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Sample records for eurisol target design

  1. 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...

  2. 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 ...

  3. EURISOL-DS Overall Design of the Multi-MW Target Station

    CERN Document Server

    Olivier Choisnet, Cyril Kharoua, Yacine Kadi, Karel Samec (CERN)

    The EURISOL Design Study investigated the feasibility of a complex instrument to push back the boundaries of current physics knowledge amidst today’s ever-increasing need for realism due to constraints imposed by safety, performance and, not least, budgetary responsibility.In order to attend to these concerns, the EURISOL Multi-Megawatt converter target, its associated fission targets and the three 100 kW direct targets are all integrated into a single facility housing the ancillary equipment as well. The overall layout of the facility, its functional break-down and the main modes of operation are presented in the current report.

  4. EURISOL High Power Targets

    CERN Document Server

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

    2009-01-01

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

  5. EURISOL-DS Multi-MW Target: A safe way to run the CGS converter

    CERN Document Server

    Cyril Kharoua, Yacine Kadi, Karel Samec (CERN)

    This technical note summarizes the design calculations performed within Task#2 of the European Isotope Separation On-Line Radioactive Ion Beam Facility Design Study (EURISOL-DS) on the safety hull of the CGS design of the mercury converter. A study was carried out in order to propose a configuration for the safety hull and the connection between the target and the accelerator. The results of these calculations show a layout and a design proposal for the safety barrier of the EURISOL DS target design.

  6. Activation calculation of the EURISOL mercury target

    Energy Technology Data Exchange (ETDEWEB)

    Rapp, B.; David, J.C.; Blideanu, V.; Dore, D.; Ridikas, D.; Thiolliere, N

    2006-08-15

    We have used MCNPX coupled to CINDER to estimate the production of radioactive nuclides in the EURISOL 4 MW liquid mercury target during a 40 years'lifetime of the installation. The calculations have been done with different intra-nuclear cascade and fission evaporation model combinations. A benchmark exercise has allowed a better understanding of differences seen between these models for the creation of tritium and fission products. To obtain a realistic production yield for tritium gas in proton induced spallation reactions, we recommend using the ISABEL-RAL model, while both CEM2k and BERTINI-RAL overestimate the production rate above 1 GeV incident proton. The best combinations of models to calculate the residual nuclei production are those using ABLA fission-evaporation model, CEM2k or combinations using RAL model are giving too broad mass distributions when compared to available data. An extensive list of radio-nuclides was obtained and is available on tabular format, we show that the 4 nuclei whose contributions to the total activity of the mercury target (after 40 years of irradiation) are the most important are the following: -) 1 day after shutdown: Y{sup 91} (15%), Y{sup 90} (13%), Hg{sup 197} (6%) and Sr{sup 89} (5%); -) 1 year after shutdown: H{sup 3} (19%), Y{sup 90} (17%), Sr{sup 90} (17%) and Nb{sup 93*} (10%); -) 10 years after shutdown: Y{sup 90} (22%), Sr{sup 90} (22%), H{sup 3} (18%) and Nb{sup 93*} (14%); and -) 100 years after shutdown: Mo{sup 93} (34%), Nb{sup 93*} (32%), Pt{sup 193} (9%) and Y{sup 90} (8%). (A.C.)

  7. EURISOL-DS MULTI-MW TARGET ISSUES: BEAM WINDOW AND TRANSVERSE FILM TARGET

    CERN Document Server

    Adonai Herrera-Martínez, Yacine Kadi

    The analysis of the EURISOL-DS Multi_MW target precise geometry (Fig.1) has proved that large fission yields can be achieved with a 4 MW, providing a technically feasible design to evacuate the power deposited in the liquid mercury. Different designs for the mercury flow have been proposed, which maintain its temperature below the boiling point with moderate flow speeds (maximum 4 m/s).

  8. Thermo-Hydraulic Optimisation of the EURISOL-DS MMW Hg target

    CERN Document Server

    M. Ashrafi-Nik

    The present document describes the thermal and the stress analysis of the final design of the EURISOL DS target. The preliminary design by Q. Prétet, R. Milenkovic and B. Smith was used as a starting point for further improvements to reduce stresses in the hull; the results of these computations are summarised in this document. All variants studied to attain the objective are documented using CFD to assess the effects of different flow configurations on the temperature distribution in the target liquid metal and structural analysis for determining the stresses and temperatures in the target structure.

  9. Mercury purification in the megawatt liquid metal spallation target of EURISOL-DS

    CERN Document Server

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

    High power spallation targets are going to be used extensively in future research and technical facilities such as spallation neutron sources, neutrino factories, radioactive beam facilities or accelerator driven systems for the transmutation of long-lived nuclear waste. Within EURISOL-DS, a 4 MW liquid metal spallation target is designed to provide neutrons for a fission target, where neutron rich radionuclides will be produced. For the spallation target, mercury is planned to be used as target material. A large amount of radionuclides ranging from atomic number Z=1 to 81 will be produced in the liquid metal during long term irradiation. It is planned to remove those radionuclides by chemical or physicochemical methods to reduce its radioactivity. For the development of a purification procedure, knowledge about the chemical state of the different elements present in the mixture is required. We present a general concept of applicable separation techniques in a target system and show some results of experiment...

  10. EURISOL-DS Multi-MW Target: Thermal Behaviour of the fission target disk arrangement inspired by the MAFF project

    CERN Document Server

    Cyril Kharoua, Yacine Kadi and the EURISOL-DS Task#2 collaboration

    This technical note summarises the design calculations performed within Task #2 of the European Isotope Separation On-Line Radioactive Ion Beam Facility Design Study (EURISOL-DS) [1] for the thermal behaviour of the fission target.A preliminary study was carried out in order to determine the heat deposition within the fissile material and estimate the temperature rise. This new solution takes into account the problems related to effusion/diffusion of radioactive isotopes inside a thick target. To enhance the extraction rates and the thermal behaviour it is proposed to study a solution where the fissile material is split into an arrangement of disks.

  11. EURISOL-DS Multi-MW Target: Risk Register

    CERN Document Server

    C. Kharoua and Y. Kadi (CERN)

    The purpose of the risk register is to identify and rank the risk inherent to the installation, operation, maintenance, dismantling and disposal of each item of the facility and to propose ways of mitigating such risks.It is an important input for the safety report which will be mandatory for the study towards the construction of the EURISOL Facility.

  12. Eurisol-DS Multi-MW target A proposal for improving overall performance in relation to the isotope yield

    CERN Document Server

    Samec, K; Kadi, Yacine; Rocca, Roberto; Kharoua, Cyril

    2008-01-01

    The Eurisol Design Study has been initiated by the European Commission to demonstrate the feasibility of a facility for producing large yields of exotic isotopes. At the core of the projected facility, the neutron source produces spallation neutrons from a proton beam impacting dense liquid metal. The neutrons emitted from the source are used to fission Uranium targets which, in turn, produce high yields of isotopes. This technical report summarises efforts to improve the overall performance of the planned facility, by optimising the neutron source and the disposition of the fission targets.

  13. EURISOL-DS Multi-MW Target. A proposal for improving overall performance in relation to the isotope yield

    CERN Document Server

    Karel Samec, Mats Lindroos, Yacine Kadi,Roberto Rocca, Cyril KharouaAB Dept. ATB

    The Eurisol Design Study has been initiated by the European Commission to demonstratethe feasibility of a facility for producing large yields of exotic isotopes.At the core of the projected facility, the neutron source produces spallation neutrons from aproton beam impacting dense liquid metal. The neutrons emitted from the source are usedto fission Uranium targets which, in turn, produce high yields of isotopes.This technical report summarises efforts to improve the overall performance of the plannedfacility, by optimising the neutron source and the disposition of the fission targets.

  14. EURISOL-DS Multi-MW Target Preliminary Study of the Liquid Metal Proton-to-Neutron Converter

    CERN Document Server

    Herrera-Martínez, A; CERN. Geneva. AB Department

    2006-01-01

    This technical note summarises the design calculations performed within Task #2 of the European Isotope Separation On-Line Radioactive Ion Beam Facility Design Study (EURISOL-DS) [1]. A preliminary study was carried out in order to determine the optimum value of relevant parameters in the target design. Different scenarios were simulated using the Monte Carlo code FLUKA [2]. Namely, sensitivity studies were performed to assess the impact of the projectile particle energy on the neutronics and energy deposition in the spallation target. The optimal target dimensions were also studied for every case as well as the proper target material for the liquid metal proton-to-neutron converter, since mercury and lead-bismuth eutectic are reasonable options. The effect of the beam width on the power densities was also evaluated, taking into account the geometrical limitations of the facility. Finally, a comparison between protons and deuterons as primary particles was performed, acknowledging the limitations of using FLU...

  15. In-target rare nuclei production rates with EURISOL single-stage configuration

    CERN Document Server

    Chabod, S P; Ene, D; Doré, D; Blideanu, V; David, J.-Ch; Ridikas, D

    2010-01-01

    We conducted calculations of exotic nuclei production rates for 320 configurations of EURISOL (European Isotope Separation On-Line Radioactive Ion Beam Facility) direct spallation targets. The nuclei yields were evaluated using neutron generation-transport codes, completed with evolution calculations to account for nuclei decays and low energy neutron interactions. The yields were optimized for 11 selected elements (Li, Be, Ne, Mg, Ar, Ni, Ga, Kr, Sn, Hg, Fr) and 23 of their isotopes, as function of the target compositions and geometries as well as the incident proton beam energies. For the considered elements, we evaluated the yield distributions as functions of the charge and mass numbers using two different spallation models.

  16. EURISOL-DS Multi-MW Target Neutronic Calculations for the Baseline Configuration of the Multi-MW Target

    CERN Document Server

    Herrera-Martínez, A

    2006-01-01

    This document summarises the study performed within the Task #2 of the European Isotope Separation On-Line Radioactive Ion Beam Facility Design Study (EURISOL DS) [1] to design the Multi-MW proton-to-neutron converter. A preliminary study [2] was carried out in order to understand the nature of the interactions taking place in the proton-to-neutron converter and their impact on the design of the facility. Namely, the target dimensions and material composition, type of incident particle, its energy and the beam profile were analysed in the aforementioned technical note, and their optimum values were suggested in the conclusions. The present work is based on the results of the previous study and uses the same methodology, namely Monte Carlo simulations with FLUKA [3]. This note describes the performance of a Hg target design and addresses more detailed issues, such as the composition of the fission target and use of a neutron reflector. It also attempts to integrate those components together and estimate the wh...

  17. Innovative Waste Management in the Mercury Loop of the EURISOL Multi-MW Converter Target

    CERN Document Server

    PSI: Jörg Neuhausen, Dorothea Schumann, Rugard Dressler, Susanne Horn, Sabrina Lüthi, Stephan Heinitz, Suresh ChirikiCERN: Thierry Stora, Martin Eller

    The choice of mercury as target material imposes various questions concerning the safe operation of such a system that are related to the physical and chemical properties of the target material itself and the nuclear reaction products produced within the target during its life time of several decades. Therefore, a subtask was created within the EURISOL-DS project that is concerned with studying an innovative waste management for the generated radioactivity by chemical means. Such a study strongly depends on the radioactive inventory and its distribution throughout the target and loop system. Radioactive inventory calculations were performed within task 5 [6]. The distribution of nuclear reaction products and their chemical state that can be expected within the target and loop system is one of the topics covered in this report. Based on the results obtained by theoretical studies as well as laboratory scale experiments, the feasibility of waste reduction using chemical methods, both conventional (e.g. leaching...

  18. TARPIPE: TARget Prototype Irradiations at PSI for EURISOL

    CERN Document Server

    E. Bouquerel1, R. Catherall1, S. Fernandes1, I. Guenther-Leopold2, F. Groeschel2, A. Kalt2, J.

    The selection of target materials for the production of radioactive nuclear beams is made on thebasis of several criteria that include the production cross-sections for isotopes of interest,diffusion, effusion, ageing and heat dissipation. Optimal target materials are often the result ofcompromises between these properties, which must be preserved under damaging operationconditions...

  19. Beam dynamics study and superconducting triple spoke cavity design for the EURISOL driver

    International Nuclear Information System (INIS)

    Ponton, A.

    2009-07-01

    EURISOL will be the next generation source of intense radioactive ion beams. Its accelerator complex consists of a driver linac, a set of targets and sources and a post-accelerator linac which aims at supplying different experimental areas with the exotic ions. The presented study deals with the driver accelerator: a superconducting RF linac capable of accelerating different ion kinds (D + , 3 He 2+ and H - ) up to a maximal power of 4 MW. First beam dynamics studies pointed out a very good acceleration efficiency when triple spoke cavities working at a frequency of 352 MHz are used in the medium energy part (0.2 < beta < 0.4). Thanks to a novel geometry, the electromagnetic design of the proposed cavity leads to 33 MV/m and 72 mT for the peak electric field and magnetic induction respectively at an ambitious accelerating field of 8 MV/m. The beam transport was then simulated and optimized in the original layout and calculations were also performed considering an alternative, periodic solution, for the low energy part. The 'all-periodic' linac keeps the beam qualities better by strongly reducing the emittance growth and the halo formation. (author)

  20. EURISOL-DS Multi-MW Target Comparative Neutronic Performance of the Baseline Configuration vs. the Hg-Jet Option

    CERN Document Server

    Herrera-Martínez, A

    2006-01-01

    This technical report summarises the comparative study between several design options for the Multi-MW target station performed within Task #2 of the European Isotope Separation On-Line Radioactive Ion Beam Facility Design Study (EURISOL DS) [1]. Previous analyses were carried out, using the Monte Carlo code FLUKA [2], to determine optimal values for relevant parameters in the target design [3] and to analyse a preliminary Multi-MW target assembly configuration [4]. The second report showed that the aimed fission rates, i.e. ~1015 fissions/s, could be achieved with such a configuration. Nevertheless, a preliminary study of the target assembly integration [5] suggested reducing some of the dimensions. Moreover, the yields of specific isotopes have yet to be assessed and compared to other target configurations. This note presents a detailed comparison of the baseline configuration and the Hg-jet option, in terms of primary and neutron distribution, power densities and fission product yields. A scaled-down versi...

  1. Eurisol-DS Multi MW Target Preliminary Study of the Windlowless Transverse Film (WTF) Liquid Metal Proton-to Neutron Converter

    CERN Document Server

    Kadi, Y; Rocca, R; Samec, K

    2008-01-01

    This technical note summarises the design calculations performed within Task#2 of the European Isotope Separation On-Line Radioactive Ion Beam Facility Design Study (EURISOL-DS) for the WTF (Windowless Transverse Film) mercur converter. A preliminary study was carried out in order to determine the heat deposition within the mercury and estimate the mercury velocity needed in the film. The geometry used is based on previous analysis simulated using the Monte Carlo code FLUKA. The results of these calculations show the baseline parameters, which will be used for the detailed design. Particularly, with a 1 GeV proton beam with a $\\sigma$ ~2 mm Gaussian distribution on a 4x30x40cm long target and with a 5m/s velocity at the peak power density region seems a suitable solution.

  2. EURISOL-DS Multi-MWatt Hg Target: Neutron flux and fission rate calculations for the MAFF configuration

    CERN Document Server

    Romanets, Y; Vaz, P; Herrera-Martinez, A; Kadi, Y; Kharoua, C; Lettry, J; Lindroos, M

    The EURISOL (The EURopean Isotope Separation On-Line Radioactive Ion Beam) project aims at producing high intensity radioactive ion beams produced by neutron induced fission on a fissile target (235U) surrounding a liquid mercury converter. A proton beam of 1 GeV and 4 MW impinges on the Hg converter generating by spallation reactions high neutron fluxes. In this work the state-of-the-art Monte Carlo codes MCNPX and FLUKA were used to assess the neutronics performance of the system which geometry, inspired from the MAFF concept, allows a versatile manipulation of the fission targets. The objective of the study was to optimize the geometry of the system and the materials used in the fuel and reflector elements of the system, in order to achieve the highest possible fission rate.

  3. Development of the EURISOL Multi-Megawatt Target Station (2005-2009): Executive Summary

    CERN Document Server

    Karel Samec et al. (CERN, IPUL, ITN and PSI)

    Advances in nano-technology, bio-technology, nuclear medicine and the fundamental sciences require a facility to continue improving current capabilities in Europe beyond the year 2010. European competitiveness could benefit greatly from a unique research facility, flexible enough to satisfy users from many different fields of science and technology. The facility would be a valuable asset enabling economies of scale and giving Europe access to cutting-edge technology at the heart of future technological advances of major economic importance. Specialised facilities already operating at full capacity such as SINQ in Switzerland, ILL in France, have demonstrated the benefits of bringing together users from different scientific backgrounds and different countries. Such a research policy may be reinforced by the improved performance and greater reach of the EURISOL project which is aimed at a larger research community. Beneficiaries include the medical sciences such as oncology, medical imagery or studies of protei...

  4. EURISOL-DS multi-MW target unit: Neutronics performance and shielding assessment, dose rate and material activation calculations for the MAFF configuration

    CERN Document Server

    Romanets, Y; Kadi, Y; Luis, R; Goncalves, I F; Tecchio, L; Kharoua, C; Vaz, P; Ene, D; David, J C; Rocca, R; Negoita, F

    2010-01-01

    One of the objectives of the EURISOL (EURopean Isotope Separation On-Line Radioactive Ion Beam) Design Study consisted of providing a safe and reliable facility layout and design for the following operational parameters and characteristics: (a) a 4 MW proton beam of 1 GeV energy impinging on a mercury target (the converter); (b) high neutron fluxes (similar to 3 x 10(16) neutrons/s) generated by spallation reactions of the protons impinging in the converter and (c) fission rate on fissile U-235 targets in excess of 10(15) fissions/s. In this work, the state-of-the-art Monte Carlo codes MCNPX (Pelowitz, 2005) and FLUKA (Vlachoudis, 2009; Ferrari et al., 2008) were used to characterize the neutronics performance and to perform the shielding assessment (Herrera-Martinez and Kadi, 2006; Cornell, 2003) of the EURISOLTarget Unit and to provide estimations of dose rate and activation of different components, in view of the radiation safety assessment of the facility. Dosimetry and activation calculations were perfor...

  5. The First Steps to EURISOL

    International Nuclear Information System (INIS)

    Butler, P.A.

    2007-01-01

    Following the results and recommendations of the EURISOL RTD conceptual design study performed within FP5, the EURISOL Design Study http://www.eurisol.org aims to carry out detailed engineering-oriented studies and technical prototyping work for the next-generation ISOL Radioactive Ion Beam (RIB) facility in Europe. Such a world-class facility, complementary to the '' in-flight '' FAIR facility being constructed at GSI, is expected to come into operation in the next decade. It would provide unique world-class research opportunities in nuclear physics, nuclear astrophysics and other applications of radioactive beam science. The Design Study addresses the major technological problems which are expected to arise in the creation of a facility able to provide exotic ions in quantities which are orders of magnitude higher than those currently available anywhere else in the world. A feasibility study into the use of the EURISOL facility for the production of pure electron-neutrinos is an integral part of the design study, the so-called '' beta-beam '' proposal. Synergies which exist between the proposed infrastructure and other European ISOL developments - MAFF, HIE-ISOLDE, SPES, and SPIRAL2 - will be exploited to mutual advantage. Twenty institutes within Europe take part in the design study as full participants, with an additional 20 in Europe, North America and Asia collaborating in the project. In this Design Study the members of the collaboration provide specific technological expertise on superconducting linear accelerators, high-power targetry, RIB production, ion sources and beam manipulation, radiation safety and nuclear instrumentation. (author)

  6. EURISOL Multi-MW Target: Investigation of the hydrodynamics of liquid metal (Hg) jet

    CERN Document Server

    Freibergs, J

    In order to develop a windowless target it is necessary to investigate the hydrodynamics of liquid metal (Hg) jet. On the basis of the schematic layout of a high-power target module presented in Ref. [2], and the parameters of the windowless target (speed of the mercury jet up to 30 m/s, diameter of jet 10-20 mm and length of jet about 1 m), a first estimation of the parameters of the main components of a Hg-loop has been obtained by the Institute of Physics, University of Latvia. A preliminary engineering design of a functional Hg-loop to be constructed soon is also proposed. A simplified water stand has been developed with the ability of testing different Hg-nozzle configurations. The tests carried out showed that the kinetic energy of the jet is so high that the coaxial water flow at contact point is transformed into small bubbles (spray). The characteristics of the jet were shown to depend on the pressure of the stand.

  7. EURISOL-DS Multi‐MW Target: Radiological Protection, Radiation Safety and Shielding Aspects

    CERN Document Server

    Y. Romanets and R. Luís (ITN)

    The objective of this work was to carry out a detailed study and analysis of all aspects related toradioprotection and radiation safety of the spallation target area and the whole spaces reservedfor the fission targets and spallation target maintenance. Operational and no‐operationalconditions were considered for an evaluation of the radiation safety conditions.An analysis of the proposed shielding dimensions and configuration was performed for thesystem during operation time. Parameters as activation, dose rate, energy deposition, etc. aremore important for the no‐operation period, in order to evaluate the hazard level anddetermine the staff access type to the maintenance areas (direct or remote control).Such elements as the fission targets and the whole structure involved on it were studied in moredetail because of the disposal issues, after operation. Activation, dose rate and residual nuclideswere studied for each element of the assembly. All parameters were analyzed according to their...

  8. Feasibility of High Power Refractory Metal Foil-Targets for EURISOL

    CERN Document Server

    R. Wilfinger, J. Lettry and the EURISOL Task 3 Workgroup

    Radioisotopes are produced by the ISOL method in thick targets. In existing ISOL facilities, only small yields have been obtained for short-lived nuclei close to the driplines due to the radioactive decay during the diffusion, effusion and ionization processes. An increase of the proton beam current increases the production rate, which is directly proportional to the primary proton flux. But at the same time, the power deposition inside the target is also increased proportional to the primary proton flux...

  9. Benchmark calculations on residue production within the EURISOL DS project; Part I: thin targets

    CERN Document Server

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

    Report on benchmark calculations on residue production in thin targets. Calculations were performed using MCNPX 2.5.0 coupled to a selection of reaction models. The results were compared to nuclide production cross-sections measured in GSI in inverse kinematics

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

    CERN Document Server

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

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

  11. EURISOL-DS Multi-MW Target: Experimental program associated to validation of CFD simulations of the mercury loop

    CERN Document Server

    Blumenfeld, Laure; Kadi, Yacine; Samec, Karel; Lindroos, Mats

    At the core of the Eurisol project facility, the neutron source produces spallation neutrons from a proton beam impacting dense liquid. The liquid circulates at high speed inside the source, a closed vessel with beam windows.This technical note summarises the needed of the hydraulic METEX 1 and METEX 2 data tests to contribute to validate CFD turbulent simulation of liquid metal with the LES model and FEM structural model as well as a-dimensional analysis of Laser Dopplet Velocimetry for cavitation measurements.

  12. Benchmark calculations on residue production within the EURISOL DS project. Part 1: thin targets

    Energy Technology Data Exchange (ETDEWEB)

    David, J.C.; Blideanu, V.; Boudard, A.; Dore, D.; Leray, S.; Rapp, B.; Ridikas, D.; Thiolliere, N

    2006-12-15

    We have begun this benchmark study using mass distribution data of reaction products obtained at GSI in inverse kinematics. This step has allowed us to make a first selection among 10 spallation models; in this way the first assessment of the quality of the models was obtained. Then, in a second part, experimental mass distributions for some elements, which either are interesting as radioactive ion beams or important due to the safety and radioprotection issues (alpha or gamma emitters), will be also compared to model calculations. These data have been obtained for an equivalent 0.8 or 1.0 GeV proton beam, which is approximately the proposed projectile energy. We note that in realistic thick targets the proton beam will be slowed down and some secondary particles will be produced. Therefore, the residual nuclei production at lower energies is also important. For this reason, we also performed in the third part of this work some excitation function calculations and the associated data obtained with gamma-spectroscopy to test the models in a wide projectile energy range. We conclude that INCL4/Abla and Isabel/Abla are the best model combinations which we recommend. We also note that the agreement between model and data are better with 1 GeV protons than with 100-200 MeV protons.

  13. Poster: The EURISOL Beta-beam facility

    CERN Document Server

    The beta-beam concept for the generation of an electron (anti-)neutrino beam was proposed by Piero Zucchelli (CERN) in 2002. A first study of the possibility of using the existing CERN machines for the acceleration for radioactive ions to a relativistic gamma of roughly 100, for later storage in a new decay ring of approximately the size of SPS, was made in 2002. The results from this very first short study were very encouraging.In 2004 it was decided to incorporate a design study for the beta-beam within the EURISOL DS proposal. EURISOL is a project name for a next-generation radioactive beam facility based on the ISOL method for the production of intense radioactive beams for nuclear physics, astrophysics and other applications. The proposal was accepted with the beta-beam task as an integral part. The design study officially started 1 February 2005 and will run for 4 years resulting in a conceptual design report for a beta-beam facility.

  14. High Power CW Superconducting Linacs for EURISOL and XADS

    CERN Document Server

    Biarrotte, J L

    2004-01-01

    A multi-MW superconducting proton linac is proposed as the baseline solution for the EURISOL and the XADS driver accelerators. In the EURISOL project, which studies the design of the next-generation European ISOL facility, it is used to produce both neutron-deficient and neutron-rich exotic nuclei far from the valley of stability. In the PDS-XADS project, which aims to the demonstration of the feasibility of an ADS system for nuclear waste transmutation, it is used to produce the neutron flux required by the associated sub-critical reactor. In this paper, we report the main results and conclusions reached within these preliminary design studies. A special emphasis is given on the on-going and future R&D to be done to accomplish the demonstration of the full technology.

  15. The Eurisol report. A feasibility study for a European isotope-separation-on-line radioactive ion beam facility

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-12-01

    The Eurisol project aims at a preliminary design study of the next-generation European isotope separation on-line (ISOL) radioactive ion beam (RIB) facility. In this document, the scientific case of high-intensity RIBs using the ISOL method is first summarised, more details being given in appendix A. It includes: 1) the study of atomic nuclei under extreme and so-far unexplored conditions of composition (i.e. as a function of the numbers of protons and neutrons, or the so-called isospin), rotational angular velocity (or spin), density and temperature, 2) the investigation of the nucleosynthesis of heavy elements in the Universe, an important part of nuclear astrophysics, 3) a study of the properties of the fundamental interactions which govern the properties of the universe, and in particular of the violation of some of their symmetries, 4) potential applications of RIBs in solid-state physics and in nuclear medicine, for example, where completely new fields could be opened up by the availability of high-intensity RIBs produced by the ISOL method. The proposed Eurisol facility is then presented, with particular emphasis on its main components: the driver accelerator, the target/ion-source assembly, the mass-selection system and post-accelerator, and the required scientific instrumentation. Special details of these components are given in appendices B to E, respectively. The estimates of the costs of the Eurisol, construction and running costs, have been performed in as much details as is presently possible. The total capital cost (installation manpower cost included) of the project is estimated to be of the order of 630 million Euros within 20%. In general, experience has shown that operational costs per annum for large accelerator facilities are about 10% of the capital cost. (A.C.)

  16. EURISOL MERCURY TARGET EXPERIMENT: CERN SAFETY REPORT

    CERN Document Server

    J. Gulley (CERN SC/GS)

    Report on a visit to the mercury-handling lab at IPUL. The aim was to provide recommendations to IPUL on general health and safety issues relatring to the handling of mercury, the objective being to reduce exposure to acceptable levels, so far as is reasonably practical.

  17. Multi-MW target station: Beam Window Issues and Transverse Film Target

    CERN Document Server

    Herrera-Martinez, A

    The analysis of the EURISOL-DS Multi_MW target precise geometry has proved that large fission yields can be achieved with a 4 MW, providing a technically feasible design to evacuate the power deposited in the liquid mercury. Different designs for the mercury flow have been proposed, which maintain its temperature below the boiling point with moderate flow speeds (maximum 4 m/s).

  18. Measurement and analysis of turbulent liquid metal flow in a high-power spallation neutron source-EURISOL

    CERN Document Server

    Samec, K; Blumenfeld, L; Kharoua, C; Dementjevs, S; Milenkovic, R Z

    2011-01-01

    The European Isotope Separation On-Line (EURISOL) design study completed in 2009 examined means of producing exotic nuclei for fundamental research. One of the critical components identified in the study was a high-power neutron spallation source in which a target material is impacted by a proton beam producing neutrons by a process known as spallation. Due to the high heat power deposition, liquid metal, in this case mercury, is the only viable choice as target material. Complex issues arise from the use of liquid metal. It is characterised by an unusually low Prandtl number and a higher thermal expansivity than conventional fluids. The turbulence structure in LM is thereby affected and still an object of intense research, hampered in part by measurement difficulties. The use of Computational Fluid Dynamics (CFD) allowed a satisfactory design for the neutron source to be found rapidly with little iteration. However it was feared that the development of the boundary layer and associated turbulence would not b...

  19. Fusion target design

    International Nuclear Information System (INIS)

    Bangerter, R.O.

    1978-01-01

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

  20. BEAM DYNAMICS SIMULATIONS OF SARAF ACCELERATOR INCLUDING ERROR PROPAGATION AND IMPLICATIONS FOR THE EURISOL DRIVER

    CERN Document Server

    J. Rodnizki, D. Berkovits, K. Lavie, I. Mardor, A. Shor and Y. Yanay (Soreq NRC, Yavne), K. Dunkel, C. Piel (ACCEL, Bergisch Gladbach), A. Facco (INFN/LNL, Legnaro, Padova), V. Zviagintsev (TRIUMF, Vancouver)

    AbstractBeam dynamics simulations of SARAF (Soreq Applied Research Accelerator Facility) superconducting RF linear accelerator have been performed in order to establish the accelerator design. The multi-particle simulation includes 3D realistic electromagnetic field distributions, space charge forces and fabrication, misalignment and operation errors. A 4 mA proton or deuteron beam is accelerated up to 40 MeV with a moderated rms emittance growth and a high real-estate gradient of 2 MeV/m. An envelope of 40,000 macro-particles is kept under a radius of 1.1 cm, well below the beam pipe bore radius. The accelerator design of SARAF is proposed as an injector for the EURISOL driver accelerator. The Accel 176 MHZ β0=0.09 and β0=0.15 HWR lattice was extended to 90 MeV based on the LNL 352 MHZ β0=0.31 HWR. The matching between both lattices ensures smooth transition and the possibility to extend the accelerator to the required EURISOL ion energy.

  1. The rapid cycling synchrotron of the Eurisol / Beta-Beam facility

    International Nuclear Information System (INIS)

    Lachaize, A.

    2008-09-01

    In order to ask for physicians requests, some neutrinos facilities are under studies to produce pure, intense, well collimated neutrinos beams with a well determined energy spectrum. One of them, the Beta-Beam project, is based on neutrinos production by radioactive ion beams decay after acceleration. The thesis is focused on one step of the complex, namely the low energy ring required for accumulation and injection of ion beams between the post-acceleration linac of the EURISOL complex (dedicated complex for radioactive ion beam production) and the CERN PS. After the description of the EURISOL complex and the Beta-Beam complex, a description of charged particles beams transport formalism is given. Then, in the second part, studies on the definition and the optimisation of the ring are given, starting by optical structure then different simulations concerning beam dynamics, i.e. multiturn injection, synchronous acceleration with beam losses localization and intensity, fast extraction, chromaticity with eddy currents correction and space charge effects. Finally, a preliminary technical design of the RCS main magnets is proposed. (author)

  2. 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.

  3. Studies on the benefit of extended capabilities of the driver accelerator for EURISOL

    CERN Document Server

    Schmidt, K.-H; Lukic, S; Ricciardi, M. V; Veselsky, M

    Possibilities are studied for the optimization of EURISOL rare nuclide yields in specific regions of the nuclear chart by building the driver accelerator in a way that enables accelerating several additional beam species, to specific energies, besides the baseline 1 GeV proton beam. Nuclide production rates with these driver beams are compared to the production rates expected with the 1 GeV proton beam in the direct-production and the high-power-converter scenarios. Arguments are presented to show that several additional driver-beam scenarios could provide substantial benefit for the production of nuclides in specific regions of the nuclear chart. The quantitative values in this report are preliminary in the sense that they depend on assumptions on the values of some key parameters which are subject to technical development, e.g. maximum beam intensities or limits on the target heat load. The different scenarios are compared from the aspect of nuclide yields. The arguments presented here, when complemented by...

  4. Design of 1+ Ion Source Coupling First Design of the Resonant Ionization Laser Ion Source For the Multi-Mega Watt Target Station

    CERN Document Server

    A. Olivier-Kaiser, F. Le Blanc, C. Lau

    The realisation of next-generation ion sources suitable for the EURISOL multi-mega-watt (MMW) target station needs exhaustive studies and developments. An exhaustive review was carried out to evaluate the capability of the ion-sources to operate under the irradiation conditions of the MMW target station. In addition, selectivity must be taken into account to avoid the spread of unwanted radioactivity out of the target-ion-source system (TIS).These studies led to consider RILIS (Resonance Ionization Laser Ion Source) as the reference ion source for this target station.

  5. Super liquid density target designs

    International Nuclear Information System (INIS)

    Pan, Y.L.; Bailey, D.S.

    1976-01-01

    The success of laser fusion depends on obtaining near isentropic compression of fuel to very high densities and igniting this fuel. To date, the results of laser fusion experiments have been based mainly on the exploding pusher implosion of fusion capsules consisting of thin glass microballoons (wall thickness of less than 1 micron) filled with low density DT gas (initial density of a few mg/cc). Maximum DT densities of a few tenths of g/cc and temperatures of a few keV have been achieved in these experiments. We will discuss the results of LASNEX target design calculations for targets which: (a) can compress fuel to much higher densities using the capabilities of existing Nd-glass systems at LLL; (b) allow experimental measurement of the peak fuel density achieved

  6. Design of the FMIT lithium target

    International Nuclear Information System (INIS)

    Hassberger, J.A.; Annese, C.E.; Greenwell, R.K.; Ingham, J.G.; Miles, R.R.; Miller, W.C.

    1981-01-01

    Development of the liquid lithium target for the Fusion Materials Irradiation Test (FMIT) Facility is described. The target concept, major design goals and design requirements are presented. Progress made in the research and development areas leading to detailed design of the target is discussed. This progress, including experimental and analytic results, demonstrates that the FMIT target design is capable of meeting its major design goals and requirements

  7. Multiple Target Laser Designator (MTLD)

    Science.gov (United States)

    2007-03-01

    Optimized Liquid Crystal Scanning Element Optimize the Nonimaging Predictive Algorithm for Target Ranging, Tracking, and Position Estimation...commercial potential. 3.0 PROGRESS THIS QUARTER 3.1 Optimization of Nonimaging Holographic Antenna for Target Tracking and Position Estimation (Task 6) In

  8. Target design for shock ignition

    International Nuclear Information System (INIS)

    Schurtz, G; Ribeyre, X; Lafon, M

    2010-01-01

    The conventional approach of laser driven inertial fusion involves the implosion of cryogenic shells of deuterium-tritium ice. At sufficiently high implosion velocities, the fuel ignites by itself from a central hot spot. In order to reduce the risks of hydrodynamic instabilities inherent to large implosion velocities, it was proposed to compress the fuel at low velocity, and ignite the compressed fuel by means of a convergent shock wave driven by an intense spike at the end of the laser pulse. This scheme, known as shock ignition, reduces the risks of shell break-up during the acceleration phase, but it may be impeded by a low coupling efficiency of the laser pulse with plasma at high intensities. This work provides a relationship between the implosion velocity and the laser intensity required to ignite the target by a shock. The operating domain of shock ignition at different energies is described.

  9. Technical Design Report, Second Target Station

    International Nuclear Information System (INIS)

    Galambos, John D.; Anderson, David E.; Bethea, Katie L.; Carden, W. F.; Chae, Steven M.; Bechtol, D.; Brown, N.; Clark, A.

    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.

  10. 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.

  11. Design of the MYRRHA Spallation Target Assembly

    International Nuclear Information System (INIS)

    Keijers, S.; Fernandez, R.; Stankovskiy, A.; Kennedy, G.; Van Tichelen, K.

    2015-01-01

    MYRRHA (Multi-purpose hybrid Research Reactor for High-tech Applications) is a multi-purpose research facility currently being developed at SCK.CEN. MYRRHA is based on the ADS (Accelerator Driven System) concept where a proton accelerator, a spallation target and a subcritical reactor are coupled. MYRRHA will demonstrate the ADS full concept by coupling these three components at a reasonable power level. As a flexible irradiation facility, the MYRRHA research reactor will be able to work in both critical and subcritical modes. In this way, MYRRHA will allow fuel developments for innovative reactor systems, material research for GEN IV and fusion reactors, and radioisotope production for medical and industrial applications. MYRRHA will be cooled by Lead Bismuth Eutectic (LBE) and will play an important role in the development of the Pb-alloys technology needed for the LFR (Lead Fast Reactor) GEN IV concept. This paper describes the evolution of the MYRRHA spallation target design. In the early phase of the MYRRHA project (XT-ADS), the target design was based on a dedicated spallation loop inside the primary reactor vessel. Within the core, the 3 central fuel assembly positions were occupied by the spallation target, which enabled a windowless design created by a free surface of LBE facing the proton beam. The windowless option was preferred because of high heat loads in combination with severe irradiation damage in the target region would result in unacceptably short lifetimes of a target window. The LBE in the loop served as spallation target and as target coolant, but was separated from the LBE cooling the reactor core. The loop was equipped with its own pump, heat exchanger and conditioning system. The change from cyclotron to linear accelerator allowed the increase in proton energy from 350 MeV to 600 MeV. This modification led to an important reduction of the specific heat load at the target level and an improvement of the neutronic performance. In addition to

  12. OMEGA polar-drive target designs

    International Nuclear Information System (INIS)

    Radha, P. B.; Marozas, J. A.; Marshall, F. J.; Shvydky, A.; Collins, T. J. B.; Goncharov, V. N.; McKenty, P. W.; Sangster, T. C.; Skupsky, S.; McCrory, R. L.; Meyerhofer, D. D.

    2012-01-01

    Low-adiabat polar-drive (PD) [Skupsky et al., Phys. Plasmas 11, 2763 (2004)] implosion designs for the OMEGA [Boehly et al., Opt. Commun. 133, 495 (1997)] laser are described. These designs for cryogenic deuterium–tritium and warm plastic shells use a temporal laser pulse shape with three pickets followed by a main pulse [Goncharov et al., Phys. Rev. Lett. 104, 165001 (2010)]. The designs are at two different on-target laser intensities, with different in-flight aspect ratios (IFARs). These designs permit studies of implosion energetics and target performance closer to ignition-relevant intensities (∼7 × 10 14 W/cm 2 at the quarter-critical surface, where nonlocal heat conduction and laser–plasma interactions can play an important role) but at lower values of IFAR ∼ 22 or at lower intensity (∼3 × 10 14 W/cm 2 ) but at a higher IFAR (IFAR ∼ 32, where shell instability can play an important role). PD geometry requires repointing of laser beams to improve shell symmetry. The higher-intensity designs optimize target performance by repointing beams to a lesser extent, compensating for the reduced equatorial drive by increasing the energies of the repointed beams. They also use custom beam profiles that improve equatorial illumination at the expense of irradiation at higher latitudes. These latter designs will be studied when new phase plates for the OMEGA Laser System, corresponding to the custom beam profiles, are obtained.

  13. CFD aspects of ADSS target design

    International Nuclear Information System (INIS)

    Shashi Kumar, G.N.; Mahendra, A.K.; Sanyal, A.; Gouthaman, G.

    2004-03-01

    The preliminary studies on CFD aspects of Accelerator Driven Sub-critical System (ADSS) target design has been presented in this report. The studies involve the thermal hydraulic analysis of the Liquid Metal Spallation Target (LMST) using Lead Bismuth Eutectic (LBE) as the target material. Apart from acting as Spallation medium LBE is used to remove the heat deposited by High Energy Proton Beam. Window of the target ( one side vacuum and other side LBE) has been reported in literature to be the most critical zone where high temperatures are reached. Numerical Simulations are carried out with Artificial Neural Network coupled Computational Fluid Dynamics (CFD) code, Various studies were carried out after the verification and validation of the initial results. Window being, the main parameter to be optimised, various designs of window were tried, along with change in the window material. The best possible combination has been proposed. The thermal hydraulic studies were carried out to arrive at the acceptable operating conditions for the target. (author)

  14. 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 ...

  15. Conceptual design study of IFMIF target system

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  16. Targeting and design of chilled water network

    International Nuclear Information System (INIS)

    Foo, Dominic C.Y.; Ng, Denny K.S.; Leong, Malwynn K.Y.; Chew, Irene M.L.; Subramaniam, Mahendran; Aziz, Ramlan; Lee, Jui-Yuan

    2014-01-01

    Highlights: • Minimum flowrate targeting for chilled water network. • Mixed series/parallel configuration of chilled water-using units. • Integrated cooling and chilled water networks. - Abstract: Chilled water is a common cooling agent used in various industrial, commercial and institutional facilities. In conventional practice, chilled water is distributed via chilled water networks (CHWNs) in parallel configuration to provide required air conditioning and/or equipment cooling in the heating, ventilating and air conditioning (HVAC) system. In this paper, process integration approach based on pinch analysis technique is used to address energy efficiency issues in the CHWN system for grassroots design problem. Graphical and algebraic targeting techniques are developed to identify the minimum chilled water flowrate needed to remove a given amount of heat load from the CHWN. Doing this leads to higher chilled water return temperature and enhanced energy efficiency of the HVAC system. A recent proposed network design technique is extended to synthesize the CHWN in a mixed series/parallel configuration. A novel concept of integrated cooling and chilled water networks (IWN) is also proposed in this work, with its targeting and design techniques presented. Hypothetical examples and an industrial case study are solved to elucidate the proposed approaches

  17. A flexible testing facility for high-power targets (Tiara FP7 program)

    CERN Document Server

    Fusco, Y.; Samec, K.; Kadi, Y.

    2014-01-01

    Building on recent experience in the field of applied physics, TIARA Work package n° 9 focuses on target applications for accelerators in Europe. A roadmap for target development has been derived from major achievements in the EU-FP6 and EU-FP7 programs such as the MEGAPIE and EURISOL experiments. The TIARA management board concluded that a worthwhile continuation of such projects would be in the development of a flexible material irradiation facility easily transportable and which could be installed in different laboratories. The power is limited to 100 kW in a very compact arrangement so as to obtain the best neutron economy from a moderate beam power which is more likely to be found in laboratories across Europe. The challenges posed by such a compact design and accompanying calculations are presented in the current work.

  18. Target design for heavy ion beam fusion

    International Nuclear Information System (INIS)

    Meyer-ter-Vehn, J.; Metzler, N.

    1981-07-01

    Target design for Heavy Ion Beam Fusion and related physics are discussed. First, a modified version of the Kidder-Bodner model for pellet gain is presented and is used to define the working point (Esub(beam) = 4.8 MJ, Gain 83) for a reactor size target. Secondly, stopping of heavy ions in hot dense plasma is investigated and numerical results for stopping powers and ranges of 10 GeV Bi-ions in Pb, Li, and PbLi-alloy are given. Finally, results of an explicit implosion calculation, using the 1-D code MINIHY, are discussed in detail. The hydrodynamic efficiency is found to be about 5%. Special attention is given to the shock sequence leading to the ignition configuration. Also the growth of Rayleigh-Taylor instability at the absorber-pusher interface is estimated. (orig.)

