluation for complex genome with overlapping ORF, which was helpful for siRNA optimal design.

  17. Phase-modulated waveform design for extended target detection in the presence of clutter.

    Science.gov (United States)

    Gong, Xuhua; Meng, Huadong; Wei, Yimin; Wang, Xiqin

    2011-01-01

    The problem to be addressed in this paper is a phase-modulated waveform design for the detection of extended targets contaminated by signal-dependent noise (clutter) and additive noise in practical radar systems. An optimal waveform design method that leads to the energy spectral density (ESD) of signal under the maximum signal-to-clutter-and-noise ratio (SCNR) criterion is introduced first. In order to make full use of the transmission power, a novel phase-iterative algorithm is then proposed for designing the phase-modulated waveform with a constant envelope, whose ESD matches the optimal one. This method is proven to be able to achieve a small SCNR loss by minimizing the mean-square spectral distance between the optimal waveform and the designed waveform. The results of extensive simulations demonstrate that our approach provides less than 1 dB SCNR loss when the signal duration is greater than 1 μs, and outperforms the stationary phase method and other phase-modulated waveform design methods.

  18. Phase-Modulated Waveform Design for Extended Target Detection in the Presence of Clutter

    Directory of Open Access Journals (Sweden)

    Xiqin Wang

    2011-07-01

    Full Text Available The problem to be addressed in this paper is a phase-modulated waveform design for the detection of extended targets contaminated by signal-dependent noise (clutter and additive noise in practical radar systems. An optimal waveform design method that leads to the energy spectral density (ESD of signal under the maximum signal-to-clutter-and-noise ratio (SCNR criterion is introduced first. In order to make full use of the transmission power, a novel phase-iterative algorithm is then proposed for designing the phase-modulated waveform with a constant envelope, whose ESD matches the optimal one. This method is proven to be able to achieve a small SCNR loss by minimizing the mean-square spectral distance between the optimal waveform and the designed waveform. The results of extensive simulations demonstrate that our approach provides less than 1 dB SCNR loss when the signal duration is greater than 1 μs, and outperforms the stationary phase method and other phase-modulated waveform design methods.

  19. Efficient targeted mutagenesis in medaka using custom-designed transcription activator-like effector nucleases.

    Science.gov (United States)

    Ansai, Satoshi; Sakuma, Tetsushi; Yamamoto, Takashi; Ariga, Hiroyoshi; Uemura, Norihito; Takahashi, Ryosuke; Kinoshita, Masato

    2013-03-01

    Transcription activator-like effector nucleases (TALENs) have become powerful tools for targeted genome editing. Here we demonstrate efficient targeted mutagenesis in medaka (Oryzias latipes), which serves as an excellent vertebrate model for genetics and genomics. We designed and constructed a pair of TALENs targeting the medaka DJ-1 gene, a homolog of human DJ-1 (PARK7). These TALENs induced a number of insertions and deletions in the injected embryos with extremely high efficiency. This induction of mutations occurred in a dose-dependent manner. All screened G0 fish injected with the TALENs transmitted the TALEN-induced mutations to the next generation with high efficiency (44-100%). We also confirmed that these TALENs induced site-specific mutations because none of the mutations were found at potential off-target sites. In addition, the DJ-1 protein was lost in DJ-1(Δ7/Δ7) fish that carried a TALEN-induced frameshift mutation in both alleles. We also investigated the effect of the N- and C-terminal regions of the transcription activator-like (TAL) effector domain on the gene-disrupting activity of DJ1-TALENs and found that 287 amino acids at the N terminus and 63 amino acids at the C terminus of the TAL domain exhibited the highest disrupting activity in the injected embryos. Our results suggest that TALENs enable us to rapidly and efficiently establish knockout medaka strains. This is the first report of targeted mutagenesis in medaka using TALENs. The TALEN technology will expand the potential of medaka as a model system for genetics and genomics.

  20. Case study of the development of the Target Acquisition Designation/Pilot Night Vision System

    OpenAIRE

    2002-01-01

    Approved for public release; distribution in unlimited. This thesis is a case study of the extent to which a series of factors influenced development of the U.S. Army Target Acquisition Designation System/Pilot Night Vision System (TADS/PNVS). This study is one of a series being prepared under an ongoing research effort sponsored by Headquarters U.S. Army Material Command (AMC). These studies will look at various weapon systems that participated in Operation Desert Storm (ODS) and will stu...

  1. Altered Intra-Nuclear Organisation of Heterochromatin and Genes in ICF Syndrome

    Science.gov (United States)

    Jefferson, Andrew; Colella, Stefano; Moralli, Daniela; Wilson, Natalie; Yusuf, Mohammed; Gimelli, Giorgio; Ragoussis, Jiannis; Volpi, Emanuela V.

    2010-01-01

    The ICF syndrome is a rare autosomal recessive disorder, the most common symptoms of which are immunodeficiency, facial anomalies and cytogenetic defects involving decondensation and instability of chromosome 1, 9 and 16 centromeric regions. ICF is also characterised by significant hypomethylation of the classical satellite DNA, the major constituent of the juxtacentromeric heterochromatin. Here we report the first attempt at analysing some of the defining genetic and epigenetic changes of this syndrome from a nuclear architecture perspective. In particular, we have compared in ICF (Type 1 and Type 2) and controls the large-scale organisation of chromosome 1 and 16 juxtacentromeric heterochromatic regions, their intra-nuclear positioning, and co-localisation with five specific genes (BTG2, CNN3, ID3, RGS1, F13A1), on which we have concurrently conducted expression and methylation analysis. Our investigations, carried out by a combination of molecular and cytological techniques, demonstrate the existence of specific and quantifiable differences in the genomic and nuclear organisation of the juxtacentromeric heterochromatin in ICF. DNA hypomethylation, previously reported to correlate with the decondensation of centromeric regions in metaphase described in these patients, appears also to correlate with the heterochromatin spatial configuration in interphase. Finally, our findings on the relative positioning of hypomethylated satellite sequences and abnormally expressed genes suggest a connection between disruption of long-range gene-heterochromatin associations and some of the changes in gene expression in ICF. Beyond its relevance to the ICF syndrome, by addressing fundamental principles of chromosome functional organisation within the cell nucleus, this work aims to contribute to the current debate on the epigenetic impact of nuclear architecture in development and disease. PMID:20613881

  2. 42 CFR 418.112 - Condition of participation: Hospices that provide hospice care to residents of a SNF/NF or ICF/MR.

    Science.gov (United States)

    2010-10-01

    ... hospice care to residents of a SNF/NF or ICF/MR. 418.112 Section 418.112 Public Health CENTERS FOR...: Hospices that provide hospice care to residents of a SNF/NF or ICF/MR. In addition to meeting the... of a SNF/NF or ICF/MR must abide by the following additional standards. (a) Standard: Resident...

  3. Overlap and Nonoverlap Between the ICF Core Sets for Hearing Loss and Otology and Audiology Intake Documentation.

    Science.gov (United States)

    van Leeuwen, Lisette M; Merkus, Paul; Pronk, Marieke; van der Torn, Marein; Maré, Marcel; Goverts, S Theo; Kramer, Sophia E

    The International Classification of Functioning Disability and Health (ICF) Core Sets for Hearing Loss (HL) were developed to serve as a standard for the assessment and reporting of the functioning and health of patients with HL. The aim of the present study was to compare the content of the intake documentation currently used in secondary and tertiary hearing care settings in the Netherlands with the content of the ICF Core Sets for HL. Research questions were (1) to what extent are the ICF Core Sets for HL represented in the Dutch Otology and Audiology intake documentation? (2) are there any extra ICF categories expressed in the intake documentation that are currently not part of the ICF Core Sets for HL, or constructs expressed that are not part of the ICF? Multicenter patient record study including 176 adult patients from two secondary, and two tertiary hearing care settings. The intake documentation was selected from anonymized patient records. The content was linked to the appropriate ICF category from the whole ICF classification using established linking rules. The extent to which the ICF Core Sets for HL were represented in the intake documentation was determined by assessing the overlap between the ICF categories in the Core Sets and the list of unique ICF categories extracted from the intake documentation. Any extra constructs that were expressed in the intake documentation but are not part of the Core Sets were described as well, differentiating between ICF categories that are not part of the Core Sets and constructs that are not part of the ICF classification. In total, otology and audiology intake documentation represented 24 of the 27 Brief ICF Core Set categories (i.e., 89%), and 60 of the 117 Comprehensive ICF Core Set categories (i.e., 51%). Various ICF Core Sets categories were not represented, including higher mental functions (Body Functions), civic life aspects (Activities and Participation), and support and attitudes of family (Environmental

  4. Rational Design of Small Molecules Targeting Oncogenic Noncoding RNAs from Sequence.

    Science.gov (United States)