  19. Investigation of IFMIF target assembly structure design

    International Nuclear Information System (INIS)

    Ida, Mizuho; Nakamura, Hiroo; Sugimoto, Masayoshi; Yamamura, Toshio

    2006-10-01

    In the International Fusion Materials Irradiation Facility (IFMIF), the back-wall of target assembly is the part suffered the highest neutron-flux. The back-wall and the assembly are designed to have lips for cutting/welding at the back-wall replacement. To reduce thermal stress and deformation of the back-wall under neutron irradiation, contact pressure between the back-wall and the assembly is one of dominant factors. Therefore, an investigation was performed for feasible clamping pressure of a mechanical clamp set in limited space around the back-wall. It was clarified that the clamp can give a pressure difference up to 0.4 MPa between the contact pressure and atmosphere pressure in the test cell room. Also a research was performed for the dissimilar metal welding in the back-wall. Use of 309 steel was found adequate as the intermediate filler metal through the research of previous welding. Maintaining a temperature of the target assembly so as to avoid a freezing of liquid lithium is needed at the lithium charge into the loop before the beam injection. The assembly is covered with thermal insulation. Therefore, a research and an investigation were performed for compact and light thermal-insulation effective even under helium (i.e. high heat-conduction) condition of the test cell room. The result was as follows; in the case that a thermal conductivity 0.008 W/m·K of one of found insulation materials is available in the temperature range up to 300degC of the IFMIF target assembly, needed thickness and weight of the insulation were respectively only 8.2 mm and 32 kg. Also a research was performed for high-heat-density heaters to maintain temperature of the back-wall which can not be cover with insulation due to limited space. A heater made of silicon-nitride was found to be adequate. Total heat of 8.4 kW on the back-wall was found to be achievable through an investigations of heater arrange. Also an investigation was performed for remote-handling device to

  20. 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.

  1. Targeted proteins for diabetes drug design

    International Nuclear Information System (INIS)

    Trang Nguyen, Ngoc Doan; Le, Ly Thi

    2012-01-01

    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. (review)

  2. Development of new target concepts for proton beams at CERN/ISOLDE

    CERN Document Server

    Delonca, Melanie; Montavon, Ghislain; Peyraut, Francois

    More and more, the power of primary beam sent onto targets increases until reaching several kiloWatts of magnitude, inducing new problematic and challenges. Consequently, the need of new target design arises and leads to new conceptual design proposal. Amongst them, a concept of Lead Bismuth Eutectic (LBE) loop target making use of an heat exchanger (HEX) and a pump has been proposed during the European project EURISOL Design Study. This concept proposed an improvement in terms of release efficiency of short-lived species by transforming the irradiated liquid into droplets shape. This thesis presents the development of this target design proposal. A prototype target has been developed and will be tested under proton beam at ISOLDE at Cern, Geneva. Several analytical tools for the study of this kind of targets are proposed, taking into account different design parameters. These tools can be applied for other high power target concept and allow an easy dimensioning of this kind of targets. As well, an innovativ...

  3. Design of the target area for the National Ignition Facility

    International Nuclear Information System (INIS)

    Foley, R.J.; Karpenko, V.P.; Adams, C.H.

    1997-01-01

    The preliminary design of the target area for the National Ignition Facility has been completed. The target area is required to meet a challenging set of engineering system design requirements and user needs. The target area must provide the appropriate conditions before, during, and after each shot. The repeated introduction of large amounts of laser energy into the chamber and subsequent target emissions represent new design challenges for ICF facility design. Prior to each shot, the target area must provide the required target illumination, target chamber vacuum, diagnostics, and optically stable structures. During the shot, the impact of the target emissions on the target chamber, diagnostics, and optical elements is minimized and the workers and public are protected from excessive prompt radiation doses. After the shot, residual radioactivation is managed to allow the required accessibility. Diagnostic data is retrieved, operations and maintenance activities are conducted, and the facility is ready for the next shot. The target area subsystems include the target chamber, target positioner, structural systems, target diagnostics, environmental systems, and the final optics assembly. The engineering design of the major elements of the target area requires a unique combination of precision engineering, structural analysis, opto-mechanical design, random vibration suppression, thermal stability, materials engineering, robotics, and optical cleanliness. The facility has been designed to conduct both x- ray driven targets and to be converted at a later date for direct drive experiments. The NIF has been configured to provide a wide range of experimental environments for the anticipated user groups of the facility. The design status of the major elements of the target area is described

  4. Review of laser mega joule target area: Design and processes

    International Nuclear Information System (INIS)

    Geitzholz, M.; Lanternier, C.

    2006-01-01

    The Laser Mega Joule (LMJ) target area is currently designed to achieve ignition and significant fusion gain in laboratory. LMJ will be composed of 240 identical large 370 mm * 370 mm square laser beams. These beams will focus 2 mega-joules of energy at the wavelength of 351 nm on the center of an experiment chamber. Design studies for target equipment are well advanced, target chamber and target holder (concrete) works have already begun. A detailed overview of the target area equipment is presented: target chamber, frame, diagnostic inserter manipulator, final optic assembly, dual diagnostic and laser reference, non cryogenic target positioner. Recent technical and architectural choices are detailed including safety transfers and alignment processes (target, laser and diagnostic). All this target equipment allows us to optimize shot chrono-gram, from target metrology to the shot, including calibration process. (authors)

  5. 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.

  6. Designing high power targets with computational fluid dynamics (CFD)

    International Nuclear Information System (INIS)

    Covrig, S. D.

    2013-01-01

    High power liquid hydrogen (LH2) targets, up to 850 W, have been widely used at Jefferson Lab for the 6 GeV physics program. The typical luminosity loss of a 20 cm long LH2 target was 20% for a beam current of 100 μA rastered on a square of side 2 mm on the target. The 35 cm long, 2500 W LH2 target for the Qweak experiment had a luminosity loss of 0.8% at 180 μA beam rastered on a square of side 4 mm at the target. The Qweak target was the highest power liquid hydrogen target in the world and with the lowest noise figure. The Qweak target was the first one designed with CFD at Jefferson Lab. A CFD facility is being established at Jefferson Lab to design, build and test a new generation of low noise high power targets

  7. Designing high power targets with computational fluid dynamics (CFD)

    Energy Technology Data Exchange (ETDEWEB)

    Covrig, S. D. [Thomas Jefferson National Laboratory, Newport News, VA 23606 (United States)

    2013-11-07

    High power liquid hydrogen (LH2) targets, up to 850 W, have been widely used at Jefferson Lab for the 6 GeV physics program. The typical luminosity loss of a 20 cm long LH2 target was 20% for a beam current of 100 μA rastered on a square of side 2 mm on the target. The 35 cm long, 2500 W LH2 target for the Qweak experiment had a luminosity loss of 0.8% at 180 μA beam rastered on a square of side 4 mm at the target. The Qweak target was the highest power liquid hydrogen target in the world and with the lowest noise figure. The Qweak target was the first one designed with CFD at Jefferson Lab. A CFD facility is being established at Jefferson Lab to design, build and test a new generation of low noise high power targets.

  8. Spallation neutron source target station design, development, and commissioning

    Energy Technology Data Exchange (ETDEWEB)

    Haines, J.R., E-mail: hainesjr@ornl.gov; McManamy, T.J.; Gabriel, T.A.; Battle, R.E.; Chipley, K.K.; Crabtree, J.A.; Jacobs, L.L.; Lousteau, D.C.; Rennich, M.J.; Riemer, B.W.

    2014-11-11

    The spallation neutron source target station is designed to safely, reliably, and efficiently convert a 1 GeV beam of protons to a high flux of about 1 meV neutrons that are available at 24 neutron scattering instrument beam lines. Research and development findings, design requirements, design description, initial checkout testing, and results from early operation with beam are discussed for each of the primary target subsystems, including the mercury target, neutron moderators and reflector, surrounding vessels and shielding, utilities, remote handling equipment, and instrumentation and controls. Future plans for the mercury target development program are also briefly discussed.

  9. Economic targets for small PWR reactor designs

    International Nuclear Information System (INIS)

    Board, J.

    1991-01-01

    Small reactors are likely to be less economic than large reactors, but the lower financial exposure with small reactors may be attractive to utilities contemplating a restart to a nuclear programme. New nuclear plant can be economic, but success will depend more on how the plant are built, rather than what type or size is built. A target for new plant for operation early in the next century should be a generation cost of 3p to 3.5 p/kWh. This corresponds to an overnight capital cost of Pound 1000/kWh to Pound 1100/kWh. (author)

  10. NIF Ignition Target 3D Point Design

    Energy Technology Data Exchange (ETDEWEB)

    Jones, O; Marinak, M; Milovich, J; Callahan, D

    2008-11-05

    We have developed an input file for running 3D NIF hohlraums that is optimized such that it can be run in 1-2 days on parallel computers. We have incorporated increasing levels of automation into the 3D input file: (1) Configuration controlled input files; (2) Common file for 2D and 3D, different types of capsules (symcap, etc.); and (3) Can obtain target dimensions, laser pulse, and diagnostics settings automatically from NIF Campaign Management Tool. Using 3D Hydra calculations to investigate different problems: (1) Intrinsic 3D asymmetry; (2) Tolerance to nonideal 3D effects (e.g. laser power balance, pointing errors); and (3) Synthetic diagnostics.

  11. Optical and mechanical design of beam-target coupling sensor

    International Nuclear Information System (INIS)

    Wang Liquan; Li Tian'en; Feng Bin; Xiang Yong; Li Keyu; Zhong Wei; Liu Guodong

    2012-01-01

    A sensor based on conjugate principle has been designed for matching the light beams and the target in inertial confinement fusion. It can avoid the direct illumination of the simulation collimating light on the target under test in targeting processes. This paper introduces the optical and mechanical design of the sensor, according to its design functions and working principle. The resolution of the optical images obtained in experiments reaches 6 μm and the beam-target matching accuracy is 8.8 μm. The sensor has been successfully applied to the Shenguang-Ⅲ facility. Statistical analyses of the four-hole CH target images derived with pinhole camera shows that the targeting accuracy of the facility is better than 25 μm, satisfying the design requirements. (authors)

  12. Deliverable D5: The Multi-Megawatt Target Station (Final Report)

    CERN Document Server

    Karel Samec et al. (CERN, IPUL, ITN, PSI)

    The Eurisol initiative seeks to develop an isotope production facility to provide the scientific community with the means to achieving high yields of isotopes and extending the variety of isotopes thus produced towards more exotic types rarely seen in existing facilities.The Multi-MW converter target at the heart of the projected facility is designed to create isotopes by fissioning uranium carbide (UC) target arranged coaxially around a 4 MW converter target. It is therefore essential that the target be as compact as possible to avoid losing neutrons to capture whilst maximising the neutron flux to enhance the number of fissions per second in the UC targets.The proposed ISOL facility would use both (a) several 100 kW proton beams on a thick solid target to produceRIBs directly, and (b) a liquid metal 4 MW ‘converter’ target to release high fluxes of spallation neutrons which would then produce RIBs by fission in a secondary uranium carbide (UCx) target. An alternative windowless liquid mercury-jet ‘con...

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

    International Nuclear Information System (INIS)

    Booth, C N; Hodgson, P; 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

    2013-01-01

    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.

  14. Adaptive Waveform Design for Cognitive Radar in Multiple Targets Situations

    Directory of Open Access Journals (Sweden)

    Xiaowen Zhang

    2018-02-01

    Full Text Available In this paper, the problem of cognitive radar (CR waveform optimization design for target detection and estimation in multiple extended targets situations is investigated. This problem is analyzed in signal-dependent interference, as well as additive channel noise for extended targets with unknown target impulse response (TIR. To address this problem, an improved algorithm is employed for target detection by maximizing the detection probability of the received echo on the promise of ensuring the TIR estimation precision. In this algorithm, an additional weight vector is introduced to achieve a trade-off among different targets. Both the estimate of TIR and transmit waveform can be updated at each step based on the previous step. Under the same constraint on waveform energy and bandwidth, the information theoretical approach is also considered. In addition, the relationship between the waveforms that are designed based on the two criteria is discussed. Unlike most existing works that only consider single target with temporally correlated characteristics, waveform design for multiple extended targets is considered in this method. Simulation results demonstrate that compared with linear frequency modulated (LFM signal, waveforms designed based on maximum detection probability and maximum mutual information (MI criteria can make radar echoes contain more multiple-target information and improve radar performance as a result.

  15. 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.

  16. 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.

  17. Design of a cryogenic deuterium gas target for neutron therapy

    International Nuclear Information System (INIS)

    Kuchnir, F.T.; Waterman, F.M.; Forsthoff, H.; Skaggs, L.S.; Vander Arend, P.C.; Stoy, S.

    1976-01-01

    A cryogenic deuterium gas target operating at 80 0 K and 10 atm pressure has been designed for use with a small cyclotron; the D(d,n) reaction is used to produce a neutron beam suitable for radiation therapy. The target is cooled by circulation of the gas in a closed loop between the target and an external heat exchanger immersed in liquid nitrogen

  18. Design and Fabrication of Titanium Target for Portable Neutron Generator

    International Nuclear Information System (INIS)

    Lee, Cheol Ho; Oh, Byunghoon; Chang, Daesik; Jang, Dohyun; In Sang Yeol; Park, Jaewon; Hong, Kwangpyo

    2014-01-01

    For the neutron generator to produce a neutron flux of the above order, a target that produces fast neutrons in the generator plays an important role, and the target is used and applied to develop the generator due to its simplicity and inexpensive. Making suitable targets for neutron production, especially mono-energy neutrons, has always been of interest. These targets have been used for neutron production reaction studies, calibration of detectors, and neutron therapy. Different studies have been carried out on deuterium and tritium for making solid targets to produce mono-energy neutron from D-D and D-T reactions. A lot of investigations have been carried out on solid target properties such as lifetime, thermal stability, neutron yield, and energy. Vaporized zirconium and titanium layers on a high thermal conductivity substrate (Cu, Mo, Ag) have been used as deuterium and tritium absorbing metals. The density of titanium is smaller than zirconium and the range of charged particles in the titanium targets is more than that in zirconium targets. Thus, titanium targets have more neutron yield than zirconium targets in a low energy beam and titanium is usually used to make a target. The titanium target was designed and simulated to determine the suitable thickness of the target. As a result of the simulation, the target was fabricated to generate fast neutrons by the reaction. The thickness of the target was measured using a profiler. The thickness of the two targets is 2.108 and 2.190 μm. The target will be applied to produce neutrons in a neutron generator

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

    Science.gov (United States)

    Luis, Raul Fernandes

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

  20. Design of ignition targets for the National Ignition Facility

    International Nuclear Information System (INIS)

    Haan, S.W.; Dittrich, T.R.; Marinak, M.M.; Hinkel, D.E.

    1999-01-01

    This is a brief update on the work being done to design ignition targets for the National Ignition Facility. Updates are presented on three areas of current activity : improvements in modeling, work on a variety of targets spanning the parameter space of possible ignition targets ; and the setting of specifications for target fabrication and diagnostics. Highlights of recent activity include : a simulation of the Rayleigh-Taylor instability growth on an imploding capsule, done in 3D on a 72degree by 72degree wedge, with enough zones to resolve modes out to 100 ; and designs of targets at 250eV and 350eV, as well as the baseline 300 eV ; and variation of the central DT gas density, which influences both the Rayleigh-Taylor growth and the smoothness of the DT ice layer

  1. Optimum design of exploding pusher target to produce maximum neutrons

    International Nuclear Information System (INIS)

    Kitagawa, Y.; Miyanaga, N.; Kato, Y.; Nakatsuka, M.; Nishiguchi, A.; Yabe, T.; Yamanaka, C.

    1985-03-01

    Exploding pusher target experiments have been conducted with the 1.052-μm GEKKO MII two-beam glass laser system to design an optimum target, which couples to the incident laser light most effectively to produce the maximum neutrons. Since hot electrons preheat the shell entirely in spite of strongly nonuniform irradiation, a simple model can design the optimum target, of which the shell/fuel interface is accelerated to 0.5 to 0.7 times the initial radius within a laser pulse. A 2-dimensional computer simulation supports this target design. The scaling of the neutron yield N with the laser power P is N ∝ P 2.4±0.4 . (author)

  2. 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.

  3. LBNF 1.2 MW Target: Conceptual Design & Fabrication

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-01

    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.

  4. Design and Characterization of High Power Targets for RIB Generation

    International Nuclear Information System (INIS)

    Zhang, Y.

    2001-01-01

    In this article, thermal modeling techniques are used to simulate ISOL targets irradiated with high power proton beams. Beam scattering effects, nuclear reactions and beam power deposition distributions in the target were computed with the Monte Carlo simulation code, GEANT4. The power density information was subsequently used as input to the finite element thermal analysis code, ANSYS, for extracting temperature distribution information for a variety of target materials. The principal objective of the studies was to evaluate techniques for more uniformly distributing beam deposited heat over the volumes of targets to levels compatible with their irradiation with the highest practical primary-beam power, and to use the preferred technique to design high power ISOL targets. The results suggest that radiation cooling, in combination, with primary beam manipulation, can be used to control temperatures in practically sized targets, to levels commensurate with irradiation with 1 GeV, 100 kW proton beams

  5. Test Information Targeting Strategies for Adaptive Multistage Testing Designs.

    Science.gov (United States)

    Luecht, Richard M.; Burgin, William

    Adaptive multistage testlet (MST) designs appear to be gaining popularity for many large-scale computer-based testing programs. These adaptive MST designs use a modularized configuration of preconstructed testlets and embedded score-routing schemes to prepackage different forms of an adaptive test. The conditional information targeting (CIT)…

  6. Water-cooled target-box design at LAMPF

    International Nuclear Information System (INIS)

    Grisham, D.; Lambert, J.

    1983-01-01

    The target boxes in the main experimental beam line (Line A) at the Clinton P. Anderson Meson Physics Facility (LAMPF) have operated since 1976. A program of replacing the boxes is underway. This paper will present past history, design considerations, calculational results and the final box design

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-07-01

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

  8. 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.

  9. Shortening User Interface Design Iterations through Realtime Visualisation of Design Actions on the Target Device

    OpenAIRE

    MESKENS, Jan; LUYTEN, Kris; CONINX, Karin

    2009-01-01

    In current mobile user interface design tools, it is time consuming to export a design to the target device. This makes it hard for designers to iterate over the user interfaces they are creating. We propose Gummy-live, a GUI builder for mobile devices allowing designers to test and observe immediately on the target device each step they take in the GUI builder. This way, designers are stimulated to iteratively test and refine user interface prototypes in order to take the target device charac...

  10. Present status of the conceptual design of IFMIF target facility

    International Nuclear Information System (INIS)

    Katsuta, H.; Kato, Y.; Konishi, S.; Miyauchi, Y.; Smith, D.; Hua, T.; Green, L.; Benamati, G.; Cevolani, S.; Roehrig, H.; Schutz, W.

    1998-01-01

    The conceptual design activity (CDA) for the international fusion materials irradiation facility (IFMIF) has been conducted. For the IFMIF target facility, the conceptual designs of the following two main components have been performed. The design concept of IFMIF utilizes a high energy deuteron beam of 30-40 MeV and total current of 250 mA, impinging on a flowing lithium jet to produce high energy neutrons for irradiation of candidate fusion materials. (1) The target assembly: The kinetic energy of the deuteron beam is deposited on a Li-jet target and neutrons are produced through the d-Li stripping reaction in this target. The assembly is designed to get a stable lithium jet and to prevent the onset of lithium boiling. For 40-MeV deuteron beam (total current of 250 mA) and a beam footprint of 5 x 20 cm 2 lithium jet dimensions are designed to be 2.5 cm thick and 26 cm wide. The lithium jet parameters are given. (2) Lithium loop: The loop circulates the lithium to and from the target assembly and removes the heat deposited by the deuteron beam containing systems for maintaining the-high purity of the lithium required for radiological safety and to minimize corrosion. The maximum lithium flow rate is 130 l/s and the total lithium inventory is about 21 m 3 . The IFMIF policy requires that the lithium loop system be designed to guarantee no combustion of lithium in the event of a lithium leak. This can be achieved by use of multiple confinement of the lithium carrying components. The radioactive waste generated by the target facilities is estimated. (orig.)

  11. Quantifying design trade-offs of beryllium targets on NIF

    Science.gov (United States)

    Yi, S. A.; Zylstra, A. B.; Kline, J. L.; Loomis, E. N.; Kyrala, G. A.; Shah, R. C.; Perry, T. S.; Kanzleiter, R. J.; Batha, S. H.; MacLaren, S. A.; Ralph, J. E.; Masse, L. P.; Salmonson, J. D.; Tipton, R. E.; Callahan, D. A.; Hurricane, O. A.

    2017-10-01

    An important determinant of target performance is implosion kinetic energy, which scales with the capsule size. The maximum achievable performance for a given laser is thus related to the largest capsule that can be imploded symmetrically, constrained by drive uniformity. A limiting factor for symmetric radiation drive is the ratio of hohlraum to capsule radii, or case-to-capsule ratio (CCR). For a fixed laser energy, a larger hohlraum allows for driving bigger capsules symmetrically at the cost of reduced peak radiation temperature (Tr). Beryllium ablators may thus allow for unique target design trade-offs due to their higher ablation efficiency at lower Tr. By utilizing larger hohlraum sizes than most modern NIF designs, beryllium capsules thus have the potential to operate in unique regions of the target design parameter space. We present design simulations of beryllium targets with a large CCR = 4.3 3.7 . These are scaled surrogates of large hohlraum low Tr beryllium targets, with the goal of quantifying symmetry tunability as a function of CCR. This work performed under the auspices of the U.S. DOE by LANL under contract DE-AC52- 06NA25396, and by LLNL under Contract DE-AC52-07NA27344.

  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. 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....... It can be argued that design to target cost may also provide a frame for developing the supply chain towards better coordination and collaboration. Thus methods of design to target cost may serve to facilitate the development of a more integrated supply chain....

  14. Design choices and issues in fixed-target B experiments

    International Nuclear Information System (INIS)

    Camilleri, L.

    1993-01-01

    The main priority of any experiment on B physics in the years to come will be an endeavour to observe CP violation in the B sector. Such measurements imply the following requirements of the experiment. Trigger: a muon trigger will be sensitive to J/ψ reactions and muon tags; an electron trigger will double the number of lepton events; in order to include kaon tags and self-tagging reactions, the experiment must not rely entirely on lepton triggers. Secondary Vertex triggers and hadron p T triggers should be included in order to have the maximum flexibility. Detector: vertex detector; particle identification; good momentum resolution; electromagnetic and hadronic calorimeters; muon detector. In addition the following issues have to be addressed: Collider or fixed-target mode? If fixed target, extracted beam or internal target? If internal target, gas jet or wire target? If a gas jet, hydrogen or a heavy gas? Beam pipe design. Silicon microvertex design and radiation damage. K s 0 decay path. Particle identification. Momentum resolution. Order of detectors. No single method stands out as the open-quotes obvious one.close quotes An extracted beam yields better vertex resolution and an internal target easier triggering. A flexible and diverse triggering scheme is of prime importance in order to be sensitive to as many reactions as possible, the experiment should not be limited to lepton triggers only. Proposed experiments (P867, HERA B) at existing machines will be invaluable for testing new devices and strategies for the LHC and SSC experiments

  15. Massively parallel de novo protein design for targeted therapeutics

    KAUST Repository

    Chevalier, Aaron; Silva, Daniel-Adriano; Rocklin, Gabriel J.; Hicks, Derrick R.; Vergara, Renan; Murapa, Patience; Bernard, Steffen M.; Zhang, Lu; Lam, Kwok-Ho; Yao, Guorui; Bahl, Christopher D.; Miyashita, Shin-Ichiro; Goreshnik, Inna; Fuller, James T.; Koday, Merika T.; Jenkins, Cody M.; Colvin, Tom; Carter, Lauren; Bohn, Alan; Bryan, Cassie M.; Ferná ndez-Velasco, D. Alejandro; Stewart, Lance; Dong, Min; Huang, Xuhui; Jin, Rongsheng; Wilson, Ian A.; Fuller, Deborah H.; Baker, David

    2017-01-01

    De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

  16. Massively parallel de novo protein design for targeted therapeutics

    KAUST Repository

    Chevalier, Aaron

    2017-09-26

    De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

  17. Massively parallel de novo protein design for targeted therapeutics

    Science.gov (United States)

    Chevalier, Aaron; Silva, Daniel-Adriano; Rocklin, Gabriel J.; Hicks, Derrick R.; Vergara, Renan; Murapa, Patience; Bernard, Steffen M.; Zhang, Lu; Lam, Kwok-Ho; Yao, Guorui; Bahl, Christopher D.; Miyashita, Shin-Ichiro; Goreshnik, Inna; Fuller, James T.; Koday, Merika T.; Jenkins, Cody M.; Colvin, Tom; Carter, Lauren; Bohn, Alan; Bryan, Cassie M.; Fernández-Velasco, D. Alejandro; Stewart, Lance; Dong, Min; Huang, Xuhui; Jin, Rongsheng; Wilson, Ian A.; Fuller, Deborah H.; Baker, David

    2018-01-01

    De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37–43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing. PMID:28953867

  18. Design considerations for foil windows for PET radioisotope targets

    International Nuclear Information System (INIS)

    Hughey, B.J.; Shefer, R.E.; Klinkowstein, R.E.; Welch, M.J.

    1992-01-01

    This paper describes the results of a study performed at SRL to develop analytical and computational techniques for optimizing the design of conduction-cooled foil windows for PET targets. Single foil conduction cooled windows have been found to be good target entrance windows for both low energy accelerators and medium energy cyclotrons. Detailed thermal analysis has given an approximate analytical expression for the maximum temperature reached in a foil window under conditions of realistic ion beam bombardment. The effects of 'hot spots' in the beam density profile were investigated. It was shown that a factor of two safety margin in window design should be adequate to compensate for any possible beam hot spots. In addition, the reduction of foil stress by slack mounting was verified by experiments. The properties of conventional and novel foil materials were investigated for use in conduction cooled windows. Novel foil materials include two-component Al/Ti and Al/Havar foil. Results on the testing of candidate foil materials for thermal conductivity and mechanical strength at elevated temperature were presented. Two optimum foil window geometries were analyzed: a high aspect ratio window and a multiply slotted window. The multiply slotted window combines the advantages of a high aspect ratio foil window with a circular beam strike and is a promising window design for both TCA and cyclotron targets. A multiply slotted window for a N 2 gas target for 15 O production was designed using the methodologies discussed above. This prototype target was successfully tested using the TCA beam at SRL. (author) 6 figs., 3 tabs., 10 refs

  19. Some Aspects on Filter Design for Target Tracking

    Directory of Open Access Journals (Sweden)

    Bertil Ekstrand

    2012-01-01

    Full Text Available Tracking filter design is discussed. It is argued that the basis of the present stochastic paradigm is questionable. White process noise is not adequate as a model for target manoeuvring, stochastic least-square optimality is not relevant or required in practice, the fact that requirements are necessary for design is ignored, and root mean square (RMS errors are insufficient as performance measure. It is argued that there is no process noise and that the covariance of the assumed process noise contains the design parameters. Focus is on the basic tracking filter, the Kalman filter, which is convenient for clarity and simplicity, but the arguments and conclusions are relevant in general. For design the possibility of an observer transfer function approach is pointed out. The issues can also be considered as a consequence of the fact that there is a difference between estimation and design. The - filter is used for illustration.

  20. Introduction to spallation physics and spallation-target design

    Energy Technology Data Exchange (ETDEWEB)

    Russell, G.J.; Pitcher, E.J.; Daemen, L.L. [Los Alamos National Laboratory, NM (United States)

    1995-10-01

    When coupled with the spallation process in appropriate target materials, high-power accelerators can be used to produce large numbers of neutrons, thus providing an alternate method to the use of nuclear reactors for this purpose. Spallation offers exciting new possibilities for generating intense neutron fluxes for a variety of applications, including: (a) spallation-neutron sources for materials science research; (b) accelerator-based production of tritium; (c) accelerator-based transmutation of waste; (d) accelerator-based destruction of plutonium; and (e) radioisotope production for medical and energy applications. Target design plays a key role in these applications, with neutron production/leakage being strongly dependent on the incident particle type and energy, and target material and geometry.

  1. 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.

  2. Rare isotope accelerator—conceptual design of target areas

    Science.gov (United States)

    Bollen, Georg; Baek, Inseok; Blideanu, Valentin; Lawton, Don; Mantica, Paul F.; Morrissey, David J.; Ronningen, Reginald M.; Sherrill, Bradley S.; Zeller, Albert; Beene, James R.; Burgess, Tom; Carter, Kenneth; Carrol, Adam; Conner, David; Gabriel, Tony; Mansur, Louis; Remec, Igor; Rennich, Mark; Stracener, Dan; Wendel, Mark; Ahle, Larry; Boles, Jason; Reyes, Susana; Stein, Werner; Heilbronn, Lawrence

    2006-06-01

    The planned rare isotope accelerator facility RIA in the US would become the most powerful radioactive beam facility in the world. RIA's driver accelerator will be a device capable of providing beams from protons to uranium at energies of at least 400 MeV per nucleon, with beam power up to 400 kW. Radioactive beam production relies on both the in-flight separation of fast beam fragments and on the ISOL technique. In both cases the high beam power poses major challenges for target technology and handling and on the design of the beam production areas. This paper will give a brief overview of RIA and discuss aspects of ongoing conceptual design work for the RIA target areas.

  3. Rare Isotope Accelerator - Conceptual Design of Target Areas

    Energy Technology Data Exchange (ETDEWEB)

    Bollen, Georg [Michigan State University, East Lansing; Baek, Inseok [Michigan State University, East Lansing; Blideanu, Valentin [CEA, Saclay, France; Lawton, Don [Michigan State University, East Lansing; Mantica, Paul F. [Michigan State University, East Lansing; Morrissey, David J. [Michigan State University, East Lansing; Ronningen, Reginald M. [Michigan State University, East Lansing; Sherrill, Bradley S. [Michigan State University, East Lansing; Zeller, Albert [Michigan State University, East Lansing; Beene, James R [ORNL; Burgess, Tom [Oak Ridge National Laboratory (ORNL); Carter, Kenneth [Oak Ridge National Laboratory (ORNL); Carrol, Adam [Oak Ridge National Laboratory (ORNL); Conner, David [ORNL; Gabriel, Tony A [ORNL; Mansur, Louis K [ORNL; Remec, Igor [ORNL; Rennich, Mark J [ORNL; Stracener, Daniel W [ORNL; Wendel, Mark W [ORNL; Ahle, Larry [Lawrence Livermore National Laboratory (LLNL); Boles, Jason [Lawrence Livermore National Laboratory (LLNL); Reyes, Susana [Lawrence Livermore National Laboratory (LLNL); Stein, Werner [Lawrence Livermore National Laboratory (LLNL); Heilbronn, Lawrence [Lawrence Berkeley National Laboratory (LBNL)

    2006-01-01

    The planned rare isotope accelerator facility RIA in the US would become the most powerful radioactive beam facility in the world. RIA s driver accelerator will be a device capable of providing beams from protons to uranium at energies of at least 400MeV per nucleon, with beam power up to 400 kW. Radioactive beam production relies on both the in-flight separation of fast beam fragments and on the ISOL technique. In both cases the high beam power poses major challenges for target technology and handling and on the design of the beam production areas. This paper will give a brief overview of RIA and discuss aspects of ongoing conceptual design work for the RIA target areas.

  4. New designs of LMJ targets for early ignition experiments

    International Nuclear Information System (INIS)

    Clerouin, C; Bonnefille, M; Dattolo, E; Fremerye, P; Galmiche, D; Gauthier, P; Giorla, J; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Poggi, F; Seytor, P

    2008-01-01

    The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 40 laser quads, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness are then designed for this purpose. A first strategy is to use scaled-down cylindrical hohlraums and capsules, taking advantage of our better understanding of the problem, set on theoretical modelling, simulations and experiments. Another strategy is to work specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, which is with parametric instabilities a crucial drawback of indirect drive. An alternative design is proposed, made up of the nominal 60 quads capsule, named A1040, in a rugby-shaped hohlraum. Robustness evaluations of these different targets are in progress

  5. New designs of LMJ targets for early ignition experiments

    Energy Technology Data Exchange (ETDEWEB)

    Clerouin, C; Bonnefille, M; Dattolo, E; Fremerye, P; Galmiche, D; Gauthier, P; Giorla, J; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Poggi, F; Seytor, P [Commissariat a l' Energie Atomique, DAM-Ile de France, BP 12 91680 Bruyeres-le-Chatel (France)], E-mail: catherine.cherfils@cea.fr

    2008-05-15

    The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 40 laser quads, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness are then designed for this purpose. A first strategy is to use scaled-down cylindrical hohlraums and capsules, taking advantage of our better understanding of the problem, set on theoretical modelling, simulations and experiments. Another strategy is to work specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, which is with parametric instabilities a crucial drawback of indirect drive. An alternative design is proposed, made up of the nominal 60 quads capsule, named A1040, in a rugby-shaped hohlraum. Robustness evaluations of these different targets are in progress.

  6. Rare isotope accelerator - conceptual design of target areas

    International Nuclear Information System (INIS)

    Bollen, Georg; Baek, Inseok; Blideanu, Valentin; Lawton, Don; Mantica, Paul F.; Morrissey, David J.; Ronningen, Reginald M.; Sherrill, Bradley S.; Zeller, Albert; Beene, James R; Burgess, Tom; Carter, Kenneth; Carrol, Adam; Conner, David; Gabriel, Tony A; Mansur, Louis K; Remec, Igor; Rennich, Mark J; Stracener, Daniel W; Wendel, Mark W; Ahle, Larry; Boles, Jason; Reyes, Susana; Stein, Werner; Heilbronn, Lawrence

    2006-01-01

    The planned rare isotope accelerator facility RIA in the US would become the most powerful radioactive beam facility in the world. RIA's driver accelerator will be a device capable of providing beams from protons to uranium at energies of at least 400MeV per nucleon, with beam power up to 400 kW. Radioactive beam production relies on both the in-flight separation of fast beam fragments and on the ISOL technique. In both cases the high beam power poses major challenges for target technology and handling and on the design of the beam production areas. This paper will give a brief overview of RIA and discuss aspects of ongoing conceptual design work for the RIA target areas

  7. Rare isotope accelerator-conceptual design of target areas

    Energy Technology Data Exchange (ETDEWEB)

    Bollen, Georg [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824 (United States)]. E-mail: bollen@nscl.msu.edu; Baek, Inseok; Blideanu, Valentin; Lawton, Don; Mantica, Paul F.; Morrissey, David J.; Ronningen, Reginald M.; Sherrill, Bradley S.; Zeller, Albert [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824 (United States); Beene, James R.; Burgess, Tom; Carter, Kenneth; Carrol, Adam; Conner, David; Gabriel, Tony; Mansur, Louis; Remec, Igor; Rennich, Mark; Stracener, Dan; Wendel, Mark [Oak Ridge National Laboratory, Oak Ridge, TN 37830 (United States); Ahle, Larry; Boles, Jason; Reyes, Susana; Stein, Werner [Lawrence Livermore Laboratory, Livermore, CA 94550 (United States); Heilbronn, Lawrence [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States)

    2006-06-23

    The planned rare isotope accelerator facility RIA in the US would become the most powerful radioactive beam facility in the world. RIA's driver accelerator will be a device capable of providing beams from protons to uranium at energies of at least 400 MeV per nucleon, with beam power up to 400 kW. Radioactive beam production relies on both the in-flight separation of fast beam fragments and on the ISOL technique. In both cases the high beam power poses major challenges for target technology and handling and on the design of the beam production areas. This paper will give a brief overview of RIA and discuss aspects of ongoing conceptual design work for the RIA target areas.

  8. Spallation neutron source target design for radioactive waste transmutation

    International Nuclear Information System (INIS)

    Beard, C.A.

    1992-01-01

    The disposal of high-level radioactive waste has long been one of the most serious problems facing the nuclear industry. Transmutation of this waste through particle bombardment has been suggested numerous times as a possible method of enhancing the waste management process. Due to advances in accelerator technology, the feasibility of an accelerator based transmutation system has increased enough to allow serious investigation of this process. Therefore, in pursuit of this goal, an accelerator target was designed for use in an accelerator based transmutation system. The target design consists of an array of tantalum rods, cooled by liquid sodium, which are arranged in a cylindrical configuration 40 cm in diameter and 125 cm in height. Tantalum was chosen as the target material over tungsten, lead, bismuth, and a lead-bismuth alloy (55 w/o bismuth) due to a large neutron yield, low activation, low chemical toxicity, and the fact that it does not produce significant amounts of long-lived isotopes through spallation or activation. The target yields a neutron source of 29.7 neutrons/proton when exposed to a 1600 MeV proton beam, and is suitable for use with both thermal or fast spectrum transmutation systems

  9. Design and implementation of typical target image database system

    International Nuclear Information System (INIS)

    Qin Kai; Zhao Yingjun

    2010-01-01

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

  10. Benchmarking CRISPR on-target sgRNA design.

    Science.gov (United States)

    Yan, Jifang; Chuai, Guohui; Zhou, Chi; Zhu, Chenyu; Yang, Jing; Zhang, Chao; Gu, Feng; Xu, Han; Wei, Jia; Liu, Qi

    2017-02-15

    CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based gene editing has been widely implemented in various cell types and organisms. A major challenge in the effective application of the CRISPR system is the need to design highly efficient single-guide RNA (sgRNA) with minimal off-target cleavage. Several tools are available for sgRNA design, while limited tools were compared. In our opinion, benchmarking the performance of the available tools and indicating their applicable scenarios are important issues. Moreover, whether the reported sgRNA design rules are reproducible across different sgRNA libraries, cell types and organisms remains unclear. In our study, a systematic and unbiased benchmark of the sgRNA predicting efficacy was performed on nine representative on-target design tools, based on six benchmark data sets covering five different cell types. The benchmark study presented here provides novel quantitative insights into the available CRISPR tools. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Preliminary design implications of SSC fixed-target operation

    International Nuclear Information System (INIS)

    Zisman, M.S.

    1984-06-01

    This paper covers some of the accelerator physics issues relevant to a possible fixed-target operating mode for the Superconducting Super Collider (SSC). In the brief time available, no attempt has been made to design this capability into the SSC. Rather, I have tried to evaluate what the performance of such a machine might be, and to indicate the hardware implications and extraction considerations that would be part of an actual design study. Where appropriate, parameters and properties of the present LBL design for the SSC have been used; these should be taken as being representative of the general class of small-aperture, high-field colliders being considered by the accelerator physics community. Thus, the numerical examples given here must ultimately be reexamined in light of the actual parameters of the particular accelerator being considered

  12. Delayed neutrons in liquid metal spallation targets

    International Nuclear Information System (INIS)

    Ridikas, D.; Bokov, P.; David, J.C.; Dore, D.; Giacri, M.L.; Van Lauwe, A.; Plukiene, R.; Plukis, A.; Ignatiev, S.; Pankratov, D.

    2003-01-01

    The next generation spallation neutron sources, neutrino factories or RIB production facilities currently being designed and constructed around the world will increase the average proton beam power on target by a few orders of magnitude. Increased proton beam power results in target thermal hydraulic issues leading to new target designs, very often based on flowing liquid metal targets such as Hg, Pb, Pb-Bi. Radioactive nuclides produced in liquid metal targets are transported into hot cells, past electronics, into pumps with radiation sensitive components, etc. Besides the considerable amount of photon activity in the irradiated liquid metal, a significant amount of the delayed neutron precursor activity can be accumulated in the target fluid. The transit time from the front of a liquid metal target into areas, where delayed neutrons may be important, can be as short as a few seconds, well within one half-life of many delayed neutron precursors. Therefore, it is necessary to evaluate the total neutron flux (including delayed neutrons) as a function of time and determine if delayed neutrons contribute significantly to the dose rate. In this study the multi-particle transport code MCNPX combined with the material evolution program CINDER'90 will be used to evaluate the delayed neutron flux and spectra. The following scientific issues will be addressed in this paper: - Modeling of a typical geometry of the liquid metal spallation target; - Predictions of the prompt neutron fluxes, fission fragment and spallation product distributions; - Comparison of the above parameters with existing experimental data; - Time-dependent calculations of delayed neutron precursors; - Neutron flux estimates due to the prompt and delayed neutron emission; - Proposal of an experimental program to measure delayed neutron spectra from high energy spallation-fission reactions. The results of this study should be directly applicable in the design study of the European MegaPie (1 MW

  13. Target designs for energetics experiments on the National Ignition Facility

    International Nuclear Information System (INIS)

    Meezan, N B; Glenzer, S H; Suter, L J

    2008-01-01

    The goal of the first hohlraum energetics experiments on the National Ignition Facility (NIF) [G. H. Miller et al, Optical Eng. 43, 2841 (2004)] is to select the hohlraum design for the first ignition experiments. Sub-scale hohlraums heated by 96 of the 192 laser beams on the NIF are used to emulate the laser-plasma interaction behavior of ignition hohlraums. These 'plasma emulator' targets are 70% scale versions of the 1.05 MJ, 300 eV ignition hohlraum and have the same energy-density as the full-scale ignition designs. Radiation-hydrodynamics simulations show that the sub-scale target is a good emulator of plasma conditions inside the ignition hohlraum, reproducing density n e within 10% and temperature T e within 15% along a laser beam path. Linear backscatter gain analysis shows the backscatter risk to be comparable to that of the ignition target. A successful energetics campaign will allow the National Ignition Campaign to focus its efforts on optimizing ignition hohlraums with efficient laser coupling

  14. High Power Molten Targets for Radioactive Ion Beam Production: from Particle Physics to Medical Applications

    CERN Document Server

    De Melo Mendonca, T M

    2014-01-01

    Megawatt-class molten targets, combining high material densities and good heat transfer properties are being considered for neutron spallation sources, neutrino physics facilities and radioactive ion beam production. For this last category of facilities, in order to cope with the limitation of long diffusion times affecting the extraction of short-lived isotopes, a lead-bismuth eutectic (LBE) target loop equipped with a diffusion chamber has been proposed and tested offline during the EURISOL design study. To validate the concept, a molten LBE loop is now in the design phase and will be prototyped and tested on-line at CERN-ISOLDE. This concept was further extended to an alternative route to produce 1013 18Ne/s for the Beta Beams, where a molten salt loop would be irradiated with 7 mA, 160 MeV proton beam. Some elements of the concept have been tested by using a molten fluoride salt static unit at CERNISOLDE. The investigation of the release and production of neon isotopes allowed the measurement of the diffu...

  15. Modern design of far-field target motion simulators

    Science.gov (United States)

    Hauser, Robin; Swamp, Michael; Havlicsek, Howard

    2006-05-01

    Target Motion Simulators (TMS) are often used in conjunction with Flight Motion Simulators (FMS) to provide a realistic simulation of tracking and target engagement. For near-field applications, the TMS has typically been implemented with two additional gimbals around the FMS. For far-field applications, such as a radar, the TMS has traditionally been implemented with curvilinear X-Y Frames. A curvilinear frame placed at the proper distance from the FMS has the benefit of always pointing the Target back to the FMS intersection of axes. In most cases the curvilinear TMS provides good results. However, the curvilinear TMS lacks the possibility to change the distance between Target and Seeker, which is needed for operation with different radar wavelengths. Acutronic has developed a new approach using a flat frame (X-Y) TMS coupled with a gimballed payload mount that has the possibility of being used at various distances without losing the functionality of continuous pointing back to the seeker. This paper describes the electro-mechanical design and gives an overview of the Computer and Controllers used. It further addresses the problem of coordination transformation that is needed to obtain the correct pointing.

  16. IFMIF target and test cell - design and integration

    International Nuclear Information System (INIS)

    Heinzel, V.