    Disney, Matthew D; Angelbello, Alicia J

    2016-12-20

    The discovery of RNA catalysis in the 1980s and the dissemination of the human genome sequence at the start of this century inspired investigations of the regulatory roles of noncoding RNAs in biology. In fact, the Encyclopedia of DNA Elements (ENCODE) project has shown that only 1-2% of the human genome encodes protein, yet 75% is transcribed into RNA. Functional studies both preceding and following the ENCODE project have shown that these noncoding RNAs have important roles in regulating gene expression, developmental timing, and other critical functions. RNA's diverse roles are often a consequence of the various folds that it adopts. The single-stranded nature of the biopolymer enables it to adopt intramolecular folds with noncanonical pairings to lower its free energy. These folds can be scaffolds to bind proteins or to form frameworks to interact with other RNAs. Not surprisingly, dysregulation of certain noncoding RNAs has been shown to be causative of disease. Given this as the background, it is easy to see why it would be useful to develop methods that target RNA and manipulate its biology in rational and predictable ways. The antisense approach has afforded strategies to target RNAs via Watson-Crick base pairing and has typically focused on targeting partially unstructured regions of RNA. Small molecule strategies to target RNA would be desirable not only because compounds could be lead optimized via medicinal chemistry but also because structured regions within an RNA of interest could be targeted to directly interfere with RNA folds that contribute to disease. Additionally, small molecules have historically been the most successful drug candidates. Until recently, the ability to design small molecules that target non-ribosomal RNAs has been elusive, creating the perception that they are "undruggable". In this Account, approaches to demystify targeting RNA with small molecules are described. Rather than bulk screening for compounds that bind to singular

  5. Designing of Anti Dengue Drug Molecule against Insilico Modeled Target DC-Sign (CD-209

    Directory of Open Access Journals (Sweden)

    Prashantha C.N

    2013-09-01

    Full Text Available The C-type lectin DC-SIGN (CD209 plays a major role in receptor on human dendritic cells, it binds to several glycoproteins of viruses that facilitate disease progression. In dengue fever, the disease targets of arbovirus infection, show dendritic and reticuloendothelial cells that may affect immune system. The phytochemical extracts of Bosenbergia rotunda (BR have been effectively used as potential small molecular inhibitors to inhibit DC-SIGN (CD209 function. Using rational drug designing the training sets include Panduratin-A and 4-hydroxypanduratin is designed from BR derivatives could be an effective inhibitor of a DC-SIGN (CD209 binding towards the drug discovery/ therapy against dengue fever.

  6. Characterizing ICF Neutron Scintillation Diagnostics on the nTOF line at SUNY Geneseo

    Science.gov (United States)

    Lawson-Keister, Pat; Padawar-Curry, Jonah; Visca, Hannah; Fletcher, Kurt; Padalino, Stephen; Sangster, T. Craig; Regan, Sean

    2015-11-01

    Neutron scintillator diagnostics for ICF and HEDP can be characterized using the neutron time-of-flight (nTOF) line on Geneseo's 1.7 MV tandem Pelletron accelerator. Neutron signals can be differentiated from gamma signals by employing coincidence methods. A 1.8-MeV beam of deuterons incident on a deuterated polyethylene target produces neutrons via the 2H(d,n)3He reaction. Neutrons emerging at a lab angle of 88° have an energy of 2.96 MeV; the 3He ions associated with these neutrons are detected at a scattering angle of 43° using a surface barrier detector. The time of flight of the neutron can be measured by using the 3He detection as a ``start'' signal and the scintillation detection as a ``stop'' signal. This time of flight requirement is used to identify the 2.96-MeV neutron signals in the scintillator. To measure the light curve produced by these monoenergetic neutrons, two photomultiplier (PMT) tubes are attached to the scintillator. The full aperture PMT establishes the nTOF coincidence. The other PMT is fitted with a pinhole to collect single events. The time between the full aperture PMT signal and the arrival of the signal in the pinhole PMT is used to determine the light curve for the scintillator. This system will enable the neutron response of various scintillators to be compared. Supported in part by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

  7. The experience of having psoriasis through the lens of the International Classification of Functioning, Disability and Health (ICF).

    Science.gov (United States)

    Campbell, Adam; Hocking, Clare; Taylor, William J

    2014-11-01

    The International Classification of Functioning, Disability and Health (ICF) was developed by the World Health Organization to comprehensively describe the ways that health conditions can affect people. The identification of ICF categories of most relevance to people with a particular disease can increase the usefulness of the ICF and create a reference for outcome studies. This study aimed to ascertain, through focus group interviews with psoriasis patients and an online Delphi survey with health professionals, the impacts of psoriasis as categorised by the ICF. We conducted and transcribed verbatim focus group interviews with 32 outpatients with psoriasis from two New Zealand cities. The interview transcripts were analysed to yield meaning units and concepts contained in the meaning units were extracted. These concepts were linked to ICF categories. An online Delphi survey among 23 health professionals was conducted to obtain similar information. The ICF categories were rated for their perceived relevance to psoriasis by health professionals over three iterations. In total, 32 patients participated in six focus groups. Interview saturation was reached after five focus groups. The concepts were linked to 83 ICF categories and two separate health conditions. Among health professionals, 167 ICF categories were rated, mostly in the moderately relevant (four to six) range. Applying the established method of meaning condensation to focus group interview transcripts allowed the accurate linking of concepts to ICF categories. This will be of use to researchers developing the first ICF core set for psoriasis in the future. © 2013 The Authors. Australasian Journal of Dermatology © 2013 The Australasian College of Dermatologists.

  8. Design on the optical screen target by using the line structured light laser

    Science.gov (United States)

    Tian, Hui; Ni, Jin-ping; Lu, Qian; Lu, Hong-Wei

    2011-06-01

    The velocity and impacting position of a flying projectile is usually measured by optical screen target at the range of shooting range measurement. In order to improve the situation of low sensitivity and the small effective sensor area in available optical screen, a laser screen target is put forward in this paper, which takes the line structured light laser as the transmitter and the silicon PIN photodiode as the receiver. In present paper the performance of the optical screen transmitter and the distribution of light energy in the whole screen are analyzed, and the graph of distribution simulated by MATLAB is given. The sensitivity of the effective sensor area is analyzed and calculated. With the verification on air gun projectile, the design of the optical screen in the effective sensor area within 5m × 5m was able to detect air gun projectile. The result demonstrated that this optical screen woks with high sensitivity, high stability and reliability, and the effective sensor area of the measuring can reach to 10m × 10m for the rifle projectile measurement. The mechanical structure and the signal process circuit can also be used on multiple optical screens target and the large space detection for early warning.

  9. Design upgrade of the ISOLDE target unit for HIE-ISOLDE

    CERN Document Server

    Montano, J; Gottberg, A

    2013-01-01

    The High Intensity and Energy HIE-ISOLDE project is a major upgrade of the existing ISOLDE and REX-ISOLDE facilities with the objective of increasing the energy and the intensity of the delivered radioactive ion beams (RIB) {[}1]. In order to accommodate the future increase of primary beam intensity delivered by the new LINAC4 H- driver to the Proton Synchrotron Booster (PSB) {[}2] and from this to ISOLDE, a major study is being carried out to upgrade the existing designs of the ISOLDE target and its supporting infrastructure. In particular, the extraction optics plays an important role in the initial beam transport and the quality of the beam supplied to the mass separators. Important factors include the emittance of the beam and the beam profile to avoid beam losses. A new double electrode extraction system has been developed for simplifying and improving the interface between the target unit and the frontend (target coupling table). Numerical and experimental studies have been performed in order to define ...

  10. Design upgrade of the ISOLDE target unit for HIE-ISOLDE

    Science.gov (United States)

    Montaño, J.; Giles, T.; Gottberg, A.

    2013-12-01

    The High Intensity and Energy HIE-ISOLDE project is a major upgrade of the existing ISOLDE and REX-ISOLDE facilities with the objective of increasing the energy and the intensity of the delivered radioactive ion beams (RIB) [1]. In order to accommodate the future increase of primary beam intensity delivered by the new LINAC4 H- driver to the Proton Synchrotron Booster (PSB) [2] and from this to ISOLDE, a major study is being carried out to upgrade the existing designs of the ISOLDE target and its supporting infrastructure. In particular, the extraction optics plays an important role in the initial beam transport and the quality of the beam supplied to the mass separators. Important factors include the emittance of the beam and the beam profile to avoid beam losses. A new double electrode extraction system has been developed for simplifying and improving the interface between the target unit and the frontend (target coupling table). Numerical and experimental studies have been performed in order to define the new extraction geometry, and the coupling table has been adapted to keep the compatibility. An alternative heating system is under study. An electron bombardment heating system is being developed as an option for avoiding the employment of big cross section cables. The results of these studies and the mechanical models developed are presented and discussed.

  11. Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes.

    Science.gov (United States)

    Li, Ting; Huang, Sheng; Zhao, Xuefeng; Wright, David A; Carpenter, Susan; Spalding, Martin H; Weeks, Donald P; Yang, Bing

    2011-08-01

    Recent studies indicate that the DNA recognition domain of transcription activator-like (TAL) effectors can be combined with the nuclease domain of FokI restriction enzyme to produce TAL effector nucleases (TALENs) that, in pairs, bind adjacent DNA target sites and produce double-strand breaks between the target sequences, stimulating non-homologous end-joining and homologous recombination. Here, we exploit the four prevalent TAL repeats and their DNA recognition cipher to develop a 'modular assembly' method for rapid production of designer TALENs (dTALENs) that recognize unique DNA sequence up to 23 bases in any gene. We have used this approach to engineer 10 dTALENs to target specific loci in native yeast chromosomal genes. All dTALENs produced high rates of site-specific gene disruptions and created strains with expected mutant phenotypes. Moreover, dTALENs stimulated high rates (up to 34%) of gene replacement by homologous recombination. Finally, dTALENs caused no detectable cytotoxicity and minimal levels of undesired genetic mutations in the treated yeast strains. These studies expand the realm of verified TALEN activity from cultured human cells to an intact eukaryotic organism and suggest that low-cost, highly dependable dTALENs can assume a significant role for gene modifications of value in human and animal health, agriculture and industry.

  12. Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes

    Energy Technology Data Exchange (ETDEWEB)

    Li, T; Huang, S; Zhao, XF; Wright, DA; Carpenter, S; Spalding, MH; Weeks, DP; Yang, B

    2011-08-08

    Recent studies indicate that the DNA recognition domain of transcription activator-like (TAL) effectors can be combined with the nuclease domain of FokI restriction enzyme to produce TAL effector nucleases (TALENs) that, in pairs, bind adjacent DNA target sites and produce double-strand breaks between the target sequences, stimulating non-homologous end-joining and homologous recombination. Here, we exploit the four prevalent TAL repeats and their DNA recognition cipher to develop a 'modular assembly' method for rapid production of designer TALENs (dTALENs) that recognize unique DNA sequence up to 23 bases in any gene. We have used this approach to engineer 10 dTALENs to target specific loci in native yeast chromosomal genes. All dTALENs produced high rates of site-specific gene disruptions and created strains with expected mutant phenotypes. Moreover, dTALENs stimulated high rates (up to 34%) of gene replacement by homologous recombination. Finally, dTALENs caused no detectable cytotoxicity and minimal levels of undesired genetic mutations in the treated yeast strains. These studies expand the realm of verified TALEN activity from cultured human cells to an intact eukaryotic organism and suggest that low-cost, highly dependable dTALENs can assume a significant role for gene modifications of value in human and animal health, agriculture and industry.

  13. Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases.

    Science.gov (United States)

    Doyon, Yannick; McCammon, Jasmine M; Miller, Jeffrey C; Faraji, Farhoud; Ngo, Catherine; Katibah, George E; Amora, Rainier; Hocking, Toby D; Zhang, Lei; Rebar, Edward J; Gregory, Philip D; Urnov, Fyodor D; Amacher, Sharon L

    2008-06-01

    We describe the use of zinc-finger nucleases (ZFNs) for somatic and germline disruption of genes in zebrafish (Danio rerio), in which targeted mutagenesis was previously intractable. ZFNs induce a targeted double-strand break in the genome that is repaired to generate small insertions and deletions. We designed ZFNs targeting the zebrafish golden and no tail/Brachyury (ntl) genes and developed a budding yeast-based assay to identify the most active ZFNs for use in vivo. Injection of ZFN-encoding mRNA into one-cell embryos yielded a high percentage of animals carrying distinct mutations at the ZFN-specified position and exhibiting expected loss-of-function phenotypes. Over half the ZFN mRNA-injected founder animals transmitted disrupted ntl alleles at frequencies averaging 20%. The frequency and precision of gene-disruption events observed suggest that this approach should be applicable to any loci in zebrafish or in other organisms that allow mRNA delivery into the fertilized egg.

  14. Tools for the rational design of bivalent microtubule-targeting drugs.

    Science.gov (United States)

    Marangon, Jacopo; Christodoulou, Michael S; Casagrande, Fancesca V M; Tiana, Guido; Dalla Via, Lisa; Aliverti, Alessandro; Passarella, Daniele; Cappelletti, Graziella; Ricagno, Stefano

    2016-10-01

    Microtubule (MT) dynamic behaviour is an attractive drug target for chemotherapy, whose regulation by MT-stabilizing and destabilizing agents has been fruitfully applied in treating several types of cancers. MT-stabilizing agents are also emerging as potential remedies for neurodegenerative conditions, such as Alzheimer's and Parkinson's disease, although single-target drugs are not expected to fully cure these complex pathologies. Drug combination often displays enhanced efficacy with respect to mono-therapies. In particular, MT-targeting bivalent compounds (MTBCs) represent a promising class of molecules; however, surprisingly, the majority of MTBCs reported so far exhibit equal if not less efficacy than their building monomers. In order to shed light on MTBCs poor performance, we characterised through a set of complementary approaches thiocolchine (TH) and two bivalent TH-homodimers as prototype molecules. First, the binding affinities of these three molecules were assessed, then we obtained the crystallographic structure of a tubulin-TH complex. The binding affinities were interpreted in light of structural data and of molecular dynamics simulations. Finally, their effects on MT cytoskeleton and cell survival were validated on HeLa cells. The ensemble of these data provides chemical and structural considerations on how a successful rational design of MTBCs should be conceived.

  15. Design Analysis of SNS Target StationBiological Shielding Monoligh with Proton Power Uprate

    Energy Technology Data Exchange (ETDEWEB)

    Bekar, Kursat B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ibrahim, Ahmad M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-05-01

    This report documents the analysis of the dose rate in the experiment area outside the Spallation Neutron Source (SNS) target station shielding monolith with proton beam energy of 1.3 GeV. The analysis implemented a coupled three dimensional (3D)/two dimensional (2D) approach that used both the Monte Carlo N-Particle Extended (MCNPX) 3D Monte Carlo code and the Discrete Ordinates Transport (DORT) two dimensional deterministic code. The analysis with proton beam energy of 1.3 GeV showed that the dose rate in continuously occupied areas on the lateral surface outside the SNS target station shielding monolith is less than 0.25 mrem/h, which complies with the SNS facility design objective. However, the methods and codes used in this analysis are out of date and unsupported, and the 2D approximation of the target shielding monolith does not accurately represent the geometry. We recommend that this analysis is updated with modern codes and libraries such as ADVANTG or SHIFT. These codes have demonstrated very high efficiency in performing full 3D radiation shielding analyses of similar and even more difficult problems.

  16. 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.

  17. Molecular design and nanoparticle-mediated intracellular delivery of functional proteins to target cellular pathways

    Science.gov (United States)

    Shah, Dhiral Ashwin

    Intracellular delivery of specific proteins and peptides represents a novel method to influence stem cells for gain-of-function and loss-of-function. Signaling control is vital in stem cells, wherein intricate control of and interplay among critical pathways directs the fate of these cells into either self-renewal or differentiation. The most common route to manipulate cellular function involves the introduction of genetic material such as full-length genes and shRNA into the cell to generate (or prevent formation of) the target protein, and thereby ultimately alter cell function. However, viral-mediated gene delivery may result in relatively slow expression of proteins and prevalence of oncogene insertion into the cell, which can alter cell function in an unpredictable fashion, and non-viral delivery may lead to low efficiency of genetic delivery. For example, the latter case plagues the generation of induced pluripotent stem cells (iPSCs) and hinders their use for in vivo applications. Alternatively, introducing proteins into cells that specifically recognize and influence target proteins, can result in immediate deactivation or activation of key signaling pathways within the cell. In this work, we demonstrate the cellular delivery of functional proteins attached to hydrophobically modified silica (SiNP) nanoparticles to manipulate specifically targeted cell signaling proteins. In the Wnt signaling pathway, we have targeted the phosphorylation activity of glycogen synthase kinase-3beta (GSK-3beta) by designing a chimeric protein and delivering it in neural stem cells. Confocal imaging indicates that the SiNP-chimeric protein conjugates were efficiently delivered to the cytosol of human embryonic kidney cells and rat neural stem cells, presumably via endocytosis. This uptake impacted the Wnt signaling cascade, indicated by the elevation of beta-catenin levels, and increased transcription of Wnt target genes, such as c-MYC. The results presented here suggest that

  18. Maximizing in vivo target clearance by design of pH-dependent target binding antibodies with altered affinity to FcRn.

    Science.gov (United States)

    Yang, Danlin; Giragossian, Craig; Castellano, Steven; Lasaro, Marcio; Xiao, Haiguang; Saraf, Himanshu; Hess Kenny, Cynthia; Rybina, Irina; Huang, Zhong-Fu; Ahlberg, Jennifer; Bigwarfe, Tammy; Myzithras, Maria; Waltz, Erica; Roberts, Simon; Kroe-Barrett, Rachel; Singh, Sanjaya

    2017-08-08

    Antibodies with pH-dependent binding to both target antigens and neonatal Fc receptor (FcRn) provide an alternative tool to conventional neutralizing antibodies, particularly for therapies where reduction in antigen level is challenging due to high target burden. However, the requirements for optimal binding kinetic framework and extent of pH dependence for these antibodies to maximize target clearance from circulation are not well understood. We have identified a series of naturally-occurring high affinity antibodies with pH-dependent target binding properties. By in vivo studies in cynomolgus monkeys, we show that pH-dependent binding to the target alone is not sufficient for effective target removal from circulation, but requires Fc mutations that increase antibody binding to FcRn. Affinity-enhanced pH-dependent FcRn binding that is double-digit nM at pH 7.4 and single-digit nM at pH 6 achieved maximal target reduction when combined with similar target binding affinities in reverse pH directions. Sustained target clearance below the baseline level was achieved 3 weeks after single-dose administration at 1.5 mg/kg. Using the experimentally derived mechanistic model, we demonstrate the essential kinetic interplay between target turnover and antibody pH-dependent binding during the FcRn recycling, and identify the key components for achieving maximal target clearance. These results bridge the demand for improved patient dosing convenience with the "know-how" of therapeutic modality by design.