    2007-01-01

    The International Fusion Material Irradiation Facility (IFMIF) aims at the qualification of appropriate materials for a Demonstration Fusion Power Plant (DEMO) to a fluence of up to 150 dpa (displacement per atom) at a DEMO typical neutron spectrum. It comprises two accelerators each providing a deuteron beam with 125 mA and 40 MeV. The deuterons strike a lithium target and create via stripping reactions neutrons. The neutrons are mainly forward directed into the High-Flux-Test-Module (HFTM). The Medium Flux-Test-Modules (MFTM) and the Low-Flux-Test-Modules (LFTM) are arranged in beam direction behind. In the HFTM a damage rate in steel of more than 20 dpa/fpy (displacement per atome per full power year) will be provide in a volume of 0.5 litre. The neutron spectrum is prone to produce helium and tritium in steel like in the first wall of a DEMO reactor. The Medium- Flux-Test-Modules are designed for creep fatigues in situ and tritium release test. The test modules are cooled with helium. The target is a lithium jet with a free surface towards the deuteron beams. The jet follows a concave curved so called back wall. Centrifugal forces increase the static pressure, which prevents lithium boiling at the beam tube pressure and the power release of 10 MW due to the deuteron beams. The target and Test Cell (TTC) houses the target and the test modules as well as the lithium supply tubes and a quench tank into which the lithium splashes after the target. The lithium containing components have a temperature of 250 to 350 C. Nuclear reactions mainly in beam direction contribute to heat releases in TTC components. The TTC is filled with a noble gas with almost atmospheric pressure. Natural convection transfers heat to the walls but also mitigates temperature peaks. The Forschungszentrum Karlsruhe (FZK) has developed or validated tools for: - The extended Monte Carlo Code McDeLicious for calculations of the neutron source term, dpa rates in the material specimens, activation

  17. Application of analytical target cascading method in multidisciplinary design optimization of ship conceptual design

    Directory of Open Access Journals (Sweden)

    WANG Jian

    2017-10-01

    Full Text Available [Objectives] Ship conceptual design requires the coordination of many different disciplines for comprehensive optimization, which presents a complicated system design problem affecting several fields of technology. However, the development of overall ship design is relatively slow compared with other subjects. [Methods] The decomposition and coordination strategy of ship design is presented, and the analytical target cascading (ATC method is applied to the multidisciplinary design optimization of the conceptual design phase of ships on this basis. A tank ship example covering the 5 disciplines of buoyancy and stability, rapidity, maneuverability, capacity and economy is established to illustrate the analysis process in the present study. [Results] The results demonstrate the stability, convergence and validity of the ATC method in dealing with the complex coupling effect occurring in ship conceptual design.[Conclusions] The proposed method provides an effective basis for optimization of ship conceptual design.

  18. Mock Target Window OTR and IR Design and Testing

    Energy Technology Data Exchange (ETDEWEB)

    Wass, Alexander Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-09-19

    In order to fully verify temperature measurements made on the target window using infrared (IR) optical non-contact methods, actual comparative measurements are made with a real beam distribution as the heat source using Argonne National Laboratory’s (ANL) 35 MeV electron accelerator. Using Monte Carlo N-Particle (MCNP) simulations and thermal Finite Element Analysis (FEA), a cooled mock target window with thermocouple implants is designed to be used in such a test to achieve window temperatures up to 700°C. An uncoated and blackcoated mock window is designed to enhance the IR temperature measurements and verify optical transmitted radiation (OTR) imagery. This allows us to fully verify and characterize our temperature accuracy with our current IR camera method and any future method we may wish to explore using actual production conditions. This test also provides us with valuable conclusions/concerns regarding the calibration method we developed using our IR test stand at TA-53 in MPF-14.

  19. Target design for materials processing very far from equilibrium

    Science.gov (United States)

    Barnard, John J.; Schenkel, Thomas

    2016-10-01

    Local heating and electronic excitations can trigger phase transitions or novel material states that can be stabilized by rapid quenching. An example on the few nanometer scale are phase transitions induced by the passage of swift heavy ions in solids where nitrogen-vacancy color centers form locally in diamonds when ions heat the diamond matrix to warm dense matter conditions at 0.5 eV. We optimize mask geometries for target materials such as silicon and diamond to induce phase transitions by intense ion pulses (e. g. from NDCX-II or from laser-plasma acceleration). The goal is to rapidly heat a solid target volumetrically and to trigger a phase transition or local lattice reconstruction followed by rapid cooling. The stabilized phase can then be studied ex situ. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of crystal targets with micro-structured masks. A simple analytical model, that includes ion heating and radial, diffusive cooling, was developed that agrees closely with the HYDRA simulations. The model gives scaling laws that can guide the design of targets over a wide range of parameters including those for NDCX-II and the proposed BELLA-i. This work was performed under the auspices of the U.S. DOE under contracts DE-AC52-07NA27344 (LLNL), DE-AC02-05CH11231 (LBNL) and was supported by the US DOE Office of Science, Fusion Energy Sciences. LLNL-ABS-697271.

  20. Modern Prodrug Design for Targeted Oral Drug Delivery

    Directory of Open Access Journals (Sweden)

    Arik Dahan

    2014-10-01

    Full Text Available The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, e.g., membrane influx/efflux transporters and cellular protein expression and distribution. This novel targeted-prodrug approach is aimed to exploit carrier-mediated transport for enhanced intestinal permeability, as well as specific enzymes to promote activation of the prodrug and liberation of the free parent drug. The purpose of this article is to provide a concise overview of this modern prodrug approach, with useful successful examples for its utilization. In the past the prodrug approach used to be viewed as a last option strategy, after all other possible solutions were exhausted; nowadays this is no longer the case, and in fact, the prodrug approach should be considered already in the very earliest development stages. Indeed, the prodrug approach becomes more and more popular and successful. A mechanistic prodrug design that aims to allow intestinal permeability by specific transporters, as well as activation by specific enzymes, may greatly improve the prodrug efficiency, and allow for novel oral treatment options.

  1. 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.

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

    International Nuclear Information System (INIS)

    Crescenzi, Fabio; Bachmann, C.; Richou, M.; Roccella, S.; Visca, E.; You, J.-H.

    2015-01-01

    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"−"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.

  3. 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.

  4. 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

  5. Designer interface peptide grafts target estrogen receptor alpha dimerization

    International Nuclear Information System (INIS)

    Chakraborty, S.; Asare, B.K.; Biswas, P.K.; Rajnarayanan, R.V.

    2016-01-01

    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

  6. 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

  7. National Ignition Facility subsystem design requirements target positioning subsystem SSDR 1.8.2

    International Nuclear Information System (INIS)

    Pittenger, L.

    1996-01-01

    This Subsystem Design Requirement document is a development specification that establishes the performance, design, development and test requirements for the target positioner subsystem (WBS 1.8.2) of the NIF Target Experimental System (WBS 1.8)

  8. The Rapid Cycling Synchrotron of the EURISOL Beta-Beam facility

    CERN Document Server

    Lachaize, A

    During the last two years, several upgrades of the initial baseline scenario were studied with the aim of increasing the average intensity of ion beams in the accelerator chain of the Beta Beam complex. This is the reason why the Rapid Cycling Synchrotron (RCS) specifications were reconsidered many times.General considerations on the optical design were presented at the Beta Beam Task Meetings held at CERN and at Saclay in 2005 (http://beta-beam.web.cern.ch/beta-beam/). More detailed beam optics studies were performed during the next months. Lattices, RF system parameters, multi-turn injection scheme, fast extraction, closed orbit correction and chromaticity correction systems were proposed for different versions of the RCS.Finally, the RCS specifications have stabilized in November 2006 after the fourth Beta Beam Task Meeting when it was decided to fix the maximum magnetic rigidity of ion beams to 14.47 T.m (3.5 GeV equivalent proton energy) and to adopt a ring physical radius of 40 m in order to facilitat...

  9. SNS Target Test Facility for remote handling design and verification

    International Nuclear Information System (INIS)

    Spampinato, P.T.; Graves, V.B.; Schrock, S.L.

    1998-01-01

    The Target Test Facility will be a full-scale prototype of the Spallation Neutron Source Target Station. It will be used to demonstrate remote handling operations on various components of the mercury flow loop and for thermal/hydraulic testing. This paper describes the remote handling aspects of the Target Test Facility. Since the facility will contain approximately 1 cubic meter of mercury for the thermal/hydraulic tests, an enclosure will also be constructed that matches the actual Target Test Cell

  10. 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.

  11. Optimization of in-target yields for RIB production: Part 1: direct targets

    International Nuclear Information System (INIS)

    Chabod, S.; Thiolliere, N.; David, J.Ch.; Dore, D.; Ene, D.; Rapp, B.; Ridikas, D.; Chabod, S.; Blideanu, V.

    2008-03-01

    In the framework of the EURISOL-DS project and within Task-11, we have performed in-target yield calculations for different configurations of thick direct targets. The target materials tested are Al 2 O 3 , SiC, Pb(molten), Ta and UC 3 . The target was irradiated with protons of 0.5, 1.0, 1.5 and 2.0 GeV. The production rates have been computed using the MCNPX transport/generation code, coupled with the CINDER-90 evolution program. The yield distributions as a function of charge number Z and mass number A have been evaluated. Their production rates have been optimized for 11 selected elements (Li, Be, Ne, Mg, Ar, Ni, Ga, Kr, Hg, Sn and Fr) and 23 of their isotopes of interest. Finally, the isotopic distributions for each of these 11 elements have been optimized in terms of the target material, its geometry, and incident proton energy

  12. Conceptual design studies for the liquid metal target META:LIC

    International Nuclear Information System (INIS)

    Class, A.G.; Fazio, C.; Fetzer, J.R.; Gordeev, S.

    2014-01-01

    When the construction of ESS (European Spallation Source) in Sweden was initiated, the target station concept selection group decided to reevaluate a variety of target designs to respect new developments in their selection process. The META:LIC (MEgawatt TArget:Lead bIsmuth Cooled) target concept was developed following an extensive analysis of existing and new proposed designs and reached the level of proof of principle within only 2 years. ESS selected META:LIC as comparative target option for licensing purposes during the design update phase of ESS. The present work describes the design motivation of META:LIC referring to properties and design features of other targets. Therefore, META:LIC design is an evolutionary target which incorporates the extensive experience of liquid metal targets. The modular LBE (Lead Bismuth Eutectic) target concept with focus on the target module is introduced. Both, a window target option for the start of operation and a windowless option with extended lifetime are foreseen. Thermohydraulic simulations show that adequate window cooling can be realized. The stability of the free surface in the windowless option has been shown. Robust target module instrumentation based on free surface levels and the MEGAPIE experience is proposed for target control. Since the META:LIC concept foresees a horizontal extraction for both moderators and target from the monolith a safety concept based on the SNS and JSNS experience is proposed

  13. 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).

  14. A flexible testing facility for high-power targets T-MIF

    International Nuclear Information System (INIS)

    Fusco, Y.; Samec, K.; Behzad, M.; Kadi, Y.

    2015-01-01

    A dedicated material test irradiation facility is being proposed. The testing station will allow critical issues concerning materials under irradiation to be addressed, such as the impact of proton beam irradiation, neutron irradiation, liquid metal corrosion and temperature. The material samples to be investigated in such a facility will be subjected to tensile stress, either constant or cyclical. The facility may also be used for sensor development under irradiation and isotope production. The goal of the current work is to propose a facility that is sufficiently versatile and compact so that it may be transported and used in different laboratories. The power is limited to 100 kW. The general aspect of the proposed irradiation facility is a cube, 2 metres deep and comprising within it all the necessary systems. The interface to the laboratory is limited to the coolant connections, the secondary circuit, the electric energy supply and the signals from the instrumentation. The liquid metal target placed in the centre of the facility contains the samples which are subjected to a proton beam, creating irradiation damage directly through protons or indirectly through neutrons created by spallation of the surrounding liquid metal by the incoming protons. The design of the target is based upon the EURISOL target. The same beam window design is used, albeit stretched horizontally to adopt an elliptical section which is compatible with the shape of the beam used to irradiate the samples. The liquid metal in the target is re-circulated by an electromagnetic pump that drives the liquid metal through a heat exchanger located at the top of the facility, the position of which was chosen to encourage natural circulation. The heat exchanger is made up of two separate parts which allow the primary and secondary circuit to separate cleanly

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

    International Nuclear Information System (INIS)

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

    1982-03-01

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

  16. Novel target design for enhanced laser driven proton acceleration

    Directory of Open Access Journals (Sweden)

    Malay Dalui

    2017-09-01

    Full Text Available We demonstrate a simple method of preparing structured target for enhanced laser-driven proton acceleration under target-normal-sheath-acceleration scheme. A few layers of genetically modified, clinically grown micron sized E. Coli bacteria cell coated on a thin metal foil has resulted in an increase in the maximum proton energy by about 1.5 times and the total proton yield is enhanced by approximately 25 times compared to an unstructured reference foil at a laser intensity of 1019 W/cm2. Particle-in-cell simulations on the system shows that the structures on the target-foil facilitates anharmonic resonance, contributing to enhanced hot electron production which leads to stronger accelerating field. The effect is observed to grow as the number of structures is increased in the focal area of the laser pulse.

  17. MEGAPIE spallation target: Design, manufacturing and preliminary tests of the first pro-typical spallation target for future ADS

    International Nuclear Information System (INIS)

    Latge, Ch.; Laffont, G.; Groeschel, F.; Thomsen, K.; Wagner, W.; Agostini, P.; Dierckx, M.; Fazio, C.; Kirchner, T.; Kurata, Y.; Song, T.; Woloshun, K.

    2006-01-01

    Partitioning and Transmutation (P and T) techniques could contribute to reduce the radioactive inventory and its associated radiotoxicity. Sub-critical Accelerator Driven Systems (ADS) are potential candidates as dedicated transmutation systems, and thus their development is a relevant R and D topic in Europe. Following a first phase focused on the understanding of the basic principles of ADS (e.g. the programme MUSE), the R and D has been streamlined and focused on practical demonstration key issues. These demonstrations cover high intensity proton accelerators (beam current in the range 1 to 20 mA), spallation targets of high power and their effective coupling with a subcritical core. Presently there is general consensus that up to 1 MW of beam power solid targets are feasible from a heat removal point of view. For higher power levels liquid metal targets are the option of choice because of their higher heat removal capability, higher spallation material density in the volume and lower specific radioactivity, Therefore, a key experiment in the ADS road map, the Megawatt Pilot Experiment (MEGAPIE) (1 MW) was initiated in 1999 in order to design and build a liquid lead-bismuth spallation target, then to operate it into the Swiss spallation neutron facility SINQ at Paul Scherrer Institute (PSI). It has to be equipped to provide the largest possible amount of scientific and technical information without jeopardizing its safe operation. The minimum design service life has been fixed at 1 year (6000 mAh). Whereas the interest of the partner institutes is driven by the development needs of ADS, PSI interest lies also in the potential use of a LM target as a SINQ standard target providing a higher neutron flux than the current solid targets. Calculations of the radial distribution of the undisturbed thermal neutron flux for the LBE target in comparison to the former Zircaloy and current steel-clad solid lead target were done with different nuclear codes; nevertheless

  18. Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

    Science.gov (United States)

    Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

    2018-03-15

    Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug

  19. 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.

  20. Membrane Transporters: Structure, Function and Targets for Drug Design

    Science.gov (United States)

    Ravna, Aina W.; Sager, Georg; Dahl, Svein G.; Sylte, Ingebrigt

    Current therapeutic drugs act on four main types of molecular targets: enzymes, receptors, ion channels and transporters, among which a major part (60-70%) are membrane proteins. This review discusses the molecular structures and potential impact of membrane transporter proteins on new drug discovery. The three-dimensional (3D) molecular structure of a protein contains information about the active site and possible ligand binding, and about evolutionary relationships within the protein family. Transporters have a recognition site for a particular substrate, which may be used as a target for drugs inhibiting the transporter or acting as a false substrate. Three groups of transporters have particular interest as drug targets: the major facilitator superfamily, which includes almost 4000 different proteins transporting sugars, polyols, drugs, neurotransmitters, metabolites, amino acids, peptides, organic and inorganic anions and many other substrates; the ATP-binding cassette superfamily, which plays an important role in multidrug resistance in cancer chemotherapy; and the neurotransmitter:sodium symporter family, which includes the molecular targets for some of the most widely used psychotropic drugs. Recent technical advances have increased the number of known 3D structures of membrane transporters, and demonstrated that they form a divergent group of proteins with large conformational flexibility which facilitates transport of the substrate.

  1. Backward Design: Targeting Depth of Understanding for All Learners

    Science.gov (United States)

    Childre, Amy; Sands, Jennifer R.; Pope, Saundra Tanner

    2009-01-01

    Curriculum design is at the center of developing student ability to construct understanding. Without appropriately designed curriculum, instruction can be ineffective at scaffolding understanding. Often students with disabilities need more explicit instruction or guidance in applying their schema to new information. Thus, instruction must not only…

  2. Seismic design and evaluation criteria based on target performance goals

    International Nuclear Information System (INIS)

    Murray, R.C.; Nelson, T.A.; Kennedy, R.P.; Short, S.A.

    1994-04-01

    The Department of Energy utilizes deterministic seismic design/evaluation criteria developed to achieve probabilistic performance goals. These seismic design and evaluation criteria are intended to apply equally to the design of new facilities and to the evaluation of existing facilities. In addition, the criteria are intended to cover design and evaluation of buildings, equipment, piping, and other structures. Four separate sets of seismic design/evaluation criteria have been presented each with a different performance goal. In all these criteria, earthquake loading is selected from seismic hazard curves on a probabilistic basis but seismic response evaluation methods and acceptable behavior limits are deterministic approaches with which design engineers are familiar. For analytical evaluations, conservatism has been introduced through the use of conservative inelastic demand-capacity ratios combined with ductile detailing requirements, through the use of minimum specified material strengths and conservative code capacity equations, and through the use of a seismic scale factor. For evaluation by testing or by experience data, conservatism has been introduced through the use of an increase scale factor which is applied to the prescribed design/evaluation input motion

  3. 1L Mark-IV Target Design Review

    Energy Technology Data Exchange (ETDEWEB)

    Koehler, Paul E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-11-16

    This presentation includes General Design Considerations; Current (Mark-III) Lower Tier; Mark-III Upper Tier; Performance Metrics; General Improvements for Material Science; General Improvements for Nuclear Science; Improving FOM for Nuclear Science; General Design Considerations Summary; Design Optimization Studies; Expected Mark-IV Performance: Material Science; Expected Mark-IV Performance: Nuclear Science (Disk); Mark IV Enables Much Wider Range of Nuclear-Science FOM Gains than Mark III; Mark-IV Performance Summary; Rod or Disk? Center or Real FOV?; and Project Cost and Schedule.

  4. Design strategies for self-assembly of discrete targets

    International Nuclear Information System (INIS)

    Madge, Jim; Miller, Mark A.

    2015-01-01

    Both biological and artificial self-assembly processes can take place by a range of different schemes, from the successive addition of identical building blocks to hierarchical sequences of intermediates, all the way to the fully addressable limit in which each component is unique. In this paper, we introduce an idealized model of cubic particles with patterned faces that allows self-assembly strategies to be compared and tested. We consider a simple octameric target, starting with the minimal requirements for successful self-assembly and comparing the benefits and limitations of more sophisticated hierarchical and addressable schemes. Simulations are performed using a hybrid dynamical Monte Carlo protocol that allows self-assembling clusters to rearrange internally while still providing Stokes-Einstein-like diffusion of aggregates of different sizes. Our simulations explicitly capture the thermodynamic, dynamic, and steric challenges typically faced by self-assembly processes, including competition between multiple partially completed structures. Self-assembly pathways are extracted from the simulation trajectories by a fully extendable scheme for identifying structural fragments, which are then assembled into history diagrams for successfully completed target structures. For the simple target, a one-component assembly scheme is most efficient and robust overall, but hierarchical and addressable strategies can have an advantage under some conditions if high yield is a priority

  5. 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.

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

    KAUST Repository

    Jardak, Seifallah

    2014-01-01

    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

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

    International Nuclear Information System (INIS)

    Lee, D.

    1996-01-01

    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

  8. RNAblueprint: flexible multiple target nucleic acid sequence design.

    Science.gov (United States)

    Hammer, Stefan; Tschiatschek, Birgit; Flamm, Christoph; Hofacker, Ivo L; Findeiß, Sven

    2017-09-15

    Realizing the value of synthetic biology in biotechnology and medicine requires the design of molecules with specialized functions. Due to its close structure to function relationship, and the availability of good structure prediction methods and energy models, RNA is perfectly suited to be synthetically engineered with predefined properties. However, currently available RNA design tools cannot be easily adapted to accommodate new design specifications. Furthermore, complicated sampling and optimization methods are often developed to suit a specific RNA design goal, adding to their inflexibility. We developed a C ++  library implementing a graph coloring approach to stochastically sample sequences compatible with structural and sequence constraints from the typically very large solution space. The approach allows to specify and explore the solution space in a well defined way. Our library also guarantees uniform sampling, which makes optimization runs performant by not only avoiding re-evaluation of already found solutions, but also by raising the probability of finding better solutions for long optimization runs. We show that our software can be combined with any other software package to allow diverse RNA design applications. Scripting interfaces allow the easy adaption of existing code to accommodate new scenarios, making the whole design process very flexible. We implemented example design approaches written in Python to demonstrate these advantages. RNAblueprint , Python implementations and benchmark datasets are available at github: https://github.com/ViennaRNA . s.hammer@univie.ac.at, ivo@tbi.univie.ac.at or sven@tbi.univie.ac.at. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

  9. 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.

  10. Flat cladding and pellets in the design of an irradiation target

    International Nuclear Information System (INIS)

    Yorio, Daniel; Denis, Alicia C.; Soba, Alejandro; Beuter, Oscar; Marajofsky, Adolfo

    2003-01-01

    The design of an enriched uranium irradiation target made of flat pellets and cladding is proposed in order to improve the fission Mo 99 production. The variation range of each one of the parameters is studied and the basic design of the target is given

  11. High gain direct drive target designs and supporting experiments with KrF

    International Nuclear Information System (INIS)

    Karasik, Max; Bates, Jason W.; Aglitskiy, Yefim

    2013-01-01

    Krypton-fluoride laser is an attractive inertial fusion energy driver from the standpoint of target physics. Target designs taking advantage of zooming, shock ignition, and favorable physics with KrF reach energy gains of 200 with sub-MJ laser energy. The designs are robust under 2D simulations. Experiments on the Nike KrF laser support the physics basis. (author)

  12. 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.

  13. 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.

  14. 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…

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

    Heller, Alfred; Gianniou, Panagiota; Katsigiannis, Emmanouil

    2014-01-01

    that there are exposed solutions where synergy effects arise that unleash extra saving potentials. Based on the insight gained by the simulations, IT intelligence and cross-component communication are to be invented to control the components and hereby to optimize the total system performance. One main strategy in doing......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...

  17. Designing decision support tools for targeted N-regulation

    DEFF Research Database (Denmark)

    Christensen, Andreas Aagaard; Piil, Kristoffer; Andersen, Peter Stubkjær

    2017-01-01

    data model for land use data – the dNmark landscape model. Based on input data which is corrected and edited by workshop participants, the tool estimates the effect of potential land use scenarios on nutrient emissions. The tool was tested in 5 scenario workshops in case areas in Denmark in 2016...... in Denmark to develop and improve a functioning decision support tool for landscape scale N-management. The aim of the study is to evaluate how a decision support tool can best be designed in order to enable landscape scale strategic N-management practices. Methods: A prototype GIS-tool for capturing......, storing, editing, displaying and modelling landscape scale farming practices and associated emission consequences was developed. The tool was designed to integrate locally held knowledge with national scale datasets in live scenario situations through the implementation of a flexible, uniform and editable...

  18. Lumican Peptides: Rational Design Targeting ALK5/TGFBRI

    Science.gov (United States)

    Gesteira, Tarsis Ferreira; Coulson-Thomas, Vivien J.; Yuan, Yong; Zhang, Jianhua; Nader, Helena B.; Kao, Winston W.-Y.

    2017-02-01

    Lumican, a small leucine rich proteoglycan (SLRP), is a component of extracellular matrix which also functions as a matrikine regulating multiple cell activities. In the cornea, lumican maintains corneal transparency by regulating collagen fibrillogenesis, promoting corneal epithelial wound healing, regulating gene expression and maintaining corneal homeostasis. We have recently shown that a peptide designed from the 13 C-terminal amino acids of lumican (LumC13) binds to ALK5/TGFBR1 (type1 receptor of TGFβ) to promote wound healing. Herein we evaluate the mechanism by which this synthetic C-terminal amphiphilic peptide (LumC13), binds to ALK5. These studies clearly reveal that LumC13-ALK5 form a stable complex. In order to determine the minimal amino acids required for the formation of a stable lumican/ALK5 complex derivatives of LumC13 were designed and their binding to ALK5 investigated in silico. These LumC13 derivatives were tested both in vitro and in vivo to evaluate their ability to promote corneal epithelial cell migration and corneal wound healing, respectively. These validations add to the therapeutic value of LumC13 (Lumikine) and aid its clinical relevance of promoting the healing of corneal epithelium debridement. Moreover, our data validates the efficacy of our computational approach to design active peptides based on interactions of receptor and chemokine/ligand.

  19. TARGETED SEQUENTIAL DESIGN FOR TARGETED LEARNING INFERENCE OF THE OPTIMAL TREATMENT RULE AND ITS MEAN REWARD.

    Science.gov (United States)

    Chambaz, Antoine; Zheng, Wenjing; van der Laan, Mark J

    2017-01-01

    This article studies the targeted sequential inference of an optimal treatment rule (TR) and its mean reward in the non-exceptional case, i.e. , assuming that there is no stratum of the baseline covariates where treatment is neither beneficial nor harmful, and under a companion margin assumption. Our pivotal estimator, whose definition hinges on the targeted minimum loss estimation (TMLE) principle, actually infers the mean reward under the current estimate of the optimal TR. This data-adaptive statistical parameter is worthy of interest on its own. Our main result is a central limit theorem which enables the construction of confidence intervals on both mean rewards under the current estimate of the optimal TR and under the optimal TR itself. The asymptotic variance of the estimator takes the form of the variance of an efficient influence curve at a limiting distribution, allowing to discuss the efficiency of inference. As a by product, we also derive confidence intervals on two cumulated pseudo-regrets, a key notion in the study of bandits problems. A simulation study illustrates the procedure. One of the corner-stones of the theoretical study is a new maximal inequality for martingales with respect to the uniform entropy integral.

  20. Conceptual design considerations and neutronics of lithium fall laser fusion target chambers

    International Nuclear Information System (INIS)

    Meier, W.R.; Thomson, W.B.

    1978-01-01

    Atomics International and Lawrence Livermore Laboratory are involved in the conceptual design of a laser fusion power plant incorporating the lithium fall target chamber. In this paper we discuss some of the more important design considerations for the target chamber and evaluate its nuclear performance. Sizing and configuration of the fall, hydraulic effects, and mechanical design considerations are addressed. The nuclear aspects examined include tritium breeding, energy deposition, and radiation damage

  1. Conceptual design considerations and neutronics of lithium fall laser target chambers

    International Nuclear Information System (INIS)

    Meier, W.R.; Thomson, W.B.

    1978-01-01

    Atomics International and Lawrence Livermore Laboratory are involved in the conceptual design of a laser fusion power plant incorporating the lithium fall target chamber. In this paper we discuss some of the more important design considerations for the target chamber and evaluate its nuclear performance. Sizing and configuration of the fall, hydraulic effects, and mechanical design considerations are addressed. The nuclear aspects examined include tritium breeding, energy deposition, and radiation damage

  2. NIF target area design support. Final summary report

    International Nuclear Information System (INIS)

    Tokheim, R.E.; Seaman, L.; Curran, D.R.

    1996-02-01

    SRI International continued support work for the National Ignition Facility, Chamber Dynamics Group at Lawrence Livermore National Laboratory (LLNL). The work entailed computational modeling of shrapnel and debris generation from copper shine shields, hohlraum, and stainless steel cryogenic support tubes for 1.8 MJ and 1.0 MJ no-yield and 20 MJ yield shots. Also, the authors addressed the effects of shrapnel at the first wall. Computations for 1.8 MJ showed an ionized gold hohlraum, but about half solid and half ionized copper shine shields, when material cell phase boundaries were maintained. This debris generation represents a potential threat to the first wall and debris shields. Further work is required to translate these results into particle size distributions based on computed strain rates. The authors used simple algorithms for x-ray loading of frost layers protecting the target support to compute peak stress attenuation. They developed algorithmic formulas for predicting damage in candidate first wall materials and they found damage algorithms for fused-silica debris shield material. They obtained very preliminary computational results at 20 MJ for predicting shrapnel mass and particle density at the first wall in spherical polar coordinate space with the hohlraum axis as the polar direction

  3. 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)

  4. Design and features of the target tracker of the Opera's target: study of the electron channel events

    International Nuclear Information System (INIS)

    Chon-Sen, N.

    2009-01-01

    Neutrino oscillations are now well acknowledged, the purpose of the Opera experiment is to show how ν τ appear in a ν μ beam. The ν μ beam is produced at CERN and crosses the earth crust on a distance of 732 km before being detected in the Gran-Sasso underground laboratory. The Opera experiment uses the technique of the photographic emulsion. The detector target is a series of walls of lead bricks, each brick being made of photographic emulsions intercalated with lead sheets. A target tracker enables the localization of the brick in which the neutrino interaction has happened. As soon as the brick is found, the brick is removed from the detector and the emulsion is developed and analysed. the target tracker is made up of plastic scintillator bars on which optic fibers are stuck to collect photons and send them to photomultipliers. The main purpose of this work is the calibration of the target tracker. The first chapter introduces the standard model, the neutrino and the neutrino oscillation phenomenon. The second chapter reviews the neutrino experiments worldwide. The third chapter describes the Opera experiment while chapter 4 and 5 are dedicated to the design and operation of the target tracker. The last chapter studies through simulation the behaviour of the target tracker when submitted to an electron beam in order to use it as a complementary tool for the identification of the τ → e channel. (A.C.)

  5. Target station design for a 1 MW pulsed spallation neutron source

    International Nuclear Information System (INIS)

    Russell, G.J.; Baker, G.D.; Brewton, R.J.

    1993-01-01

    Target stations are vital components of the 1 MW, next generation spallation neutron source proposed for LANSCE. By and large, target stations design determines the overall performance of the facility. Many traditional concepts will probably have to be rethought, and many new concepts will have to be put forward to meet the 1 MW challenge. This article gives a brief overview of the proposed neutron spallation source from the target station viewpoint, as well as the general philosophy adopted for the design of the LANSCE-II target stations. Some of the saliant concepts and features envisioned for LANSCE-II are briefly described

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

    International Nuclear Information System (INIS)

    Piet, S.J.

    1987-09-01

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

  7. Dead-blow hammer design applied to a calibration target mechanism to dampen excessive rebound

    Science.gov (United States)

    Lim, Brian Y.

    1991-01-01

    An existing rotary electromagnetic driver was specified to be used to deploy and restow a blackbody calibration target inside of a spacecraft infrared science instrument. However, this target was much more massive than any other previously inherited design applications. The target experienced unacceptable bounce when reaching its stops. Without any design modification, the momentum generated by the driver caused the target to bounce back to its starting position. Initially, elastomeric dampers were used between the driver and the target. However, this design could not prevent the bounce, and it compromised the positional accuracy of the calibration target. A design that successfully met all the requirements incorporated a sealed pocket 85 percent full of 0.75 mm diameter stainless steel balls in the back of the target to provide the effect of a dead-blow hammer. The energy dissipation resulting from the collision of balls in the pocket successfully dampened the excess momentum generated during the target deployment. The disastrous effects of new requirements on a design with a successful flight history, the modifications that were necessary to make the device work, and the tests performed to verify its functionality are described.

  8. Conceptual design of a high current ISOL target area at TRIUMF

    International Nuclear Information System (INIS)

    Beveridge, J.L.; Buchmann, L.; Clark, G.S.; Sprenger, H.; Thorson, I.; Vincent, J.; D'Auria, J.M.; Dombsky, M.

    1993-05-01

    Two similar conceptual designs for the handling of highly activated components at the target area of a high current radioactive beam facility have been investigated. The proposed designs are sufficiently flexible that practical detailed designs could be realized. Personnel exposure to radiation during the handling procedures is expected to be minimal. (author) 3 refs., 4 figs

  9. Target designs for the Brookhaven National Laboratory 5-MW pulsed spallation neutron source

    International Nuclear Information System (INIS)

    Ludewig, H.; Todosow, M.; Powell, J.R.

    1996-01-01

    A feasibility study of a compact high power density target for a spallation neutron source was under-taken. The target arrangement consists primarily of heavy metal, with appropriate cooling passages. A high intensity proton beam of intermediate energy is directed at the target, where it interacts with the heavy metal nuclei. The subsequent spallation reactions produce several neutrons per proton resulting in an intense neutron source. The proton beam is assumed to havean energy of 5 MW, and to be cyclic with a repetition rate of 10Hz and 50Hz. The study was divided into two broad sections. First, an analysis of preliminary target designs was undertaken to ensure the overall feasibility of the concepts involved in the design and eventual construction of such a high power density target. Second, two proposed target designs, based on the first set of analyses, are investigated in more detail. Special care is taken to ensure that the neutron fluxes in the moderator are at the desired level no material compatibility problems exist,and the target is able to operate in a reliable and safe manner. Several target materials, coolant types, and target arrangements are investigated in the first section. The second section concentrates on a single target material and geometric arrangement. However, several structural material choices continue to be investigated with the aim of minimizing the effects of structural heating, and associated thermally induced stresses. In the final section the conclusions of this preliminary study are summarized

  10. Design of a tripartite network for the prediction of drug targets

    Science.gov (United States)

    Kunimoto, Ryo; Bajorath, Jürgen

    2018-02-01

    Drug-target networks have aided in many target prediction studies aiming at drug repurposing or the analysis of side effects. Conventional drug-target networks are bipartite. They contain two different types of nodes representing drugs and targets, respectively, and edges indicating pairwise drug-target interactions. In this work, we introduce a tripartite network consisting of drugs, other bioactive compounds, and targets from different sources. On the basis of analog relationships captured in the network and so-called neighbor targets of drugs, new drug targets can be inferred. The tripartite network was found to have a stable structure and simulated network growth was accompanied by a steady increase in assortativity, reflecting increasing correlation between degrees of connected nodes leading to even network connectivity. Local drug environments in the tripartite network typically contained neighbor targets and revealed interesting drug-compound-target relationships for further analysis. Candidate targets were prioritized. The tripartite network design extends standard drug-target networks and provides additional opportunities for drug target prediction.

  11. Translating Genetic Research into Preventive Intervention: The Baseline Target Moderated Mediator Design.

    Science.gov (United States)

    Howe, George W; Beach, Steven R H; Brody, Gene H; Wyman, Peter A

    2015-01-01

    In this paper we present and discuss a novel research approach, the baseline target moderated mediation (BTMM) design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research. We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets. We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in that target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes. We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials. We use simulated data to illustrate a BTMM, and end with a discussion of some of the advantages and limitations of this approach.

  12. Translating genetic research into preventive intervention: The baseline target moderated mediator design

    Directory of Open Access Journals (Sweden)

    George W. Howe

    2016-01-01

    Full Text Available In this paper we present and discuss a novel research approach, the baseline target moderated mediation (BTMM design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research. We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets. We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in that target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes. We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials. We end with a discussion of some of the advantages and limitations of this approach.

  13. 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...

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  15. National Ignition Facility subsystem design requirements target area auxiliary subsystem SSDR 1.8.6

    International Nuclear Information System (INIS)

    Reitz, T.

    1996-01-01

    This Subsystem Design Requirement (SSDR) establishes the performance, design, development, and test requirements for the Target Area Auxiliary Subsystems (WBS 1.8.6), which is part of the NIF Target Experimental System (WBS 1.8). This document responds directly to the requirements detailed in NIF Target Experimental System SDR 003 document. Key elements of the Target Area Auxiliary Subsystems include: WBS 1.8.6.1 Local Utility Services; WBS 1.8.6.2 Cable Trays; WBS 1.8.6.3 Personnel, Safety, and Occupational Access; WBS 1.8.6.4 Assembly, Installation, and Maintenance Equipment; WBS 1.8.6.4.1 Target Chamber Service System; WBS 1.8.6.4.2 Target Bay Service Systems

  16. Design principles for target stations and methods of remote handling at PSI

    International Nuclear Information System (INIS)

    Steiner, E.W.

    1992-01-01

    Two design concepts for target stations used at Paul Scherrer Institute (PSI) are shown. The method of the remote handling of activated elements is described and some conclusions with respect to a radioactive beam facility are given

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

    International Nuclear Information System (INIS)

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

    1978-03-01

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

  18. 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.

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

    International Nuclear Information System (INIS)

    Nitti, F.S.; Ibarra, A.; Ida, M.; Favuzza, P.; Furukawa, T.; Groeschel, F.; Heidinger, R.; Kanemura, T.; Knaster, J.; Kondo, H.; Micchiche, G.; Sugimoto, M.; Wakai, E.

    2015-01-01

    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. Verification of the hydraulic design of the FMIT liquid lithium target

    International Nuclear Information System (INIS)

    Miles, R.R.; Annese, C.E.; Ingham, J.G.

    1983-01-01

    A liquid lithium target is being developed to generate a neutron flux for material testing in a fusion-like environment. The target consists of a thin, high speed, curved wall jet of lithium which is formed by an asymmetric nozzle. A prototype target was designed using potential flow analysis and was tested in water. Measurements of jet thickness and velocity in water and thickness in lithium were compared with isothermal design predictions and were shown to match within 1% for thickness and 5% for jet velocity

  1. Generic study on the design and operation of high power targets

    Directory of Open Access Journals (Sweden)

    A. Ahmad

    2014-02-01

    Full Text Available With the move towards beam power in the range of 1–10 MW, a thorough understanding of the response of target materials and auxiliary systems to high power densities and intense radiation fields is required. This paper provides insight into three major aspects related to the design and operation of high power solid targets: thermal stresses, coolant performance, and radiation damage. Where appropriate, a figure-of-merit approach is followed to facilitate the comparison between different target or coolant candidates. The section on radiation damage reports total and spatial variations of displacement-per-atom and helium production levels in different target materials.

  2. 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.

  3. Design and Preliminary Testing of the International Docking Adapter's Peripheral Docking Target

    Science.gov (United States)

    Foster, Christopher W.; Blaschak, Johnathan; Eldridge, Erin A.; Brazzel, Jack P.; Spehar, Peter T.

    2015-01-01

    The International Docking Adapter's Peripheral Docking Target (PDT) was designed to allow a docking spacecraft to judge its alignment relative to the docking system. The PDT was designed to be compatible with relative sensors using visible cameras, thermal imagers, or Light Detection and Ranging (LIDAR) technologies. The conceptual design team tested prototype designs and materials to determine the contrast requirements for the features. This paper will discuss the design of the PDT, the methodology and results of the tests, and the conclusions pertaining to PDT design that were drawn from testing.

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

    International Nuclear Information System (INIS)

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

    1991-12-01

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

  5. RobOKoD: microbial strain design for (over)production of target compounds.

    Science.gov (United States)

    Stanford, Natalie J; Millard, Pierre; Swainston, Neil

    2015-01-01

    Sustainable production of target compounds such as biofuels and high-value chemicals for pharmaceutical, agrochemical, and chemical industries is becoming an increasing priority given their current dependency upon diminishing petrochemical resources. Designing these strains is difficult, with current methods focusing primarily on knocking-out genes, dismissing other vital steps of strain design including the overexpression and dampening of genes. The design predictions from current methods also do not translate well-into successful strains in the laboratory. Here, we introduce RobOKoD (Robust, Overexpression, Knockout and Dampening), a method for predicting strain designs for overproduction of targets. The method uses flux variability analysis to profile each reaction within the system under differing production percentages of target-compound and biomass. Using these profiles, reactions are identified as potential knockout, overexpression, or dampening targets. The identified reactions are ranked according to their suitability, providing flexibility in strain design for users. The software was tested by designing a butanol-producing Escherichia coli strain, and was compared against the popular OptKnock and RobustKnock methods. RobOKoD shows favorable design predictions, when predictions from these methods are compared to a successful butanol-producing experimentally-validated strain. Overall RobOKoD provides users with rankings of predicted beneficial genetic interventions with which to support optimized strain design.

  6. 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.

  7. 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.

  8. 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.

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

    International Nuclear Information System (INIS)

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

    1993-05-01

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

  10. Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.

    Science.gov (United States)

    Fu, Rong-Geng; Sun, Yuan; Sheng, Wen-Bing; Liao, Duan-Fang

    2017-08-18

    The dominant paradigm in drug discovery is to design ligands with maximum selectivity to act on individual drug targets. With the target-based approach, many new chemical entities have been discovered, developed, and further approved as drugs. However, there are a large number of complex diseases such as cancer that cannot be effectively treated or cured only with one medicine to modulate the biological function of a single target. As simultaneous intervention of two (or multiple) cancer progression relevant targets has shown improved therapeutic efficacy, the innovation of multi-targeted drugs has become a promising and prevailing research topic and numerous multi-targeted anticancer agents are currently at various developmental stages. However, most multi-pharmacophore scaffolds are usually discovered by serendipity or screening, while rational design by combining existing pharmacophore scaffolds remains an enormous challenge. In this review, four types of multi-pharmacophore modes are discussed, and the examples from literature will be used to introduce attractive lead compounds with the capability of simultaneously interfering with different enzyme or signaling pathway of cancer progression, which will reveal the trends and insights to help the design of the next generation multi-targeted anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  12. 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.

  13. European DEMO divertor target: Operational requirements and material-design interface

    Directory of Open Access Journals (Sweden)

    J.H. You

    2016-12-01

    Full Text Available Recently, an integrated program of conceptual design activities for the European DEMO reactor was launched in the framework of the EUROfusion Consortium, where reliable power handling capability was identified as one of the most critical scientific as well as technological challenges for a DEMO reactor. The divertor is the key in-vessel plasma-facing component being in charge of power exhaust and removal of impurity particles. The DEMO divertor target will have to withstand extreme thermal loads where the local peak heat flux is expected to reach up to 20 MW/m2 during slow transient events in DEMO. To assure sufficient heat removal capability of the divertor target against normal and transient operational scenarios under expected cumulative neutron dose of up to 13 dpa is one of the fundamental engineering challenges imposed on target design. To develop the design of the DEMO divertor and related technologies, an R&D work package ‘Divertor’ has been set up in this consortium. The subproject ‘Target Development’ is devoted to the development of the conceptual design and the core technologies of the plasma-facing target. Devising and implementing novel structural heat sink materials (e.g. W/Cu composites to advanced target design concepts is one of the major objectives of this subproject. In this paper, the underlying design requirements imposed by the envisaged power exhaust goal and the prominent material-design interface issues are discussed. In addition, the candidate design concepts being currently considered are presented together with the related material issues. Finally, the first results achieved so far are presented.

  14. 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.

  15. 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 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.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.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 for specifically targeting tumors with nanoparticle

  16. 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.

  17. Data driven polypharmacological drug design for lung cancer: analyses for targeting ALK, MET, and EGFR

    DEFF Research Database (Denmark)

    Narayanan, Dilip; Gani, Osman ABSM; Gruber, Franz XE

    2017-01-01

    encoded into molecular mechanics force fields. Cheminformatics analyses of binding data show EGFR to be dissimilar to ALK and MET, but its structure shows how it may be co-targeted with the addition of a covalent trap. This suggests a strategy for the design of a focussed chemical library based on a pan......Drug design of protein kinase inhibitors is now greatly enabled by thousands of publicly available X-ray structures, extensive ligand binding data, and optimized scaffolds coming off patent. The extensive data begin to enable design against a spectrum of targets (polypharmacology); however...... consider polypharmacological targeting of protein kinases ALK, MET, and EGFR (and its drug resistant mutant T790M) in non small cell lung cancer as an example. Both EGFR and ALK represent sources of primary oncogenic lesions, while drug resistance arises from MET amplification and EGFR mutation. A drug...

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

    Science.gov (United States)

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

    2014-02-21

    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.