  19. Thermo-structural analysis and design consideration of the replaceable backwall in IFMIF liquid lithium target

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, H. [Japan Atomic Energy Agency, Tokai-mura, Ibaraki 319-1195 (Japan)]. E-mail: nakamura.hiroo@jaea.go.jp; Ida, M. [Japan Atomic Energy Agency, Tokai-mura, Ibaraki 319-1195 (Japan); Chida, T. [Japan Atomic Energy Agency, Tokai-mura, Ibaraki 319-1195 (Japan); Shiba, K. [Japan Atomic Energy Agency, Tokai-mura, Ibaraki 319-1195 (Japan); Shimizu, K. [Mitsubishi Heavy Industry, Hyogo 652-8585 (Japan); Sugimoto, M. [Japan Atomic Energy Agency, Tokai-mura, Ibaraki 319-1195 (Japan)

    2007-08-01

    The IFMIF is an accelerator-based intense neutron source for testing candidate materials for fusion reactors. Intense neutrons are emitted inside the Li flow through a backwall. The backwall made of 316L stainless steel or RAFM is attached to the target assembly with a lip seal welded by a YAG laser. Since the backwall is operating under a severe neutron irradiation of 50 dpa/year and a maximum nuclear heating rate of 25 W/cm{sup 3}, thermo-structural design is one of critical issues in a target design. Thermal stress was calculated using the ABAQUS code. As a permissible stress, yield strength at 300 {sup o}C was used. In the case of the 316 stainless steel backwall, the maximum thermal stress was more than the permissible stress (164 MPa). On the other hand, in case of the F82H backwall, a maximum thermal stress was below the permissible stress (455 MPa). Therefore, F82H is recommended as the backwall material.

  20. Design and implementation of random noise radar with spectral-domain correlation for moving target detection

    Science.gov (United States)

    Kim, Jeong Phill; Jeong, Chi Hyun; Kim, Cheol Hoo

    2011-06-01

    A correlation processing algorithm in the spectral domain is proposed for detecting moving targets with random noise radar. AD converted reference and Rx signals are passed through FFT block, and they are multiplied after the reference signal is complex conjugated. Now inverse FFT yields the sub-correlation results, and range and velocity information can be accurately extracted by an additional FFT processing. In this design procedure, specific considerations have to be made for correlation length, averaging number, and number of sub-correlation data for Doppler processing. The proposed algorithm was verified by Simulink (Mathworks) simulation, and its logic was implemented with Xilinx FPGA device (Vertex5 series) by System Generator block sets (Xilinx) in the Simulink environment. A CW X-band random-FM noise radar prototype with an instantaneous bandwidth of 100 MHz was designed and implemented, and laboratory and field tests were conducted to detect moving targets, and the observed results showed the validity of the proposed algorithm and the operation of implemented FPGA logics.

  1. Computer-aided Molecular Design of Compounds Targeting Histone Modifying Enzymes.

    Science.gov (United States)

    Andreoli, Federico; Del Rio, Alberto

    2015-01-01

    Growing evidences show that epigenetic mechanisms play crucial roles in the genesis and progression of many physiopathological processes. As a result, research in epigenetic grew at a fast pace in the last decade. In particular, the study of histone post-translational modifications encountered an extraordinary progression and many modifications have been characterized and associated to fundamental biological processes and pathological conditions. Histone modifications are the catalytic result of a large set of enzyme families that operate covalent modifications on specific residues at the histone tails. Taken together, these modifications elicit a complex and concerted processing that greatly contribute to the chromatin remodeling and may drive different pathological conditions, especially cancer. For this reason, several epigenetic targets are currently under validation for drug discovery purposes and different academic and industrial programs have been already launched to produce the first pre-clinical and clinical outcomes. In this scenario, computer-aided molecular design techniques are offering important tools, mainly as a consequence of the increasing structural information available for these targets. In this mini-review we will briefly discuss the most common types of known histone modifications and the corresponding operating enzymes by emphasizing the computer-aided molecular design approaches that can be of use to speed-up the efforts to generate new pharmaceutically relevant compounds.

  2. Designed Amino Acid Feed in Improvement of Production and Quality Targets of a Therapeutic Monoclonal Antibody.

    Directory of Open Access Journals (Sweden)

    Fatemeh Torkashvand

    Full Text Available Cell culture feeds optimization is a critical step in process development of pharmaceutical recombinant protein production. Amino acids are the basic supplements of mammalian cell culture feeds with known effect on their growth promotion and productivity. In this study, we reported the implementation of the Plackett-Burman (PB multifactorial design to screen the effects of amino acids on the growth promotion and productivity of a Chinese hamster ovary DG-44 (CHO-DG44 cell line producing bevacizumab. After this screening, the amino acid combinations were optimized by the response surface methodology (RSM to determine the most effective concentration in feeds. Through this strategy, the final monoclonal antibody (mAb titre was enhanced by 70%, compared to the control group. For this particular cell line, aspartic acid, glutamic acid, arginine and glycine had the highest positive effects on the final mAb titre. Simultaneously, the impact of the designed amino acid feed on some critical quality attributes of bevacizumab was examined in the group with highest productivity. The product was analysed for N-glycan profiles, charge variant distribution, and low molecular weight forms. The results showed that the target product quality has been improved using this feeding strategy. It was shown how this strategy could significantly diminish the time and number of experiments in identifying the most effective amino acids and related concentrations in target product enhancement. This model could be successfully applied to other components of culture media and feeds.

  3. Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design

    Directory of Open Access Journals (Sweden)

    Sare Andalib

    2012-01-01

    Full Text Available Background: Nanostructured lipid carriers (NLC are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. Materials and Methods: The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol, lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. Results: The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of −25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. Conclusions: The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

  4. An Enhanced Analytical Target Cascading and Kriging Model Combined Approach for Multidisciplinary Design Optimization

    Directory of Open Access Journals (Sweden)

    Ping Jiang

    2015-01-01

    Full Text Available Multidisciplinary design optimization (MDO has been applied widely in the design of complex engineering systems. To ease MDO problems, analytical target cascading (ATC organizes MDO process into multilevels according to the components of engineering systems, which provides a promising way to deal with MDO problems. ATC adopts a coordination strategy to coordinate the couplings between two adjacent levels in the design optimization process; however, existing coordination strategies in ATC face the obstacles of complicated coordination process and heavy computation cost. In order to conquer this problem, a quadratic exterior penalty function (QEPF based ATC (QEPF-ATC approach is proposed, where QEPF is adopted as the coordination strategy. Moreover, approximate models are adopted widely to replace the expensive simulation models in MDO; a QEPF-ATC and Kriging model combined approach is further proposed to deal with MDO problems, owing to the comprehensive performance, high approximation accuracy, and robustness of Kriging model. Finally, the geometric programming and reducer design cases are given to validate the applicability and efficiency of the proposed approach.

  5. Analysis of variance of designed chromatographic data sets: The analysis of variance-target projection approach.

    Science.gov (United States)

    Marini, Federico; de Beer, Dalene; Joubert, Elizabeth; Walczak, Beata

    2015-07-31

    Direct application of popular approaches, e.g., Principal Component Analysis (PCA) or Partial Least Squares (PLS) to chromatographic data originating from a well-designed experimental study including more than one factor is not recommended. In the case of a well-designed experiment involving two or more factors (crossed or nested), data are usually decomposed into the contributions associated with the studied factors (and with their interactions), and the individual effect matrices are then analyzed using, e.g., PCA, as in the case of ASCA (analysis of variance combined with simultaneous component analysis). As an alternative to the ASCA method, we propose the application of PLS followed by target projection (TP), which allows a one-factor representation of the model for each column in the design dummy matrix. PLS application follows after proper deflation of the experimental matrix, i.e., to what are called the residuals under the reduced ANOVA model. The proposed approach (ANOVA-TP) is well suited for the study of designed chromatographic data of complex samples. It allows testing of statistical significance of the studied effects, 'biomarker' identification, and enables straightforward visualization and accurate estimation of between- and within-class variance. The proposed approach has been successfully applied to a case study aimed at evaluating the effect of pasteurization on the concentrations of various phenolic constituents of rooibos tea of different quality grades and its outcomes have been compared to those of ASCA.

  6. Targeted repression of AXIN2 and MYC gene expression using designer TALEs

    Energy Technology Data Exchange (ETDEWEB)

    Rennoll, Sherri A.; Scott, Samantha A.; Yochum, Gregory S., E-mail: gsy3@psu.edu

    2014-04-18

    Highlights: • We designed TALE–SID fusion proteins to target AXIN2 and MYC. • TALE–SIDs bound the chromosomal AXIN2 and MYC genes and repressed their expression. • TALE–SIDs repress β-catenin{sup S45F}-dependent AXIN2 and MYC transcription. - Abstract: Designer TALEs (dTALEs) are chimeric transcription factors that can be engineered to regulate gene expression in mammalian cells. Whether dTALEs can block gene transcription downstream of signal transduction cascades, however, has yet to be fully explored. Here we tested whether dTALEs can be used to target genes whose expression is controlled by Wnt/β-catenin signaling. TALE DNA binding domains were engineered to recognize sequences adjacent to Wnt responsive enhancer elements (WREs) that control expression of axis inhibition protein 2 (AXIN2) and c-MYC (MYC). These custom DNA binding domains were linked to the mSin3A interaction domain (SID) to generate TALE–SID chimeric repressors. The TALE–SIDs repressed luciferase reporter activity, bound their genomic target sites, and repressed AXIN2 and MYC expression in HEK293 cells. We generated a novel HEK293 cell line to determine whether the TALE–SIDs could function downstream of oncogenic Wnt/β-catenin signaling. Treating these cells with doxycycline and tamoxifen stimulates nuclear accumulation of a stabilized form of β-catenin found in a subset of colorectal cancers. The TALE–SIDs repressed AXIN2 and MYC expression in these cells, which suggests that dTALEs could offer an effective therapeutic strategy for the treatment of colorectal cancer.

  7. Challenges in the design of clinically useful brain-targeted drug nanocarriers.

    Science.gov (United States)

    Costantino, L; Boraschi, D; Eaton, M

    2014-01-01

    Nowadays, the delivery of drugs by means of intravenously administered nanosized drug carriers - polymerdrug conjugates, liposomes and micelles, is technically possible. These delivery systems are mainly designed for tumour therapy, and accumulate passively into tumours by means of the well known EPR effect. Targeted nanocarriers, that additionally contain ligands for receptors expressed on cell surfaces, are also widely studied but products of this kind are not marketed, and only a few are in clinical trial. Polymeric nanoparticles (Np) able to deliver drugs to the CNS were pioneered in 1995; a number of papers have been published dealing with brain-targeted drug delivery using polymeric Np able to cross the BBB, mainly for the treatment of brain tumours. At present, however, the translation potential of these Np seems to have been exceeded by targeted liposomes, a platform based on a proven technology. This drug delivery system entered clinical trials soon after its discovery, while the challenges in formulation, characterization and manufacturing of brain-targeted polymeric Np and the cost/benefit ratio could be the factors that have prevented their development. A key issue is that it is virtually impossible to define the in vivo fate of polymers, especially in the brain, which is a regulatory requirement; perhaps this is why no progress has been made. The most advanced Np for brain tumours treatment will be compared here with the published data available for those in clinical trial for tumours outside the CNS, to highlight the knowledge gaps that still penalise these delivery systems. At present, new approaches for brain tumours are emerging, such as lipid Np or the use of monoclonal antibody (mAb)-drug conjugates, which avoid polymers. The success or failure in the approval of the polymeric Np currently in clinical trials will certainly affect the field. At present, the chances of their approval appear to be very low.

  8. Status of LDRD-DR 20070518 development of a magnetically driven target for thermo-nuclear burn studies (u)

    Energy Technology Data Exchange (ETDEWEB)

    Watt, Robert G [Los Alamos National Laboratory; Atchison, W L [Los Alamos National Laboratory; Colgate, S A [Los Alamos National Laboratory; Goforth, J [Los Alamos National Laboratory; Griego, J [Los Alamos National Laboratory; Guzik, J [Los Alamos National Laboratory; Holtkamp, D [Los Alamos National Laboratory; Idzorek, G [Los Alamos National Laboratory; Kirkpatrick, R [Los Alamos National Laboratory; Menikoff, R [Los Alamos National Laboratory; Meyer, R [Los Alamos National Laboratory; Oona, H [Los Alamos National Laboratory; Reardon, P [Los Alamos National Laboratory; Rousculp, C L [Los Alamos National Laboratory; Sgro, A G [Los Alamos National Laboratory; Tabaka, L [Los Alamos National Laboratory

    2010-01-20

    This project is developing a magnetically driven cylindrical confinement system for the creation of a small region of material existing under extreme conditions. Using a Ranchero High Explosive Pulsed Power generator (HEPP) with maximum current ranging from 25- 50 MA depending on the load, a current driven Al cylinder will impact a series of nested, less massive Au shells. Each subsequent shell's inner surface velocity will increase due to it's smaller mass by the ratio 2.01( 1+ m{sub i+ 1}/m i), along with radial convergence. Attaining this ideal result requires highly efficient energy transfer which in turn requires plastic cushions. The final velocity of the last sequential shell will be used to drive a central experimental package in which extreme material conditions will be produced. The inexpensive nature of HEPP and the extreme conditions attainable allow many studies to be conducted in regimes not currently available in the laboratory. One potential central experimental package consists of a cylindrical Inertial Confinement Fusion (ICF) target; a cylindrical Au pusher surrounding frozen DT. This target is used as a design tool. The ICF conditions achieved with such a target would be similar to those created in a double shell ignition capsule at the National Ignition Facility. The system being developed has a range of potential applications.

  9. An integrated in silico approach to design specific inhibitors targeting human poly(a-specific ribonuclease.

    Directory of Open Access Journals (Sweden)

    Dimitrios Vlachakis

    Full Text Available Poly(A-specific ribonuclease (PARN is an exoribonuclease/deadenylase that degrades 3'-end poly(A tails in almost all eukaryotic organisms. Much of the biochemical and structural information on PARN comes from the human enzyme. However, the existence of PARN all along the eukaryotic evolutionary ladder requires further and thorough investigation. Although the complete structure of the full-length human PARN, as well as several aspects of the catalytic mechanism still remain elusive, many previous studies indicate that PARN can be used as potent and promising anti-cancer target. In the present study, we attempt to complement the existing structural information on PARN with in-depth bioinformatics analyses, in order to get a hologram of the molecular evolution of PARNs active site. In an effort to draw an outline, which allows specific drug design targeting PARN, an unequivocally specific platform was designed for the development of selective modulators focusing on the unique structural and catalytic features of the enzyme. Extensive phylogenetic analysis based on all the publicly available genomes indicated a broad distribution for PARN across eukaryotic species and revealed structurally important amino acids which could be assigned as potentially strong contributors to the regulation of the catalytic mechanism of PARN. Based on the above, we propose a comprehensive in silico model for the PARN's catalytic mechanism and moreover, we developed a 3D pharmacophore model, which was subsequently used for the introduction of DNP-poly(A amphipathic substrate analog as a potential inhibitor of PARN. Indeed, biochemical analysis revealed that DNP-poly(A inhibits PARN competitively. Our approach provides an efficient integrated platform for the rational design of pharmacophore models as well as novel modulators of PARN with therapeutic potential.

  10. Design, development and characterization of multi-functionalized gold nanoparticles for biodetection and targeted boron delivery in BNCT applications.

    NARCIS (Netherlands)

    Mandal, S.; Bakeine, G.J.; Krol, S.; Ferrari, C.; Clerici, A.M.; Zonta, C.; Cansolino, L.; Ballarini, F.; Bortolussi, S.; Stella, S.; Protti, N.; Bruschi, P.; Altieri, S.

    2011-01-01

    The aim of this study is to optimize targeted boron delivery to cancer cells and its tracking down to the cellular level. To this end, we describe the design and synthesis of novel nanovectors that double as targeted boron delivery agents and fluorescent imaging probes. Gold nanoparticles were coate

  11. Use of The International Classification of Functioning, Disability and Health (ICF as a conceptual framework and common language for disability statistics and health information systems

    Directory of Open Access Journals (Sweden)

    Kostanjsek Nenad

    2011-05-01

    Full Text Available Abstract A common framework for describing functional status information is needed in order to make this information comparable and of value. The World Health Organization’s International Classification of Functioning, Disability and Health (ICF, which has been approved by all its member states, provides this common language and framework. The article provides an overview of ICF taxonomy, introduces the conceptual model which underpins ICF and elaborates on how ICF is used at population and clinical level. Furthermore, the article presents key features of the ICF tooling environment and outlines current and future developments of the classification.

  12. The Impact of Verification Area Design on Tropical Cyclone Targeted Observations Based on the CNOP Method

    Institute of Scientific and Technical Information of China (English)

    ZHOU Feifan; MU Mu

    2011-01-01

    This study investigated the impact of different verification-area designs on the sensitive areas identified using the conditional nonlinear optimal perturbation (CNOP) method for tropical cyclone targeted observations.The sensitive areas identified using the first singular vector (FSV) method,which is the linear approximation of CNOP,were also investigated for comparison.By analyzing the validity of the sensitive areas,the proper design of a verification area was developed.Tropical cyclone Rananim,which occurred in August 2004 in the northwest Pacific Ocean,was studied.Two sets of verification areas were designed; one changed position,and the other changed both size and position.The CNOP and its identified sensitive areas were found to be less sensitive to small variations of the verification areas than those of the FSV and its sensitive areas.With larger variations of the verification area,the CNOP and the FSV as well as their identified sensitive areas changed substantially.In terms of reducing forecast errors in the verification area,the CNOP-identified sensitive areas were more beneficial than those identified using FSV.The design of the verification area is important for cyclone prediction.The verification area should be designed with a proper size according to the possible locations of the cyclone obtained from the ensemble forecast results.In addition,the development trend of the cyclone analyzed from its dynamic mechanisms was another reference.When the general position of the verification area was determined,a small variation in size or position had little influence on the results of CNOP.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-04-21

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

  14. Design of a ribozyme targeting human telomerase reverse transcriptase and cloning of it's gene

    Institute of Scientific and Technical Information of China (English)

    Zhi-Ming Hap; Jin-Yan Luo; Jin Cheng; Quan-Yin Wang; Guang-Xiao Yang

    2003-01-01

    AIM: To design a hammerhead ribozyme targeting humantelomerase reverse transcriptase (hTERT) and clone it's genefor future use in the study of tumor gene therapy.METHODS: Using the software RNAstructure, the secondarystructure of hTERT mRNA was predicted and the cleavagesite of ribozyme was selected. A hammerhead ribozymetargeting this site was designed and bimolecular fold betweenthe ribozyme and hTERT was predicted. The DNA encodingthe ribozyme was synthesized and cloned into pGEMEX-1and the sequence of the ribozyme gene was confirmed byDNA sequencing.RESULTS: Triplet GUC at 1742 of hTERT mRNA was chosenas the cleavage site of the ribozyme. The designed ribozymewas comprised of 22nt catalytic core and 17nt flankingsequence. Computer-aided prediction suggested that theribozyme and hTERT mRNA could cofold into a properconformation. Endonuclease restriction and DNA sequencingconfirmed the correct insertion of the ribozyme gene intothe vector pGEMEX-1.CONCLUSION: This fundamental work of successfuldesigning and cloning of an anti-hTERT hammerheadribozyme has paved the way for further study of inhibitingtumor cell growth by cleaving hTERT mRNA with ribozyme.