  19. Designing and modeling a centrifugal microfluidic device to separate target blood cells

    International Nuclear Information System (INIS)

    Shamloo, Amir; Selahi, AmirAli; Madadelahi, Masoud

    2016-01-01

    The objective of this study is to design a novel and efficient portable lab-on-a-CD (LOCD) microfluidic device for separation of specific cells (target cells) using magnetic beads. In this study the results are shown for neutrophils as target cells. However, other kinds of target cells can be separated in a similar approach. The designed microfluidics can be utilized as a point of care system for neutrophil detection. This microfluidic system employs centrifugal and magnetic forces for separation. After model validation by the experimental data in the literature (that may be used as a design tool for developing centrifugo-magnetophoretic devices), two models are presented for separation of target cells using magnetic beads. The first model consists of one container in the inlet section and two containers in the outlets. Initially, the inlet container is filled with diluted blood sample which is a mixture of red blood cells (RBCs) plus neutrophils which are attached to Magnetic beads. It is shown that by using centrifugal and magnetic forces, this model can separate all neutrophils with recovery factor of ∼100%. In the second model, due to excess of magnetic beads in usual experimental analysis (to ensure that all target cells are attached to them) the geometry is improved by adding a third outlet for these free magnetic beads. It is shown that at angular velocity of 45 rad s −1 , recovery factor of 100% is achievable for RBCs, free magnetic beads and neutrophils as target cells. (paper)

  20. Designing and modeling a centrifugal microfluidic device to separate target blood cells

    Science.gov (United States)

    Shamloo, Amir; Selahi, AmirAli; Madadelahi, Masoud

    2016-03-01

    The objective of this study is to design a novel and efficient portable lab-on-a-CD (LOCD) microfluidic device for separation of specific cells (target cells) using magnetic beads. In this study the results are shown for neutrophils as target cells. However, other kinds of target cells can be separated in a similar approach. The designed microfluidics can be utilized as a point of care system for neutrophil detection. This microfluidic system employs centrifugal and magnetic forces for separation. After model validation by the experimental data in the literature (that may be used as a design tool for developing centrifugo-magnetophoretic devices), two models are presented for separation of target cells using magnetic beads. The first model consists of one container in the inlet section and two containers in the outlets. Initially, the inlet container is filled with diluted blood sample which is a mixture of red blood cells (RBCs) plus neutrophils which are attached to Magnetic beads. It is shown that by using centrifugal and magnetic forces, this model can separate all neutrophils with recovery factor of ~100%. In the second model, due to excess of magnetic beads in usual experimental analysis (to ensure that all target cells are attached to them) the geometry is improved by adding a third outlet for these free magnetic beads. It is shown that at angular velocity of 45 rad s-1, recovery factor of 100% is achievable for RBCs, free magnetic beads and neutrophils as target cells.

  1. Design and Certification of Targets for Drop Tests at the NTRC Packaging Research Facility

    International Nuclear Information System (INIS)

    Ludwig, S.B.

    2003-01-01

    This report provides documentation of the design and certification of drop pad (targets) at the National Transportation Research Center (NTRC) Packaging Research Facility(PRF). Based on the evaluation performed, it has been demonstrated that the small (interior) drop pad (target) meets the regulatory definition of a flat, essentially unyielding, horizontal surface for packages weighing up to 3,150 lb (1,432 kg). The large (exterior) drop pad (target) meets the regulatory definition of a flat, essentially unyielding, horizontal surface for packages weighing up to 28,184 lb (12,811 kg)

  2. Design and fabrication of foam-insulated cryogenic target for wet-wall laser fusion reactor

    International Nuclear Information System (INIS)

    Norimatsu, T.; Takeda, T.; Nagai, K.; Mima, K.; Yamanaka, T.

    2003-01-01

    A foam insulated cryogenic target was proposed for use in a future laser fusion reactor with a wet wall. This scheme can protect the solid DT layer from melting due to surface heating by adsorption of metal vapor without significant reduction in the target gain. Design spaces for the injection velocity and the acceptable vapor pressure in the reactor are discussed. Basic technology to fabricate such structure was demonstrated by emulsion process. Concept of a cryogenic fast-ignition target with a gold guiding cone was proposed together with direct injection filling of liquid DT. (author)

  3. Shielding design for the target room of the proton accelerator research center

    International Nuclear Information System (INIS)

    Min, Y. S.; Lee, C. W.; Mun, K. J.; Nam, J.; Kim, J. Y.

    2010-01-01

    The Proton Engineering Frontier Project (PEFP) has been developing a 100-MeV proton linear accelerator. Also, PEFP has been designing the Proton Accelerator Research Center (PARC). In the Accelerator Tunnel and Beam Experiment Hall in PARC, 10 target rooms for the 20- and 100-MeV beamline facilities exist in the Beam Experiment Hall. For the 100-MeV target rooms during 100-MeV proton beam extraction, a number of high energy neutrons, ranging up to 100-MeV, are produced. Because of the high beam current and space limitations of each target room, the shielding design of each target room should be considered seriously. For the shielding design of the 100-MeV target rooms of the PEFP, a permanent and removable local shield structure was adopted. To optimize shielding performance, we evaluated four different shield materials (concrete, HDPE, lead, iron). From the shielding calculation results, we confirmed that the proposed shielding design made it possible to keep the dose rate below the 'as low as reasonably achievable (ALARA)' objective.

  4. Ligand design for riboswitches, an emerging target class for novel antibiotics.

    Science.gov (United States)

    Rekand, Illimar Hugo; Brenk, Ruth

    2017-09-01

    Riboswitches are cis-acting gene regulatory elements and constitute potential targets for new antibiotics. Recent studies in this field have started to explore these targets for drug discovery. New ligands found by fragment screening, design of analogs of the natural ligands or serendipitously by phenotypic screening have shown antibacterial effects in cell assays against a range of bacteria strains and in animal models. In this review, we highlight the most advanced drug design work of riboswitch ligands and discuss the challenges in the field with respect to the development of antibiotics with a new mechanism of action.

  5. A novel graphical technique for Pinch Analysis applications: Energy Targets and grassroots design

    International Nuclear Information System (INIS)

    Gadalla, Mamdouh A.

    2015-01-01

    Graphical abstract: A new HEN graphical design. - Highlights: • A new graphical technique for heat exchanger networks design. • Pinch Analysis principles and design rules are better interpreted. • Graphical guidelines for optimum heat integration. • New temperature-based graphs provide user-interactive features. - Abstract: Pinch Analysis is for decades a leading tool to energy integration for retrofit and design. This paper presents a new graphical technique, based on Pinch Analysis, for the grassroots design of heat exchanger networks. In the new graph, the temperatures of hot streams are plotted versus those of the cold streams. The temperature–temperature based graph is constructed to include temperatures of hot and cold streams as straight lines, horizontal lines for hot streams, and vertical lines for cold streams. The graph is applied to determine the pinch temperatures and Energy Targets. It is then used to synthesise graphically a complete exchanger network, achieving the Energy Targets. Within the new graph, exchangers are represented by inclined straight lines, whose slopes are proportional to the ratio of heat capacities and flows. Pinch Analysis principles for design are easily interpreted using this new graphical technique to design a complete exchanger network. Network designs achieved by the new technique can guarantee maximum heat recovery. The new technique can also be employed to simulate basic designs of heat exchanger networks. The strengths of the new tool are that it is simply applied using computers, requires no commercial software, and can be used for academic purposes/engineering education

  6. 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.

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

    International Nuclear Information System (INIS)

    Nakamura, Hiroo; Ida, Mizuho; Sugimoto, Masayoshi; Takeuchi, Hiroshi; Yutani, Toshiaki

    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 2 ) up to 200 dpa and a sufficient irradiation volume (500 cm 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)

  8. Target/blanket conceptual design for the Los Alamos ATW concept

    International Nuclear Information System (INIS)

    Ames, K.; Cappiello, M.; Ireland, J.; Sapir, J.; Farnum, G.

    1992-01-01

    The Los Alamos Accelerator Transmutation of Waste (ATW) concept has many potential applications that include defense waste transmutation, defense material production (i.e., tritium and 238 Pu), and the transmutation of hazardous nuclear wastes from commercial nuclear reactors (fission products and actinides). A more advanced long-term Los Alamos effort is investigating the potential of an accelerator- driven system to produce fission energy with a minimal nuclear waste stream. All applications employ a high-energy (800- to 1600-MeV), high-current (25--250 mA) proton linear accelerator as the driver. In this report, we discuss only the target/blanket conceptual design for the commercial nuclear waste application. A conceptual design for the target/blanket of the Los Alamos ATW concept has been presented. The neutronics, mechanical design, and heat transfer have been investigated in some detail for the base-case design. Much more work needs to be done, but at this point it appears that the design is feasible and will approach the design goal of supporting two commercial power reactors with each target/blanket module

  9. Experimental study of lithium free-surface flow for IFMIF target design

    International Nuclear Information System (INIS)

    Kondo, H.; Fujisato, A.; Yamaoka, N.; Inoue, S.; Miyamoto, S.; Iida, T.; Nakamura, H.; Ida, M.; Matushita, I.; Muroga, T.; Horiike, H.

    2006-01-01

    Lithium free-surface flow experiments to verify the design of IFMIF target have been carried out at Osaka University. The present report summarizes experimental results of surface phenomena, and cavitation characteristics of the loop, so as to try to apply these results to design parameters. Waves on the lithium flow surface is similar to that on water, and can be predicted by a linear stability theory. The wave amplitude is measured by an electro-contact probe. Surface roughness on a target nozzle, caused for example by attached chemical compounds and/or wastages by erosion and corrosion, can lead to a significant loss of target flow stability as well as surface wakes. The need of a polishing manipulator or exchange of the nozzle may be anticipated. Cavitation characteristic of the loop was measured by an accelerometer. From the results, a friction factor could be estimated fort he lithium flow

  10. EDRP public local inquiry, UKAEA/BNFL precognition on: Risk targets and EDRP design

    International Nuclear Information System (INIS)

    Brown, M.L.

    1986-06-01

    A full description is presented of the extent to which risk is controlled by the targets to be implemented in the proposed EDRP design, including a discussion of a particular accident sequence. Risk expressions and the usefulness of risk criteria are reviewed. Details are given of the accident consequence modelling as used by the UKAEA. Terrorist attack and sabotage are briefly discussed. (UK)

  11. 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

  12. 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

  13. Design of a deuterium and tritium-ablator shock ignition target for the National Ignition Facility

    International Nuclear Information System (INIS)

    Terry, Matthew R.; Perkins, L. John; Sepke, Scott M.

    2012-01-01

    Shock ignition presents a viable path to ignition and high gain on the National Ignition Facility (NIF). In this paper, we describe the development of the 1D design of 0.5 MJ class, all-deuterium and tritium (fuel and ablator) shock ignition target that should be reasonably robust to Rayleigh-Taylor fluid instabilities, mistiming, and hot electron preheat. The target assumes “day one” NIF hardware and produces a yield of 31 MJ with reasonable allowances for laser backscatter, absorption efficiency, and polar drive power variation. The energetics of polar drive laser absorption require a beam configuration with half of the NIF quads dedicated to launching the ignitor shock, while the remaining quads drive the target compression. Hydrodynamic scaling of the target suggests that gains of 75 and yields 70 MJ may be possible.

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

    International Nuclear Information System (INIS)

    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. (paper)

  15. Target design for high fusion yield with the double Z-pinch-driven hohlraum

    International Nuclear Information System (INIS)

    Vesey, R. A.; Herrmann, M. C.; Lemke, R. W.; Desjarlais, M. P.; Cuneo, M. E.; Stygar, W. A.; Bennett, G. R.; Campbell, R. B.; Christenson, P. J.; Mehlhorn, T. A.; Porter, J. L.; Slutz, S. A.

    2007-01-01

    A key demonstration on the path to inertial fusion energy is the achievement of high fusion yield (hundreds of MJ) and high target gain. Toward this goal, an indirect-drive high-yield inertial confinement fusion (ICF) target involving two Z-pinch x-ray sources heating a central secondary hohlraum is described by Hammer et al. [Phys. Plasmas 6, 2129 (1999)]. In subsequent research at Sandia National Laboratories, theoretical/computational models have been developed and an extensive series of validation experiments have been performed to study hohlraum energetics, capsule coupling, and capsule implosion symmetry for this system. These models have been used to design a high-yield Z-pinch-driven ICF target that incorporates the latest experience in capsule design, hohlraum symmetry control, and x-ray production by Z pinches. An x-ray energy output of 9 MJ per pinch, suitably pulse-shaped, is sufficient for this concept to drive 0.3-0.5 GJ capsules. For the first time, integrated two-dimensional (2D) hohlraum/capsule radiation-hydrodynamics simulations have demonstrated adequate hohlraum coupling, time-dependent radiation symmetry control, and the successful implosion, ignition, and burn of a high-yield capsule in the double Z-pinch hohlraum. An important new feature of this target design is mode-selective symmetry control: the use of burn-through shields offset from the capsule that selectively tune certain low-order asymmetry modes (P 2 ,P 4 ) without significantly perturbing higher-order modes and without a significant energy penalty. This paper will describe the capsule and hohlraum design that have produced 0.4-0.5 GJ yields in 2D simulations, provide a preliminary estimate of the Z-pinch load and accelerator requirements necessary to drive the system, and suggest future directions for target design work

  16. Proton-beam window design for a transmutation facility operating with a liquid lead target

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, C.; Lypsch, F.; Lizana, P. [Institute for Safety Research and Reactor Technology, Juelich (Germany)] [and others

    1995-10-01

    The proton beam target of an accelerator-driven transmutation facility can be designed as a vertical liquid lead column. To prevent lead vapor from entering the accelerator vacuum, a proton-beam window has to separate the area above the lead surface from the accelerator tube. Two radiation-cooled design alternatives have been investigated which should withstand a proton beam of 1.6 GeV and 25 mA. Temperature calculations based on energy deposition calculations with the Monte Carlo code HETC, stability analysis and spallation-induced damage calculations have been performed showing the applicability of both designs.

  17. 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. Copyright © 2013 John Wiley & Sons, Ltd.

  18. 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.

  19. Recent Developments in the VISRAD 3-D Target Design and Radiation Simulation Code

    Science.gov (United States)

    Macfarlane, Joseph; Golovkin, Igor; Sebald, James

    2017-10-01

    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 LMJ. 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 conveniently assess beam capture on target and beam clearance of diagnostic components, as well as plans for future developments.

  20. Assistant in design of tissue targeting leads with radio-combinatorial screening vivo

    International Nuclear Information System (INIS)

    Liu Ciyi; Zeng Jun; Xie Wenhui; Hu Silong; Jin Muxiu

    2004-01-01

    The diagnostic and therapeutic efficiency of drug depends highly on the drug distribution in target tissues (tumor for example) both specifically and accumulatively. We report here a powerful approach in design of tissue targeting leads with the assistant of radio-combinatorial screening technique developed in our laboratory. Methods: The C-terminal amide tripeptide libraries were synthesized on Rink Amide-MBHA resin in the OXX aO1OXaO1O2O positional scanning format and iterative protoco. A technetium (V) oxo core[(TcO)3+] was bound to the N4-triligands of tripeptide libraries via four deprotonated anfide nitrogen atoms to form a structure of 99Tcm-tripeptoid libraries. The radio-combinatorial screening (RCS) in vivo was then carried out after SD rats and A549 tumor bearing mice received i.v. with 99Tcm-tripeptoid libraries. Results: Signals of tissue distribution and metabolism of libraries were recorded by g counting or imaging. From library of 8,000 99Tcm-tripeptoid members, the tissue targeting leads had been identified by RCS. Those included 99Tcm-DSG (RES), 99Tcm-VAA, and 99Tcm-VIG that had specific tissue targeting in kidney, stomach, and liver respectively. The percent injected dose per gram tissue (%ID/g) of 99Tcm labeled leads in their target tissues was highly structure-dependent The discovery of 99Tcm-VAA and 99Tcm-VIG indicates that side chain methyl at positionl and 2 are crucial for stomach and liver accumulating 99Tcm-tripeptoids. In the case of kidney targeting, Ser in the position 2 and 3 is crucial for 99Tcm-tripeptoids renal excretion and accumulation characteristics respectively. Conclusion: RCS in vivo is a powerful tool for design of tissue targeting leads. (authors)

  1. Design of a tensor polarized deuterium target polarized by spin-exchange with optically pumped NA

    International Nuclear Information System (INIS)

    Green, M.C.

    1984-01-01

    A proposed design for a tensor polarized deuterium target (approx. 10 15 atoms/cm 2 ) for nuclear physics studies in an electron storage ring accelerator is presented. The deuterium atoms undergo electron spin exchange with a highly polarized sodium vapor; this polarization is transferred to the deuterium nuclei via the hyperfine interaction. The deuterium nuclei obtain their tensor polarization through repeated electron spin exchange/hyperfine interactions. The sodium vapor polarization is maintained by standard optical pumping techniques. Model calculations are presented in detail leading to a discussion of the expected performance and the technical obstacles to be surmounted in the development of such a target

  2. Design of a tensor polarized deuterium target polarized by spin-exchange with optically pumped NA

    International Nuclear Information System (INIS)

    Green, M.C.

    1984-05-01

    A proposed design for a tensor polarized deuterium target (approx. 10 15 atoms/cm 2 ) for nuclear physics studies in an electron storage ring accelerator is presented. The deuterium atoms undergo electron spin exchange with a highly polarized sodium vapor; this polarization is transferred to the deuterium nuclei via the hyperfine interaction. The deuterium nuclei obtain their tensor polarization through repeated electron spin exchange/hyperfine interactions. The sodium vapor polarization is maintained by standard optical pumping techniques. Model calculations are presented in detail leading to a discussion of the expected performance and the technical obstacles to be surmounted in the development of such a target. 15 references, 10 figures

  3. 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

  4. 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

  5. Design of an ignition target for the laser megajoule, mitigating parametric instabilities

    International Nuclear Information System (INIS)

    Laffite, S.; Loiseau, P.

    2010-01-01

    Laser plasma interaction (LPI) is a critical issue in ignition target design. Based on both scaling laws and two-dimensional calculations, this article describes how we can constrain a laser megajoule (LMJ) [J. Ebrardt and J. M. Chaput, J. Phys.: Conf. Ser. 112, 032005 (2008)] target design by mitigating LPI. An ignition indirect drive target has been designed for the 2/3 LMJ step. It requires 0.9 MJ and 260 TW of laser energy and power, to achieve a temperature of 300 eV in a rugby-shaped Hohlraum and give a yield of about 20 MJ. The study focuses on the analysis of linear gain for stimulated Raman and Brillouin scatterings. Enlarging the focal spot is an obvious way to reduce linear gains. We show that this reduction is nonlinear with the focal spot size. For relatively small focal spot area, linear gains are significantly reduced by enlarging the focal spot. However, there is no benefit in too large focal spots because of necessary larger laser entrance holes, which require more laser energy. Furthermore, this leads to the existence, for a given design, of a minimum value for linear gains for which we cannot go below.

  6. Design of an ignition target for the laser megajoule, mitigating parametric instabilities

    Science.gov (United States)

    Laffite, S.; Loiseau, P.

    2010-10-01

    Laser plasma interaction (LPI) is a critical issue in ignition target design. Based on both scaling laws and two-dimensional calculations, this article describes how we can constrain a laser megajoule (LMJ) [J. Ebrardt and J. M. Chaput, J. Phys.: Conf. Ser. 112, 032005 (2008)] target design by mitigating LPI. An ignition indirect drive target has been designed for the 2/3 LMJ step. It requires 0.9 MJ and 260 TW of laser energy and power, to achieve a temperature of 300 eV in a rugby-shaped Hohlraum and give a yield of about 20 MJ. The study focuses on the analysis of linear gain for stimulated Raman and Brillouin scatterings. Enlarging the focal spot is an obvious way to reduce linear gains. We show that this reduction is nonlinear with the focal spot size. For relatively small focal spot area, linear gains are significantly reduced by enlarging the focal spot. However, there is no benefit in too large focal spots because of necessary larger laser entrance holes, which require more laser energy. Furthermore, this leads to the existence, for a given design, of a minimum value for linear gains for which we cannot go below.

  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. Package design and nutritional profile of foods targeted at children in supermarkets in Montevideo, Uruguay

    Directory of Open Access Journals (Sweden)

    Ana Giménez

    Full Text Available Abstract: 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.

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

    International Nuclear Information System (INIS)

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

    1997-09-01

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

  10. Primary design of Si cooling arm structure in ICF cryogenic target

    International Nuclear Information System (INIS)

    Zhang Yong; Yi Yong; Tang Changhuan; Zhang Jicheng

    2013-01-01

    According to the requirement of the cryogenic target system to the Si cooling arm structure, the Si cooling arm was primarily designed based on the USA National Ignition Facility (NIF) target. A new three-dimensional model of Si cooling arm was developed by SolidWorks software, and the simulation and analysis of Si cooling arm in aspect of mechanical property, thermal response and assembly were made based on the model. A law about the effect of the arm length of Si cooling arm and the width and the length of bifurcation on Si cooling arm was achieved. The research may provide the theoretical foundation and reference for the further improvement of cryogenic target. (authors)

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

    Directory of Open Access Journals (Sweden)

    Lin Xinwei

    2015-01-01

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

  12. TRAC analysis of design basis events for the accelerator production of tritium target/blanket

    International Nuclear Information System (INIS)

    Lin, J.C.; Elson, J.

    1997-01-01

    A two-loop primary cooling system with a residual heat removal system was designed to mitigate the heat generated in the tungsten neutron source rods inside the rungs of the ladders and the shell of the rungs. The Transient Reactor Analysis Code (TRAC) was used to analyze the thermal-hydraulic behavior of the primary cooling system during a pump coastdown transient; a cold-leg, large-break loss-of-coolant accident (LBLOCA); a hot-leg LBLOCA; and a target downcomer LBLOCA. The TRAC analysis results showed that the heat generated in the tungsten neutron source rods can be mitigated by the primary cooling system for the pump coastdown transient and all the LBLOCAs except the target downcomer LBLOCA. For the target downcomer LBLOCA, a cavity flood system is required to fill the cavity with water at a level above the large fixed headers

  13. Thermal-hydraulic design concept of the solid-target system of spallation neutron source

    International Nuclear Information System (INIS)

    Tanaka, F.; Hibiki, T.; Saito, Y.; Takeda, T.; Mishima, K.

    2001-01-01

    In relation to thermal-hydraulic design of the N-Arena solid-target system of the JHF project, heat transfer experiments were performed to obtain experimental data systematically on heat transfer coefficient and CHF for vertical upward and horizontal flows in a thin rectangular channel simulating a coolant channel of the proposed spallation neutron source. Thermal-hydraulic correlations which can be used for design calculations were proposed based on the obtained data. Finally tentative results of feasibility study on maximum beam power which could be attained with a solid target were presented. The result indicated that the condition for the onset of nucleate boiling is the most significant limiting factor to the maximum beam power. (author)

  14. Conceptual design of low activation target chamber and components for the National Ignition Facility

    International Nuclear Information System (INIS)

    Streckert, H.H.; Schultz, K.R.; Sager, G.T.; Kantner, R.D.

    1996-01-01

    The baseline design for the target chamber and chamber components for the National Ignition Facility (NIF) consists of aluminum alloy structural material. Low activation composite chamber and components have important advantages including enhanced environmental and safety characteristics and improved accessibility due to reduced neutron-induced radioactivity. A low activation chamber can be fabricated from carbon fiber reinforced epoxy using thick wall laminate technology similar to submarine bow dome fabrication for the U.S. Navy. A risk assessment analysis indicates that a composite chamber has a reasonably high probability of success, but that an aluminum alloy chamber represents a lower risk. Use of low activation composite materials for several chamber components such as the final optics assemblies, the target positioner and inserter, the diagnostics manipulator tubes, and the optics beam tubes would offer an opportunity to make significant reductions in post-shot radiation dose rate with smaller, less immediate impact on the NIF design. 7 refs., 3 figs

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  16. LH2 Target Design & Position Survey Techniques for the MUSE experiment for Precise Proton Radius Measurement

    Science.gov (United States)

    Le Pottier, Luc; Roy, Pryiashee; Lorenzon, Wolfgang; Raymond, Richard; Steinberg, Noah; Rossi de La Fuente, Erick; MUSE (MUon proton Scattering Experiment) Collaboration

    2017-09-01

    The proton radius puzzle is a currently unresolved problem which has intrigued the scientific community, dealing with a 7 σ discrepancy between the proton radii determined from muonic hydrogen spectroscopy and electron scattering measurements. The MUon Scattering Experiment (MUSE) aims to resolve this puzzle by performing the first simultaneous elastic scattering measurements of both electrons and muons on the proton, which will allow the comparison of the radii from the two interactions with reduced systematic uncertainties. The data from this experiment is expected to provide the best test of lepton universality to date. The experiment will take place at the Paul Scherrer Institute in Switzerland in 2018. An essential component of the experiment is a liquid hydrogen (LH2) cryotarget system. Our group at the University of Michigan is responsible for the design, fabrication and installation of this system. Here we present our LH2 target cell design and fabrication techniques for successful operation at 20 K and 1 atm, and our computer vision-based target position survey system which will determine the position of the target, installed inside a vacuum chamber, with 0.01 mm or better precision at the height of the liquid hydrogen target and along the beam direction during the experiment.

  17. The Design of New HIV-IN Tethered Bifunctional Inhibitors using Multiple Microdomain Targeted Docking.

    Science.gov (United States)

    Ciubotaru, Mihai; Musat, Mihaela Georgiana; Surleac, Marius; Ionita, Elena; Petrescu, Andrei Jose; Abele, Edgars; Abele, Ramona

    2018-04-05

    Currently used antiretroviral HIV therapy drugs exclusively target critical groups in the enzymes essential for the viral life cycle. Increased mutagenesis of their genes, changes these viral enzymes which once mutated can evade therapeutic targeting, effects which confer drug resistance. To circumvent this, our review addresses a strategy to design and derive HIV-Integrase (HIV-IN) inhibitors which simultaneously target two IN functional domains, rendering it inactive even if the enzyme accumulates many mutations. First we review the enzymatic role of IN to insert the copied viral DNA into a chromosome of the host T lymphocyte, highlighting its main functional and structural features to be subjected to inhibitory action. From a functional and structural perspective we present all classes of HIV-IN inhibitors with their most representative candidates. For each chosen compound we also explain its mechanism of IN inhibition. We use the recently resolved cryo EM IN tetramer intasome DNA complex [1] onto which we dock various reference IN inhibitory chemical scaffolds such as to target adjacent functional IN domains. Pairing compounds with complementary activity, which dock in the vicinity of a IN structural microdomain, we design bifunctional new drugs which may not only be more resilient to IN mutations but also may be more potent inhibitors than their original counterparts. In the end of our review we propose synthesis pathways to link such paired compounds with enhanced synergistic IN inhibitory effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Beams configuration design in target area with successive quadratic programming method

    International Nuclear Information System (INIS)

    Shi Zhiquan; Tan Jichun; Wei Xiaofeng; Man Jongzai; Zhang Xiaomin; Yuan Jing; Yuan Xiaodong

    1998-01-01

    The author describes the application of successive quadratic programming method (SQP) to design laser beam configuration in target area. Based on the requirement of ICF experiment physics, a math model of indirect-driver beam geometry is given. A 3D wire-frame is plotted, in which support lines represent 60 laser entireties and 240 turning points of support lines' segments stand for the spatial positions of reflectors

  19. Design and Implementation of the Automated Rendezvous Targeting Algorithms for Orion

    Science.gov (United States)

    DSouza, Christopher; Weeks, Michael

    2010-01-01

    The Orion vehicle will be designed to perform several rendezvous missions: rendezvous with the ISS in Low Earth Orbit (LEO), rendezvous with the EDS/Altair in LEO, a contingency rendezvous with the ascent stage of the Altair in Low Lunar Orbit (LLO) and a contingency rendezvous in LLO with the ascent and descent stage in the case of an aborted lunar landing. Therefore, it is not difficult to realize that each of these scenarios imposes different operational, timing, and performance constraints on the GNC system. To this end, a suite of on-board guidance and targeting algorithms have been designed to meet the requirement to perform the rendezvous independent of communications with the ground. This capability is particularly relevant for the lunar missions, some of which may occur on the far side of the moon. This paper will describe these algorithms which are designed to be structured and arranged in such a way so as to be flexible and able to safely perform a wide variety of rendezvous trajectories. The goal of the algorithms is not to merely fly one specific type of canned rendezvous profile. Conversely, it was designed from the start to be general enough such that any type of trajectory profile can be flown.(i.e. a coelliptic profile, a stable orbit rendezvous profile, and a expedited LLO rendezvous profile, etc) all using the same rendezvous suite of algorithms. Each of these profiles makes use of maneuver types which have been designed with dual goals of robustness and performance. They are designed to converge quickly under dispersed conditions and they are designed to perform many of the functions performed on the ground today. The targeting algorithms consist of a phasing maneuver (NC), an altitude adjust maneuver (NH), and plane change maneuver (NPC), a coelliptic maneuver (NSR), a Lambert targeted maneuver, and several multiple-burn targeted maneuvers which combine one of more of these algorithms. The derivation and implementation of each of these

  20. 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

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

    Science.gov (United States)

    Sun, Lihui; Wang, Yongzhong; He, Yongqiang

    2007-01-01

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

  2. Optimized beryllium target design for indirectly driven inertial confinement fusion experiments on the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Simakov, Andrei N., E-mail: simakov@lanl.gov; Wilson, Douglas C.; Yi, Sunghwan A.; Kline, John L.; Batha, Steven H. [Los Alamos National Laboratory, P.O. Box 1663, Los Alamos, New Mexico 87545 (United States); Clark, Daniel S.; Milovich, Jose L.; Salmonson, Jay D. [Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, California 94551 (United States)

    2014-02-15

    For indirect drive inertial confinement fusion, Beryllium (Be) ablators offer a number of important advantages as compared with other ablator materials, e.g., plastic and high density carbon. In particular, the low opacity and relatively high density of Be lead to higher rocket efficiencies giving a higher fuel implosion velocity for a given X-ray drive; and to higher ablation velocities providing more ablative stabilization and reducing the effect of hydrodynamic instabilities on the implosion performance. Be ablator advantages provide a larger target design optimization space and can significantly improve the National Ignition Facility (NIF) [J. D. Lindl et al., Phys. Plasmas 11, 339 (2004)] ignition margin. Herein, we summarize the Be advantages, briefly review NIF Be target history, and present a modern, optimized, low adiabat, Revision 6 NIF Be target design. This design takes advantage of knowledge gained from recent NIF experiments, including more realistic levels of laser-plasma energy backscatter, degraded hohlraum-capsule coupling, and the presence of cross-beam energy transfer.

  3. 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Target selection and mass estimation for manned NEO exploration using a baseline mission design

    Science.gov (United States)

    Boden, Ralf C.; Hein, Andreas M.; Kawaguchi, Junichiro

    2015-06-01

    In recent years Near-Earth Objects (NEOs) have received an increased amount of interest as a target for human exploration. NEOs offer scientifically interesting targets, and at the same time function as a stepping stone for achieving future Mars missions. The aim of this research is to identify promising targets from the large number of known NEOs that qualify for a manned sample-return mission with a maximum duration of one year. By developing a baseline mission design and a mass estimation model, mission opportunities are evaluated based on on-orbit mass requirements, safety considerations, and the properties of the potential targets. A selection of promising NEOs is presented and the effects of mission requirements and restrictions are discussed. Regarding safety aspects, the use of free-return trajectories provides the lowest on-orbit mass, when compared to an alternative design that uses system redundancies to ensure return of the spacecraft to Earth. It is discovered that, although a number of targets are accessible within the analysed time frame, no NEO offers both easy access and high incentive for its exploration. Under the discussed aspects a first human exploration mission going beyond the vicinity of Earth will require a trade off between targets that provide easy access and those that are of scientific interest. This lack of optimal mission opportunities can be seen in the small number of only 4 NEOs that meet all requirements for a sample-return mission and remain below an on-orbit mass of 500 metric Tons (mT). All of them require a mass between 315 and 492 mT. Even less ideal, smaller asteroids that are better accessible require an on-orbit mass that exceeds the launch capability of future heavy lift vehicles (HLV) such as SLS by at least 30 mT. These mass requirements show that additional efforts are necessary to increase the number of available targets and reduce on-orbit mass requirements through advanced mission architectures. The need for on

  5. Optimum design of beam window's diameter and thickness of Hyper target system

    International Nuclear Information System (INIS)

    Cho, C. H.; Tak, N. I.; Song, T. Y.; Park, W. S.

    2002-01-01

    HYPER is designed to transmute long-lived TRU and fission products such as Tc-99 and I-129. Pb-Bi is used as the coolant and spallation target material at the same time. HYPER is expected to need about 20mA proton beam to sustain a 1000MW th power level. The cylindrical beam tube and spherical window is adopted as the basic window shape of HYPER. The window diameter and the window thickness are varied to find the maximum allowable current based on the design criteria : Pb-Bi temperature < 500 .deg. C, window temperature < 600 .deg. C, Pb-Bi velocity < 2m/s and window stress < 160MPa. The LAHET code is used to simulate heat generation. CFX is also used for the thermal-hydraulics calculation. Based on our design criteria, the maximum allowable current is calculated to be about 9.2mA, which is smaller than the required current. Therefore, an upgrade of the target system design is required

  6. Design of the solid target structure and the study on the coolant flow distribution in the solid target using the 2-dimensional flow analysis

    International Nuclear Information System (INIS)

    Haga, Katsuhiro; Terada, Atsuhiko; Ishikura, Shuichi; Teshigawara, Makoto; Kinoshita, Hidetaka; Kobayashi, Kaoru; Kaminaga, Masaki; Hino, Ryutaro; Susuki, Akira

    1999-11-01

    A solid target cooled by heavy water is presently under development under the Neutron Science Research Project of the Japan Atomic Energy Research Institute (JAERI). Target plates of several millimeters thickness made of heavy metal are used as the spallation target material and they are put face to face in a row with one to two millimeters gaps in between though which heavy water flows, as the coolant. Based on the design criteria regarding the target plate cooling, the volume percentage of the coolant, and the thermal stress produced in the target plates, we conducted thermal and hydraulic analysis with a one dimensional target plate model. We choosed tungsten as the target material, and decided on various target plate thicknesses. We then calculated the temperature and the thermal stress in the target plates using a two dimensional model, and confirmed the validity of the target plate thicknesses. Based on these analytical results, we proposed a target structure in which forty target plates are divided into six groups and each group is cooled using a single pass of coolant. In order to investigate the relationship between the distribution of the coolant flow, the pressure drop, and the coolant velocity, we conducted a hydraulic analysis using the general purpose hydraulic analysis code. As a result, we realized that an uniform coolant flow distribution can be achieved under a wide range of flow velocity conditions in the target plate cooling channels from 1 m/s to 10 m/s. The pressure drop along the coolant path was 0.09 MPa and 0.17 MPa when the coolant flow velocity was 5 m/s and 7 m/s respectively, which is required to cool the 1.5 MW and 2.5 MW solid targets. (author)

  7. Design, construction, and characterization of high-performance membrane fusion devices with target-selectivity.

    Science.gov (United States)

    Kashiwada, Ayumi; Yamane, Iori; Tsuboi, Mana; Ando, Shun; Matsuda, Kiyomi

    2012-01-31

    Membrane fusion proteins such as the hemagglutinin glycoprotein have target recognition and fusion accelerative domains, where some synergistically working elements are essential for target-selective and highly effective native membrane fusion systems. In this work, novel membrane fusion devices bearing such domains were designed and constructed. We selected a phenylboronic acid derivative as a recognition domain for a sugar-like target and a transmembrane-peptide (Leu-Ala sequence) domain interacting with the target membrane, forming a stable hydrophobic α-helix and accelerating the fusion process. Artificial membrane fusion behavior between the synthetic devices in which pilot and target liposomes were incorporated was characterized by lipid-mixing and inner-leaflet lipid-mixing assays. Consequently, the devices bearing both the recognition and transmembrane domains brought about a remarkable increase in the initial rate for the membrane fusion compared with the devices containing the recognition domain alone. In addition, a weakly acidic pH-responsive device was also constructed by replacing three Leu residues in the transmembrane-peptide domain by Glu residues. The presence of Glu residues made the acidic pH-dependent hydrophobic α-helix formation possible as expected. The target-selective liposome-liposome fusion was accelerated in a weakly acidic pH range when the Glu-substituted device was incorporated in pilot liposomes. The use of this pH-responsive device seems to be a potential strategy for novel applications in a liposome-based delivery system. © 2011 American Chemical Society

  8. Preconceptual engineering design for the APT 3He Target/Blanket concept

    International Nuclear Information System (INIS)

    Mensink, D.L.

    1994-01-01

    A preconceptual engineering design has been developed for the 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 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 3 He gas; containment of the gas and radionuclides; remote handling; material compatibility; minimization of 3 He, D 2 O, and activated waste; modularity; and manufacturability. The design provides a basis for estimating the cost to implement the system

  9. GLRS-R 2-colour retroreflector target design and predicted performance

    Science.gov (United States)

    Lund, Glenn

    1993-01-01

    This paper reports on the retroreflector ground-target design for the GLRS-R spaceborne dual-wavelength laser ranging system. The described passive design flows down from the requirements of high station autonomy, high global FOV (up to 60 degrees zenith angle), little or no multiple pulse returns, and adequate optical cross section for most ranging geometries. The proposed solution makes use of 5 hollow cube-corner retroreflectors of which one points to the zenith and the remaining four are inclined from the vertical at uniform azimuthal spacings. The need for fairly large (is approximately 10 cm) retroreflectors is expected (within turbulence limitations) to generate quite narrow diffraction lobes, thus placing non-trivial requirements on the vectorial accuracy of velocity aberration corrections. A good compromise solution is found by appropriately spoiling just one of the retroreflector dihedral angles from 90 degrees, thus generating two symmetrically oriented diffraction lobes in the return beam. The required spoil angles are found to have little dependence on ground target latitude. Various link budget analyses are presented, showing the influence of such factors as point-ahead optimization, turbulence, ranging angle, atmospheric visibility and ground target thermal deformations.

  10. Injector design for liner-on-target gas-puff experiments

    Science.gov (United States)

    Valenzuela, J. C.; Krasheninnikov, I.; Conti, F.; Wessel, F.; Fadeev, V.; Narkis, J.; Ross, M. P.; Rahman, H. U.; Ruskov, E.; Beg, F. N.

    2017-11-01

    We present the design of a gas-puff injector for liner-on-target experiments. The injector is composed of an annular high atomic number (e.g., Ar and Kr) gas and an on-axis plasma gun that delivers an ionized deuterium target. The annular supersonic nozzle injector has been studied using Computational Fluid Dynamics (CFD) simulations to produce a highly collimated (M > 5), ˜1 cm radius gas profile that satisfies the theoretical requirement for best performance on ˜1-MA current generators. The CFD simulations allowed us to study output density profiles as a function of the nozzle shape, gas pressure, and gas composition. We have performed line-integrated density measurements using a continuous wave (CW) He-Ne laser to characterize the liner gas density. The measurements agree well with the CFD values. We have used a simple snowplow model to study the plasma sheath acceleration in a coaxial plasma gun to help us properly design the target injector.

  11. 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

    2017-11-15

    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.

  12. 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...

  13. Recycling issues facing target and RTL materials of inertial fusion designs

    International Nuclear Information System (INIS)

    El-Guebaly, L.; Wilson, P.; Sawan, M.; Henderson, D.; Varuttamaseni, A.

    2005-01-01

    Designers of heavy ion (HI) and Z-pinch inertial fusion power plants have explored the potential of recycling the target and recyclable transmission line (RTL) materials as an alternate option to disposal in a geological repository. This work represents the first time a comprehensive recycling assessment was performed on both machines with an exact pulse history. Our results offer two divergent conclusions on the recycling issue. For the HI concept, target recycling is not a 'must' requirement and the preferred option is the one-shot use scenario as target materials represent a small waste stream, less than 1% of the total nuclear island waste. We recommend using low-cost hohlraum materials once-through and then disposing of them instead of recycling expensive materials such as Au and Gd. On the contrary, RTL recycling is a 'must' requirement for the Z-pinch concept in order to minimize the RTL inventory and enhance the economics. The RTLs meet the low level waste and recycling dose requirements with a wide margin when recycled for the entire plant life even without a cooling period. While recycling offers advantages to the Z-pinch system, it adds complexity and cost to the HI designs

  14. Design specification for the European Spallation Source neutron generating target element

    International Nuclear Information System (INIS)

    Aguilar, A.; Sordo, F.; Mora, T.; Mena, L.; Mancisidor, M.; Aguilar, J.; Bakedano, G.; Herranz, I.; Luna, P.; Magan, M.; Vivanco, R.; Jimenez-Villacorta, F.; Sjogreen, K.; Oden, U.; Perlado, J.M.

    2017-01-01

    The paper addresses some of the most relevant issues concerning the thermal hydraulics and radiation damage of the neutron generation target to be built at the European Spallation Source as recently approved after a critical design review. The target unit consists of a set of Tungsten blocks placed inside a wheel of 2.5 m diameter which rotates at some 0.5 Hz in order to distribute the heat generated from incoming protons which reach the target in the radial direction. The spallation material elements are composed of an array of Tungsten pieces which rest on a rotating steel support (the cassette) and are distributed in a cross-flow configuration. The thermal, mechanical and radiation effects resulting from the impact of a 2 GeV proton pulse are analysed in detail as well as an evaluation of the inventory of spallation products. The current design is found to conform to specifications and found to be robust enough to deal with several accident scenarios.

  15. Design specification for the European Spallation Source neutron generating target element

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar, A. [Consorcio ESS-BILBAO. Parque Tecnológico Bizkaia. Poligono Ugaldeguren III, Pol. A, 7B, 48170 Zamudio (Spain); Sordo, F., E-mail: fernando.sordo@essbilbao.org [Consorcio ESS-BILBAO. Parque Tecnológico Bizkaia. Poligono Ugaldeguren III, Pol. A, 7B, 48170 Zamudio (Spain); Instituto de Fusión Nuclear, José Gutiérrez Abascal, 2, 28006 Madrid (Spain); Mora, T. [Consorcio ESS-BILBAO. Parque Tecnológico Bizkaia. Poligono Ugaldeguren III, Pol. A, 7B, 48170 Zamudio (Spain); Mena, L. [Consorcio ESS-BILBAO. Parque Tecnológico Bizkaia. Poligono Ugaldeguren III, Pol. A, 7B, 48170 Zamudio (Spain); Instituto de Fusión Nuclear, José Gutiérrez Abascal, 2, 28006 Madrid (Spain); Mancisidor, M.; Aguilar, J.; Bakedano, G.; Herranz, I.; Luna, P. [Consorcio ESS-BILBAO. Parque Tecnológico Bizkaia. Poligono Ugaldeguren III, Pol. A, 7B, 48170 Zamudio (Spain); Magan, M.; Vivanco, R. [Consorcio ESS-BILBAO. Parque Tecnológico Bizkaia. Poligono Ugaldeguren III, Pol. A, 7B, 48170 Zamudio (Spain); Instituto de Fusión Nuclear, José Gutiérrez Abascal, 2, 28006 Madrid (Spain); Jimenez-Villacorta, F. [Consorcio ESS-BILBAO. Parque Tecnológico Bizkaia. Poligono Ugaldeguren III, Pol. A, 7B, 48170 Zamudio (Spain); Sjogreen, K.; Oden, U. [European Spallation Source ERIC, P.O Box 176, SE-221 00 Lund (Sweden); Perlado, J.M. [Instituto de Fusión Nuclear, José Gutiérrez Abascal, 2, 28006 Madrid (Spain); and others

    2017-06-01

    The paper addresses some of the most relevant issues concerning the thermal hydraulics and radiation damage of the neutron generation target to be built at the European Spallation Source as recently approved after a critical design review. The target unit consists of a set of Tungsten blocks placed inside a wheel of 2.5 m diameter which rotates at some 0.5 Hz in order to distribute the heat generated from incoming protons which reach the target in the radial direction. The spallation material elements are composed of an array of Tungsten pieces which rest on a rotating steel support (the cassette) and are distributed in a cross-flow configuration. The thermal, mechanical and radiation effects resulting from the impact of a 2 GeV proton pulse are analysed in detail as well as an evaluation of the inventory of spallation products. The current design is found to conform to specifications and found to be robust enough to deal with several accident scenarios.

  16. [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.

  17. Progress in bipolar disorder drug design toward the development of novel therapeutic targets: a clinician's perspective.

    Science.gov (United States)

    Fornaro, Michele; Kardash, Lubna; Novello, Stefano; Fusco, Andrea; Anastasia, Annalisa; De Berardis, Domenico; Perna, Giampaolo; Carta, Mauro Giovanni

    2018-03-01

    Bipolar disorder (BD) is a considerable burden to the affected individual. The need for novel drug targets and improved drug design (DD) in BD is therefore clear. Areas covered: The following article provides a brief, narrative, clinician-oriented overview of the most promising novel pharmacological targets for BD along with a concise overview regarding the general DD process and the unmet needs relevant to BD. Expert opinion: A number of novel potential drug targets have been investigated. With the notable exception of the kynurenine pathway, available evidence is too scarce to highlight a definitive roadmap for forthcoming DD in BD. BD itself may present with different facets, as it is a polymorphic clinical spectrum. Therefore, promoting clinical-case stratification should be based on precision medicine, rather than on novel biological targets. Furthermore, the full release of raw study data to the scientific community and the development of uniform clinical trial standards (including more realistic outcomes) should be promoted to facilitate the DD process in BD.

  18. SU-E-T-244: Designing Low-Z Targets To Enhance Surface Dose: A Monte Carlo Simulation

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, R [Nova Scotia Cancer Centre, Halifax, NS (Canada); Robar, J [Capital District Health Authority, Halifax, NS (Canada); Parsons, D [Dalhousie University, Halifax, Nova Scotia (Canada)

    2015-06-15

    Purpose: Recent developments in The Varian Truebeam linac platform allows for the introduction of low-Z targets into the beam line for the imaging purposes. We have proposed using a low-Z target for radiation therapy purposes to enhance the surface dose during radiation treatment. The target arm of the Varian Truebeam accelerator consists of multiple targets with are linearly translated into the beam line. We have designed two Low-Z targets made of carbon: 1) a step target consisting of three steps of 15%, 30% and 60% CSDA range for 2.5 MeV electrons Figure 1a; 2) and a ramp target, an incline plane 2cm long with thicknesses ranging from 0% to 60% CSDA range, Figure 1b. The purpose of this work will determine the spectral characteristics of these target designs and determine if they have practical clinical applications for enhancing surface dose. Methods: To calculate the spectral characteristics of these targets, a standard Monte Carlo model of a Varian Clinac accelerator was used. Simulations were performed with a carbon step target, and a carbon ramp target, located at the same position as the electron foil in the rotating carousel. Simulations were carried out using a 2.5 MeV electron beam. Results: The step target design produced spectral characteristics which were similar to spectral model using a single disk target of the same thickness. The ramp target provides a means to have positional variation of the spectral components of the beam, however, the electron component as 60% CSDA us much broader than the step target. Conclusion: The carbon step-target provides a spectral distribution which is similar to a carbon disk of comparable thickness. The spectral distribution from the ramp-target can be modified as a function of position to provide a wide range of low energy electrons for surface dose enhancement.

  19. Lujan Center Mark-IV Target Neutronics Design Internal Review Report

    Energy Technology Data Exchange (ETDEWEB)

    Lisowski, Paul W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gallmeier, Franz [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Guber, Klaus [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2018-02-26

    The 1L Target Moderator Reflector System (TMRS) at the Lujan Center will need to be replaced before the CY 2020 operating cycle. A Physics Division design team investigated options for improving the overall target performance for nuclear science research with minimal reduction in performance for materials science. This review concluded that devoting an optimized arrangement of the Lujan TMRS upper tier to nuclear science and using the lower tier for materials science can achieve those goals. This would open the opportunity for enhanced nuclear science research in an important neutron energy range for NNSA. There will be no other facility in the US that will compete in the keV energy range provided flight paths and instrumentation are developed to take advantage of the neutron flux and resolution.

  20. 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.

  1. Heterogeneity in head and neck IMRT target design and clinical practice

    International Nuclear Information System (INIS)

    Hong, Theodore S.; Tomé, Wolfgang A.; Harari, Paul M.

    2012-01-01

    Purpose: To assess patterns of H and N IMRT practice with particular emphasis on elective target delineation. Materials and methods: Twenty institutions with established H and N IMRT expertise were solicited to design clinical target volumes for the identical H and N cancer case. To limit contouring variability, a primary tonsil GTV and ipsilateral level II node were pre-contoured. Participants were asked to accept this GTV, and contour their recommended CTV and PTV. Dose prescriptions, contouring time, and recommendations regarding chemotherapy were solicited. Results: All 20 institutions responded. Remarkable heterogeneity in H and N IMRT design and practice was identified. Seventeen of 20 centers recommended treatment of bilateral necks whereas 3/20 recommended treatment of the ipsilateral neck only. The average CTV volume was 250 cm 3 (range 37–676 cm 3 ). Although there was high concordance in coverage of ipsilateral neck levels II and III, substantial variation was identified for levels I, V, and the contralateral neck. Average CTV expansion was 4.1 mm (range 0–15 mm). Eight of 20 centers recommended chemotherapy (cisplatin), whereas 12/20 recommended radiation alone. Responders prescribed on average 69 and 68 Gy to the tumor and metastatic node GTV, respectively. Average H and N target volume contouring time was 102.5 min (range 60–210 min). Conclusion: This study identifies substantial heterogeneity in H and N IMRT target definition, prescription, neck treatment, and use of chemotherapy among practitioners with established H and N IMRT expertise. These data suggest that continued efforts to standardize and simplify the H and N IMRT process are desirable for the safe and effective global advancement of H and N IMRT practice.

  2. Targeting the dopamine D3 receptor: an overview of drug design strategies.

    Science.gov (United States)

    Cortés, Antoni; Moreno, Estefanía; Rodríguez-Ruiz, Mar; Canela, Enric I; Casadó, Vicent

    2016-07-01

    Dopamine is a neurotransmitter widely distributed in both the periphery and the central nervous system (CNS). Its physiological effects are mediated by five closely related G protein-coupled receptors (GPCRs) that are divided into two major subclasses: the D1-like (D1, D5) and the D2-like (D2, D3, D4) receptors. D3 receptors (D3Rs) have the highest density in the limbic areas of the brain, which are associated with cognitive and emotional functions. These receptors are therefore attractive targets for therapeutic management. This review summarizes the functional and pharmacological characteristics of D3Rs, including the design and clinical relevance of full agonists, partial agonists and antagonists, as well as the capacity of these receptors to form active homodimers, heterodimers or higher order receptor complexes as pharmacological targets in several neurological and neurodegenerative disorders. The high sequence homology between D3R and the D2-type challenges the development of D3R-selective compounds. The design of new D3R-preferential ligands with improved physicochemical properties should provide a better pharmacokinetic/bioavailability profile and lesser toxicity than is found with existing D3R ligands. It is also essential to optimize D3R affinity and, especially, D3R vs. D2-type binding and functional selectivity ratios. Developing allosteric and bitopic ligands should help to improve the D3R selectivity of these drugs. As most evidence points to the ability of GPCRs to form homomers and heteromers, the most promising therapeutic strategy in the future is likely to involve the application of heteromer-selective drugs. These selective ligands would display different affinities for a given receptor depending on the receptor partners within the heteromer. Therefore, designing novel compounds that specifically target and modulate D1R-D3R heteromers would be an interesting approach for the treatment of levodopa (L-DOPA)-induced dyskinesias.

  3. Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

    Science.gov (United States)

    Khan, M A; Hossain, M U; Rakib-Uz-Zaman, S M; Morshed, M N

    2015-07-01

    Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments. © 2015 John Wiley & Sons Ltd.

  4. High-resolution imaging and target designation through clouds or smoke

    Science.gov (United States)

    Perry, Michael D.

    2003-01-01

    A method and system of combining gated intensifiers and advances in solid-state, short-pulse laser technology, compact systems capable of producing high resolution (i.e., approximately less than 20 centimeters) optical images through a scattering medium such as dense clouds, fog, smoke, etc. may be achieved from air or ground based platforms. Laser target designation through a scattering medium is also enabled by utilizing a short pulse illumination laser and a relatively minor change to the detectors on laser guided munitions.

  5. Design, synthesis, and evaluation of an alpha-helix mimetic library targeting protein-protein interactions.

    Science.gov (United States)

    Shaginian, Alex; Whitby, Landon R; Hong, Sukwon; Hwang, Inkyu; Farooqi, Bilal; Searcey, Mark; Chen, Jiandong; Vogt, Peter K; Boger, Dale L

    2009-04-22

    The design and solution-phase synthesis of an alpha-helix mimetic library as an integral component of a small-molecule library targeting protein-protein interactions are described. The iterative design, synthesis, and evaluation of the candidate alpha-helix mimetic was initiated from a precedented triaryl template and refined by screening the designs for inhibition of MDM2/p53 binding. Upon identifying a chemically and biologically satisfactory design and consistent with the screening capabilities of academic collaborators, the corresponding complete library was assembled as 400 mixtures of 20 compounds (20 x 20 x 20-mix), where the added subunits are designed to mimic all possible permutations of the naturally occurring i, i + 4, i + 7 amino acid side chains of an alpha-helix. The library (8000 compounds) was prepared using a solution-phase synthetic protocol enlisting acid/base liquid-liquid extractions for purification on a scale that insures its long-term availability for screening campaigns. Screening of the library for inhibition of MDM2/p53 binding not only identified the lead alpha-helix mimetic upon which the library was based, but also suggests that a digestion of the initial screening results that accompany the use of such a comprehensive library can provide insights into the nature of the interaction (e.g., an alpha-helix mediated protein-protein interaction) and define the key residues and their characteristics responsible for recognition.

  6. Developing plan and pre-conceptual design of target system for JAERI`s high intensity neutron source

    Energy Technology Data Exchange (ETDEWEB)

    Hino, Ryutaro; Kaminaga, Masanori; Haga, Katsuhiro; Ishikura, Syuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Nakamura, Fumito; Uchida, Shoji

    1997-11-01

    This paper presents an outline of developing plan of a target system and topics obtained by a pre-conceptual design, which aims to establish a technology base of the target system and to make clear a system concept. In the plan, two types of target - solid and mercury targets - are to be developed for a neutron scattering facility. Information obtained through the development shall be applied to designs of an irradiation and a transmutation facilities. Through the pre-conceptual design, system arrangement, scale etc. were made clear: total weight will be 12000 ton, and 26 beam lines with beam shutters will be equipped for 4 moderators. Engineering problems were also made clear through the design; high flux heat removal, dynamic stress caused by thermal shock and pressure wave, loop technology for the mercury target and a slurry moderator consisting of methane pellets and liquefied hydrogen. We are now constructing new test apparatuses and arranging computer codes for solving these problems. (author)

  7. Design of a distributed radiator target for inertial fusion driven from two sides with heavy ion beams

    International Nuclear Information System (INIS)

    Tabak, M.; Callahan-Miller, D.

    1997-01-01

    We describe the status of a distributed radiator heavy ion target design. In integrated calculations this target ignited and produced 390-430 MJ of yieldwhen driven with 5.8-6.5 MJ of 3-4 GeV Pb ions. The target has cylindrical symmetry with disk endplates. The ions uniformly illuminate these endplates in a 5mm radius spot. We discuss the considerations which led to this design together with some previously unused design features: low density hohlraum walls in approximate pressure balance with internal low-Z fill materials, radiationsymmetry determined by the position of the radiator materials and particle ranges, and early time pressure symmetry possibly influenced by radiation shims. We discuss how this target scales to lower input energy or to lower beam power. Variant designs with more realistic beam focusing strategies are also discussed. We show the tradeoffs required for targets which accept higher particle energies

  8. Optimal Design of Gradient Materials and Bi-Level Optimization of Topology Using Targets (BOTT)

    Science.gov (United States)

    Garland, Anthony

    The objective of this research is to understand the fundamental relationships necessary to develop a method to optimize both the topology and the internal gradient material distribution of a single object while meeting constraints and conflicting objectives. Functionally gradient material (FGM) objects possess continuous varying material properties throughout the object, and they allow an engineer to tailor individual regions of an object to have specific mechanical properties by locally modifying the internal material composition. A variety of techniques exists for topology optimization, and several methods exist for FGM optimization, but combining the two together is difficult. Understanding the relationship between topology and material gradient optimization enables the selection of an appropriate model and the development of algorithms, which allow engineers to design high-performance parts that better meet design objectives than optimized homogeneous material objects. For this research effort, topology optimization means finding the optimal connected structure with an optimal shape. FGM optimization means finding the optimal macroscopic material properties within an object. Tailoring the material constitutive matrix as a function of position results in gradient properties. Once, the target macroscopic properties are known, a mesostructure or a particular material nanostructure can be found which gives the target material properties at each macroscopic point. This research demonstrates that topology and gradient materials can both be optimized together for a single part. The algorithms use a discretized model of the domain and gradient based optimization algorithms. In addition, when considering two conflicting objectives the algorithms in this research generate clear 'features' within a single part. This tailoring of material properties within different areas of a single part (automated design of 'features') using computational design tools is a novel benefit

  9. Mechanical design of experimental apparatus for FIREX cryo-target cooling

    Science.gov (United States)

    Iwamoto, A.; Norimatsu, T.; Nakai, M.; Sakagami, H.; Fujioka, S.; Shiraga, H.; Azechi, H.

    2016-05-01

    Mechanical design of an experimental apparatus for FIREX cryo-target cooling is described. Gaseous helium (GHe) sealing system at a cryogenic environment is an important issue for laser fusion experiments. The dedicated loading system was designed for a metal gasket. We take U-TIGHTSEAL® (Usui Kokusai Sangyo Kaisha. Ltd.) with an indium plated copper jacket as an example. According to its specification, a linear load of 110 N/m along its circumference is the optimum compression; however a lower load would still maintain helium (He) leak below the required level. Its sealing performance was investigated systematically. Our system demanded 27 N/mm of the load to keep He leak tightness in a cryogenic environment. Once leak tightness was obtained, it could be reduced to 9.5 N/mm.

  10. Design improvement of the target elements of Wendelstein 7-X divertor

    International Nuclear Information System (INIS)

    Boscary, J.; Peacock, A.; Friedrich, T.; Greuner, H.; Böswirth, B.; Tittes, H.; Schulmeyer, W.; Hurd, F.

    2012-01-01

    Highlights: ► Improvement of the cooling structure design. ► Improvement of the CFC tile arrangement at the element end. ► Design and fabrication validated with high heat flux testing. ► Selected solution removes stationary heat load of 5 MW/m 2 and 2 MW/m 2 on the top and on the side facing the pumping gap of the element, respectively. - Abstract: The actively cooled high-heat flux divertor of the Wendelstein 7-X stellarator consists of individual target elements made of a water-cooled CuCrZr copper alloy heat sink armored with CFC tiles. The so-called “bi-layer” technology developed in collaboration with the company Plansee for the bonding of the tiles onto the heat sink has reliably demonstrated the removal of the specified heat load of 10 MW/m 2 in the central area of the divertor. However, due to geometrical constraints, the loading performance at the ends of the elements is reduced compared to the central part. Design modifications compatible with industrial processes have been made to improve the cooling capabilities at this location. These changes have been validated during test campaigns of full-scale prototypes carried out in the neutral beam test facility GLADIS. The tested solution can remove reliably the stationary heat load of 5 MW/m 2 and 2 MW/m 2 on the top and on the side of the element, respectively. The results of the testing allowed the release of the design and fabrication processes for the next manufacturing phase of the target elements.

  11. 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.

  12. Activation loop targeting strategy for design of receptor-interacting protein kinase 2 (RIPK2) inhibitors.

    Science.gov (United States)

    Suebsuwong, Chalada; Pinkas, Daniel M; Ray, Soumya S; Bufton, Joshua C; Dai, Bing; Bullock, Alex N; Degterev, Alexei; Cuny, Gregory D

    2018-02-15

    Development of selective kinase inhibitors remains a challenge due to considerable amino acid sequence similarity among family members particularly in the ATP binding site. Targeting the activation loop might offer improved inhibitor selectivity since this region of kinases is less conserved. However, the strategy presents difficulties due to activation loop flexibility. Herein, we report the design of receptor-interacting protein kinase 2 (RIPK2) inhibitors based on pan-kinase inhibitor regorafenib that aim to engage basic activation loop residues Lys169 or Arg171. We report development of CSR35 that displayed >10-fold selective inhibition of RIPK2 versus VEGFR2, the target of regorafenib. A co-crystal structure of CSR35 with RIPK2 revealed a resolved activation loop with an ionic interaction between the carboxylic acid installed in the inhibitor and the side-chain of Lys169. Our data provides principle feasibility of developing activation loop targeting type II inhibitors as a complementary strategy for achieving improved selectivity. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Current therapeutic molecules and targets in neurodegenerative diseases based on in silico drug design.

    Science.gov (United States)

    Sehgal, Sheikh Arslan; Hammad, Mirza A; Tahir, Rana Adnan; Akram, Hafiza Nisha; Ahmad, Faheem

    2018-03-15

    As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases. Review of literature published since 1997 against neurodegenerative diseases, utilizing as keywords: in silico, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis ALS, and Huntington's disease. Due to the costs associated with experimentation and current ethical law, performing experiments directly on living organisms has become much more difficult. In this scenario, in silico techniques have been successful and have become powerful tools in the search to cure disease. Researchers use the Computer Aided Drug Design pipeline which: 1) generates 3-dimensional structures of target proteins through homology modeling 2) achieves stabilization through molecular dynamics simulation, and 3) exploits molecular docking through large compound libraries. Next generation sequencing is continually producing enormous amounts of raw sequence data while neuroimaging is producing a multitude of raw image data. To solve such pressing problems, these new tools and algorithms are required. This review elaborates precise in silico tools and techniques for drug targets, active molecules, and molecular docking studies, together with future prospects and challenges concerning possible breakthroughs in Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, and Huntington's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. 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 ...

  15. Deep Extragalactic VIsible Legacy Survey (DEVILS): Motivation, Design and Target Catalogue

    Science.gov (United States)

    Davies, L. J. M.; Robotham, A. S. G.; Driver, S. P.; Lagos, C. P.; Cortese, L.; Mannering, E.; Foster, C.; Lidman, C.; Hashemizadeh, A.; Koushan, S.; O'Toole, S.; Baldry, I. K.; Bilicki, M.; Bland-Hawthorn, J.; Bremer, M. N.; Brown, M. J. I.; Bryant, J. J.; Catinella, B.; Croom, S. M.; Grootes, M. W.; Holwerda, B. W.; Jarvis, M. J.; Maddox, N.; Meyer, M.; Moffett, A. J.; Phillipps, S.; Taylor, E. N.; Windhorst, R. A.; Wolf, C.

    2018-06-01

    The Deep Extragalactic VIsible Legacy Survey (DEVILS) is a large spectroscopic campaign at the Anglo-Australian Telescope (AAT) aimed at bridging the near and distant Universe by producing the highest completeness survey of galaxies and groups at intermediate redshifts (0.3 < z < 1.0). Our sample consists of ˜60,000 galaxies to Y<21.2 mag, over ˜6 deg2 in three well-studied deep extragalactic fields (Cosmic Origins Survey field, COSMOS, Extended Chandra Deep Field South, ECDFS and the X-ray Multi-Mirror Mission Large-Scale Structure region, XMM-LSS - all Large Synoptic Survey Telescope deep-drill fields). This paper presents the broad experimental design of DEVILS. Our target sample has been selected from deep Visible and Infrared Survey Telescope for Astronomy (VISTA) Y-band imaging (VISTA Deep Extragalactic Observations, VIDEO and UltraVISTA), with photometry measured by PROFOUND. Photometric star/galaxy separation is done on the basis of NIR colours, and has been validated by visual inspection. To maximise our observing efficiency for faint targets we employ a redshift feedback strategy, which continually updates our target lists, feeding back the results from the previous night's observations. We also present an overview of the initial spectroscopic observations undertaken in late 2017 and early 2018.

  16. 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

  17. 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

    2017-10-01

    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.

  18. Defilade, Stationary Target and Moving Target Embankment, Low Water Crossing, and Course Road Designs for Soil Loss Prevention

    National Research Council Canada - National Science Library

    Svendsen, Niels G; Kalita, Prasanta K; Gebhart, Dick L; Denight, Michael L

    2006-01-01

    .... Additionally, incorporating sustainability into the range designs should remain a high priority to meet environmental compliance regulations and provide a durable long-lasting structure useful...

  19. IFMIF Li target back-plate design integration and thermo-mechanical analysis

    International Nuclear Information System (INIS)

    Riccardi, B.; Roccella, S.; Micciche, G.

    2006-01-01

    The International Fusion Materials Irradiation Facility (IFMIF) is an accelerator-driven intense neutron source where fusion reactor candidate materials will be tested. The neutron flux is produced by means of a deuteron beam (current 250 mA, energy 40 MeV) that strikes a liquid lithium target circulating in a lithium loop. The support on which the liquid lithium flows, i.e. the back-plate, is the most heavily exposed component to neutron flux. A '' bayonet '' concept solution for the back-plate was proposed by ENEA with the objectives of improving the back-plate reliability and simplifying the remote handling procedures. On the base of this concept, a back-plate mock-up was fabricated and validated. Starting from the findings of the mock up design, a back-plate design integration exercise was carried out in order to check if the back-plate geometrical features are compatible with the target assembly and the Vertical Test Assemblies (VTA). The work carried out has demonstrated that even with the changes operated for the design integration (increase of in-plane dimensions and reduction of thickness) the bayonet concept is able to guarantee a tight connection to the target assembly. A thermo-mechanical analysis of the back-plate has been carried out by means of ABAQUS code. The thermal load used as input for the calculations, i.e. the neutron heat generation, has been estimated by means of Monte Carlo Mc-Delicious code. The two boundary constraint cases (full and minimum contact with target assembly) considered for each back-plate geometry option represent the extreme cases of the real operating condition of the plate. The influence of the contact heat exchange coefficient and the back-plate thickness has been also evaluated. For all these reasons, the results of the analysis can be considered as the domain of variability of the real working conditions. The results show that AISI 316L steel is not suitable as black-plate material: the stress induced in the plate, in

  20. 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. PMID:26082827

  1. 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.

  2. An optimized target-field method for MRI transverse biplanar gradient coil design

    International Nuclear Information System (INIS)

    Zhang, Rui; Xu, Jing; Huang, Kefu; Zhang, Jue; Fang, Jing; Fu, Youyi; Li, Yangjing

    2011-01-01

    Gradient coils are essential components of magnetic resonance imaging (MRI) systems. In this paper, we present an optimized target-field method for designing a transverse biplanar gradient coil with high linearity, low inductance and small resistance, which can well satisfy the requirements of permanent-magnet MRI systems. In this new method, the current density is expressed by trigonometric basis functions with unknown coefficients in polar coordinates. Following the standard procedures, we construct an objective function with respect to the total square errors of the magnetic field at all target-field points with the penalty items associated with the stored magnetic energy and the dissipated power. By adjusting the two penalty factors and minimizing the objective function, the appropriate coefficients of the current density are determined. Applying the stream function method to the current density, the specific winding patterns on the planes can be obtained. A novel biplanar gradient coil has been designed using this method to operate in a permanent-magnet MRI system. In order to verify the validity of the proposed approach, the gradient magnetic field generated by the resulted current density has been calculated via the Biot–Savart law. The results have demonstrated the effectiveness and advantage of this proposed method

  3. Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design.

    Science.gov (United States)

    Andalib, Sare; Varshosaz, Jaleh; Hassanzadeh, Farshid; Sadeghi, Hojjat

    2012-01-01

    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. 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. 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. The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

  4. 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.

  5. Targeted repression of AXIN2 and MYC gene expression using designer TALEs

    International Nuclear Information System (INIS)

    Rennoll, Sherri A.; Scott, Samantha A.; Yochum, Gregory S.

    2014-01-01

    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 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

  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. MIDAS: a practical Bayesian design for platform trials with molecularly targeted agents.

    Science.gov (United States)

    Yuan, Ying; Guo, Beibei; Munsell, Mark; Lu, Karen; Jazaeri, Amir

    2016-09-30

    Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time and thus not efficient for this task. We propose a Bayesian phase II platform design, the multi-candidate iterative design with adaptive selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and 'graduate' the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Report on the R&D of Uranium Carbide targets by the PLOG collaboration at PNPI-Gatchina

    CERN Document Server

    A.E. Barzakh, D.V. Fedorov, A.M. Ionan, V.S. Ivanov, M.P. Levchenko, K.A. Mezilev, F.V. Moroz, S.Yu. Orlov, V.N. Panteleev, Yu.M. Volkov,O. Alyakrinskiy, A. Andrighetto, A. Lanchais, G. Lhersonneau*, V. Rizzi, L. Stroe#, L.B. Tecchio,O. Bajeat, M. Cheikh Mhamed, S. Essabaa, C. Lau, B. Roussière,M. Dubois, C. Eléon, G. Gaubert, P. Jardin, N. Lecesne, R. Leroy, J.Y. Pacquet, M. -G. Saint Laurent, A.C.C. Villari.

    The aim of this report is to summarize the experimental results of the R&D program on Uranium Carbide targets for Radioactive Ion Beam (RIB) production performed at the Petersburg Nuclear Physics Institute (PNPI) of Gatchina (Russia). The targets have been irradiated with 1 GeV protons delivered by the Synchrocyclotron and the measurements were carried out at the IRIS isotope separator on-line. Different compositions of Uranium Carbide targets as well as different kinds of ion sources have been tested in order to evaluate efficiency and release times of the reaction products. The report includes the results of experiments performed in the period of time going from November 2001 up to March 2006. This R&D program was performed in the framework of the collaboration with the EURISOL, SPES and SPIRAL-2 projects and ISTC program.

  9. Design and verification experiments for the windowless spallation target of the ADS prototype Myrrha

    International Nuclear Information System (INIS)

    Kantrien Van, Tichelen; Kupschus, P.; Arien, B.; Ait Abderrahim, H.

    2003-01-01

    SCKxCEN, the Belgian Nuclear Research Centre, works on the conceptual design and basic engineering of a multipurpose ADS for R and D, dubbed MYRRHA, a small high-performance irradiation facility with fast neutron fluxes up to 1.10 15 n/cm 2 /s to start operation in about 2010. Specific to the MYRRHA ADS system is the choice for a windowless spallation target at the centre of the subcritical core. Apart from the space limitations and material property short-comings, the current and power density figures would make the design of a solid window for the spallation source next to impossible: the chosen 5 mA at the relative low energy of 350 MeV leads to a current density of order 150 μA/cm 2 (as far as we know at least a factor of 3 higher than any window design that has been attempted to meet). This is the main reason for adopting the windowless design for MYRRHA which has as a consequence that the free surface ultimately has to be compatible with the vacuum requirements of the beam transport system of the accelerator. The total beam energy will be dumped into a volume of ca 0.5 1 leading to a heating power density of ca 3 kW/cm 3 . In order to remove this heat from the LM with an average temperature increase of 100 deg C on top of the temperature of the inlet flow of 240 deg C a total flow rate of 101/s at an average flow speed of 2.5 m/s is required. It is suggested from estimates that the evaporation from 'hot spots' with elevated temperatures beyond the average 340 deg C - close to the free surface in the re-circulation zone - is then still acceptable. The design investigations are therefore directed to assess and minimise the re-circulation zone inherent in the free surface formation under the geometry and flow requirements. This paper will summarize the design programme for the windowless design of the spallation source at the centre of the subcritical core. It will include the main findings reported in (Van Tichelen, 2000) and (Van Tichelen, 2001) and the

  10. 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.

  11. Defilade, Stationary Target and Moving Target Embankment, Low Water Crossing, and Course Road Designs for Soil Loss Prevention

    National Research Council Canada - National Science Library

    Svendsen, Niels G; Kalita, Prasanta K; Gebhart, Dick L; Denight, Michael L

    2006-01-01

    ... for military training requirements. This report proposes several new range structure designs to begin the iterative process of developing new range edifices that reduce soil loss, control erosion, promote sustainability, and enhance training...

  12. 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

  13. Small UAS Analysis of Laser Designation and Search and Target Acquisition Capabilities in an Urban Environment

    National Research Council Canada - National Science Library

    Harclerode, Eric

    2008-01-01

    Conclusions: -Small UAS has extreme difficulty lasing moving targets in high density urban environments -Lasing moving targets in medium density terrain is possible but not certain -Lasing of stationary targets...

  14. Circular revisit orbits design for responsive mission over a single target

    Science.gov (United States)

    Li, Taibo; Xiang, Junhua; Wang, Zhaokui; Zhang, Yulin

    2016-10-01

    The responsive orbits play a key role in addressing the mission of Operationally Responsive Space (ORS) because of their capabilities. These capabilities are usually focused on supporting specific targets as opposed to providing global coverage. One subtype of responsive orbits is repeat coverage orbit which is nearly circular in most remote sensing applications. This paper deals with a special kind of repeating ground track orbit, referred to as circular revisit orbit. Different from traditional repeat coverage orbits, a satellite on circular revisit orbit can visit a target site at both the ascending and descending stages in one revisit cycle. This typology of trajectory allows a halving of the traditional revisit time and does a favor to get useful information for responsive applications. However the previous reported numerical methods in some references often cost lots of computation or fail to obtain such orbits. To overcome this difficulty, an analytical method to determine the existence conditions of the solutions to revisit orbits is presented in this paper. To this end, the mathematical model of circular revisit orbit is established under the central gravity model and the J2 perturbation. A constraint function of the circular revisit orbit is introduced, and the monotonicity of that function has been studied. The existent conditions and the number of such orbits are naturally worked out. Taking the launch cost into consideration, optimal design model of circular revisit orbit is established to achieve a best orbit which visits a target twice a day in the morning and in the afternoon respectively for several days. The result shows that it is effective to apply circular revisit orbits in responsive application such as reconnoiter of natural disaster.

  15. Modern dose-finding designs for cancer phase I trials drug combinations and molecularly targeted agents

    CERN Document Server

    Hirakawa, Akihiro; Daimon, Takashi; Matsui, Shigeyuki

    2018-01-01

    This book deals with advanced methods for adaptive phase I dose-finding clinical trials for combination of two agents and molecularly targeted agents (MTAs) in oncology. It provides not only methodological aspects of the dose-finding methods, but also software implementations and practical considerations in applying these complex methods to real cancer clinical trials. Thus, the book aims to furnish researchers in biostatistics and statistical science with a good summary of recent developments of adaptive dose-finding methods as well as providing practitioners in biostatistics and clinical investigators with advanced materials for designing, conducting, monitoring, and analyzing adaptive dose-finding trials. The topics in the book are mainly related to cancer clinical trials, but many of those topics are potentially applicable or can be extended to trials for other diseases. The focus is mainly on model-based dose-finding methods for two kinds of phase I trials. One is clinical trials with combinations of tw...

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

    International Nuclear Information System (INIS)

    Watanabe, N.

    1991-01-01

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

  17. A trajectory design method via target practice for air-breathing hypersonic vehicle

    Science.gov (United States)

    Kong, Xue; Yang, Ming; Ning, Guodong; Wang, Songyan; Chao, Tao

    2017-11-01

    There are strong coupling interactions between aerodynamics and scramjet, this kind of aircraft also has multiple restrictions, such as the range and difference of dynamic pressure, airflow, and fuel. On the one hand, we need balance the requirement between maneuverability of vehicle and stabilization of scramjet. On the other hand, we need harmonize the change of altitude and the velocity. By describing aircraft's index system of climbing capability, acceleration capability, the coupling degree in aerospace, this paper further propose a rapid design method which based on target practice. This method aimed for reducing the coupling degree, it depresses the coupling between aircraft and engine in navigation phase, satisfy multiple restriction conditions to leave some control buffer and create good condition for control implementation. According to the simulation, this method could be used for multiple typical fly commissions such as climbing, acceleration or both.

  18. 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.

  19. 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.

  20. Oral heparin delivery: design and in vivo evaluation of a stomach-targeted mucoadhesive delivery system.

    Science.gov (United States)

    Schmitz, Thierry; Leitner, Verena M; Bernkop-Schnürch, Andreas

    2005-05-01

    Low molecular weight heparin (LMWH) is an agent of choice in the anti-coagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, the therapeutic use is partially limited due to a poor oral bioavailability. It was therefore the aim of this study to design and evaluate a highly efficient stomach-targeted oral delivery system for LMWH. In order to appraise the influence of the molecular weight on the oral bioavailability, mini-tablets comprising 3 kDa (279 IU) and 6 kDa (300 IU) LMWH, respectively, were generated and tested in vivo in rats. The potential of the test formulations based on thiolated polycarbophil, was evaluated in comparison to hydroxyethylcellulose (HEC) as control carrier matrix. The plasma levels of LMWH after oral versus subcutaneous administration were determined in order to calculate the relative bioavailability. With the delivery system containing 3 kDa LMWH (279 IU) a relative bioavailability of 19.1% was achieved, offering a significantly (p thiolated polymers are a promising tool for the non-invasive stomach-targeted systemic delivery of LMWH as model for a hydrophilic macromolecular polysaccharide. Copyright 2005 Wiley-Liss, Inc

  1. Designs of contraction nozzle and concave back-wall for IFMIF target

    Energy Technology Data Exchange (ETDEWEB)

    Ida, Mizuho E-mail: ida@ifmif.tokai.jaeri.go.jp; Nakamura, Hideo; Nakamura, Hiroo; Takeuchi, Hiroshi

    2004-02-01

    For the liquid lithium flow target of International Fusion Materials Irradiation Facility (IFMIF), the double reducer (two-step contraction) nozzle with a high-contraction ratio of 10 which generated high-speed uniform jet flows up to 20 m/s was proposed. Multi-dimensional hydraulic analyses were carried out to verify the performance of the proposed nozzle. The analytical results showed that the double reducer nozzle would well generate high-speed uniform flow, while one-step contraction nozzle generated non-uniform flow and resulted in flow thickening at the beam footprint. For the target design, the range of the concave back-wall radius with no lithium boiling due to the centrifugal force and proper component arrangement in the irradiation test cell was determined by the thermal-hydraulic analysis of a free-surface flow. It was verified that the back-wall radius from 0.25 to 10 m was acceptable in the velocity range of 10-20 m/s.

  2. Designs of contraction nozzle and concave back-wall for IFMIF target

    International Nuclear Information System (INIS)

    Ida, Mizuho; Nakamura, Hideo; Nakamura, Hiroo; Takeuchi, Hiroshi

    2004-01-01

    For the liquid lithium flow target of International Fusion Materials Irradiation Facility (IFMIF), the double reducer (two-step contraction) nozzle with a high-contraction ratio of 10 which generated high-speed uniform jet flows up to 20 m/s was proposed. Multi-dimensional hydraulic analyses were carried out to verify the performance of the proposed nozzle. The analytical results showed that the double reducer nozzle would well generate high-speed uniform flow, while one-step contraction nozzle generated non-uniform flow and resulted in flow thickening at the beam footprint. For the target design, the range of the concave back-wall radius with no lithium boiling due to the centrifugal force and proper component arrangement in the irradiation test cell was determined by the thermal-hydraulic analysis of a free-surface flow. It was verified that the back-wall radius from 0.25 to 10 m was acceptable in the velocity range of 10-20 m/s

  3. 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.

  4. Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria.

    Science.gov (United States)

    Inaoka, Daniel Ken; Shiba, Tomoo; Sato, Dan; Balogun, Emmanuel Oluwadare; Sasaki, Tsuyoshi; Nagahama, Madoka; Oda, Masatsugu; Matsuoka, Shigeru; Ohmori, Junko; Honma, Teruki; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu

    2015-07-07

    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.

  5. Design criteria for a high energy Compton Camera and possible application to targeted cancer therapy

    Science.gov (United States)

    Conka Nurdan, T.; Nurdan, K.; Brill, A. B.; Walenta, A. H.

    2015-07-01

    The proposed research focuses on the design criteria for a Compton Camera with high spatial resolution and sensitivity, operating at high gamma energies and its possible application for molecular imaging. This application is mainly on the detection and visualization of the pharmacokinetics of tumor targeting substances specific for particular cancer sites. Expected high resolution (animals with a human tumor xenograft which is one of the first steps in evaluating the potential utility of a candidate gene. The additional benefit of high sensitivity detection will be improved cancer treatment strategies in patients based on the use of specific molecules binding to cancer sites for early detection of tumors and identifying metastasis, monitoring drug delivery and radionuclide therapy for optimum cell killing at the tumor site. This new technology can provide high resolution, high sensitivity imaging of a wide range of gamma energies and will significantly extend the range of radiotracers that can be investigated and used clinically. The small and compact construction of the proposed camera system allows flexible application which will be particularly useful for monitoring residual tumor around the resection site during surgery. It is also envisaged as able to test the performance of new drug/gene-based therapies in vitro and in vivo for tumor targeting efficacy using automatic large scale screening methods.

  6. Analytical study of narrow channel flow for a spallation target system design

    Energy Technology Data Exchange (ETDEWEB)

    Islam, Md. Shafiqul; Monde, Masanori [Saga Univ., Saga (Japan); Terada, Atsuhiko; Kinoshita, Hidetaka; Hino, Ryutaro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2001-07-01

    Heat transfer and pressure drop characteristics under fully developed turbulent water flow condition were analyzed over a two-dimensional narrow rectangular channel whose height is H=1.2 mm. The channel configuration and water flow condition simulate forced convection cooling of a spallation target system components design such as a solid target and a proton beam window. The high-Reynolds number form of the standard k - {epsilon} and RNG k - {epsilon} models employing wall functions for the Reynolds number (Re) range of 7,000 to 22,000 were used in the analyses. As for heat transfer characteristics of a smooth channel, the Nusselt number obtained by the standard k - {epsilon} model agreed very well with the Dittus-Boelter correlation. No significant differences in friction factors for the smooth channel were observed for these two models, which agreed well with the Blasius correlation. However, the standard k - {epsilon} model could not predict friction factors well for the rib-roughened channel. (author)

  7. Analytical study of narrow channel flow for a spallation target system design

    International Nuclear Information System (INIS)

    Islam, Md. Shafiqul; Monde, Masanori; Terada, Atsuhiko; Kinoshita, Hidetaka; Hino, Ryutaro

    2001-07-01

    Heat transfer and pressure drop characteristics under fully developed turbulent water flow condition were analyzed over a two-dimensional narrow rectangular channel whose height is H=1.2 mm. The channel configuration and water flow condition simulate forced convection cooling of a spallation target system components design such as a solid target and a proton beam window. The high-Reynolds number form of the standard k - ε and RNG k - ε models employing wall functions for the Reynolds number (Re) range of 7,000 to 22,000 were used in the analyses. As for heat transfer characteristics of a smooth channel, the Nusselt number obtained by the standard k - ε model agreed very well with the Dittus-Boelter correlation. No significant differences in friction factors for the smooth channel were observed for these two models, which agreed well with the Blasius correlation. However, the standard k - ε model could not predict friction factors well for the rib-roughened channel. (author)

  8. A Rationally Designed Agonist Defines Subfamily IIIA Abscisic Acid Receptors As Critical Targets for Manipulating Transpiration.

    Science.gov (United States)

    Vaidya, Aditya S; Peterson, Francis C; Yarmolinsky, Dmitry; Merilo, Ebe; Verstraeten, Inge; Park, Sang-Youl; Elzinga, Dezi; Kaundal, Amita; Helander, Jonathan; Lozano-Juste, Jorge; Otani, Masato; Wu, Kevin; Jensen, Davin R; Kollist, Hannes; Volkman, Brian F; Cutler, Sean R

    2017-11-17

    Increasing drought and diminishing freshwater supplies have stimulated interest in developing small molecules that can be used to control transpiration. Receptors for the plant hormone abscisic acid (ABA) have emerged as key targets for this application, because ABA controls the apertures of stomata, which in turn regulate transpiration. Here, we describe the rational design of cyanabactin, an ABA receptor agonist that preferentially activates Pyrabactin Resistance 1 (PYR1) with low nanomolar potency. A 1.63 Å X-ray crystallographic structure of cyanabactin in complex with PYR1 illustrates that cyanabactin's arylnitrile mimics ABA's cyclohexenone oxygen and engages the tryptophan lock, a key component required to stabilize activated receptors. Further, its sulfonamide and 4-methylbenzyl substructures mimic ABA's carboxylate and C6 methyl groups, respectively. Isothermal titration calorimetry measurements show that cyanabactin's compact structure provides ready access to high ligand efficiency on a relatively simple scaffold. Cyanabactin treatments reduce Arabidopsis whole-plant stomatal conductance and activate multiple ABA responses, demonstrating that its in vitro potency translates to ABA-like activity in vivo. Genetic analyses show that the effects of cyanabactin, and the previously identified agonist quinabactin, can be abolished by the genetic removal of PYR1 and PYL1, which form subclade A within the dimeric subfamily III receptors. Thus, cyanabactin is a potent and selective agonist with a wide spectrum of ABA-like activities that defines subfamily IIIA receptors as key target sites for manipulating transpiration.

  9. 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.

  10. 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

  11. Rational Design of Iron Oxide Nanoparticles as Targeted Nanomedicines for Cancer Therapy

    Science.gov (United States)

    Kievit, Forrest M.

    2011-07-01

    Nanotechnology provides a flexible platform for the development of effective therapeutic nanomaterials that can interact specifically with a target in a biological system and provoke a desired biological response. Of the nanomaterials studied, superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as one of top candidates for cancer therapy due to their intrinsic superparamagnetism that enables non-invasive magnetic resonance imaging (MRI) and biodegradability favorable for in vivo application. This dissertation is aimed at development of SPION-based nanomedicines to overcome the current limitations in cancer therapy. These limitations include non-specificity of therapy which can harm healthy tissue, the difficulty in delivering nucleic acids for gene therapy, the formation of drug resistance, and the inability to detect and treat micrometastases. First, a SPION-based non-viral gene delivery vehicle was developed through functionalization of the SPION core with a co-polymer designed to provide stable binding of DNA and low toxicity which showed excellent gene delivery in vitro and in vivo. This SPION-based non-viral gene delivery vehicle was then activated with a targeting agent to improve gene delivery throughout a xenograft tumor of brain cancer. It was found that targeting did not promote the accumulation of SPIONs at the tumor site, but rather improved the distribution of SPIONs throughout the tumor so a higher proportion of cells received treatment. Next, the high surface area of SPIONs was utilized for loading large amounts of drug which was shown to overcome the multidrug resistance acquired by many cancer cells. Drug bound to SPIONs showed significantly higher multidrug resistant cell uptake as compared to free drug which translated into improved cell kill. Also, an antibody activated SPION was developed and was shown to be able to target micrometastases in a transgenic animal model of metastatic breast cancer. These SPION-based nanomedicines

  12. Finite Element Based Design Optimization of WENDELSTEIN 7-X Divertor Targets

    International Nuclear Information System (INIS)

    Plankensteiner, A.; Leuprecht, A.; Schedler, B.; Scheiber, K.; Greuner, H.