  15. LANL Q2 2016 Quarterly Progress Report. Science Campaign and ICF

    Energy Technology Data Exchange (ETDEWEB)

    Douglas, Melissa Rae [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-04-07

    This progress report includes highlights for the Science Campaign and ICF about Advanced Certification and Assessment Methodologies, Implosion Hydrodynamics (C-1, SCE), Materials and Nuclear Science (C-1, C-2), Capabilities for Nuclear Intelligence, and High Energy Density Science (C-1, C-4, C-10). Upcoming meetings, briefings, and experiments are then listed for April and May.

  16. Disability and Functional Profiles of Patients with Myasthenia Gravis Measured with ICF Classification

    Science.gov (United States)

    Leonardi, Matilde; Raggi, Alberto; Antozzi, Carlo; Confalonieri, Paolo; Maggi, Lorenzo; Cornelio, Ferdinando; Mantegazza, Renato

    2009-01-01

    The objective of this study is to describe functional profiles of patients with myasthenia gravis (MG), and the relationships among symptoms, activities and environmental factors (EF), by using WHO's International Classification of Functioning Disability and Health (ICF). Patients were consecutively enrolled at the Besta Institute of Milan, Italy.…

  17. Disability and Profiles of Functioning of Patients with Parkinson's Disease Described with ICF Classification

    Science.gov (United States)

    Raggi, Alberto; Leonardi, Matilde; Ajovalasit, Daniela; Carella, Francesco; Soliveri, Paola; Albanese, Alberto; Romito, Luigi

    2011-01-01

    The objective of this study was to describe the functional profiles of patients with Parkinson's disease (PD), and the relationships between impairment in body functions, limitations in activities, and environmental factors, using the World Health Organization's International Classification of Functioning, Disability, and Health (ICF). Patients…

  18. Rehabilitation of traumatic brain injury in the light of the ICF.

    Science.gov (United States)

    Laxe, Sara; Cieza, Alarcos; Castaño-Monsalve, Beatriz

    2015-01-01

    Traumatic brain injury is a sudden and unexpected condition that gives rise to different impairments in body functions and structures leading to dramatic life changes, not only to the patient but also to his or her family and ultimately in the wider society. As a health strategy, rehabilitation aims to reduce disability and increasing the quality of life of those people that suffer from TBI but also to reduce the social burden associated with it. Functioning is the starting point of rehabilitation and the use of measurement instruments and classifications are commonly used tools for its definition. Within the endorsement of the ICF by WHO, there is now a classification and a conceptual framework for the description of functioning providing an opportunity of a full understanding of the experience of TBI. This paper aims to identify the utility of ICF in TBI as well as bringing new challenges for further clinical practice and research. ICF has shown itself to be useful in the content comparison of measurement instruments. It has also been used to describe the functional profile of individuals with TBI in both acute and chronic phases making it possible to draw comparisons across other health conditions. Furthermore, the development of the TBI ICF Core Sets provided an item bank to describe not only functional status but also to set goals and plan interventions. Overall, we now have a potentially useful tool in rehabilitation of TBI that allows us to understand the full burden of traumatic brain injury.

  19. Implications of the International Classification of Functioning, Disability and Health (ICF) for Test Development and Use

    Science.gov (United States)

    Carlson, Janet F.; Benson, Nicholas; Oakland, Thomas

    2010-01-01

    Implications of the International Classification of Functioning, Disability and Health (ICF) on the development and use of tests in school settings are enumerated. We predict increased demand for behavioural assessments that consider a person's activities, participation and person-environment interactions, including measures that: (a) address…

  20. The ICF core sets for hearing loss project: functioning and disability from the patient perspective.

    Science.gov (United States)

    Granberg, Sarah; Pronk, Marieke; Swanepoel, De Wet; Kramer, Sophia E; Hagsten, Hanna; Hjaldahl, Jennie; Möller, Claes; Danermark, Berth

    2014-11-01

    To explore areas of functioning, disability, and environmental factors of adults with hearing loss (HL) by using the ICF classification as a tool to determine and document each element. A qualitative study applying mainly focus-group methodology was applied. Thirty-six Dutch and South African adults (≥ 18 years of age) with HL (20-95 dB HL) who used oral communication as first communication. Summative content analysis was performed on the transcripts by linkage to appropriate ICF categories. 143 ICF categories were identified, most of which belonged to the Activities & Participation (d) component, closely followed by the Environmental factors component. Participants specifically mentioned categories related to oral communication and interaction. Assistive technology (such as hearing aids), noise, and support by and attitudes of others in the environment of the participants were considered highly influential for functioning and disability. The present study illustrates the complex and encompassing nature of aspects involved in functioning and disability of adults with HL. Findings highlight the necessity of using a multidimensional tool, such as the ICF, to map functioning and disability with hearing loss, allowing consideration and evaluation of aspects that are both internal and external.

  1. Interphase chromosomal abnormalities and mitotic missegregation of hypomethylated sequences in ICF syndrome cells.

    NARCIS (Netherlands)

    Gisselsson, D.; Shao, C.; Tuck-Muller, C.M.; Sogorovic, S.; Palsson, E.; Smeets, D.F.C.M.; Ehrlich, M.

    2005-01-01

    The immunodeficiency, centromeric region instability, facial anomalies (ICF) syndrome is a rare autosomal recessive disease. Usually, it is caused by mutations in the DNA methyltransferase 3B gene, which result in decreased methylation of satellite DNA in the juxtacentromeric heterochromatin at 1qh,

  2. Developmental Language Impairment through the Lens of the ICF: An Integrated Account of Children's Functioning

    Science.gov (United States)

    Dempsey, Lynn; Skarakis-Doyle, Elizabeth

    2010-01-01

    The conceptual framework of the World Health Organization's International Classification of Functioning, Disability and Health (ICF) has the potential to advance understanding of developmental language impairment (LI) and enhance clinical practice. The framework provides a systematic way of unifying numerous lines of research, which have linked a…

  3. Utility of the International Classification of Functioning, Disability and Health (ICF) for Educational Psychologists' Work

    Science.gov (United States)

    Aljunied, Mariam; Frederickson, Norah

    2014-01-01

    Despite embracing a bio-psycho-social perspective, the World Health Organization's International Classification of Functioning, Disability and Health (ICF) assessment framework has had limited application to date with children who have special educational needs (SEN). This study examines its utility for educational psychologists' work with…

  4. Choice-Making among Medicaid HCBS and ICF/MR Recipients in Six States

    Science.gov (United States)

    Lakin, K. Charlie; Doljanac, Robert; Byun, Soo-Yong; Stancliffe, Roger; Taub, Sarah; Chiri, Giuseppina

    2008-01-01

    Choice in everyday decisions and in support-related decisions was addressed among 2,398 adults with intellectual and developmental disabilities receiving Medicaid Home and Community Based Services (HCBS) and Intermediate Care Facility (ICF/MR) services and living in nonfamily settings in six states. Everyday choice in daily life and in…

  5. Site support program plan for ICF Kaiser Hanford Company, Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-10-01

    This document is the general administrative plan implemented by the Hanford Site contractor, ICF Kaiser Hanford Company. It describes the mission, administrative structure, projected staffing, to be provided by the contractor. The report breaks out the work responsibilities within the different units of the company, a baseline schedule for the different groups, and a cost summary for the different operating units.

  6. A Conceptual Definition of Vocational Rehabilitation Based on the ICF : building a shared global model

    NARCIS (Netherlands)

    Escorpizo, Reuben; Reneman, Michiel F.; Ekholm, Jan; Fritz, Julie; Krupa, Terry; Marnetoft, Sven-Uno; Maroun, Claude E.; Guzman, Julietta Rodriguez; Suzuki, Yoshiko; Stucki, Gerold; Chan, Chetwyn C. H.

    2011-01-01

    Background The International Classification of Functioning, Disability and Health (ICF) is a conceptual framework and classification system by the World Health Organization (WHO) to understand functioning. The objective of this discussion paper is to offer a conceptual definition for vocational reha

  7. Disability and Functional Profiles of Patients with Myasthenia Gravis Measured with ICF Classification

    Science.gov (United States)

    Leonardi, Matilde; Raggi, Alberto; Antozzi, Carlo; Confalonieri, Paolo; Maggi, Lorenzo; Cornelio, Ferdinando; Mantegazza, Renato

    2009-01-01

    The objective of this study is to describe functional profiles of patients with myasthenia gravis (MG), and the relationships among symptoms, activities and environmental factors (EF), by using WHO's International Classification of Functioning Disability and Health (ICF). Patients were consecutively enrolled at the Besta Institute of Milan, Italy.…

  8. 42 CFR 442.40 - Availability of FFP during appeals for ICFs/MR.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Availability of FFP during appeals for ICFs/MR. 442... INTERMEDIATE CARE FACILITIES FOR THE MENTALLY RETARDED Provider Agreements § 442.40 Availability of FFP during..., and effective date—(1) Scope. This section sets forth the extent of FFP in State Medicaid payments...