    2006-01-01

    In the fusion experiment WENDELSTEIN 7-X divertor plasma facing components have to withstand severe loading conditions. In general thermally induced mechanical stressing turns out to be most critical with respect to life time predictions of the component. In the specific case flat tiles of CFC grade NB31 are joined to the precipitation hardened CuCrZr heat sink by employing an active metal cast (AMC)-Cu as an interlayer between CFC and CuCrZr. Residual stresses resulting from the manufacturing process act as initial stresses in the subsequent operational heat flux loading. For the latter loading regime these stresses intrinsically are generated due to the large contrast in the CTE for CFC and Cu. Different design variants of those CFC flat tile armoured target elements have been analysed via the finite element package ABAQUS aiming at derivation of an optimized component design. The numerical study comprises variants with different degrees of tessellation of the CFC flat tile section, orientation of the CFC, lamellar design of the AMC-interlayer, and different designs of the cooling channels. The thermo-mechanical material characteristics are accounted for the finite element models with elastic-plastic properties being assigned to the metallic sections CuCrZr and AMC-Cu, respectively, and orthotropic nonlinear-elastic properties being used to the CFC section. The latter has been realized in form of a user-defined material subroutine that is used at the integration point level of the finite element model. In particular, twelve scalar-type damage parameters obeying their own evolution equations with respect to the loading history account for specific stress-strain relationships in the three principal material directions and planes with six damage parameters being used for normal loading under tensile and compressive stress states, respectively, and six parameters being used for shear loading. For the aim of model verification calculated surface temperatures, global

  13. Role of Bioreactor Technology in Tissue Engineering for Clinical Use and Therapeutic Target Design

    Directory of Open Access Journals (Sweden)

    Clare Selden

    2018-04-01

    Full Text Available Micro and small bioreactors are well described for use in bioprocess development in pre-production manufacture, using ultra-scale down and microfluidic methodology. However, the use of bioreactors to understand normal and pathophysiology by definition must be very different, and the constraints of the physiological environment influence such bioreactor design. This review considers the key elements necessary to enable bioreactors to address three main areas associated with biological systems. All entail recreation of the in vivo cell niche as faithfully as possible, so that they may be used to study molecular and cellular changes in normal physiology, with a view to creating tissue-engineered grafts for clinical use; understanding the pathophysiology of disease at the molecular level; defining possible therapeutic targets; and enabling appropriate pharmaceutical testing on a truly representative organoid, thus enabling better drug design, and simultaneously creating the potential to reduce the numbers of animals in research. The premise explored is that not only cellular signalling cues, but also mechano-transduction from mechanical cues, play an important role.

  14. Design and Demonstration of a Material-Plasma Exposure Target Station for Neutron Irradiated Samples

    Energy Technology Data Exchange (ETDEWEB)

    Rapp, Juergen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Aaron, A. M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bell, Gary L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Burgess, Thomas W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ellis, Ronald James [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Giuliano, D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Howard, R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kiggans, James O. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lessard, Timothy L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ohriner, Evan Keith [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Perkins, Dale E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Varma, Venugopal Koikal [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-10-20

    Fusion energy is the most promising energy source for the future, and one of the most important problems to be solved progressing to a commercial fusion reactor is the identification of plasma-facing materials compatible with the extreme conditions in the fusion reactor environment. The development of plasma–material interaction (PMI) science and the technology of plasma-facing components are key elements in the development of the next step fusion device in the United States, the so-called Fusion Nuclear Science Facility (FNSF). All of these PMI issues and the uncertain impact of the 14-MeV neutron irradiation have been identified in numerous expert panel reports to the fusion community. The 2007 Greenwald report classifies reactor plasma-facing materials (PFCs) and materials as the only Tier 1 issues, requiring a “. . . major extrapolation from the current state of knowledge, need for qualitative improvements and substantial development for both the short and long term.” The Greenwald report goes on to list 19 gaps in understanding and performance related to the plasma–material interface for the technology facilities needed for DEMO-oriented R&D and DEMO itself. Of the 15 major gaps, six (G7, G9, G10, G12, G13) can possibly be addressed with ORNL’s proposal of an advanced Material Plasma Exposure eXperiment. Establishing this mid-scale plasma materials test facility at ORNL is a key element in ORNL’s strategy to secure a leadership role for decades of fusion R&D. That is to say, our end goal is to bring the “signature facility” FNSF home to ORNL. This project is related to the pre-conceptual design of an innovative target station for a future Material–Plasma Exposure eXperiment (MPEX). The target station will be designed to expose candidate fusion reactor plasma-facing materials and components (PFMs and PFCs) to conditions anticipated in fusion reactors, where PFCs will be exposed to dense high-temperature hydrogen plasmas providing steady

  15. Design and Demonstration of a Material-Plasma Exposure Target Station for Neutron Irradiated Samples

    International Nuclear Information System (INIS)

    Rapp, Juergen; Aaron, A. M.; Bell, Gary L.; Burgess, Thomas W.; Ellis, Ronald James; Giuliano, D.; Howard, R.; Kiggans, James O.; Lessard, Timothy L.; Ohriner, Evan Keith; Perkins, Dale E.; Varma, Venugopal Koikal

    2015-01-01

    Fusion energy is the most promising energy source for the future, and one of the most important problems to be solved progressing to a commercial fusion reactor is the identification of plasma-facing materials compatible with the extreme conditions in the fusion reactor environment. The development of plasma-material interaction (PMI) science and the technology of plasma-facing components are key elements in the development of the next step fusion device in the United States, the so-called Fusion Nuclear Science Facility (FNSF). All of these PMI issues and the uncertain impact of the 14-MeV neutron irradiation have been identified in numerous expert panel reports to the fusion community. The 2007 Greenwald report classifies reactor plasma-facing materials (PFCs) and materials as the only Tier 1 issues, requiring a ''. . . major extrapolation from the current state of knowledge, need for qualitative improvements and substantial development for both the short and long term.'' The Greenwald report goes on to list 19 gaps in understanding and performance related to the plasma-material interface for the technology facilities needed for DEMO-oriented R&D and DEMO itself. Of the 15 major gaps, six (G7, G9, G10, G12, G13) can possibly be addressed with ORNL's proposal of an advanced Material Plasma Exposure eXperiment. Establishing this mid-scale plasma materials test facility at ORNL is a key element in ORNL's strategy to secure a leadership role for decades of fusion R&D. That is to say, our end goal is to bring the ''signature facility'' FNSF home to ORNL. This project is related to the pre-conceptual design of an innovative target station for a future Material-Plasma Exposure eXperiment (MPEX). The target station will be designed to expose candidate fusion reactor plasma-facing materials and components (PFMs and PFCs) to conditions anticipated in fusion reactors, where PFCs will be exposed to dense high-temperature hydrogen plasmas providing steady-state heat fluxes of

  16. Conceptual Biorefinery Design and Research Targeted for 2022: Hydrothermal Liquefacation Processing of Wet Waste to Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Snowden-Swan, Lesley J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zhu, Yunhua [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bearden, Mark D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Seiple, Timothy E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Jones, Susanne B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Schmidt, Andrew J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Billing, Justin M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hallen, Richard T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hart, Todd R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Liu, Jian [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Albrecht, Karl O. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Fox, Samuel P. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Maupin, Gary D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Elliott, Douglas C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2017-12-28

    represents a goal case for the pathway, targeting performance that is anticipated to be achievable by 2022 with further research and development. The year 2022 is BETO’s target year for verification of hydrocarbon biofuel pathways. As this analysis represents a goal case, assumed values of several design parameters represent improvements in the technology relative to what has currently been demonstrated in the laboratory. While HTL is fairly well developed and may therefore be ready for commercialization prior to 2022, there are specific advancements addressed in this analysis that are necessary to enhance performance compared to what has been demonstrated to date. In addition, an important aspect to the pathway is the upgrading of biocrude to fuel blendstock, an area that has received much less attention and requires significant research to validate the goal case performance parameters. The estimated plant gate minimum fuel selling price for fuel blendstock from sludge HTL and upgrading is $3.46/gasoline gallon equivalent (gge). This price is within the tolerance (+$0.49/gge) of BETO’s $3/gge programmatic cost target and illustrates that fuel blendstocks generated from HTL of sludge and centralized biocrude upgrading have the potential to be competitive with fossil fuels. This analysis illustrates the feasibility of HTL for point-of-generation conversion of waste feedstock at a scale 1/20th that of the standard lignocellulosic biorefinery scale typically used in BETO design cases. The relevance of this work reaches beyond wastewater treatment sludge to lay the groundwork for application to other distributed wet wastes and blends that together represent a significant resource of underutilized biomass.

  17. The need for rotational margins in intensity-modulated radiotherapy and a new method for planning target volume design

    International Nuclear Information System (INIS)

    Langer, Mark Peter; Papiez, Lech; Spirydovich, Siarhei; Thai, Van

    2005-01-01

    Purpose: The effect of rotational errors on the coverage of clinical target volumes (CTVs) is examined. A new planning target volume (PTV) construction that considers the individual paths traced by movements of the target boundary points is developed. Methods and Materials: A standard uniform margin expansion was compared with a PTV constructed from the space swept out by a concave moving target. A new method formed the PTV by aggregating the separate convex hulls taken of the positions of the individual target boundary points in a sampling of CTV displacements. Results: A 0.5-cm uniform margin adequate for translations was inadequate given CTV rotation about a fixed off-center axis. A PTV formed of the target's swept-out area was 22% smaller than needed for coverage by a uniform margin, but computationally is not readily extended to translations combined with rotations about a shifting axis. Forming instead the union of convex hulls of the boundary points in a sampling of CTV displacements represented these movements in the PTV design and retained the target's concave shape. Conclusions: Planning target volumes should accommodate target rotation. The union of convex hulls of the boundary point positions in a sampling of displacements can effectively represent multiple sources of deviations while preserving target concavities

  18. Design of Solid Form Xenon-124 Target for Producing I-123 Radioisotope Using Computer Simulation Techniques

    International Nuclear Information System (INIS)

    Kamali Moghaddam, K.; Sadeghi, M.; Kakavand, T.; Shokri Bonab, S.

    2006-01-01

    Recently in Cyclotron and Nuclear Medicine Department of NRCAM, at Atomic Energy organization of Iran (AEOI), a system for producing 1-123 via Xe-124 gas target technology, has been constructed and installed. One of the major problems in this system is the highly expensive cost of the enriched Xenon-124 gas. Therefore, saving this gas inside the system is very important. Unfortunately, by accidental rupture of the window foil or bad function of O-rings, the whole Xenon gas will escape from the system immediately. In this paper, by using computer codes; ALICE91, SRIM and doing some calculations we are going to demonstrate our latest effort for feasibility study of producing I-123 with the above mentioned reactions, but using Xe-124 solid target instead. According to our suggested design, a conical shaped irradiation vessel made of copper with 1 mm thickness, 1 cm outlet diameter, 5 cm length and 12 deg. angle at summit can be fixed inside a liquid nitrogen housing chamber. The Xenon-124 gas will be sent to the inside of this very cold conical trap and eventually deposited on its surface in solid form. Our calculation shows that during bombardment with 17-28 MeV proton energy, the thickness of solidified Xenon layer will remain around .28 mm. Likewise; thermo-dynamical calculation shows that in order to prevent the evaporation of solidified Xenon, the maximum permissible proton beam current for this system should be less than 1.4 μA. According to these working conditions, the production yield of I-123 can be predicted to be around 150 mCi/μAh. (authors)

  19. Investigation of the effect of physical parameters on the design of tumour targeting agents

    Science.gov (United States)

    Casey, Joanne Lois

    Tumour targeting using radiolabelled antibodies for radioimmunodetection (RAID) and radioimmunotherapy (RIT) has been studied for many years. The main factors that have limited clinical success are low tumour uptake, immunogenicity and poor therapeutic ratios. This thesis has applied current technology to make advances in this area of research. The effect of physical parameters (antibody size, valency, affinity and charge) on the design of tumour targeting agents was studied by constructing divalent (DFM) and trivalent (TFM) forms of the murine anti-CEA antibody A5B7 Fab' by chemical cross-linking. This involves partial reduction of the hinge disulphides to expose thiol (-SH) groups and subsequent reaction with a maleimide cross-linker to form a thioether bond at the hinge region. Previous studies have suggested that the stability of thioether bonds is superior to naturally occurring disulphide bonds present at the hinge region of IgG and F(ab')2. The aim was to compare the functional affinities and in vivo tumour targeting in nude mice bearing human tumour xenografts of DFM and TFM to similar sized parent IgG and F(ab')2. Radiolabelling with 131I and 90Y was also compared with a view to determine which combination would be optimal for RIT. Results clearly demonstrated a significantly faster on-rate of DFM compared to all other antibody forms and estimated dosimetry analysis suggested that DFM would be the most suitable antibody form radiolabelled with 131I for RIT. Both F(ab')2 and DFM showed high kidney uptake levels on labelling with which is unacceptable for RIT. Despite the improved tumour: blood ratios for TFM, the increased estimated dose to normal tissues and lower therapeutic effect in RIT studies suggests that the most promising combination with the radionuclide appears to be IgG. A humanised version of A5B7 hFab' has been constructed previously in order to reduce its immunogenicity in man. The in vivo stability of hDFM proved to be superior to hF(ab')2

  20. Conceptual design of the handling and storage system of the spent target vessel for neutron scattering facility 2

    International Nuclear Information System (INIS)

    Adachi, Junichi; Kaminaga, Masanori; Sasaki, Shinobu; Haga, Katsuhiro; Aso, Tomokazu; Kinoshita, Hidetaka; Hino, Ryutaro

    2002-01-01

    In designing the neutron scattering facility, a spent target vessel should be replaced with remote handling devices in order to protect radioactive exposure, since it would be highly activated through the high energy neutron irradiation caused by the spallation reaction between mercury of the target material and the MW-class proton beam. In the storage of the spent target vessel, it is necessary to consider decay heat of the target vessel and mercury contamination caused by vaporization of the residual mercury in the vessel. A conceptual design has been carried out to establish basic concept and to clarify its specification of main equipments on handling and storage systems for the spent target vessel. This report presents the basic concept and a system plot plan based on latest design works of remote handling devices such as a spent target vessel storage cask and a target vessel exchange trolley, which aim at reasonability and simplification. In addition, storage systems for the spent moderator vessel, the spent proton beam window and the spent reflector vessel are also investigated based on the plot plan. (author)

  1. Examination of CRISPR/Cas9 design tools and the effect of target site accessibility on Cas9 activity.

    Science.gov (United States)

    Lee, Ciaran M; Davis, Timothy H; Bao, Gang

    2018-04-01

    What is the topic of this review? In this review, we analyse the performance of recently described tools for CRISPR/Cas9 guide RNA design, in particular, design tools that predict CRISPR/Cas9 activity. What advances does it highlight? Recently, many tools designed to predict CRISPR/Cas9 activity have been reported. However, the majority of these tools lack experimental validation. Our analyses indicate that these tools have poor predictive power. Our preliminary results suggest that target site accessibility should be considered in order to develop better guide RNA design tools with improved predictive power. The recent adaptation of the clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system for targeted genome engineering has led to its widespread application in many fields worldwide. In order to gain a better understanding of the design rules of CRISPR/Cas9 systems, several groups have carried out large library-based screens leading to some insight into sequence preferences among highly active target sites. To facilitate CRISPR/Cas9 design, these studies have spawned a plethora of guide RNA (gRNA) design tools with algorithms based solely on direct or indirect sequence features. Here, we demonstrate that the predictive power of these tools is poor, suggesting that sequence features alone cannot accurately inform the cutting efficiency of a particular CRISPR/Cas9 gRNA design. Furthermore, we demonstrate that DNA target site accessibility influences the activity of CRISPR/Cas9. With further optimization, we hypothesize that it will be possible to increase the predictive power of gRNA design tools by including both sequence and target site accessibility metrics. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

  2. FEA Analysis of AP-0 Target Hall Collection Lens (Current Design)

    International Nuclear Information System (INIS)

    Hurh, P.G.; Tang, Z.

    2001-01-01

    The AP-0 Target Hall Collection Lens is a pulsed device which focuses anti-protons just downstream of the Target. Since the angles at which the anti-protons depart the Target can be quite large, a very high focusing strength is required to maximize anti-proton capture into the downstream Debuncher Ring. The current design of the Collection Lens was designed to operate with a focusing gradient of 1,000 T/m. However, multiple failures of early devices resulted in lowering the normal operating gradient to about 750 T/m. At this gradient, the Lens design fares much better, lasting several million pulses, but ultimately still fails. A Finite Element Analysis (FEA) has been performed on this Collection Lens design to help determine the cause and/or nature of the failures. The Collection Lens magnetic field is created by passing high current through a central conductor cylinder. A uniform current distribution through the cylinder will create a tangential or azimuthal magnetic field that varies linearly from zero at the center of the cylinder to a maximum at the outer surface of the cylinder. Anti-proton particles passing through this cylinder (along the longitudinal direction) will see an inward focusing kick back toward the center of the cylinder proportional to the magnetic field strength. For the current Lens design a gradient of 1,000 T/m requires a current of about 580,000 amps. Since the DC power and cooling requirements would be prohibitive, the Lens is operated in a pulsed mode. Each pulse is half sine wave in shape with a pulse duration of about 350 microseconds. Because of the skin effect, the most uniform current density actually occurs about two-thirds of the way through the pulse. This means that the maximum current of the pulse is actually higher than that required in the DC case (about 670,000 amps). Since the beam must pass through the central conductor cylinder it must be made of a conducting material that is also very 'transparent' to the beam. For the

  3. Target/Blanket Design for the Accelerator Production of Tritium Plant

    International Nuclear Information System (INIS)

    Cappiello, M. W.

    1997-01-01

    The Accelerator Production of Tritium Target/Blanket (T/B) system is comprised of the T/B assembly and the attendant heat removal systems. The T/B assembly produces tritium using a high energy proton beam, and a spallation neutron source. The supporting heat removal systems safely remove the heat deposited by the proton beam during both normal and off-normal conditions. All systems reside within the T/B building, which is located at the end of a linear accelerator. Protons are accelerated to an energy of 1700 MeV at a current of 100 mA and are directed onto the T/B assembly. The protons interact with tungsten and lead nuclei to produce neutrons through the process of nuclear spallation. Neutron capture in 3 He gas produces tritium which is removed on a continual basis in an adjacent Tritium Separation Facility (TSF). The T/B assembly is modular to allow for replacement of spent components and minimization of waste. Systems and components are designed with safety as a primary consideration to minimize risk to the workers and the public

  4. Magnetic field pattern synthesis and its application in targeted drug delivery: Design and implementation.

    Science.gov (United States)

    Hajiaghajani, Amirhossein; Abdolali, Ali

    2018-05-01

    In cancer therapy, magnetic drug targeting is considered as an effective treatment to reduce chemotherapy's side effects. The accurate design and shaping of magnetic fields are crucial for healthy cells to be immune from chemotherapeutics. In this paper, arbitrary 2-dimensional spatial patterns of magnetic fields from DC to megahertz are represented in terms of spatial Fourier spectra with sinusoidal eigenfunctions. Realization of each spatial frequency was investigated by a set of elliptical coils. Therefore, it is shown that the desired pattern was synthesized by simultaneous use of coil sets. Currents running on each set were obtained via fast and straightforward analytical Fourier series calculation. Experimentally scanned sample patterns were in close agreement with full wave analysis. Discussions include the evaluation of the Fourier series approximation error and cross-polarization of produced magnetic fields. It was observed that by employing the controlled magnetic field produced by the proposed setup, we were able to steer therapeutic particles toward the right or left half-spheres of the breast, with an efficiency of 90%. Such a pattern synthesizer may be employed in numerous human arteries as well as other bioelectromagnetic patterning applications, e.g., wireless power transfer, magnetic innervation, and tomography. Bioelectromagnetics. 39:325-338, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  5. The genetics of age-related macular degeneration (AMD)--Novel targets for designing treatment options?

    Science.gov (United States)

    Grassmann, Felix; Fauser, Sascha; Weber, Bernhard H F

    2015-09-01

    Age-related macular degeneration (AMD) is a progressive disease of the central retina and the main cause of legal blindness in industrialized countries. Risk to develop the disease is conferred by both individual as well as genetic factors with the latter being increasingly deciphered over the last decade. Therapeutically, striking advances have been made for the treatment of the neovascular form of late stage AMD while for the late stage atrophic form of the disease, which accounts for almost half of the visually impaired, there is currently no effective therapy on the market. This review highlights our current knowledge on the genetic architecture of early and late stage AMD and explores its potential for the discovery of novel, target-guided treatment options. We reflect on current clinical and experimental therapies for all forms of AMD and specifically note a persisting lack of efficacy for treatment in atrophic AMD. We further explore the current insight in AMD-associated genes and pathways and critically question whether this knowledge is suited to design novel treatment options. Specifically, we point out that known genetic factors associated with AMD govern the risk to develop disease and thus may not play a role in its severity or progression. Treatments based on such knowledge appear appropriate rather for prevention than treatment of manifest disease. As a consequence, future research in AMD needs to be greatly focused on approaches relevant to the patients and their medical needs. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route

    Directory of Open Access Journals (Sweden)

    Surjyanarayan Mandal

    2015-09-01

    Full Text Available This study aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of Ibuprofen through intranasal route. Ibuprofen loaded mucoadhesive microemulsion (MMEI was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (MEI and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of ibuprofen via nasal route was studied by performing biodistribution study in Swiss albino rats. MEI was found to be transparent, stable and non ciliotoxic with 66.29 ± 4.15 nm, -20.9 ± 3.98 mV and 98.66 ± 1.01% as average globule size, zeta potential and drug content respectively. Transmission Electron Microscopy (TEM study revealed the narrow globule size distribution of MEI. Following single intranasal administration of MMEI and MEI at a dose of 2.86 mg/kg, uptake of ibuprofen in the olfactory bulb was around 3.0 and 1.7 folds compared with intravenous injection of ibuprofen solution (IDS. The ratios of AUC in brain tissues to that in plasma obtained after nasal administration of MMEI were significantly higher than those after intravenous administration of IDS. Findings of the present investigation revealed that the developed mucoadhesive microemulsion gel could be a promising approach for brain targeting of ibuprofen through intranasal route.

  7. Rational design of micro-RNA-like bifunctional siRNAs targeting HIV and the HIV coreceptor CCR5.

    Science.gov (United States)

    Ehsani, Ali; Saetrom, Pål; Zhang, Jane; Alluin, Jessica; Li, Haitang; Snøve, Ola; Aagaard, Lars; Rossi, John J

    2010-04-01

    Small-interfering RNAs (siRNAs) and micro-RNAs (miRNAs) are distinguished by their modes of action. SiRNAs serve as guides for sequence-specific cleavage of complementary mRNAs and the targets can be in coding or noncoding regions of the target transcripts. MiRNAs inhibit translation via partially complementary base-pairing to 3' untranslated regions (UTRs) and are generally ineffective when targeting coding regions of a transcript. In this study, we deliberately designed siRNAs that simultaneously direct cleavage and translational suppression of HIV RNAs, or cleavage of the mRNA encoding the HIV coreceptor CCR5 and suppression of translation of HIV. These bifunctional siRNAs trigger inhibition of HIV infection and replication in cell culture. The design principles have wide applications throughout the genome, as about 90% of genes harbor sites that make the design of bifunctional siRNAs possible.

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

    International Nuclear Information System (INIS)

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

    2000-01-01

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

  9. Rational design of nanoparticles towards targeting antigen-presenting cells and improved T cell priming.

    Science.gov (United States)

    Zupančič, Eva; Curato, Caterina; Paisana, Maria; Rodrigues, Catarina; Porat, Ziv; Viana, Ana S; Afonso, Carlos A M; Pinto, João; Gaspar, Rogério; Moreira, João N; Satchi-Fainaro, Ronit; Jung, Steffen; Florindo, Helena F

    2017-07-28

    Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules. Ovalbumin (OVA) was used as a model antigen in combination with the engraftment of CD4 + and CD8 + T cells, carrying a transgenic OVA-responding T cell receptor (TCR), to trace and characterize the activation of antigen-specific CD4 + and CD8 + lymph node T cells upon NP vaccination. Accordingly, the phenotype and frequency of immune cell stimulation induced by the NP loaded with OVA, isolated or in combination with synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) motifs, were characterized. DC-NP interactions increased with incubation time, presenting internalization values between 50 and 60% and 30-40%, in vitro and in vivo, respectively. Interestingly, animal immunization with antigen-adsorbed NP up-regulated major histocompatibility complex (MHC) class II (MHCII), while NP entrapping the antigen up-regulated MHCI, suggesting a more efficient cross-presentation. On the other hand, rather surprisingly, the surfactant used in the NP formulation had a major impact on the activation of antigen presenting cells (APC). In fact, DC collected from lymph nodes of animals immunized with NP prepared using poly(vinil alcohol) (PVA), as a surfactant, expressed significantly higher levels of CD86, MHCI and MHCII. In addition, those NP prepared with PVA and co-entrapping OVA and the toll

  10. OptMAVEn--a new framework for the de novo design of antibody variable region models targeting specific antigen epitopes.

    Directory of Open Access Journals (Sweden)

    Tong Li

    Full Text Available Antibody-based therapeutics provides novel and efficacious treatments for a number of diseases. Traditional experimental approaches for designing therapeutic antibodies rely on raising antibodies against a target antigen in an immunized animal or directed evolution of antibodies with low affinity for the desired antigen. However, these methods remain time consuming, cannot target a specific epitope and do not lead to broad design principles informing other studies. Computational design methods can overcome some of these limitations by using biophysics models to rationally select antibody parts that maximize affinity for a target antigen epitope. This has been addressed to some extend by OptCDR for the design of complementary determining regions. Here, we extend this earlier contribution by addressing the de novo design of a model of the entire antibody variable region against a given antigen epitope while safeguarding for immunogenicity (Optimal Method for Antibody Variable region Engineering, OptMAVEn. OptMAVEn simulates in silico the in vivo steps of antibody generation and evolution, and is capable of capturing the critical structural features responsible for affinity maturation of antibodies. In addition, a humanization procedure was developed and incorporated into OptMAVEn to minimize the potential immunogenicity of the designed antibody models. As case studies, OptMAVEn was applied to design models of neutralizing antibodies targeting influenza hemagglutinin and HIV gp120. For both HA and gp120, novel computational antibody models with numerous interactions with their target epitopes were generated. The observed rates of mutations and types of amino acid changes during in silico affinity maturation are consistent with what has been observed during in vivo affinity maturation. The results demonstrate that OptMAVEn can efficiently generate diverse computational antibody models with both optimized binding affinity to antigens and reduced

  11. Conceptual design of a 6-10 MJ driver for a high gain target development facility

    International Nuclear Information System (INIS)

    Olson, R.E.

    1986-01-01

    Commercial application of inertial confinement fusion would require low yield (≅200-500 MJ), high gain (≥80) fusion targets. It is thought that the development off such targets would reqiure a 5-10 year research program utilizing one or more dedicated nuclear facilities with drivers capable of delivering on-target pulses of 6-10 MJ at the rate of several shots per day. The ''Target Development Facility'' (TDF) is the light ion driven version of such a facility. A TDF driver concept based upon reasonable extrapolation from present-day technology is described in this paper

  12. Impact of neutron and gamma radiation on the design of NIF diagnostics and target-bay systems

    Energy Technology Data Exchange (ETDEWEB)

    Eder, D.C.; Song, P.M.; Latkowski, J.F.; Reyes, S.; O' Brien, D.W.; Lee, F.D.; Young, B.K.; Koch, J.A.; Moran, M.J.; Watts, P.W.; Kimbrough, J.R.; Ng, E.W.; Landen, O.L.; MacGowan, B.J. [Lawrence Livermore National Lab., Livermore, CA (United States)

    2006-06-15

    The design of a wide range of components in and near the target bay of the National Ignition Facility (NIF) must allow for significant radiation from neutrons and gammas. Detailed 3-dimensional Monte Carlo simulations are critical to determine neutron and gamma fluxes for all target-bay components to allow optimization of location and auxiliary shielding. Demonstration of ignition poses unique challenges because of the large range (about 3 orders of magnitude) in the yield for any given attempt at ignition. Some diagnostics will provide data independent of yield, while others will provide data for lower yields and only survive high yields with little or no damage. In addition, for a given yield there is a more than 10 orders of magnitude range in neutron and gamma fluxes depending on location in the facility. For example, sensitive components in the diagnostic mezzanines and switchyards require auxiliary shielding for high-yield shots even though they are greater than 17 meters from target chamber center (TCC) and shielded by the 2 m-thick target-bay wall. In contrast, there are components 0.2 to 2 m from TCC with little or no shielding. For these components, particular attention is being made to use low-activation material because of the extremely high neutron loading levels. Many of the components closest to target center are designed to be single use to reduce worker dose from having to refurbish highly activated components. The cryogenic target positioner is an example where activation and ease of component replacement is an important part of the design. We are developing a design process for all target-bay systems that will assure reliable operation for the full range of planned yields. (authors)

  13. Impact of neutron and gamma radiation on the design of NIF diagnostics and target-bay systems

    Science.gov (United States)

    Eder, D. C.; Song, P. M.; Latkowski, J. F.; Reyes, S.; O'Brien, D. W.; Lee, F. D.; Young, B. K.; Koch, J. A.; Moran, M. J.; Watts, P. W.; Kimbrough, J. R.; Ng, E. W.; Landen, O. L.; MacGowan, B. J.

    2006-06-01

    The design of a wide range of components in and near the target bay of the National Ignition Facility (NIF) must allow for significant radiation from neutrons and gammas. Detailed 3D Monte Carlo simulations are critical to determine neutron and gamma fluxes for all target-bay components to allow optimization of location and auxiliary shielding. Demonstration of ignition poses unique challenges because of the large range (˜ 3 orders of magnitude) in the yield for any given attempt at ignition. Some diagnostics will provide data independent of yield, while others will provide data for lower yields and only survive high yields with little or no damage. In addition, for a given yield there is a more than 10 orders of magnitude range in neutron and gamma fluxes depending on location in the facility. For example, sensitive components in the diagnostic mezzanines and switchyards require auxiliary shielding for high-yield shots even though they are greater than 17 meters from target chamber center (TCC) and shielded by the 2 m-thick target-bay wall. In contrast, there are components 0.2 to 2 m from TCC with little or no shielding. For these components, particular attention is being made to use low-activation material because of the extremely high neutron loading levels. Many of the components closest to target center are designed to be single use to reduce worker dose from having to refurbish highly activated components. The cryogenic target positioner is an example where activation and ease of component replacement is an important part of the design. We are developing a design process for all target-bay systems that will assure reliable operation for the full range of planned yields.

  14. Synthesis and characterization of an MRI Gd-based probe designed to target the translocator protein

    International Nuclear Information System (INIS)

    Cerutti, Erika; Aime, Silvio; Damont, Annelaure; Dolle, Frederic; Baroni, Simona

    2013-01-01

    DPA-713 is the lead compound of a recently reported pyrazolo[1,5-a]pyrimidine acetamide series, targeting the translocator protein (TSPO 18 kDa), and as such, this structure, as well as closely related derivatives, have been already successfully used as positron emission tomography radioligands. On the basis of the pharmacological core of this ligands series, a new magnetic resonance imaging probe, coded DPA-C6-(Gd)DOTAMA was designed and successfully synthesized in six steps and 13% overall yield from DPA-713. The Gd-DOTA monoamide cage (DOTA = 1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid) represents the magnetic resonance imaging reporter, which is spaced from the phenyl-pyrazolo[1,5-a]pyrimidine acetamide moiety (DPA-713 motif) by a six carbon-atom chain. DPA-C6-(Gd)DOTAMA relaxometric characterization showed the typical behavior of a small-sized molecule (relaxivity value: 6.02 mM -1 s -1 at 20 MHz). The good hydrophilicity of the metal chelate makes DPAC6-(Gd)DOTAMA soluble in water, affecting thus its biodistribution with respect to the parent lipophilic DPA-713 molecule. For this reason, it was deemed of interest to load the probe to a large carrier in order to increase its residence lifetime in blood. Whereas DPA-C6-(Gd)DOTAMA binds to serum albumin with a low affinity constant, it can be entrapped into liposomes (both in the membrane and in the inner aqueous cavity). The stability of the supramolecular adduct formed by the Gd-complex and liposomes was assessed by a competition test with albumin. (authors)

  15. Assessment of a pay-for-performance program in primary care designed by target users.

    Science.gov (United States)

    Kirschner, Kirsten; Braspenning, Jozé; Akkermans, Reinier P; Jacobs, J E Annelies; Grol, Richard

    2013-04-01

    Evidence for pay-for-performance (P4P) has been searched for in the last decade as financial incentives increased to influence behaviour of health care professionals to improve quality of care. The effectiveness of P4P is inconclusive, though some reviews reported significant effects. To assess changes in performance after introducing a participatory P4P program. An observational study with a pre- and post-measurement. Setting and subjects. Sixty-five general practices in the south of the Netherlands. Intervention. A P4P program designed by target users containing indicators for chronic care, prevention, practice management and patient experience (general practitioner's [GP] functioning and organization of care). Quality indicators were calculated for each practice. A bonus with a maximum of 6890 Euros per 1000 patients was determined by comparing practice performance with a benchmark. Quality indicators for clinical care (process and outcome) and patient experience. We included 60 practices. After 1 year, significant improvement was shown for the process indicators for all chronic conditions ranging from +7.9% improvement for cardiovascular risk management to +11.5% for asthma. Five outcome indicators significantly improved as well as patients' experiences with GP's functioning and organization of care. No significant improvements were seen for influenza vaccination rate and the cervical cancer screening uptake. The clinical process and outcome indicators, as well as patient experience indicators were affected by baseline measures. Smaller practices showed more improvement. A participatory P4P program might stimulate quality improvement in clinical care and improve patient experiences with GP's functioning and the organization of care.

  16. In Silico Design and Experimental Validation of siRNAs Targeting Conserved Regions of Multiple Hepatitis C Virus Genotypes.

    Directory of Open Access Journals (Sweden)

    Mahmoud ElHefnawi

    Full Text Available RNA interference (RNAi is a post-transcriptional gene silencing mechanism that mediates the sequence-specific degradation of targeted RNA and thus provides a tremendous opportunity for development of oligonucleotide-based drugs. Here, we report on the design and validation of small interfering RNAs (siRNAs targeting highly conserved regions of the hepatitis C virus (HCV genome. To aim for therapeutic applications by optimizing the RNAi efficacy and reducing potential side effects, we considered different factors such as target RNA variations, thermodynamics and accessibility of the siRNA and target RNA, and off-target effects. This aim was achieved using an in silico design and selection protocol complemented by an automated MysiRNA-Designer pipeline. The protocol included the design and filtration of siRNAs targeting highly conserved and accessible regions within the HCV internal ribosome entry site, and adjacent core sequences of the viral genome with high-ranking efficacy scores. Off-target analysis excluded siRNAs with potential binding to human mRNAs. Under this strict selection process, two siRNAs (HCV353 and HCV258 were selected based on their predicted high specificity and potency. These siRNAs were tested for antiviral efficacy in HCV genotype 1 and 2 replicon cell lines. Both in silico-designed siRNAs efficiently inhibited HCV RNA replication, even at low concentrations and for short exposure times (24h; they also exceeded the antiviral potencies of reference siRNAs targeting HCV. Furthermore, HCV353 and HCV258 siRNAs also inhibited replication of patient-derived HCV genotype 4 isolates in infected Huh-7 cells. Prolonged treatment of HCV replicon cells with HCV353 did not result in the appearance of escape mutant viruses. Taken together, these results reveal the accuracy and strength of our integrated siRNA design and selection protocols. These protocols could be used to design highly potent and specific RNAi-based therapeutic

  17. STRUCTURAL DESIGN CRITERIA FOR TARGET/BLANKET SYSTEM COMPONENT MATERIALS FOR THE ACCELERATOR PRODUCTION OF TRITIUM PROJECT

    Energy Technology Data Exchange (ETDEWEB)

    W. JOHNSON; R. RYDER; P. RITTENHOUSE

    2001-01-01

    The design of target/blanket system components for the Accelerator Production of Tritium (APT) plant is dependent on the development of materials properties data specified by the designer. These data are needed to verify that component designs are adequate. The adequacy of the data will be related to safety, performance, and economic considerations, and to other requirements that may be deemed necessary by customers and regulatory bodies. The data required may already be in existence, as in the open technical literature, or may need to be generated, as is often the case for the design of new systems operating under relatively unique conditions. The designers' starting point for design data needs is generally some form of design criteria used in conjunction with a specified set of loading conditions and associated performance requirements. Most criteria are aimed at verifying the structural adequacy of the component, and often take the form of national or international standards such as the ASME Boiler and Pressure Vessel Code (ASME B and PV Code) or the French Nuclear Structural Requirements (RCC-MR). Whether or not there are specific design data needs associated with the use of these design criteria will largely depend on the uniqueness of the conditions of operation of the component. A component designed in accordance with the ASME B and PV Code, where no unusual environmental conditions exist, will utilize well-documented, statistically-evaluated developed in conjunction with the Code, and will not be likely to have any design data needs. On the other hand, a component to be designed to operate under unique APT conditions, is likely to have significant design data needs. Such a component is also likely to require special design criteria for verification of its structural adequacy, specifically accounting for changes in materials properties which may occur during exposure in the service environment. In such a situation it is common for the design criteria

  18. The impact of applying different metrics in target definitions : lessons for policy design

    NARCIS (Netherlands)

    Harmsen, Robert

    2016-01-01

    The objective of this paper is to analyse the impact of the use of different metrics in the EU renewable energy target definition. The analysis, using a case study of the Dutch renewable energy support for illustration, reveals that a target based on primary energy would have led to a ranking in

  19. Design study and heat transfer analysis of a neutron converter target for medical radioisotope production

    International Nuclear Information System (INIS)

    Masoud Behzad; Sang-In Bak; Seung-Woo Hong; Jong-Seo Chai; Yacine Kadi; Claudio Tenreiro; University of Talca, Talca

    2014-01-01

    A worldwide challenge in the near future will be to find a way of producing radioisotopes in sufficient quantity without relying on research reactors. The motivation for this innovative work on targets lies in the accelerator-based production of radioisotopes using a neutron converter target as in the transmutation by adiabatic resonance crossing concept. Thermal analysis of a multi-channel helium cooled device is performed with the computational fluid dynamics code CFX. Different boundary conditions are taken into account in the simulation process and many important parameters such as maximum allowable solid target temperature as well as uniform inlet velocity and outlet pressure changes in the channels are investigated. The results confirm that the cooling configuration works well; hence such a solid target could be operated safely and may be considered for a prototype target. (author)

  20. Design study on large-scale mercury loop for engineering test of target of high-intensity proton accelerator

    International Nuclear Information System (INIS)

    Hino, Ryutaro; Haga, Katsuhiro; Aita, Hideki; Sekita, Kenji; Sudo, Yukio; Koiso, Kohji; Kaminaga, Masanori; Takahashi, Hiromichi.

    1997-03-01

    A heavy liquid-metal target has been proposed as a representative target of a 5MW-scale neutron source for a neutron scattering facility coupled with a high-intensity proton accelerator. In the report, about mercury considered to be the best material of the heavy liquid-metal target, its properties needed for the design were formulated, and results of research on mercury treatment and of evaluation of heat removal performance on the basis of generating heat obtained by a numerical calculation of a spallation reaction were presented. From these results, a 1.5MW-scale mercury loop which equals to that for the first stage operation of the neutron science program of JAERI was designed conceptually for obtaining design data of the mercury target, and basic flow diagram of the loop and specifications of components were decided: diameter of pipelines flowing mercury at the velocity below 1m/s, power of an electro-magnet pump and structure of a cooler. Through the design, engineering problems were made clear such as selection and development of mercury-resistant materials and optimization of the loop and components for decreasing mercury inventory. (author)

  1. Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases.

    Science.gov (United States)

    Sarafianos, Stefan G; Das, Kalyan; Hughes, Stephen H; Arnold, Eddy

    2004-12-01

    HIV undergoes rapid genetic variation; this variation is caused primarily by the enormous number of viruses produced daily in an infected individual. Because of this variation, HIV presents a moving target for drug and vaccine development. The variation within individuals has led to the generation of diverse HIV-1 subtypes, which further complicates the development of effective drugs and vaccines. In general, it is more difficult to hit a moving target than a stationary target. Two broad strategies for hitting a moving target (in this case, HIV replication) are to understand the movement and to aim at the portions that move the least. In the case of anti-HIV drug development, the first option can be addressed by understanding the mechanism(s) of drug resistance and developing drugs that effectively inhibit mutant viruses. The second can be addressed by designing drugs that interact with portions of the viral machinery that are evolutionarily conserved, such as enzyme active sites.

  2. Long-rod projectiles against oblique targets: analysis and design recommendations

    International Nuclear Information System (INIS)

    Norris, D.M.; McMaster, W.H.; Wilkins, M.L.

    1976-01-01

    Computer calculations provide an understanding of impact phenomena associated with long rod penetrators striking targets at oblique angles. The rod and target material behaviors are described by elastic-plastic work-hardening constitutive models. Ductile fracture is simulated by setting all tensile and shear stresses to zero when the calculated plastic deformation reaches a critical value. The important penetration material properties to defeat a given target are identified. There is no single material property of overriding importance; a combination of properties is required for an efficient penetrator. Experimental results are presented to demonstrate the effects of ductility and toughness on penetration performance. Recommendations for possible improvement are suggested

  3. Conceptual design of a 10-MJ driver for a high gain target development facility

    International Nuclear Information System (INIS)

    Olson, R.E.

    1987-01-01

    Commercial application of inertial confinement fusion (ICF) will require inexpensive, high gain (>80) fusion targets. It is thought that the development of such targets will require a 5 to 10 year search effort utilizing a dedicated nuclear research facility with a driver capable of providing a 10 MJ, 300 to 1000 TW pulse of on-target energy. The Terget Development Facility (TDF) is a light ion driven concept for such a facility. A TDF driver based upon extrapolations from present-day pulsed power technology is described in the present paper

  4. Atomic Beam Merging and Suppression of Alkali Contaminants in Multi Body High Power Targets: Design and Test of Target and Ion Source Prototypes at ISOLDE

    CERN Document Server

    Bouquerel, Elian J A; Lettry, J; Stora, T

    2009-01-01

    The next generation of high power ISOL-facilities will deliver intense and pure radioactive ion beams. Two key issues of developments mandatory for the forthcoming generation of ISOL target-ion source units are assessed and demonstrated in this thesis. The design and production of target and ion-source prototypes is described and dedicated measurements at ISOLDE-CERN of their radioisotope yields are analyzed. The purity of short lived or rare radioisotopes suffer from isobaric contaminants, notably alkalis which are highly volatile and easily ionized elements. Therefore, relying on their chemical nature, temperature controlled transfer lines were equipped with a tube of quartz that aimed at trapping these unwanted elements before they reached the ion source. The successful application yields high alkali-suppression factors for several elements (ie: 80, 82mRb, 126, 142Cs, 8Li, 46K, 25Na, 114In, 77Ga, 95, 96Sr) for quartz temperatures between 300ºC and 1100ºC. The enthalpies of adsorption on quartz were measu...

  5. Structure-based drug design approach to target toll-like receptor ...

    African Journals Online (AJOL)

    TLRs are now viewed as potential therapeutic targets in the treatment of autoimmune diseases. This ... Vascular endothelial growth factor. NMR .... induces the release of tumor necrosis factor ... Alternative anticancer drugs called CpG-based.

  6. Progress towards a high-gain and robust target design for heavy ion fusion

    Energy Technology Data Exchange (ETDEWEB)

    Henestroza, Enrique; Grant Logan, B. [Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

    2012-07-15

    Recently [E. Henestroza et al., Phys. Plasmas 18, 032702 (2011)], a new inertial-fusion target configuration, the X-target, using one-sided axial illumination has been explored. This class of target uses annular and solid-profile heavy ion beams to compress and ignite deuterium-tritium (DT) fuel that fills the interior of metal cases that have side-view cross sections in the shape of an 'X.' X-targets using all-DT-filled metal cases imploded by three annular ion beams resulted in fuel densities of {approx}50 g/cm{sup 3} at peak compression, and fusion gains of {approx}50, comparable to heavy ion driven hohlraum targets [D. A. Callahan-Miller and M. Tabak, Phys. Plasmas 7, 2083 (2000)]. This paper discusses updated X-target configurations that incorporate inside the case a propellant (plastic) and a pusher (aluminum) surrounding the DT fuel. The updated configurations are capable of assembling higher fuel areal densities {approx}2 g/cm{sup 2} using two annular beams to implode the target to peak DT densities {approx}100 g/cm{sup 3}, followed by a fast-ignition solid ion beam which heats the high-density fuel to thermonuclear temperatures in {approx}200 ps to start the burn propagation, obtaining gains of {approx}300. These targets have been modeled using the radiation-hydrodynamics code HYDRA [M. M. Marinak et al., Phys. Plasmas 8, 2275 (2001)] in two- and three- dimensions to study the properties of the implosion as well as the ignition and burn propagation phases. At typical Eulerian mesh resolutions of a few microns, the aluminum-DT interface shows negligible Rayleigh-Taylor (RT) and Richtmyer-Meshkov instability growth; also, the shear flow of the DT fuel as it slides along the metal X-target walls, which drives the RT and Kelvin Helmholtz instabilities, does not have a major effect on the burning rate. An analytic estimate of the RT instability process at the Al-DT interface shows that the aluminum spikes generated during the pusher deceleration phase

  7. Update on design simulations for NIF ignition targets, and the roll-up of all specifications into an error budget

    International Nuclear Information System (INIS)

    Haan, S.W.; Herrmann, M.C.; Salmonson, J.D.; Amendt, P.A.; Callahan, D.A.; Dittrich, T.R.; Edwards, M.J.; Jones, O.S.; Marinak, M.M.; Munro, D.H.; Pollaine, S.M.; Spears, B.K.; Suter, L.J.