  9. Disability and Profiles of Functioning of Patients with Parkinson's Disease Described with ICF Classification

    Science.gov (United States)

    Raggi, Alberto; Leonardi, Matilde; Ajovalasit, Daniela; Carella, Francesco; Soliveri, Paola; Albanese, Alberto; Romito, Luigi

    2011-01-01

    The objective of this study was to describe the functional profiles of patients with Parkinson's disease (PD), and the relationships between impairment in body functions, limitations in activities, and environmental factors, using the World Health Organization's International Classification of Functioning, Disability, and Health (ICF). Patients…

  10. ICF and ICD codes provide a standard language of disability in young children.

    Science.gov (United States)

    Simeonsson, Rune J; Scarborough, Anita A; Hebbeler, Kathleen M

    2006-04-01

    The aim of this study was to examine the utility of a hierarchical algorithm incorporating codes from the International Classification of Functioning, Disability and Health--ICF (WHO, 2001) and the International Statistical Classification of Diseases-ICD (WHO, 1994) to classify reasons for eligibility of young children in early intervention. The database for this study was a nationally representative enrollment sample of more than 5,500 children in a longitudinal study of early intervention. Reasons for eligibility were reviewed and matched to the closest ICF or ICD codes under one of four major categories (Body Functions/Structures, Activities/Participation, Health Conditions, and Environmental Factors). The average number of reasons for eligibility provided per child was 1.5, resulting in a population summary exceeding 100%. A total of 305 ICF and ICD codes were used with most (77%) of the children having codes in the category of Body Function/Structures. Forty-one percent of the sample had codes of Health Conditions, whereas the proportions with codes in the Activities/Partipication and Environmental Categories were 10 and 5%, respectively. The results demonstrate that ICD and ICF can be jointly used as a common language to document disability characteristics of children in early intervention.

  11. A real-time brain-machine interface combining motor target and trajectory intent using an optimal feedback control design.

    Science.gov (United States)

    Shanechi, Maryam M; Williams, Ziv M; Wornell, Gregory W; Hu, Rollin C; Powers, Marissa; Brown, Emery N

    2013-01-01

    Real-time brain-machine interfaces (BMI) have focused on either estimating the continuous movement trajectory or target intent. However, natural movement often incorporates both. Additionally, BMIs can be modeled as a feedback control system in which the subject modulates the neural activity to move the prosthetic device towards a desired target while receiving real-time sensory feedback of the state of the movement. We develop a novel real-time BMI using an optimal feedback control design that jointly estimates the movement target and trajectory of monkeys in two stages. First, the target is decoded from neural spiking activity before movement initiation. Second, the trajectory is decoded by combining the decoded target with the peri-movement spiking activity using an optimal feedback control design. This design exploits a recursive Bayesian decoder that uses an optimal feedback control model of the sensorimotor system to take into account the intended target location and the sensory feedback in its trajectory estimation from spiking activity. The real-time BMI processes the spiking activity directly using point process modeling. We implement the BMI in experiments consisting of an instructed-delay center-out task in which monkeys are presented with a target location on the screen during a delay period and then have to move a cursor to it without touching the incorrect targets. We show that the two-stage BMI performs more accurately than either stage alone. Correct target prediction can compensate for inaccurate trajectory estimation and vice versa. The optimal feedback control design also results in trajectories that are smoother and have lower estimation error. The two-stage decoder also performs better than linear regression approaches in offline cross-validation analyses. Our results demonstrate the advantage of a BMI design that jointly estimates the target and trajectory of movement and more closely mimics the sensorimotor control system.

  12. A real-time brain-machine interface combining motor target and trajectory intent using an optimal feedback control design.

    Directory of Open Access Journals (Sweden)

    Maryam M Shanechi

    Full Text Available Real-time brain-machine interfaces (BMI have focused on either estimating the continuous movement trajectory or target intent. However, natural movement often incorporates both. Additionally, BMIs can be modeled as a feedback control system in which the subject modulates the neural activity to move the prosthetic device towards a desired target while receiving real-time sensory feedback of the state of the movement. We develop a novel real-time BMI using an optimal feedback control design that jointly estimates the movement target and trajectory of monkeys in two stages. First, the target is decoded from neural spiking activity before movement initiation. Second, the trajectory is decoded by combining the decoded target with the peri-movement spiking activity using an optimal feedback control design. This design exploits a recursive Bayesian decoder that uses an optimal feedback control model of the sensorimotor system to take into account the intended target location and the sensory feedback in its trajectory estimation from spiking activity. The real-time BMI processes the spiking activity directly using point process modeling. We implement the BMI in experiments consisting of an instructed-delay center-out task in which monkeys are presented with a target location on the screen during a delay period and then have to move a cursor to it without touching the incorrect targets. We show that the two-stage BMI performs more accurately than either stage alone. Correct target prediction can compensate for inaccurate trajectory estimation and vice versa. The optimal feedback control design also results in trajectories that are smoother and have lower estimation error. The two-stage decoder also performs better than linear regression approaches in offline cross-validation analyses. Our results demonstrate the advantage of a BMI design that jointly estimates the target and trajectory of movement and more closely mimics the sensorimotor control system.

  13. To adopt is to adapt: the process of implementing the ICF with an acute stroke multidisciplinary team in England.

    Science.gov (United States)

    Tempest, Stephanie; Harries, Priscilla; Kilbride, Cherry; De Souza, Lorraine

    2012-01-01

    The success of the International Classification of Functioning, Disability and Health (ICF) depends on its uptake in clinical practice. This project aimed to explore ways the ICF could be used with an acute stroke multidisciplinary team and identify key learning from the implementation process. Using an action research approach, iterative cycles of observe, plan, act and evaluate were used within three phases: exploratory; innovatory and reflective. Thematic analysis was undertaken, using a model of immersion and crystallisation, on data collected via interview and focus groups, e-mail communications, minutes from relevant meetings, field notes and a reflective diary. Two overall themes were determined from the data analysis which enabled implementation. There is a need to: (1) adopt the ICF in ways that meet local service needs; and (2) adapt the ICF language and format. The empirical findings demonstrate how to make the ICF classification a clinical reality. First, we need to adopt the ICF as a vehicle to implement local service priorities e.g. to structure a multidisciplinary team report, thus enabling ownership of the implementation process. Second, we need to adapt the ICF terminology and format to make it acceptable for use by clinicians.

  14. Systematic Literature Review on ICF From 2001 to 2013 in the Nordic Countries Focusing on Clinical and Rehabilitation Context.

    Science.gov (United States)

    Maribo, Thomas; Petersen, Kirsten S; Handberg, Charlotte; Melchiorsen, Hanne; Momsen, Anne-Mette H; Nielsen, Claus V; Leonardi, Matilde; Labriola, Merete

    2016-01-01

    We present a systematic review on International Classification of Functioning, Disability and Health (ICF) used in the Nordic countries from 2001 through 2013, describing and quantifying the development in utilization of ICF, and describe the extent to which the different components of the ICF have been used. A search was conducted in EMBASE, MEDLINE and PsycInfo. Papers from Nordic countries were included if ICF was mentioned in title or abstract. Papers were assigned to one of eight categories covering the wide rehabilitation area; furthermore, area of focus was assigned. Use of ICF components and intervention were coded in papers categorized as "clinical and/or rehabilitation contexts" or "non-clinical contexts". One hundred seventy papers were included, of these 99 papers were from the categories "clinical and/or rehabilitation contexts" or "non-clinical contexts". Forty-two percent of the 170 included papers were published in the period 2011 - 2013. There was an increase in ICF-relevant papers from 2001 to 2013, especially in the categories "clinical and/or rehabilitation contexts" and "non-clinical contexts". The most represented focus areas were neurology, musculoskeletal, and work-related areas. All five or at least four ICF components were mentioned in the results or discussions in most papers, and activity was most frequently mentioned.

  15. To adopt is to adapt: the process of implementing the ICF with an acute stroke multidisciplinary team in England

    Science.gov (United States)

    Tempest, Stephanie; Harries, Priscilla; Kilbride, Cherry; De Souza, Lorraine

    2012-01-01

    Purpose: The success of the International Classifcation of Functioning, Disability and Health (ICF) depends on its uptake in clinical practice. This project aimed to explore ways the ICF could be used with an acute stroke multidisciplinary team and identify key learning from the implementation process. Method: Using an action research approach, iterative cycles of observe, plan, act and evaluate were used within three phases: exploratory; innovatory and refective. Thematic analysis was undertaken, using a model of immersion and crystallisation, on data collected via interview and focus groups, e-mail communications, minutes from relevant meetings, feld notes and a refective diary. Results: Two overall themes were determined from the data analysis which enabled implementation. There is a need to: (1) adopt the ICF in ways that meet local service needs; and (2) adapt the ICF language and format. Conclusions: The empirical fndings demonstrate how to make the ICF classifcation a clinical reality. First, we need to adopt the ICF as a vehicle to implement local service priorities e.g. to structure a multidisciplinary team report, thus enabling ownership of the implementation process. Second, we need to adapt the ICF terminology and format to make it acceptable for use by clinicians. PMID:22372376

  16. Psychometric properties of an instrument to measure activities and participation according to the ICF concept in patients with mental disorders.