    2007-01-01

    Targets intended to produce ignition on NIF are being simulated and the simulations are used to set specifications for target fabrication and other program elements. Recent design work has focused on designs that assume only 1.0 MJ of laser energy instead of the previous 1.6 MJ. To perform with less laser energy, the hohlraum has been redesigned to be more efficient than previously, and the capsules are slightly smaller. Three hohlraum designs are being examined: gas fill, SiO 2 foam fill, and SiO 2 lined. All have a cocktail wall, and shields mounted between the capsule and the laser entrance holes. Two capsule designs are being considered. One has a graded doped Be(Cu) ablator, and the other graded doped CH(Ge). Both can perform acceptably with recently demonstrated ice layer quality, and with recently demonstrated outer surface roughness. Complete tables of specifications are being prepared for both targets, to be completed this fiscal year. All the specifications are being rolled together into an error budget indicating adequate margin for ignition with the new designs. The dominant source of error is hohlraum asymmetry at intermediate modes 4-8, indicating the importance of experimental techniques to measure and control this asymmetry. (authors)

  8. Exploring the Trypanosoma brucei Hsp83 potential as a target for structure guided drug design.

    Directory of Open Access Journals (Sweden)

    Juan Carlos Pizarro

    Full Text Available Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs--whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp, while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83--a homolog of human Hsp90--as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF. Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite.

  9. A Bombesin-Shepherdin Radioconjugate Designed for Combined Extra- and Intracellular Targeting

    Directory of Open Access Journals (Sweden)

    Christiane A. Fischer

    2014-05-01

    Full Text Available Radiolabeled peptides which target tumor-specific membrane structures of cancer cells represent a promising class of targeted radiopharmaceuticals for the diagnosis and therapy of cancer. A potential drawback of a number of reported radiopeptides is the rapid washout of a substantial fraction of the initially delivered radioactivity from cancer cells and tumors. This renders the initial targeting effort in part futile and results in a lower imaging quality and efficacy of the radiotracer than achievable. We are investigating the combination of internalizing radiopeptides with molecular entities specific for an intracellular target. By enabling intracellular interactions of the radioconjugate, we aim at reducing/decelerating the externalization of radioactivity from cancer cells. Using the “click-to-chelate” approach, the 99mTc-tricarbonyl core as a reporter probe for single-photon emission computed tomography (SPECT was combined with the binding sequence of bombesin for extracellular targeting of the gastrin-releasing peptide receptor (GRP-r and peptidic inhibitors of the cytosolic heat shock 90 protein (Hsp90 for intracellular targeting. Receptor-specific uptake of the multifunctional radioconjugate could be confirmed, however, the cellular washout of radioactivity was not improved. We assume that either endosomal trapping or lysosomal degradation of the radioconjugate is accountable for these observations.

  10. Comprehensive Needs Assessment Study and Deployment of QFD Targeted at New Wheelchair Design

    Directory of Open Access Journals (Sweden)

    Sumit Desai

    2017-11-01

    Discussion: The results of this study are useful in understanding the perspective of Indian wheelchair users’ needs toward evidence-based wheelchair design. The design parameters with high absolute and relative technical importance can be selected to design new wheelchairs for Indian users in order to enhance the quality of life, comfort, and safety of people with disability.

  11. Targeting Allostery with Avatars to Design Inhibitors Assessed by Cell Activity: Dissecting MRE11 Endo- and Exonuclease Activities.

    Science.gov (United States)

    Moiani, Davide; Ronato, Daryl A; Brosey, Chris A; Arvai, Andrew S; Syed, Aleem; Masson, Jean-Yves; Petricci, Elena; Tainer, John A

    2018-01-01

    For inhibitor design, as in most research, the best system is question dependent. We suggest structurally defined allostery to design specific inhibitors that target regions beyond active sites. We choose systems allowing efficient quality structures with conformational changes as optimal for structure-based design to optimize inhibitors. We maintain that evolutionarily related targets logically provide molecular avatars, where this Sanskrit term for descent includes ideas of functional relationships and of being a physical embodiment of the target's essential features without requiring high sequence identity. Appropriate biochemical and cell assays provide quantitative measurements, and for biomedical impacts, any inhibitor's activity should be validated in human cells. Specificity is effectively shown empirically by testing if mutations blocking target activity remove cellular inhibitor impact. We propose this approach to be superior to experiments testing for lack of cross-reactivity among possible related enzymes, which is a challenging negative experiment. As an exemplary avatar system for protein and DNA allosteric conformational controls, we focus here on developing separation-of-function inhibitors for meiotic recombination 11 nuclease activities. This was achieved not by targeting the active site but rather by geometrically impacting loop motifs analogously to ribosome antibiotics. These loops are neighboring the dimer interface and active site act in sculpting dsDNA and ssDNA into catalytically competent complexes. One of our design constraints is to preserve DNA substrate binding to geometrically block competing enzymes and pathways from the damaged site. We validate our allosteric approach to controlling outcomes in human cells by reversing the radiation sensitivity and genomic instability in BRCA mutant cells. © 2018 Elsevier Inc. All rights reserved.

  12. Thermal-hydraulic design of cross-flow type mercury target for JAERI/KEK joint project

    International Nuclear Information System (INIS)

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

    2001-01-01

    The Japan Atomic Energy Research Institute (JAERI) and the High Energy Accelerator Research Organization (KEK) are promoting a plan to construct a neutron scattering facility. In the facility, 1 MW pulsed proton beam from a high-intensity proton accelerator will be injected into a mercury target in order to produce high-intensity neutrons for use in the fields of life and material sciences. In the spallation mercury target system design, an integrated structure of target vessel with a safety hull was proposed to ensure the safety and to collect mercury in case of mercury leakage caused by the target beam window failure. The inner structure arrangement of the mercury target vessel was determined based on the thermal hydraulic analytical results of 3 GeV, 1 MW proton beam injection. The safety hull consists of vessels for helium and heavy water. The vessels for mercury target, helium and heavy water will be connected each other by reinforcement ribs mounted on the surface of each vessel. From the structural analyses, the structural integrity of the safety hull would be maintained under the static pressure of 0.5 MPa. (author)

  13. Requirements for design of accelerator, beam transport, and target in a study of thermonuclear reaction cross section

    Energy Technology Data Exchange (ETDEWEB)

    Itahashi, T.; Takahisa, K.; Ohsumi, H.; Komori, M.; Fujiwara, M.; Toki, H. [Osaka Univ., Suita (Japan)

    1997-02-01

    The process of pp-de{sup +}{nu} is the basic fusion reaction for hydrogen burning in the sun and the prime reaction in chain producing photons and neutrinos. There are many works of the theoretical estimation of the reaction rate in the reaction chain in the sun. The precise measurement of the nutrinos from the sun is one of the most important current physics issues. The rate of the pp-de{sup +}{nu} is too small to be measured in laboratories. The construction of a compact ion accelerator facility with high current, low energy transport and plasma target is planned at the underground laboratory in Otoh Cosmo Observatory of Research Center for Nuclear Physics. The plasma target by using the EBIS type synthesized plasma was proposed as a bare {sup 3}He target. The production of helium ions of each charge state was tested by using the present NEOMAFIOS ECR ion source, and the obtained current is shown. For noncontaminated, high current beam transport, the strong focusing system was introduced. The design of windowless gas target, plasma target, the detection of the energetic reaction particles of protons, digital calorimeter, the couple of ECR ion source and plasma target, and the underground laboratory are reported. (K.I.)

  14. Rational Design of Multifunctional Gold Nanoparticles via Host-Guest Interaction for Cancer-Targeted Therapy.

    Science.gov (United States)

    Chen, Wei-Hai; Lei, Qi; Luo, Guo-Feng; Jia, Hui-Zhen; Hong, Sheng; Liu, Yu-Xin; Cheng, Yin-Jia; Zhang, Xian-Zheng

    2015-08-12

    A versatile gold nanoparticle-based multifunctional nanocomposite AuNP@CD-AD-DOX/RGD was constructed flexibly via host-guest interaction for targeted cancer chemotherapy. The pH-sensitive anticancer prodrug AD-Hyd-DOX and the cancer-targeted peptide AD-PEG8-GRGDS were modified on the surface of AuNP@CD simultaneously, which endowed the resultant nanocomposite with the capability to selectively eliminate cancer cells. In vitro studies indicated that the AuNP@CD-AD-DOX/RGD nanocomposite was preferentially uptaken by cancer cells via receptor-mediated endocytosis. Subsequently, anticancer drug DOX was released rapidly upon the intracellular trigger of the acid microenvirenment of endo/lysosomes, inducing apoptosis in cancer cells. As the ideal drug nanocarrier, the multifunctional gold nanoparticles with the active targeting and controllable intracellular release ability hold the great potential in cancer therapy.

  15. A role for fragment-based drug design in developing novel lead compounds for central nervous system targets

    Directory of Open Access Journals (Sweden)

    Michael J. Wasko

    2015-09-01

    Full Text Available Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacologic screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening, which employs computer models of the target protein to narrow the search for possible leads. A variant of virtual screening is fragment-based drug design, an emerging in silico lead discovery method that introduces low molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for growing the lead candidate. Current efforts in virtual fragment-based drug design within central nervous system (CNS targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor binding pocket using the fragment as a scaffold. This process places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

  16. Approaches in the design of 99mTc based peptide radiolabelling for tumour targeting

    International Nuclear Information System (INIS)

    Yokoyama, A.; Horiuchi, K.; Arano, Y.

    2001-01-01

    . Neogalactoalbumin (NGA), a specific protein that was incorporated by hepatic parenchymal cell via receptor-mediated endocytosis immediately after administration, was selected as a biological tool. The fate of the radiolabelled NGA after lysosomal proteolysis in hepatocytes was studied in liver homogenates. Subcellular distribution and identification of radiometabolites were performed using multiple analytical methods such as electrophoresis, TLC, and size exclusion and reverse phase HPLC. The data indicated that the chemical bonding between 99m Tc and HYNIC remains stable in the lysosomes but the persistent liver localization was due to a radiometabolite identified as 99m Tc-HYNIC-lysine (tricine)2, demonstrated by the similar HPLC data obtained with the synthesized and radiolabelled metabolite. Better co-ligands or new ligands or new design of the peptides are required in order to reduce the residence time of radioactivity in non-target tissue for future peptide use in radiodiagnosis or radiotherapy. (author)

  17. Design of effective energy efficiency policies. An analysis in the frame of target setting, monitoring and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Schlomann, Barbara

    2014-07-01

    Energy efficiency is widely acknowledged as the most important strategy for achieving global energy and climate targets. Apart from its contribution to the reduction of energy consumption and energy-related greenhouse gas emissions (GHG), improving energy efficiency can deliver a range of co-benefits to the economy and society. There are, however, indications that energy efficiency policy is still insufficiently anchored both in the EU and many Member States as well as at an international level. This thesis focuses on the question how to create more favourable preconditions for an effective anchoring of energy efficiency policy in energy and climate policy. The design of energy efficiency policies is analyzed in the frame of the setting of energy efficiency targets and the monitoring and evaluation of their success. This provides new insights in the functioning of policies and hence their improvement in view of target achievement.

  18. Design, development and characterization of multi-functionalized gold nanoparticles for biodetection and targeted boron delivery in BNCT applications

    Energy Technology Data Exchange (ETDEWEB)

    Mandal, Subhra [Department of Tumor Immunology, Radboud University Nijmegen Medical Centre (Netherlands); Bakeine, Gerald J., E-mail: Jamesbakeine1@yahoo.com [Department of Internal Medicine and Therapeutics-Section of Clinical Toxicology, University of Pavia, Piazza Botta 10, 27100 Pavia (Italy); Krol, Silke [Institute of Neurology, Fondazione IRCCS Carlo Besta, Milan (Italy); Ferrari, Cinzia; Clerici, Anna M.; Zonta, Cecilia; Cansolino, Laura [Department of Surgery, Laboratory of Experimental Surgery, University of Pavia (Italy); Ballarini, Francesca [Department of Nuclear and Theoretical Physics, University of Pavia (Italy); Bortolussi, Silva [Department of Nuclear and Theoretical Physics, University of Pavia (Italy)] [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy); Stella, Subrina; Protti, Nicoletta [Department of Nuclear and Theoretical Physics, University of Pavia (Italy); Bruschi, Piero [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy); Altieri, Saverio [Department of Nuclear and Theoretical Physics, University of Pavia (Italy)] [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy)

    2011-12-15

    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 coated with multilayers of polyelectrolytes functionalized with the fluorescent dye (FITC), boronophenylalanine and folic acid. In vitro confocal fluorescence microscopy demonstrated significant uptake of the nanoparticles in cancer cells that are known to overexpress folate receptors. - Highlights: Black-Right-Pointing-Pointer Synthesis of multi-labeled gold nanoparticles for selective boron delivery to tumor cells. Black-Right-Pointing-Pointer Tumor selectivity is achieved through folic acid receptor targeting. Black-Right-Pointing-Pointer Optical fluorescent microscopy allows tracking of cellular uptake of the gold nanoparticle. Black-Right-Pointing-Pointer In vitro tests demonstrate selective nanoparticle up in folate receptor positive tumor cells.

  19. Requirements for design of accelerator, beam transport, and target in a study of thermonuclear reaction cross section

    Energy Technology Data Exchange (ETDEWEB)

    Itahashi, T; Takahisa, K; Fujiwara, M; Toki, H; Ejiri, H [Osaka Univ., Ibaraki (Japan). Research Center for Nuclear Physics; Ohsumi, H; Komori, M

    1997-03-01

    A compact accelerator with high current ion source, low energy beam transport elements and windowless gas target was designed to investigate the thermonuclear reaction cross section. The idea of this project focused on the cross section measurement of the fusion reaction data {sup 3}He+{sup 3}He-{sup 4}He+p+p at 25keV. The system will be installed in Otoh Cosmo Observatory (1270m.w.e.) to get rid of the huge cosmic and environmental background. It consists of NANOGUN ECR ion source, focusing elements made of permanent magnets window less {sup 3}He gas target and/or He{sup 3} plasma target and detector telescopes with low noise and low background. Requirements for these were discussed technically and various ideas were proposed. (author)

  20. Computational design and application of endogenous promoters for transcriptionally targeted gene therapy for rheumatoid arthritis.

    NARCIS (Netherlands)

    Geurts, J.; Joosten, L.A.B.; Takahashi, N.; Arntz, O.J.; Gluck, A.; Bennink, M.B.; Berg, W.B. van den; Loo, F.A.J. van de

    2009-01-01

    The promoter regions of genes that are differentially regulated in the synovial membrane during the course of rheumatoid arthritis (RA) represent attractive candidates for application in transcriptionally targeted gene therapy. In this study, we applied an unbiased computational approach to define

  1. Proteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Bálint Mészáros

    2011-07-01

    Full Text Available Lengthy co-evolution of Homo sapiens and Mycobacterium tuberculosis, the main causative agent of tuberculosis, resulted in a dramatically successful pathogen species that presents considerable challenge for modern medicine. The continuous and ever increasing appearance of multi-drug resistant mycobacteria necessitates the identification of novel drug targets and drugs with new mechanisms of action. However, further insights are needed to establish automated protocols for target selection based on the available complete genome sequences. In the present study, we perform complete proteome level comparisons between M. tuberculosis, mycobacteria, other prokaryotes and available eukaryotes based on protein domains, local sequence similarities and protein disorder. We show that the enrichment of certain domains in the genome can indicate an important function specific to M. tuberculosis. We identified two families, termed pkn and PE/PPE that stand out in this respect. The common property of these two protein families is a complex domain organization that combines species-specific regions, commonly occurring domains and disordered segments. Besides highlighting promising novel drug target candidates in M. tuberculosis, the presented analysis can also be viewed as a general protocol to identify proteins involved in species-specific functions in a given organism. We conclude that target selection protocols should be extended to include proteins with complex domain architectures instead of focusing on sequentially unique and essential proteins only.

  2. Design and development of a magnetic device for mesenchymal stem cell retaining in deep targets

    Science.gov (United States)

    Banis, G. C.

    2017-12-01

    This paper focuses on the retaining of mesenchymal stem cells in blood flow conditions using the appropriate magnetic field. Mesenchymal stem cells can be tagged with magnetic nanoparticles and thus, they can be manipulated from distance, through the application of an external magnetic field. In this paper the case of kidney as target of the therapy is being studied.

  3. Implosion physics, alternative targets design and neutron effects on inertial fusion systems

    International Nuclear Information System (INIS)

    Velarde, G.; Martinez-Val, J.M.; Perlado, J.M.

    2001-01-01

    A new radiation transport code has been coupled with an existing multimaterial fluidynamics code using Adaptive Mesh Refinement (AMR) and its testing is presented, solving ray effect and shadow problems in SN classical methods. Important advances in atomic physics, opacity calculations and NLTE calculations, participating in significant experiments (LULI/France), have been obtained. Our new 1D target simulation model allows considering the effect of inverse Compton scattering in DT x targets (x<3%) working in a catalytic regime, showing the effectiveness of such tritium-less targets. Neutron activation of all natural elements in IFE reactors for waste management and that of target debris in NIF-type facilities have been completed. Pulse activation in structural walls is presented with a new modeling. Tritium atmospheric dispersion results indicate large uncertainties in environmental responses and needs to treat the two chemical forms. We recognise recombination barriers (metastable defects) and compute first systematic high-energy displacement cascade analysis in SiC, and radiation damage pulses by atomistic models in metals. Using Molecular Dynamics we explain the experimental evidence of low-temperature amorphization by damage accumulation in SiC. (author)

  4. The DESI Experiment Part I: Science,Targeting, and Survey Design

    Energy Technology Data Exchange (ETDEWEB)

    Aghamousa, Amir; et al.

    2016-10-31

    DESI (Dark Energy Spectroscopic Instrument) is a Stage IV ground-based dark energy experiment that will study baryon acoustic oscillations (BAO) and the growth of structure through redshift-space distortions with a wide-area galaxy and quasar redshift survey. To trace the underlying dark matter distribution, spectroscopic targets will be selected in four classes from imaging data. We will measure luminous red galaxies up to $z=1.0$. To probe the Universe out to even higher redshift, DESI will target bright [O II] emission line galaxies up to $z=1.7$. Quasars will be targeted both as direct tracers of the underlying dark matter distribution and, at higher redshifts ($ 2.1 < z < 3.5$), for the Ly-$\\alpha$ forest absorption features in their spectra, which will be used to trace the distribution of neutral hydrogen. When moonlight prevents efficient observations of the faint targets of the baseline survey, DESI will conduct a magnitude-limited Bright Galaxy Survey comprising approximately 10 million galaxies with a median $z\\approx 0.2$. In total, more than 30 million galaxy and quasar redshifts will be obtained to measure the BAO feature and determine the matter power spectrum, including redshift space distortions.

  5. Hohlraum Target Alignment from X-ray Detector Images using Starburst Design Patterns

    International Nuclear Information System (INIS)

    Leach, R.R.; Conder, A.; Edwards, O.; Kroll, J.; Kozioziemski, B.; Mapoles, E.; McGuigan, D.; Wilhelmsen, K.

    2010-01-01

    National Ignition Facility (NIF) is a high-energy laser facility comprised of 192 laser beams focused with enough power and precision on a hydrogen-filled spherical, cryogenic target to initiate a fusion reaction. The target container, or hohlraum, must be accurately aligned to an x-ray imaging system to allow careful monitoring of the frozen fuel layer in the target. To achieve alignment, x-ray images are acquired through starburst-shaped windows cut into opposite sides of the hohlraum. When the hohlraum is in alignment, the starburst pattern pairs match nearly exactly and allow a clear view of the ice layer formation on the edge of the target capsule. During the alignment process, x-ray image analysis is applied to determine the direction and magnitude of adjustment required. X-ray detector and source are moved in concert during the alignment process. The automated pointing alignment system described here is both accurate and efficient. In this paper, we describe the control and associated image processing that enables automation of the starburst pointing alignment.

  6. The preparation and composition design of boron-rich lanthanum hexaboride target for sputtering

    International Nuclear Information System (INIS)

    Chen, Defang; Min, Guanghui; Wu, Yan; Yu, Huashun; Zhang, Lin

    2015-01-01

    Highlights: • High-purity LaB 6 powder was prepared due to significant reduction of residual B 4 C and effective purification process. • The effects of raw materials ratio on the size, morphology, phase structure and crystalline size of LaB 6 were studied. • The correlation of component between LaB 6 films and boron-rich targets was established. • The variation of densities of LaB 6 targets with sintering time and sintering temperature was investigated. - Abstract: Lanthanum Hexaboride (LaB 6 ) nano-film has been proved to be promising transparent thermal insulation material, while its properties are limited on purity and composition. High-purity LaB 6 polycrystalline powder was prepared through boron carbide reduction method in this work. A series of techniques such as scanning electron microscopy, X-ray diffraction, laser particle analyzer and inductively coupled plasma emission spectrometer were employed to characterize LaB 6 powder. As raising the content of La 2 O 3 in reactants, more uniform, finer (2.686 μm) and purer (99.5139 wt%) LaB 6 powder is prepared, with only 0.4434 wt% residual B 4 C. The density of targets increases with the rise of sintering temperature and the extension of sintering time, while crystallite size increases simultaneously with the extension of sintering time. The introduction of B powder in target is conductive to sintering process, increasing hardness and flexural strength of targets. X-ray photoelectron spectrometer was used to characterize the composition and microstructure of LaB 6 nano-film which is tentatively considered to be composed of LaB 6 nanocrystalline and amorphous microstructure of La and B atoms. The film LaB 6.0627±0.02 was obtained when the ratio of B and La of sputtering target reached 12.5. The thickness and deposition rate decrease with the increase of B content in targets

  7. Optimizations of siRNA design for the activation of gene transcription by targeting the TATA-box motif.

    Directory of Open Access Journals (Sweden)

    Miaomiao Fan

    Full Text Available Small interfering RNAs (siRNAs are widely used to repress gene expression by targeting mRNAs. Some reports reveal that siRNAs can also activate or inhibit gene expression through targeting the gene promoters. Our group has found that microRNAs (miRNAs could activate gene transcription via interaction with the TATA-box motif in gene promoters. To investigate whether siRNA targeting the same region could upregulate the promoter activity, we test the activating efficiency of siRNAs targeting the TATA-box motif of 16 genes and perform a systematic analysis to identify the common features of the functional siRNAs for effective activation of gene promoters. Further, we try various modifications to improve the activating efficiency of siRNAs and find that it is quite useful to design the promoter-targeting activating siRNA by following several rules such as (a complementary to the TATA-box-centered region; (b UA usage at the first two bases of the antisense strand; (c twenty-three nucleotides (nts in length; (d 2'-O-Methyl (2'-OMe modification at the 3' terminus of the antisense strand; (e avoiding mismatches at the 3' end of the antisense strand. The optimized activating siRNAs potently enhance the expression of interleukin-2 (IL-2 gene in human and mouse primary CD4+ T cells with a long-time effect. Taken together, our study provides a guideline for rational design the promoter-targeting siRNA to sequence-specifically enhance gene expression.

  8. [sgRNA design for the CRISPR/Cas9 system and evaluation of its off-target effects].

    Science.gov (United States)

    Xie, Sheng-song; Zhang, Yi; Zhang, Li-sheng; Li, Guang-lei; Zhao, Chang-zhi; Ni, Pan; Zhao, Shu-hong

    2015-11-01

    The third generation of CRISPR/Cas9-mediated genome editing technology has been successfully applied to genome modification of various species including animals, plants and microorganisms. How to improve the efficiency of CRISPR/Cas9 genome editing and reduce its off-target effects has been extensively explored in this field. Using sgRNA (Small guide RNA) with high efficiency and specificity is one of the critical factors for successful genome editing. Several software have been developed for sgRNA design and/or off-target evaluation, which have advantages and disadvantages respectively. In this review, we summarize characters of 16 kinds online and standalone software for sgRNA design and/or off-target evaluation and conduct a comparative analysis of these different kinds of software through developing 38 evaluation indexes. We also summarize 11 experimental approaches for testing genome editing efficiency and off-target effects as well as how to screen highly efficient and specific sgRNA.

  9. Development of whole-building energy design targets for commercial buildings: Phase 1, Planning: Volume 2, Technical report

    Energy Technology Data Exchange (ETDEWEB)

    Crawley, D.B.; Briggs, R.S.; Jones, J.W.; Seaton, W.W.; Kaufman, J.E.; Deringer, J.J.; Kennett, E.W.

    1987-08-01

    This is the second volume of the Phase 1 report and discusses the 10 tasks performed in Phase 1. The objective of this research is to develop a methodology for setting energy design targets to provide voluntary guidelines for the buildings industry. The whole-building energy targets project is being conducted at the Pacific Northwest Laboratory (PNL) for the US Department of Energy (DOE) to encourage the construction of energy-efficient buildings by informing designers and owners about cost-effective goals for energy use in new commercial buildings. The outcome of this research will be a flexible methodology for setting such targets. The tasks are listed and discussed in this report as follows: Task 1 - Develop Detailed Project Goals and Objectives; Task 2 - Establish Buildings-Industry Liaison; Task 3 - Develop Approaches to the Energy Targets Model, Building Operations, and Climate; Task 4 - Develop an Approach for Treating Economic Considerations; Task 5 - Develop an Approach for Treating Energy Sources; Task 6 - Collect Energy-Use Data; Task 7 - Survey Energy Expert Opinion; Task 8 - Evaluation Procedure Specification and Integration; Task 9 - Phase 1 Report Development; and Task 10 - Phase 1 Review Planning.

  10. New "persona" concept helps site designers cater to target user segments' needs.

    Science.gov (United States)

    2004-09-01

    Using the relatively new "persona" design concept, Web strategists create a set of archetypical user characters, each one representing one of their site's primary audiences. Then, as their site is constructed or upgraded, they champion the personas, arguing on their behalf and forcing the design team to take each audience's needs and wants into account.

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

  12. Thick target benchmark test for the code used in the design of high intensity proton accelerator project

    International Nuclear Information System (INIS)

    Meigo, Shin-ichiro; Harada, Masatoshi

    2003-01-01

    In the neutronics design for the JAERI and KEK Joint high intensity accelerator facilities, transport codes of NMTC/JAM, MCNPX and MARS are used. In order to confirm the predict ability for these code, it is important to compare with the experiment result. For the validation of the source term of neutron, the calculations are compared with the experimental spectrum of neutrons produced from thick target, which are carried out at LANL and KEK. As for validation of low energy incident case, the calculations are compared with experiment carried out at LANL, in which target of C, Al, Fe, and 238 U are irradiated with 256-MeV protons. By the comparison, it is found that both NMTC/JAM and MCNPX show good agreement with the experiment within by a factor of 2. MARS shows good agreement for C and Al target. MARS, however, gives rather underestimation for all targets in the neutron energy region higher than 30 MeV. For the validation high incident energy case, the codes are compared with the experiment carried out at KEK. In this experiment, W and Pb targets are bombarded with 0.5- and 1.5-GeV protons. Although slightly disagreement exists, NMTC/JAM, MCNPX and MARS are in good agreement with the experiment within by a factor of 2. (author)

  13. Design, construction and performance evaluation of the target tissue thickness measurement system in intraoperative radiotherapy for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yazdani, Mohammad Reza, E-mail: myazdani@aut.ac.ir [Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Setayeshi, Saeed, E-mail: setayesh@aut.ac.ir [Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Arabalibeik, Hossein, E-mail: arabalibeik@tums.ac.ir [Research Center for Biomedical Technology and Robotics (RCBTR), Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Akbari, Mohammad Esmaeil [Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2017-05-21

    Intraoperative electron radiation therapy (IOERT), which uses electron beams for irradiating the target directly during the surgery, has the advantage of delivering a homogeneous dose to a controlled layer of tissue. Since the dose falls off quickly below the target thickness, the underlying normal tissues are spared. In selecting the appropriate electron energy, the accuracy of the target tissue thickness measurement is critical. In contrast to other procedures applied in IOERT, the routine measurement method is considered to be completely traditional and approximate. In this work, a novel mechanism is proposed for measuring the target tissue thickness with an acceptable level of accuracy. An electronic system has been designed and manufactured with the capability of measuring the tissue thickness based on the recorded electron density under the target. The results indicated the possibility of thickness measurement with a maximum error of 2 mm for 91.35% of data. Aside from system limitation in estimating the thickness of 5 mm phantom, for 88.94% of data, maximum error is 1 mm.

  14. Design of a novel integration-deficient lentivector technology that incorporates genetic and posttranslational elements to target human dendritic cells.

    Science.gov (United States)

    Tareen, Semih U; Kelley-Clarke, Brenna; Nicolai, Christopher J; Cassiano, Linda A; Nelson, Lisa T; Slough, Megan M; Vin, Chintan D; Odegard, Jared M; Sloan, Derek D; Van Hoeven, Neal; Allen, James M; Dubensky, Thomas W; Robbins, Scott H

    2014-03-01

    As sentinels of the immune system, dendritic cells (DCs) play an essential role in regulating cellular immune responses. One of the main challenges of developing DC-targeted therapies includes the delivery of antigen to DCs in order to promote the activation of antigen-specific effector CD8 T cells. With the goal of creating antigen-directed immunotherapeutics that can be safely administered directly to patients, Immune Design has developed a platform of novel integration-deficient lentiviral vectors that target and deliver antigen-encoding nucleic acids to human DCs. This platform, termed ID-VP02, utilizes a novel genetic variant of a Sindbis virus envelope glycoprotein with posttranslational carbohydrate modifications in combination with Vpx, a SIVmac viral accessory protein, to achieve efficient targeting and transduction of human DCs. In addition, ID-VP02 incorporates safety features in its design that include two redundant mechanisms to render ID-VP02 integration-deficient. Here, we describe the characteristics that allow ID-VP02 to specifically transduce human DCs, and the advances that ID-VP02 brings to conventional third-generation lentiviral vector design as well as demonstrate upstream production yields that will enable manufacturing feasibility studies to be conducted.

  15. Direct molecular mimicry enables off-target cardiovascular toxicity by an enhanced affinity TCR designed for cancer immunotherapy.

    Science.gov (United States)

    Raman, Marine C C; Rizkallah, Pierre J; Simmons, Ruth; Donnellan, Zoe; Dukes, Joseph; Bossi, Giovanna; Le Provost, Gabrielle S; Todorov, Penio; Baston, Emma; Hickman, Emma; Mahon, Tara; Hassan, Namir; Vuidepot, Annelise; Sami, Malkit; Cole, David K; Jakobsen, Bent K

    2016-01-13

    Natural T-cell responses generally lack the potency to eradicate cancer. Enhanced affinity T-cell receptors (TCRs) provide an ideal approach to target cancer cells, with emerging clinical data showing significant promise. Nevertheless, the risk of off target reactivity remains a key concern, as exemplified in a recent clinical report describing fatal cardiac toxicity, following administration of MAGE-A3 specific TCR-engineered T-cells, mediated through cross-reactivity with an unrelated epitope from the Titin protein presented on cardiac tissue. Here, we investigated the structural mechanism enabling TCR cross-recognition of MAGE-A3 and Titin, and applied the resulting data to rationally design mutants with improved antigen discrimination, providing a proof-of-concept strategy for altering the fine specificity of a TCR towards an intended target antigen. This study represents the first example of direct molecular mimicry leading to clinically relevant fatal toxicity, mediated by a modified enhanced affinity TCR designed for cancer immunotherapy. Furthermore, these data demonstrate that self-antigens that are expressed at high levels on healthy tissue should be treated with extreme caution when designing immuno-therapeutics.

  16. A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets.

    Science.gov (United States)

    Wasko, Michael J; Pellegrene, Kendy A; Madura, Jeffry D; Surratt, Christopher K

    2015-01-01

    Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacological screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening (VS), which employs computer models of the target protein to narrow the search for possible leads. A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for "growing" the lead candidate. Current efforts in virtual FBDD within central nervous system (CNS) targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor-binding pocket using the fragment as a scaffold. This process not only places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

  17. Quality system target on a detail design activity irradiator ISG 500

    International Nuclear Information System (INIS)

    Reinhard Pardede

    2010-01-01

    Currently, an engineering team of Nuclear Equipment Engineering Center PRPN has been beening technology innovation detail design of Irradiator ISG 500, then enter continuing to a construction phase. A schedule detail design still being not finish yet. The installation of Irradiator ISG 500 will be used to preservative the result of agricultural product in Indonesia. It is known as an export commodity and row material for food. However, its quality need some improvements in order to meet internal and foreign consumer standard. To enhance a quality system in detail design phase has already used ISO 9001: 2008 on clausul-7: Product Realization-design. It also needs a radioactive regulation Bapeten-Indonesian Nuclear Energy Surveillance Agency compliance with IAEA GS-R 3: 2006 as well. Scope of activity design is Instrumentation and Control system; Mechanical- Electrical; Radiation and Safety and Dosimetry; Civil Structured; Quality Assurance and Technoeconomic. Technology Innovating be applied to achieved economics through Costumer and Market Focused. Gamma irradiation of Irradiator ISG 500 can be used to improve hygienic quality in terms of technological as well as economical aspects. Technology innovation fit with the state of the arts right now. Assessment should be done base not only internal audit but also monitoring and surveillance as well. By application of a Quality System on detail design activity hopefully to enhance quality on detail design, construction, more over irradiator operation. (author)

  18. Deployment Design of Wireless Sensor Network for Simple Multi-Point Surveillance of a Moving Target

    Science.gov (United States)

    Tsukamoto, Kazuya; Ueda, Hirofumi; Tamura, Hitomi; Kawahara, Kenji; Oie, Yuji

    2009-01-01

    In this paper, we focus on the problem of tracking a moving target in a wireless sensor network (WSN), in which the capability of each sensor is relatively limited, to construct large-scale WSNs at a reasonable cost. We first propose two simple multi-point surveillance schemes for a moving target in a WSN and demonstrate that one of the schemes can achieve high tracking probability with low power consumption. In addition, we examine the relationship between tracking probability and sensor density through simulations, and then derive an approximate expression representing the relationship. As the results, we present guidelines for sensor density, tracking probability, and the number of monitoring sensors that satisfy a variety of application demands. PMID:22412326

  19. Utilisation of computational fluid dynamics techniques for design of molybdenum target specification

    International Nuclear Information System (INIS)

    Yeoh, G.H.; Wassink, D.

    2003-01-01

    A three-dimensional computational fluid dynamics (CFD) model to investigate the hydraulic behaviour within a model of the liner and irradiation rig, located in the central portion of the HIFAR fuel element is described. Flow visualisation and LDV measurements are performed to better understand the fluid flow around the narrow spaces within the irradiation rig, annular target cans and liner. Based on the unstructured meshing consisted of triangular elements and tetrahedrons within the flow space generated for the geometrical structure, the CFD model was able to predict complex flow structures inside the liner containing the irradiation rig and target cans. The reliability of the model was validated against experiments. The predicted flow behaviour was comparable to the experimental observations. Predicted velocities were also found to be in good agreement with LDV measurements. (author)

  20. Designing the nanobiointerface of fluorescent nanodiamonds: highly selective targeting of glioma cancer cells.

    Science.gov (United States)

    Slegerova, Jitka; Hajek, Miroslav; Rehor, Ivan; Sedlak, Frantisek; Stursa, Jan; Hruby, Martin; Cigler, Petr

    2015-01-14

    Core-shell nanoparticles based on fluorescent nanodiamonds coated with a biocompatible N-(2-hydroxypropyl)methacrylamide copolymer shell were developed for background-free near-infrared imaging of cancer cells. The particles showed excellent colloidal stability in buffers and culture media. After conjugation with a cyclic RGD peptide they selectively targeted integrin αvβ3 receptors on glioblastoma cells with high internalization efficacy.

  1. Drug design with Cdc7 kinase: a potential novel cancer therapy target

    Directory of Open Access Journals (Sweden)

    Masaaki Sawa

    2008-11-01

    Full Text Available Masaaki Sawa1, Hisao Masai21Carna Biosciences, Inc., Kobe, Japan; 2Genome Dynamics Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanAbstract: Identification of novel molecular targets is critical in development of new and efficient cancer therapies. Kinases are one of the most common drug targets with a potential for cancer therapy. Cell cycle progression is regulated by a number of kinases, some of which are being developed to treat cancer. Cdc7 is a serine-threonine kinase originally discovered in budding yeast, which has been shown to be necessary to initiate the S phase. Inhibition of Cdc7 in cancer cells retards the progression of the S phase, accumulates DNA damage, and induces p53-independent cell death, but the same treatment in normal cells does not significantly affect viability. Low-molecular-weight compounds that inhibit Cdc7 kinase with an IC50 of less than 10 nM have been identified, and shown to be effective in the inhibition of tumor growth in animal models. Thus Cdc7 kinase can be recognized as a novel molecular target for cancer therapy.Keywords: Cdc7 kinase, cell cycle, replication fork, genome stability, DNA damages, ATP-binding pocket, kinase inhibitor

  2. Formulation design for target delivery of iron nanoparticles to TCE zones.

    Science.gov (United States)

    Wang, Ziheng; Acosta, Edgar

    2013-12-01

    Nanoparticles of zero-valent iron (NZVI) are effective reducing agents for some dense non-aqueous phase liquid (DNAPL) contaminants such as trichloroethylene (TCE). However, target delivery of iron nanoparticles to DNAPL zones in the aquifer remains an elusive feature for NZVI technologies. This work discusses three strategies to deliver iron nanoparticles to DNAPL zones. To this end, iron oxide nanoparticles coated with oleate (OL) ions were used as stable analogs for NZVI. The OL-coated iron oxide nanoparticles are rendered lipophilic via (a) the addition of CaCl2, (b) acidification, or (c) the addition of a cationic surfactant, benzethonium chloride (BC). Mixtures of OL and BC show promise as a target delivery strategy due to the high stability of the nanoparticles in water, and their preferential partition into TCE in batch experiments. Column tests show that while the OL-BC coated iron oxide nanoparticles remain largely mobile in TCE-free columns, a large fraction of these particles are retained in TCE-contaminated columns, confirming the effectiveness of this target delivery strategy. © 2013.

  3. Magnetron target designs to improve wafer edge trench filling in ionized metal physical vapor deposition

    International Nuclear Information System (INIS)

    Lu Junqing; Yoon, Jae-Hong; Shin, Keesam; Park, Bong-Gyu; Yang Lin

    2006-01-01

    Severe asymmetry of the metal deposits on the trench sidewalls occurs near the wafer edge during low pressure ionized metal physical vapor deposition of Cu seed layer for microprocessor interconnects. To investigate this process and mitigate the asymmetry, an analytical view factor model based on the analogy between metal sputtering and diffuse thermal radiation was constructed. The model was validated based on the agreement between the model predictions and the reported experimental values for the asymmetric metal deposition at trench sidewalls near the wafer edge for a 200 mm wafer. This model could predict the thickness of the metal deposits across the wafer, the symmetry of the deposits on the trench sidewalls at any wafer location, and the angular distributions of the metal fluxes arriving at any wafer location. The model predictions for the 300 mm wafer indicate that as the target-to-wafer distance is shortened, the deposit thickness increases and the asymmetry decreases, however the overall uniformity decreases. Up to reasonable limits, increasing the target size and the sputtering intensity for the outer target portion significantly improves the uniformity across the wafer and the symmetry on the trench sidewalls near the wafer edge

  4. Design of the Next Generation Target at the Lujan Neutron Scattering Center, LANSCE

    Energy Technology Data Exchange (ETDEWEB)

    Ferres, Laurent [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); National Graduate School of Engineering and Research Center (ENSICAEN), Caen (France)

    2016-08-03

    Los Alamos National Laboratory (LANL) supports scientific research in many diverse fields such as biology, chemistry, and nuclear science. The Laboratory was established in 1943 during the Second World War to develop nuclear weapons. Today, LANL is one of the largest laboratories dedicated to nuclear defense and operates an 800 MeV proton linear accelerator for basic and applied research including: production of high- and low-energy neutrons beams, isotope production for medical applications and proton radiography. This accelerator is located at the Los Alamos Neutron Science Center (LANSCE). The work performed involved the redesign of the target for the low-energy neutron source at the Lujan Neutron Scattering Center, which is one of the facilities built around the accelerator. The redesign of the target involves modeling various arrangements of the moderator-reflector-shield for the next generation neutron production target. This is done using Monte Carlo N-Particle eXtended (MCNPX), and ROOT analysis framework, a C++ based-software, to analyze the results.

  5. CRISPRscan: designing highly efficient sgRNAs for CRISPR/Cas9 targeting in vivo

    Science.gov (United States)

    Moreno-Mateos, Miguel A.; Vejnar, Charles E.; Beaudoin, Jean-Denis; Fernandez, Juan P.; Mis, Emily K.; Khokha, Mustafa K.; Giraldez, Antonio J.

    2015-01-01

    CRISPR/Cas9 technology provides a powerful system for genome engineering. However, variable activity across different single guide RNAs (sgRNAs) remains a significant limitation. We have analyzed the molecular features that influence sgRNA stability, activity and loading into Cas9 in vivo. We observe that guanine enrichment and adenine depletion increase sgRNA stability and activity, while loading, nucleosome positioning and Cas9 off-target binding are not major determinants. We additionally identified truncated and 5′ mismatch-containing sgRNAs as efficient alternatives to canonical sgRNAs. Based on these results, we created a predictive sgRNA-scoring algorithm (CRISPRscan.org) that effectively captures the sequence features affecting Cas9/sgRNA activity in vivo. Finally, we show that targeting Cas9 to the germ line using a Cas9-nanos-3′-UTR fusion can generate maternal-zygotic mutants, increase viability and reduce somatic mutations. Together, these results provide novel insights into the determinants that influence Cas9 activity and a framework to identify highly efficient sgRNAs for genome targeting in vivo. PMID:26322839

  6. Designing calcium phosphate-based bifunctional nanocapsules with bone-targeting properties

    Energy Technology Data Exchange (ETDEWEB)

    Khung, Yit-Lung; Bastari, Kelsen; Cho, Xing Ling; Yee, Wu Aik; Loo, Say Chye Joachim, E-mail: joachimloo@ntu.edu.sg [Nanyang Technological University, School of Materials Science and Engineering (Singapore)

    2012-06-15

    Using sodium dodecyl sulphate micelles as template, hollow-cored calcium phosphate nanocapsules were produced. The surfaces of the nanocapsule were subsequently silanised by a polyethylene glycol (PEG)-based silane with an N-hydroxysuccinimide ester end groups which permits for further attachment with bisphosphonates (BP). Characterisations of these nanocapsules were investigated using Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy, Fourier Transform Infra-Red Spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Dynamic Light Scattering. To further validate the bone-targeting potential, dentine discs were incubated with these functionalised nanocapsules. FESEM analysis showed that these surface-modified nanocapsules would bind strongly to dentine surfaces compared to non-functionalised nanocapsules. We envisage that respective components would give this construct a bifunctional attribute, whereby (1) the shell of the calcium phosphate nanocapsule would serve as biocompatible coating aiding in gradual osteoconduction, while (2) surface BP moieties, acting as targeting ligands, would provide the bone-targeting potential of these calcium phosphate nanocapsules.