    Science.gov (United States)

    Brütt, Anna Levke; Schulz, Holger; Andreas, Sylke

    2015-01-01

    The International Classification of Functioning, Disability and Health (ICF) conceptualizes the bio-psycho-social model of health and illness, but cannot be used as an assessment instrument in routine care. The objective of this study was to psychometrically test a self-report instrument for measuring activities and social participation (ICF-Mental-A&P) of psychotherapy patients. For the psychometric evaluation of the ICF-Mental-A&P, participants completed a questionnaire on symptoms, interpersonal problems and quality of life at admission and at discharge of in-patient treatment. A consecutive sample of 2256 patients diagnosed with at least one mental disorder was recruited from eight in-patient units in Germany. After item selection, the ICF-Mental-A&P contained 31 items comprising six subscales examined by confirmatory factor analysis. Subscales had acceptable internal consistency (α = 0.78-0.90) and test-retest correlations (r = 0.71-0.86). There were several expected correlations (r ≥ 0.6) between ICF-Mental-A&P scores and measures of symptoms and interpersonal problems. Findings suggest that the ICF-Mental-A&P is a comprehensive, reliable measure of activities and participation according to the ICF concept for patients with mental disorders. It may therefore be an important instrument in clinical practice and could help to determine and evaluate functioning-related and patient-focused treatment outcomes.

  17. Soft computing model for optimized siRNA design by identifying off target possibilities using artificial neural network model.

    Science.gov (United States)

    Murali, Reena; John, Philips George; Peter S, David

    2015-05-15

    The ability of small interfering RNA (siRNA) to do posttranscriptional gene regulation by knocking down targeted genes is an important research topic in functional genomics, biomedical research and in cancer therapeutics. Many tools had been developed to design exogenous siRNA with high experimental inhibition. Even though considerable amount of work has been done in designing exogenous siRNA, design of effective siRNA sequences is still a challenging work because the target mRNAs must be selected such that their corresponding siRNAs are likely to be efficient against that target and unlikely to accidentally silence other transcripts due to sequence similarity. In some cases, siRNAs may tolerate mismatches with the target mRNA, but knockdown of genes other than the intended target could make serious consequences. Hence to design siRNAs, two important concepts must be considered: the ability in knocking down target genes and the off target possibility on any nontarget genes. So before doing gene silencing by siRNAs, it is essential to analyze their off target effects in addition to their inhibition efficacy against a particular target. Only a few methods have been developed by considering both efficacy and off target possibility of siRNA against a gene. In this paper we present a new design of neural network model with whole stacking energy (ΔG) that enables to identify the efficacy and off target effect of siRNAs against target genes. The tool lists all siRNAs against a particular target with their inhibition efficacy and number of matches or sequence similarity with other genes in the database. We could achieve an excellent performance of Pearson Correlation Coefficient (R=0. 74) and Area Under Curve (AUC=0.906) when the threshold of whole stacking energy is ≥-34.6 kcal/mol. To the best of the author's knowledge, this is one of the best score while considering the "combined efficacy and off target possibility" of siRNA for silencing a gene. The proposed model

  18. Design and generation of DVD-Ig™ molecules for dual-specific targeting.

    Science.gov (United States)

    DiGiammarino, Enrico; Ghayur, Tariq; Liu, Junjian

    2012-01-01

    The dual variable domain immunoglobulin (DVD-Ig™) protein is a new type of dual-specific IgG. As a novel therapeutic class, the great potential of the DVD-Ig protein is to simultaneously target two mediators of disease by a single pharmaceutical entity. The molecule contains an Fc region and constant regions in a configuration similar to a conventional IgG; however, the DVD-Ig protein is unique in that each arm of the molecule contains two variable domains (VDs). The VDs within an arm are linked in tandem and can possess different binding specificities. Here, we discuss critical design features of the DVD-Ig protein and describe a methodology for cloning, expressing, and purifying the molecules.

  19. Design and synthesis of benzylpiperidine inhibitors targeting the menin-MLL1 interface.

    Science.gov (United States)

    Ren, Jing; Xu, Wei; Tang, Le; Su, Minbo; Chen, Danqi; Chen, Yue-Lei; Zang, Yi; Li, Jia; Shen, Jingkang; Zhou, Yubo; Xiong, Bing

    2016-09-15

    Menin is an essential oncogenic cofactor for mixed lineage leukemia (MLL)-mediated leukemogenesis, functioning through its direct interaction with MLL1 protein. Therefore, targeting the menin-MLL1 protein-protein interface represents a promising strategy to block MLL-mediated leukemogenesis. On the basis of co-crystal structure analysis, starting from thienopyrimidine chemotype, we have investigated the detailed structure-activity relationship of the piperazinyl-dihydrothiazole moiety. Several compounds were found with potent inhibitory activity against menin and better activities in cell-based experiments than MI-2-2. Molecular docking analysis revealed a less explored subpocket, which could be used for the design of new menin-MLL1 inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Progress in the Design of the Stabilized Liner Compressor for MTF/MIF Plasma Target Development

    Science.gov (United States)

    Frese, Sherry; Frese, Michael; Turchi, Peter; Gale, Don

    2016-10-01

    The Stabilized Liner Compressor (SLC) seeks to extend concepts for repetitive, rotationally stabilized, liquid-metal liners driven by free-pistons to much higher drive pressures (25 vs 5 kpsi) and faster implosion speeds (2000 vs 100 m/s) than previously demonstrated. Such extension is needed to enable experiments with magnetized-plasma targets presently offering sizes and lifetimes of 10's cm diam and 10's microsec. SLC represents the confluence of several difficult technologies, including pulsed high pressures, high-speed rotating machinery and alkali-metal (Na, NaK) handling. Solution of the two-dimensional, unsteady, compressible flow of a rotating liquid-metal liner requires advanced numerical techniques. We report the use of the 2-1/2 dimensional MHD code MACH2 to explore flow options, including magnetic flux compression, and to provide pulsed pressure distributions for mechanical design. Supported by ARPA-E ALPHA Program.

  1. Preliminary shielding analysis in support of the CSNS target station shutter neutron beam stop design

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bin; CHEN Yi-Xue; WANG Wei-Jin; YANG Shou-Hai; WU Jun; YIN Wen; LIANG Tian-Jiao; JIA Xue-Jun

    2011-01-01

    The construction of China Spallation Neutron Source (CSNS) has been initiated in Dongguan,Guangdong, China.Thus a detailed radiation transport analysis of the shutter neutron beam stop is of vital importance. The analyses are performed using the coupled Monte Carlo and multi-dimensional discrete ordinates method. The target of calculations is to optimize the neutron beamline shielding design to guarantee personal safety and minimize cost. Successful elimination of the primary ray effects via the two-dimensional uncollided flux and the first collision source methodology is also illustrated. Two-dimensional dose distribution is calculated. The dose at the end of the neutron beam line is less than 2.5μSv/h. The models have ensured that the doses received by the hall staff members are below the standard limit required.

  2. Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria

    Directory of Open Access Journals (Sweden)

    Daniel Ken Inaoka

    2015-07-01

    Full Text Available Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM. In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.

  3. Rational design of small molecule inhibitors targeting the Ras GEF, SOS1

    Science.gov (United States)

    Evelyn, Chris R.; Duan, Xin; Biesiada, Jacek; Seibel, William L.; Meller, Jaroslaw; Zheng, Yi

    2014-01-01

    Summary Ras GTPases regulate intracellular signaling involved in cell proliferation. Elevated Ras signaling activity has been associated with human cancers. Ras activation is catalyzed by guanine-nucleotide exchange factors (GEFs), of which SOS1 is a major member that transduces receptor tyrosine kinase signaling to Ras. We have developed a rational approach coupling virtual screening with experimental screening in identifying small-molecule inhibitors targeting the catalytic site of SOS1 and SOS1-regulated Ras activity. A lead inhibitor, NSC-658497, is found to bind to SOS1, competitively suppresses SOS1-Ras interaction, and dose-dependently inhibits SOS1 GEF activity. Mutagenesis and structure-activity relationship studies map the NSC-658497 site of action to the SOS1 catalytic site, and define the chemical moieties in the inhibitor essential for the activity. NSC-658497 showed dose-dependent efficacy in inhibiting Ras, downstream signaling activities, and associated cell proliferation. These studies establish a proof of principle for rational design of small-molecule inhibitors targeting Ras GEF enzymatic activity. PMID:25455859

  4. Rational design of small molecule inhibitors targeting the Ras GEF, SOS1.

    Science.gov (United States)

    Evelyn, Chris R; Duan, Xin; Biesiada, Jacek; Seibel, William L; Meller, Jaroslaw; Zheng, Yi

    2014-12-18

    Ras GTPases regulate intracellular signaling involved in cell proliferation. Elevated Ras signaling activity has been associated with human cancers. Ras activation is catalyzed by guanine nucleotide exchange factors (GEFs), of which SOS1 is a major member that transduces receptor tyrosine kinase signaling to Ras. We have developed a rational approach coupling virtual screening with experimental screening in identifying small-molecule inhibitors targeting the catalytic site of SOS1 and SOS1-regulated Ras activity. A lead inhibitor, NSC-658497, was found to bind to SOS1, competitively suppress SOS1-Ras interaction, and dose-dependently inhibit SOS1 GEF activity. Mutagenesis and structure-activity relationship studies map the NSC-658497 site of action to the SOS1 catalytic site, and define the chemical moieties in the inhibitor essential for the activity. NSC-658497 showed dose-dependent efficacy in inhibiting Ras, downstream signaling activities, and associated cell proliferation. These studies establish a proof of principle for rational design of small-molecule inhibitors targeting Ras GEF enzymatic activity.

  5. Design and preparation of a novel colon-targeted tablet of hydrocortisone

    Directory of Open Access Journals (Sweden)

    Yachao Ren

    Full Text Available ABSTRACT The objective of this research was to design a new c