  7. Designing calcium phosphate-based bifunctional nanocapsules with bone-targeting properties

    International Nuclear Information System (INIS)

    Khung, Yit-Lung; Bastari, Kelsen; Cho, Xing Ling; Yee, Wu Aik; Loo, Say Chye Joachim

    2012-01-01

    Using sodium dodecyl sulphate micelles as template, hollow-cored calcium phosphate nanocapsules were produced. The surfaces of the nanocapsule were subsequently silanised by a polyethylene glycol (PEG)-based silane with an N-hydroxysuccinimide ester end groups which permits for further attachment with bisphosphonates (BP). Characterisations of these nanocapsules were investigated using Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy, Fourier Transform Infra-Red Spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Dynamic Light Scattering. To further validate the bone-targeting potential, dentine discs were incubated with these functionalised nanocapsules. FESEM analysis showed that these surface-modified nanocapsules would bind strongly to dentine surfaces compared to non-functionalised nanocapsules. We envisage that respective components would give this construct a bifunctional attribute, whereby (1) the shell of the calcium phosphate nanocapsule would serve as biocompatible coating aiding in gradual osteoconduction, while (2) surface BP moieties, acting as targeting ligands, would provide the bone-targeting potential of these calcium phosphate nanocapsules.

  8. Design and Testing of Bi-Functional, P-Loop-Targeted MDM2 Inhibitors

    National Research Council Canada - National Science Library

    Prives, Carol L; Stockwell, Brent R

    2007-01-01

    Our proposal is to design and evaluate a novel class of bifunctional MDM2 inhibitors, based on the discovery that nucleotides can bind to the P-loop of MDM2 and cause its relocalization to the nucleolus...

  9. Design and Testing of Bi-Functional, P-Loop-Targeted MDM2 Inhibitors

    National Research Council Canada - National Science Library

    Prives, Carol L

    2006-01-01

    This proposal is to design and evaluate a novel class of bifunctional MDM2 inhibitors, based on the discovery that nucleotides can bind to the P-loop of MDM2 and cause its relocalization to the nucleolus...

  10. Targeting a heterologous protein to multiple plant organelles via rationally designed 5? mRNA tags

    NARCIS (Netherlands)

    Voges, M.J.; Silver, P.A.; Way, J.C.; Mattozzi, M.D.

    2013-01-01

    Background Plant bioengineers require simple genetic devices for predictable localization of heterologous proteins to multiple subcellular compartments. Results We designed novel hybrid signal sequences for multiple-compartment localization and characterize their function when fused to GFP in

  11. Design of Operation Parameters to Resolve Two Targets using Proximity Sensors

    Science.gov (United States)

    2010-07-01

    network,” in MOBIHOC, EPF Lausanne, Switzerland, 2002. [12] V. Cevher and L. Kaplan, “Acoustic sensor net- work design for position estimation,” ACM Trans- actions on Sensor Networks, vol. 4, 2009.

  12. Designing the nanoparticle-biomolecule interface for "targeting and therapeutic delivery".

    Science.gov (United States)

    Mahon, Eugene; Salvati, Anna; Baldelli Bombelli, Francesca; Lynch, Iseult; Dawson, Kenneth A

    2012-07-20

    The endogenous transport mechanisms which occur in living organisms have evolved to allow selective transport and processing operate on a scale of tens of nanometers. This presents the possibility of unprecedented access for engineered nanoscale materials to organs and sub-cellular locations, materials which may in principle be targeted to precise locations for diagnostic or therapeutic gain. For this reason, nano-architectures could represent a truly radical departure as delivery agents for drugs, genes and therapies to treat a host of diseases. Thus, for active targeting, unlike the case of small molecular drugs where molecular structure has evolved to promote higher physiochemical affinity to specific sites, one aims to exploit these energy dependant endogenous processes. Many active targeting strategies have been developed, but despite this truly remarkable potential, in applications they have met with mixed success to date. This situation may have more to do with our current understanding and integration of knowledge across disciplines, than any intrinsic limitation on the vision itself. In this review article we suggest that much more fundamental and detailed control of the nanoparticle-biomolecule interface is required for sustained and general success in this field. In the simplest manifestation, pristine nanoparticles in biological fluids act as a scaffold for biomolecules, which adsorb rapidly to the nanoparticles' surface, conferring a new biological identity to the nanoparticles. It is this nanoparticle-biomolecule interface that is 'read' and acted upon by the cellular machinery. Moreover, where targeting moieties are grafted onto nanoparticles, they may not retain their function as a result of poor orientation, and structural or conformational disruption. Further surface adsorption of biomolecules from the surrounding environment i.e. the formation of a biomolecule corona may also obscure specific surface recognition. To transfer the remarkable

  13. Conceptual Design of Targeted Scrum: Applying Mission Command to Agile Software Development

    Science.gov (United States)

    2014-06-01

    on design. Drury et al. (2012) report that many of the decisions made during Scrum planning were more tactical in nature (i.e., which tasks to...Coram, R. (2002). Boyd: The fighter pilot who changed the art of war. Boston, MA: Little, Brown and Company. Drury , M., Conboy, K., & Power, K. (2012...responsiveness (Hochmüller, 2011) (Hoda et al., 2010) • Lack of design focus → Planning decisions more tactical than strategic ( Drury et al., 2012

  14. Validation of FLUKA calculated cross-sections for radioisotope production in proton-on-target collisions at proton energies around 1 GeV

    CERN Document Server

    Felcini, M

    2006-01-01

    The production cross-sections of several radioisotopes induced by 1 GeV protons impinging on different target materials have been calculated using the FLUKA Monte Carlo and compared to measured cross-sections. The emphasis of this study is on the production of alpha and beta/gamma emitters of interest for activation evaluations at a research complex, such as the EURISOL complex, using several MW power proton driver at an energy of 1 GeV. The comparisons show that in most of the cases of interest for such evaluations, the FLUKA Monte Carlo reproduces radioisotope production cross-sections within less than a factor of two with respect to the measured values. This result implies that the FLUKA calculations are adequately accurate for proton induced activation estimates at a 1 GeV high power proton driver complex.

  15. Nonlocal heat transport and improved target design for x-ray heating studies at x-ray free electron lasers

    Science.gov (United States)

    Hoidn, Oliver; Seidler, Gerald T.

    2018-01-01

    The extremely high-power densities and short durations of single pulses of x-ray free electron lasers (XFELs) have opened new opportunities in atomic physics, where complex excitation-relaxation chains allow for high ionization states in atomic and molecular systems, and in dense plasma physics, where XFEL heating of solid-density targets can create unique dense states of matter having temperatures on the order of the Fermi energy. We focus here on the latter phenomena, with special emphasis on the problem of optimum target design to achieve high x-ray heating into the warm dense matter (WDM) state. We report fully three-dimensional simulations of the incident x-ray pulse and the resulting multielectron relaxation cascade to model the spatial energy density deposition in multicomponent targets, with particular focus on the effects of nonlocal heat transport due to the motion of high energy photoelectrons and Auger electrons. We find that nanoscale high-Z /low-Z multicomponent targets can give much improved energy density deposition in lower-Z materials, with enhancements reaching a factor of 100. This has three important benefits. First, it greatly enlarges the thermodynamic parameter space in XFEL x-ray heating studies of lower-Z materials. Second, it allows the use of higher probe photon energies, enabling higher-information content x-ray diffraction (XRD) measurements such as in two-color XFEL operations. Third, while this is merely one step toward optimization of x-ray heating target design, the demonstration of the importance of nonlocal heat transport establishes important common ground between XFEL-based x-ray heating studies and more traditional laser plasma methods.

  16. Laser ablation caused by geometrically constrained illumination and inventive target design

    Science.gov (United States)

    Inogamov, N. A.; Zhakhovsky, V. V.; Khokhlov, V. A.

    2018-01-01

    Modern laser technologies use very sophisticated manipulations with (i) a photon cloud forming an irradiation beam and with (ii) disign of a target. E.g. high numerical aperture illumination at very small, diffraction limited conditions is employed for fabrication of the tiny solitary nanoformations on surface of specially prepared thin films deposited onto usually dielectric or semiconductor substrate. In the paper below we list such cases and consider an example with a free standing gold nanofilm modified by tightly focused femtosecond laser pulse.

  17. Designing Appropriate Exchange Rate Regimes for East Asia: Inflation Targeting and Monetary Policy Rules

    OpenAIRE

    Tony Cavoli; Ramkishen Rajan

    2003-01-01

    While favoring relatively more flexible regimes, emerging economies in East Asia and elsewhere appear to heavily manage their currencies despite being officially described as “floaters”. In other words, revealed preferences of regional monetary authorities appear to indicate a high degree of “fear of floating”. The paper first explores the reasons for this fear of floating. It then goes on to examine the case for and operational mechanics behind an open inflation targeting regime which ha...

  18. Design and syntheses of mono and multivalent mannosyl-lipoconjugates for targeted liposomal drug delivery.

    Science.gov (United States)

    Štimac, Adela; Cvitaš, Jelena TrmĿiĿ; Frkanec, Leo; Vugrek, Oliver; Frkanec, Ruža

    2016-09-10

    Multivalent mannosyl-lipoconjugates may be of interest for glycosylation of liposomes and targeted drug delivery because the mannose specifically binds to C-type lectin receptors on the particular cells. In this paper syntheses of two types of novel O-mannosides are presented. Conjugates 1 and 2 with a COOH- and NH2-functionalized spacer and the connection to a lysine and FmocNH-PEG-COOH, are described. The coupling reactions of prepared intermediates 6 and 4 with a PEGylated-DSPE or palmitic acid, respectively, are presented. Compounds 5, mono-, 8, di- and 12, tetravalent mannosyl-lipoconjugates, were synthesized. The synthesized compounds were incorporated into liposomes and liposomal preparations featuring exposed mannose units were characterized. Carbohydrate liposomal quartz crystal microbalance based assay has been established for studying carbohydrate-lectin binding. It was demonstrated that liposomes with incorporated mannosyl-lipoconjugates were effectively recognized by Con A and have great potential to be used for targeted liposomal drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Target design for the cylindrical compression of matter driven by heavy ion beams

    Energy Technology Data Exchange (ETDEWEB)

    Piriz, A.R. [E. T. S. I. Industriales, Universidad de Castilla-La Mancha, 13071 Ciudad Real (Spain)]. E-mail: roberto.piriz@uclm.es; Temporal, M. [E. T. S. I. Industriales, Universidad de Castilla-La Mancha, 13071 Ciudad Real (Spain); Lopez Cela, J.J. [E. T. S. I. Industriales, Universidad de Castilla-La Mancha, 13071 Ciudad Real (Spain); Grandjouan, N. [LULI, UMR 7605, Ecole Polytechnique-CNRS-CEA-Universite Paris VI, Palaiseau (France); Tahir, N.A. [GSI Darmstadt, Plankstrasse 1, 64291 Darmstadt (Germany); Serna Moreno, M.C. [E. T. S. I. Industriales, Universidad de Castilla-La Mancha, 13071 Ciudad Real (Spain); Portugues, R.F. [E. T. S. I. Industriales, Universidad de Castilla-La Mancha, 13071 Ciudad Real (Spain); Hoffmann, D.H.H. [GSI Darmstadt, Plankstrasse 1, 64291 Darmstadt (Germany)

    2005-05-21

    The compression of a cylindrical sample of hydrogen contained in a hollow shell of Pb or Au has been analyzed in the framework of the experiments to be performed in the heavy ion synchrotron SIS100 to be constructed at the Gesellschaft fuer Schwerionenforschung (GSI) Darmstadt. The target implosion is driven by an intense beam of heavy ions with a ring-shaped focal spot. We report the results of a parametric study of the final state of the compressed hydrogen in terms of the target and beam parameters. We consider the generation of the annular heated region by means of a radio-frequency wobbler that rotates the beam at extremely high frequencies in order to accommodate symmetry constraints. We have also studied the hydrogen conditions that can be achieved with a non-rotating beam with Gaussian focal spot and the possibility to use a beam stopper as an alternative way to avoid the direct heating of the sample. Finally, we report the analysis of the hydrodynamic instabilities that affect the implosion and the mitigating effects of the elastoplastic properties of the shell.

  20. Target design for the cylindrical compression of matter driven by heavy ion beams

    International Nuclear Information System (INIS)

    Piriz, A.R.; Temporal, M.; Lopez Cela, J.J.; Grandjouan, N.; Tahir, N.A.; Serna Moreno, M.C.; Portugues, R.F.; Hoffmann, D.H.H.

    2005-01-01

    The compression of a cylindrical sample of hydrogen contained in a hollow shell of Pb or Au has been analyzed in the framework of the experiments to be performed in the heavy ion synchrotron SIS100 to be constructed at the Gesellschaft fuer Schwerionenforschung (GSI) Darmstadt. The target implosion is driven by an intense beam of heavy ions with a ring-shaped focal spot. We report the results of a parametric study of the final state of the compressed hydrogen in terms of the target and beam parameters. We consider the generation of the annular heated region by means of a radio-frequency wobbler that rotates the beam at extremely high frequencies in order to accommodate symmetry constraints. We have also studied the hydrogen conditions that can be achieved with a non-rotating beam with Gaussian focal spot and the possibility to use a beam stopper as an alternative way to avoid the direct heating of the sample. Finally, we report the analysis of the hydrodynamic instabilities that affect the implosion and the mitigating effects of the elastoplastic properties of the shell

  1. Indirect-drive noncryogenic double-shell ignition targets for the National Ignition Facility: Design and analysis

    International Nuclear Information System (INIS)

    Amendt, Peter; Colvin, J.D.; Tipton, R.E.; Hinkel, D.E.; Edwards, M.J.; Landen, O.L.; Ramshaw, J.D.; Suter, L.J.; Varnum, W.S.; Watt, R.G.

    2002-01-01

    Analysis and design of indirect-drive National Ignition Facility double-shell targets with hohlraum temperatures of 200 eV and 250 eV are presented. The analysis of these targets includes the assessment of two-dimensional radiation asymmetry and nonlinear mix. Two-dimensional integrated hohlraum simulations indicate that the x-ray illumination can be adjusted to provide adequate symmetry control in hohlraums specially designed to have high laser-coupling efficiency [Suter et al., Phys. Plasmas 7, 2092 (2000)]. These simulations also reveal the need to diagnose and control localized 10-15 keV x-ray emission from the high-Z hohlraum wall because of strong absorption by the high-Z inner shell. Preliminary estimates of the degree of laser backscatter from an assortment of laser-plasma interactions suggest comparatively benign hohlraum conditions. The application of a variety of nonlinear mix models and phenomenological tools, including buoyancy-drag models, multimode simulations and fall-line optimization, indicates a possibility of achieving ignition, i.e., fusion yields greater than 1 MJ. Planned experiments on the Omega laser will test current understanding of high-energy radiation flux asymmetry and mix-induced yield degradation in double-shell targets

  2. Target-aimed versus wishful-thinking in designing efficient GHG reduction strategies for a metropolitan city: Taipei

    International Nuclear Information System (INIS)

    Liu, C.-M.; Liou, M.-L.; Yeh, S.-C.; Shang, N.-C.

    2009-01-01

    In recent years, many national and local governments claim for a specific GHG (greenhouse gas) reduction goal targeted for many years later. In 2005, the Taipei City government announced that Taipei's total GHG emission in 2015 will reach the same level as that in 2005 and then down to 75% of that level at year 2030. However, based on the estimated energy consumption and GHG emission and the proposed emission reduction plans from the local government, it is clear that these goals are not going to be accomplished. In Taipei, the residential and commercial sector contributes more than 78% of the total GHG emission. Thus, in a business as usual scenario, the total GHG emission in 2030 would be 79% more than that in 2005, far more than the target value proclaimed. As many key factors are uncontrollable by the local government, a target-aimed strategy designing process by looking into changes in Taipei and identifying major targets is proposed in this study. It is demonstrated that such a universally applicable approach will give more confidence to the public on working toward the expected GHG reduction goal

  3. Applying Theory of Mind Concepts When Designing Interventions Targeting Social Cognition among Youth Offenders

    Science.gov (United States)

    Noel, Kristine K.; Westby, Carol

    2014-01-01

    This study employed a multiple baseline, across-participants, single-subject design to investigate the feasibility of an individual, narrative-based, social problem-solving intervention on the social problem-solving, narrative, and theory of mind (ToM) abilities of 3 incarcerated adolescent youth offenders identified as having emotional…

  4. Designing Probes for Immunodiagnostics: Structural Insights into an Epitope Targeting Burkholderia Infections.

    Science.gov (United States)

    Capelli, Riccardo; Matterazzo, Elena; Amabili, Marco; Peri, Claudio; Gori, Alessandro; Gagni, Paola; Chiari, Marcella; Lertmemongkolchai, Ganjana; Cretich, Marina; Bolognesi, Martino; Colombo, Giorgio; Gourlay, Louise J

    2017-10-13

    Structure-based epitope prediction drives the design of diagnostic peptidic probes to reveal specific antibodies elicited in response to infections. We previously identified a highly immunoreactive epitope from the peptidoglycan-associated lipoprotein (Pal) antigen from Burkholderia pseudomallei, which could also diagnose Burkholderia cepacia infections. Here, considering the high phylogenetic conservation within Burkholderia species, we ask whether cross-reactivity can be reciprocally displayed by the synthetic epitope from B. cenocepacia. We perform comparative analyses of the conformational preferences and diagnostic performances of the corresponding epitopes from the two Burkholderia species when presented in the context of the full-length proteins or as isolated peptides. The effects of conformation on the diagnostic potential and cross-reactivity of Pal peptide epitopes are rationalized on the basis of the 1.8 Å crystal structure of B. cenocepacia Pal and through computational analyses. Our results are discussed in the context of designing new diagnostic molecules for the early detection of infectious diseases.

  5. Design of a liquid metal target loop for a high power spallation

    CERN Document Server

    Andreas Vetter (PSI)

    Diplomarbeit zur Erlangung des Grades Diplom-IngenieurTechnische Universität BerlinThis thesis shows the lay-out of the liquid metal loop, which is designed to evacuate 3.0 MW of thermal power. It describes the function and sizing of the piping and components. The thesis deals with the choice of the pump, the expansion tank/gas separator and the heat exchanger using water as cooling fluid as well as instrumentation.

  6. A weighted sampling algorithm for the design of RNA sequences with targeted secondary structure and nucleotide distribution.

    Science.gov (United States)

    Reinharz, Vladimir; Ponty, Yann; Waldispühl, Jérôme

    2013-07-01

    The design of RNA sequences folding into predefined secondary structures is a milestone for many synthetic biology and gene therapy studies. Most of the current software uses similar local search strategies (i.e. a random seed is progressively adapted to acquire the desired folding properties) and more importantly do not allow the user to control explicitly the nucleotide distribution such as the GC-content in their sequences. However, the latter is an important criterion for large-scale applications as it could presumably be used to design sequences with better transcription rates and/or structural plasticity. In this article, we introduce IncaRNAtion, a novel algorithm to design RNA sequences folding into target secondary structures with a predefined nucleotide distribution. IncaRNAtion uses a global sampling approach and weighted sampling techniques. We show that our approach is fast (i.e. running time comparable or better than local search methods), seedless (we remove the bias of the seed in local search heuristics) and successfully generates high-quality sequences (i.e. thermodynamically stable) for any GC-content. To complete this study, we develop a hybrid method combining our global sampling approach with local search strategies. Remarkably, our glocal methodology overcomes both local and global approaches for sampling sequences with a specific GC-content and target structure. IncaRNAtion is available at csb.cs.mcgill.ca/incarnation/. Supplementary data are available at Bioinformatics online.

  7. Low Density Supersonic Decelerator Flight Dynamics Test-1 Flight Design and Targeting

    Science.gov (United States)

    Ivanov, Mark

    2015-01-01

    NASA's Low Density Supersonic Decelerator (LDSD) program was established to identify, develop, and eventually qualify to Test [i.e. Technology] Readiness Level (TRL) - 6 aerodynamic decelerators for eventual use on Mars. Through comprehensive Mars application studies, two distinct Supersonic Inflatable Aerodynamic Decelerator (SIAD) designs were chosen that afforded the optimum balance of benefit, cost, and development risk. In addition, a Supersonic Disk Sail (SSDS) parachute design was chosen that satisfied the same criteria. The final phase of the multi-tiered qualification process involves Earth Supersonic Flight Dynamics Tests (SFDTs) within environmental conditions similar to those that would be experienced during a Mars Entry, Descent, and Landing (EDL) mission. The first of these flight tests (i.e. SFDT-1) was completed on June 28, 2014 with two more tests scheduled for the summer of 2015 and 2016, respectively. The basic flight design for all the SFDT flights is for the SFDT test vehicle to be ferried to a float altitude of 120 kilo-feet by a 34 thousand cubic feet (Mcf) heavy lift helium balloon. Once float altitude is reached, the test vehicle is released from the balloon, spun-up for stability, and accelerated to supersonic speeds using a Star48 solid rocket motor. After burnout of the Star48 motor the vehicle decelerates to pre-flight selected test conditions for the deployment of the SIAD system. After further deceleration with the SIAD deployed, the SSDS parachute is then deployed stressing the performance of the parachute in the wake of the SIAD augmented blunt body. The test vehicle/SIAD/parachute system then descends to splashdown in the Pacific Ocean for eventual recovery. This paper will discuss the development of both the test vehicle and the trajectory sequence including design trade-offs resulting from the interaction of both engineering efforts. In addition, the SFDT-1 nominal trajectory design and associated sensitivities will be discussed

  8. Production yields of noble-gas isotopes from ISOLDE UC$_{x}$/graphite targets

    CERN Document Server

    Bergmann, U C; Catherall, R; Cederkäll, J; Diget, C A; Fraile-Prieto, L M; Franchoo, S; Fynbo, H O U; Gausemel, H; Georg, U; Giles, T; Hagebø, E; Jeppesen, H B; Jonsson, O C; Köster, U; Lettry, Jacques; Nilsson, T; Peräjärvi, K; Ravn, H L; Riisager, K; Weissman, L; Äystö, J

    2003-01-01

    Yields of He, Ne, Ar, Kr and Xe isotopic chains were measured from UC$_{x}$/graphite and ThC$_{x}$/graphite targets at the PSB-ISOLDE facility at CERN using isobaric selectivity achieved by the combination of a plasma-discharge ion source with a water-cooled transfer line. %The measured half-lives allowed %to calculate the decay losses of neutron-rich isotopes in the %target and ion-source system, and thus to obtain information on the in-target %productions from the measured yields. The delay times measured for a UC$_x$/graphite target allow for an extrapolation to the expected yields of very neutron-rich noble gas isotopes, in particular for the ``NuPECC reference elements'' Ar and Kr, at the next-generation radioactive ion-beam facility EURISOL. \\end{abstract} \\begin{keyword} % keywords here, in the form: keyword \\sep keyword radioactive ion beams \\sep release \\sep ion yields \\sep ISOL (Isotope Separation On-Line) \\sep uranium and thorium carbide targets. % PACS codes here, in the form: \\PACS code \\sep code...

  9. Advances in implosion physics, alternative targets design, and neutron effects on heavy ion fusion reactors

    Science.gov (United States)

    Velarde, G.; Perlado, J. M.; Alonso, E.; Alonso, M.; Domínguez, E.; Rubiano, J. G.; Gil, J. M.; Gómez del Rio, J.; Lodi, D.; Malerba, L.; Marian, J.; Martel, P.; Martínez-Val, J. M.; Mínguez, E.; Piera, M.; Ogando, F.; Reyes, S.; Salvador, M.; Sanz, J.; Sauvan, P.; Velarde, M.; Velarde, P.

    2001-05-01

    The coupling of a new radiation transport (RT) solver with an existing multimaterial fluid dynamics code (ARWEN) using Adaptive Mesh Refinement named DAFNE, has been completed. In addition, improvements were made to ARWEN in order to work properly with the RT code, and to make it user-friendlier, including new treatment of Equations of State, and graphical tools for visualization. The evaluation of the code has been performed, comparing it with other existing RT codes (including the one used in DAFNE, but in the single-grid version). These comparisons consist in problems with real input parameters (mainly opacities and geometry parameters). Important advances in Atomic Physics, Opacity calculations and NLTE atomic physics calculations, with participation in significant experiments in this area, have been obtained. Early published calculations showed that a DT x fuel with a small tritium initial content ( x<3%) could work in a catalytic regime in Inertial Fusion Targets, at very high burning temperatures (≫100 keV). Otherwise, the cross-section of DT remains much higher than that of DD and no internal breeding of tritium can take place. Improvements in the calculation model allow to properly simulate the effect of inverse Compton scattering which tends to lower Te and to enhance radiation losses, reducing the plasma temperature, Ti. The neutron activation of all natural elements in First Structural Wall (FSW) component of an Inertial Fusion Energy (IFE) reactor for waste management, and the analysis of activation of target debris in NIF-type facilities has been completed. Using an original efficient modeling for pulse activation, the FSW behavior in inertial fusion has been studied. A radiological dose library coupled to the ACAB code is being generated for assessing impact of environmental releases, and atmospheric dispersion analysis from HIF reactors indicate the uncertainty in tritium release parameters. The first recognition of recombination barriers in Si

  10. Advances in implosion physics, alternative targets design, and neutron effects on heavy ion fusion reactors

    Energy Technology Data Exchange (ETDEWEB)

    Velarde, G.; Perlado, J.M. E-mail: mperlado@denim.upm.es; Alonso, E.; Alonso, M.; Dominguez, E.; Rubiano, J.G.; Gil, J.M.; Gomez del Rio, J.; Lodi, D.; Malerba, L.; Marian, J.; Martel, P.; Martinez-Val, J.M.; Minguez, E.; Piera, M.; Ogando, F.; Reyes, S.; Salvador, M.; Sanz, J.; Sauvan, P.; Velarde, M.; Velarde, P

    2001-05-21

    The coupling of a new radiation transport (RT) solver with an existing multimaterial fluid dynamics code (ARWEN) using Adaptive Mesh Refinement named DAFNE, has been completed. In addition, improvements were made to ARWEN in order to work properly with the RT code, and to make it user-friendlier, including new treatment of Equations of State, and graphical tools for visualization. The evaluation of the code has been performed, comparing it with other existing RT codes (including the one used in DAFNE, but in the single-grid version). These comparisons consist in problems with real input parameters (mainly opacities and geometry parameters). Important advances in Atomic Physics, Opacity calculations and NLTE atomic physics calculations, with participation in significant experiments in this area, have been obtained. Early published calculations showed that a DT{sub x} fuel with a small tritium initial content (x<3%) could work in a catalytic regime in Inertial Fusion Targets, at very high burning temperatures ({>=}100 keV). Otherwise, the cross-section of DT remains much higher than that of DD and no internal breeding of tritium can take place. Improvements in the calculation model allow to properly simulate the effect of inverse Compton scattering which tends to lower T{sub e} and to enhance radiation losses, reducing the plasma temperature, T{sub i}. The neutron activation of all natural elements in First Structural Wall (FSW) component of an Inertial Fusion Energy (IFE) reactor for waste management, and the analysis of activation of target debris in NIF-type facilities has been completed. Using an original efficient modeling for pulse activation, the FSW behavior in inertial fusion has been studied. A radiological dose library coupled to the ACAB code is being generated for assessing impact of environmental releases, and atmospheric dispersion analysis from HIF reactors indicate the uncertainty in tritium release parameters. The first recognition of recombination

  11. Design and Validation of CRISPR/Cas9 Systems for Targeted Gene Modification in Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Lee, Ciaran M; Zhu, Haibao; Davis, Timothy H; Deshmukh, Harshahardhan; Bao, Gang

    2017-01-01

    The CRISPR/Cas9 system is a powerful tool for precision genome editing. The ability to accurately modify genomic DNA in situ with single nucleotide precision opens up new possibilities for not only basic research but also biotechnology applications and clinical translation. In this chapter, we outline the procedures for design, screening, and validation of CRISPR/Cas9 systems for targeted modification of coding sequences in the human genome and how to perform genome editing in induced pluripotent stem cells with high efficiency and specificity.

  12. Korea's emission trading scheme and policy design issues to achieve market-efficiency and abatement targets

    International Nuclear Information System (INIS)

    Park, Hojeong; Hong, Won Kyung

    2014-01-01

    In 2008, the government of Republic of Korea (Korea) announced the national abatement target aiming at 30% reductions from the Business-as-Usual projections by 2020. Accordingly, the Emission Trading Scheme (ETS) will be implemented from 2015 onwards. As ETS performance substantially depends on the structural design, it is critically important to examine the details of Korean ETS for the achievement of cost effectiveness and concurrent development of an active emission trading market. This paper addresses several policy design issues for this purpose. After providing an overview on the current framework of Korean ETS, we propose ways to achieve flexibility, consistency and market efficiency of the program in consideration of the preexisting policies. Issues in policy design are discussed by focusing on allowance allocation, market stabilization measures and price mechanism in the emission and energy markets in Korea. This paper will serve as a practical guideline for establishing sustainable and market-efficient Korean ETS that can be compatible with the international standards as in the EU ETS. - Highlights: • Emission Trading Scheme (ETS) will be implemented from 2015 in Korea to reduce CO 2 . • ETS performance substantially depends on structural design. • We provide policy overview on the current framework of Korean ETS. • Several policy design issues are discussed for developing policy consistency. • We focus on allowance allocation, allowance reserve and market stabilization measures

  13. Plant-Scale Concentration Column Designs for SHINE Target Solution Utilizing AG 1 Anion Exchange Resin

    Energy Technology Data Exchange (ETDEWEB)

    Stepinski, Dominique C. [Argonne National Lab. (ANL), Argonne, IL (United States); Vandegrift, G. F. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-09-30

    Argonne is assisting SHINE Medical Technologies (SHINE) in their efforts to develop SHINE, an accelerator-driven process that will utilize a uranyl-sulfate solution for the production of fission product Mo-99. An integral part of the process is the development of a column for the separation and recovery of Mo-99, followed by a concentration column to reduce the product volume from 15-25 L to <1 L. Argonne has collected data from batch studies and breakthrough column experiments to utilize the VERSE (Versatile Reaction Separation) simulation program (Purdue University) to design plant-scale product recovery and concentration processes.

  14. Detectability Measurement of GPR for Buried Target in Self-Designed Test Field

    International Nuclear Information System (INIS)

    Son, Soo Jung; Shin, Byoung Chul

    2000-01-01

    In this paper, we were investigated the detectability on various specimen in self-designed test field using the GPR system with three antenna elements. The GPR system was constantly radiated 730MHz frequency. To examine the detectability on various condition, the test were experimented using different materials, size and buried depth. As an adjusted wave-propagation velocity, the location of hyperbolic curve pattern were displayed B-scan CRT. And the pattern was exactly positioned when it was compared to the real buried-depth. Therefore, we can confirm similarity between the wave-propagation velocity and previous results

  15. Application of gene targeting to designed mutation breeding of high-tryptophan rice.

    Science.gov (United States)

    Saika, Hiroaki; Oikawa, Akira; Matsuda, Fumio; Onodera, Haruko; Saito, Kazuki; Toki, Seiichi

    2011-07-01

    Site-directed mutagenesis via gene targeting (GT) based on homologous recombination is the ultimate mutation breeding technology because it enables useful information acquired from structural- and computational-based protein engineering to be applied directly to molecular breeding, including metabolic engineering, of crops. Here, we employed this rationale to introduce precise mutations in OASA2--an α-subunit of anthranilate synthase that is a key enzyme of tryptophan (Trp) biosynthesis in rice (Oryza sativa)--via GT, with subsequent selection of GT cells using a Trp analog. The expression level of OASA2 in plants homozygous and heterozygous for modified OASA2 was similar to that of nontransformants, suggesting that OASA2 transcription in GT plants was controlled in the same manner as endogenous OASA2, and that GT could lead to a lower risk of gene silencing than in conventional overexpression approaches. Moreover, we showed that enzymatic properties deduced from protein engineering or in vitro analysis could be reproduced in GT plants as evidenced by Trp accumulation levels. Interestingly, mature seeds of homozygous GT plants accumulated Trp levels 230-fold higher than in nontransformants without any apparent morphological or developmental changes. Thus, we have succeeded in producing a novel rice plant of great potential nutritional benefit for both man and livestock that could not have been selected using conventional mutagenesis approaches. Our results demonstrate the effectiveness of directed crop improvement by combining precision mutagenesis via GT with a knowledge of protein engineering.

  16. Designing Novel Nanoformulations Targeting Glutamate Transporter Excitatory Amino Acid Transporter 2: Implications in Treating Drug Addiction.

    Science.gov (United States)

    Rao, Pss; Yallapu, Murali M; Sari, Youssef; Fisher, Paul B; Kumar, Santosh

    Chronic drug abuse is associated with elevated extracellular glutamate concentration in the brain reward regions. Deficit of glutamate clearance has been identified as a contributing factor that leads to enhanced glutamate concentration following extended drug abuse. Importantly, normalization of glutamate level through induction of glutamate transporter 1 (GLT1)/ excitatory amino acid transporter 2 (EAAT2) expression has been described in several in vivo studies. GLT1 upregulators including ceftriaxone, a beta-lactam antibiotic, have been effective in attenuating drug-seeking and drug-consumption behavior in rodent models. However, potential obstacles toward clinical translation of GLT1 (EAAT2) upregulators as treatment for drug addiction might include poor gastrointestinal absorption, serious peripheral adverse effects, and/or suboptimal CNS concentrations. Given the growing success of nanotechnology in targeting CNS ailments, nanoformulating known GLT1 (EAAT2) upregulators for selective uptake across the blood brain barrier presents an ideal therapeutic approach for treating drug addiction. In this review, we summarize the results obtained with promising GLT1 (EAAT2) inducing compounds in animal models recapitulating drug addiction. Additionally, the various nanoformulations that can be employed for selectively increasing the CNS bioavailability of GLT1 (EAAT2) upregulators are discussed. Finally, the applicability of GLT1 (EAAT2) induction via central delivery of drug-loaded nanoformulations is described.

  17. 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.

  18. Topical report on a preconceptual design for the Spallation-Induced Lithium Conversion (SILC) target for the accelerator production of tritium (APT)

    International Nuclear Information System (INIS)

    Van Tuyle, G.J.; Cokinos, D.M.; Czajkowski, C.; Franz, E.M.; Kroeger, P.; Todosow, M.; Youngblood, R.; Zucker, M.

    1993-01-01

    The preconceptual design of the APT Li-Al target system, also referred to as the Spallation-Induced Lithium Conversion (SILC), target system, is summarized in this report. The system has been designed to produce a ''3/8 Goal'' quantity of tritium using the 200-mA, 1.0 GeV proton beam emerging from the LANL-designed LINAC. The SILC target system consists of a beam expander, a heavy-water-cooled lead spallation neutron source assembly surrounded by light-water-cooled Li-Al blankets, a target window, heat removal systems, and related safety systems. The preconceptual design of each of these major components is described. Descriptions are also provided for the target fabrication, tritium extraction, and waste-steam processes. Performance characteristics are presented and discussed

  19. Topical report on a preconceptual design for the Spallation-Induced Lithium Conversion (SILC) target for the accelerator production of tritium (APT)

    Energy Technology Data Exchange (ETDEWEB)

    Van Tuyle, G.J.; Cokinos, D.M.; Czajkowski, C.; Franz, E.M.; Kroeger, P.; Todosow, M.; Youngblood, R.; Zucker, M.

    1993-09-30

    The preconceptual design of the APT Li-Al target system, also referred to as the Spallation-Induced Lithium Conversion (SILC), target system, is summarized in this report. The system has been designed to produce a ``3/8 Goal`` quantity of tritium using the 200-mA, 1.0 GeV proton beam emerging from the LANL-designed LINAC. The SILC target system consists of a beam expander, a heavy-water-cooled lead spallation neutron source assembly surrounded by light-water-cooled Li-Al blankets, a target window, heat removal systems, and related safety systems. The preconceptual design of each of these major components is described. Descriptions are also provided for the target fabrication, tritium extraction, and waste-steam processes. Performance characteristics are presented and discussed.

  20. The Use of Stilbene Scaffold in Medicinal Chemistry and Multi- Target Drug Design.

    Science.gov (United States)

    Giacomini, Elisa; Rupiani, Sebastiano; Guidotti, Laura; Recanatini, Maurizio; Roberti, Marinella

    2016-01-01

    The stilbene scaffold is a basic element for a number of biologically active natural and synthetic compounds, and it is considered as a privileged structure. Stilbenes exemplified by resveratrol, combretastatin A-4 and pterostilbene are of significant interest for drug research and development because of their potential in therapeutic and preventive application. Resveratrol, present in grapes and other food products, plays a role in the prevention of several human pathological processes and has been suggested as an anticancer agent. Moreover, recent evidence has revealed its potential effect on the aging process, diabetes and neurological dysfunction. Combretastatin A-4, from the bark of South African bush willow Combretum caffrum, also shows significant antitumor activity. Pterostilbene is closely related to resveratrol, sharing the same unique therapeutic potential as anti-inflammatory, antineoplastic and antioxidant agent. Therefore, research and development of stilbene-based medicinal chemistry have become rapidly evolving and increasingly active topics covering almost the whole range of therapeutic fields. In the present review, we provide an overview of the role of stilbenes in medicinal chemistry. In this context, we highlight the chemical methodologies adopted for the synthesis of stilbene derivatives, and outline the successful design of novel stilbene based hybrids in the field of cancer, Alzheimer's and other relevant diseases. This information may be useful in further design of stilbene-based molecules as new leads for the development of novel agents with clinical potential or as effective chemical probes to dissect biological processes.

  1. Design and construction of a time-of-flight wall detector at External Target Facility of HIRFL-CSR

    Science.gov (United States)

    Sun, Y.; Sun, Z. Y.; Yu, Y. H.; Yan, D.; Tang, S. W.; Sun, Y. Z.; Wang, S. T.; Zhang, X. H.; Yue, K.; Fang, F.; Chen, J. L.; Zhang, Y. J.; Hu, B. T.

    2018-06-01

    A Time-Of-Flight Wall (TOFW) detector has been designed and constructed at the External Target Facility (ETF) of HIRFL-CSR. The detector covers a sensitive area of 1.2 × 1.2 m2 and consists of 30 modules. Each module is composed of a long plastic scintillator bar with two photo-multiplier tubes coupled at both ends for readout. The design and manufacture details are described and the test results are reported. The performance of the TOFW detector has been tested and measured with cosmic rays and a 310 MeV/u 40Ar beam. The results show that the time resolutions of all the TOFW modules are better than 128 ps, satisfying the requirements of the experiments which will be carried out at the ETF.

  2. Genetic modification of hematopoietic cells using retroviral and lentiviral vectors: safety considerations for vector design and delivery into target cells.

    Science.gov (United States)

    Dropulic, Boro

    2005-07-01

    The recent development of leukemia in three patients following retroviral vector gene transfer in hematopoietic stem cells, resulting in the death of one patient, has raised safety concerns for the use of integrating gene transfer vectors for human gene therapy. This review discusses these serious adverse events from the perspective of whether restrictions on vector design and vector-modified target cells are warranted at this time. A case is made against presently establishing specific restrictions for vector design and transduced cells; rather, their safety should be ascertained by empiric evaluation in appropriate preclinical models on a case-by-case basis. Such preclinical data, coupled with proper informed patient consent and a risk-benefit ratio analysis, provide the best available prospective evaluation of gene transfer vectors prior to their translation into the clinic.

  3. Rational Design of Glycomimetic Compounds Targeting the Saccharomyces cerevisiae Transglycosylase Gas2.

    Science.gov (United States)

    Delso, Ignacio; Valero-González, Jessika; Marca, Eduardo; Tejero, Tomás; Hurtado-Guerrero, Ramón; Merino, Pedro

    2016-02-01

    The transglycosylase Saccharomyces cerevisiae Gas2 (ScGas2) belongs to a large family of enzymes that are key players in yeast cell wall remodeling. Despite its biologic importance, no studies on the synthesis of substrate-based compounds as potential inhibitors have been reported. We have synthesized a series of docking-guided glycomimetics that were evaluated by fluorescence spectroscopy and saturation-transfer difference (STD) NMR experiments, revealing that a minimum of three glucose units linked via a β-(1,3) linkage are required for achieving molecular recognition at the binding donor site. The binding mode of our compounds is further supported by STD-NMR experiments using the active site-mutants Y107Q and Y244Q. Our results are important for both understanding of ScGas2-substrate interactions and setting up the basis for future design of glycomimetics as new antifungal agents. © 2015 John Wiley & Sons A/S.

  4. Graphene stirrer with designed movements: Targeting on environmental remediation and supercapacitor applications

    Directory of Open Access Journals (Sweden)

    Yang Huang

    2018-01-01

    Full Text Available Beyond the traditional focus on improvements in mechanical, electronic and absorption properties, controllability, actuation, and dynamic response of monoliths have received increasing attentions for practical applications. However, most of them could only realize simple response to constant conditions (e.g. a stationary magnetic field while carrying out humdrum motions. By controlling distribution of metal organic framework obtained carbon-enriched Fe3O4 nanoparticles in self-assembly reduced graphene oxide (RGO monoliths, we could achieve two distinctive RGO–Fe3O4 stirrers that could dynamically respond to the rapidly changing magnetic field while executing designed movements precisely: rotating with lying down posture or standing straight posture. These stirrers can not only be applied in environmental remediation (e.g. suction skimmer, but also be recycled as electrode active materials for supercapacitors after fulfilling their destiny, realizing transformation of trash to treasure, which will inspire other dynamically responsive monoliths for various applications.

  5. Design of multifunctional magnetic iron oxide nanoparticles/mitoxantrone-loaded liposomes for both magnetic resonance imaging and targeted cancer therapy.

    Science.gov (United States)

    He, Yingna; Zhang, Linhua; Zhu, Dunwan; Song, Cunxian

    2014-01-01

    Tumor-targeting multifunctional liposomes simultaneously loaded with magnetic iron oxide nanoparticles (MIONs) as a magnetic resonance imaging (MRI) contrast agent and anticancer drug, mitoxantrone (Mit), were developed for targeted cancer therapy and ultrasensitive MRI. The gonadorelin-functionalized MION/Mit-loaded liposome (Mit-GML) showed significantly increased uptake in luteinizing hormone-releasing hormone (LHRH) receptor overexpressing MCF-7 (Michigan Cancer Foundation-7) breast cancer cells over a gonadorelin-free MION/Mit-loaded liposome (Mit-ML) control, as well as in an LHRH receptor low-expressing Sloan-Kettering HER2 3+ Ovarian Cancer (SK-OV-3) cell control, thereby leading to high cytotoxicity against the MCF-7 human breast tumor cell line. The Mit-GML formulation was more effective and less toxic than equimolar doses of free Mit or Mit-ML in the treatment of LHRH receptors overexpressing MCF-7 breast cancer xenografts in mice. Furthermore, the Mit-GML demonstrated much higher T2 enhancement than did Mit-ML controls in vivo. Collectively, the study indicates that the integrated diagnostic and therapeutic design of Mit-GML nanomedicine potentially allows for the image-guided, target-specific treatment of cancer.

  6. Targeting (cellular) lysosomal acid ceramidase by B13: design, synthesis and evaluation of novel DMG-B13 ester prodrugs.

    Science.gov (United States)

    Bai, Aiping; Szulc, Zdzislaw M; Bielawski, Jacek; Pierce, Jason S; Rembiesa, Barbara; Terzieva, Silva; Mao, Cungui; Xu, Ruijuan; Wu, Bill; Clarke, Christopher J; Newcomb, Benjamin; Liu, Xiang; Norris, James; Hannun, Yusuf A; Bielawska, Alicja

    2014-12-15

    Acid ceramidase (ACDase) is being recognized as a therapeutic target for cancer. B13 represents a moderate inhibitor of ACDase. The present study concentrates on the lysosomal targeting of B13 via its N,N-dimethylglycine (DMG) esters (DMG-B13 prodrugs). Novel analogs, the isomeric mono-DMG-B13, LCL522 (3-O-DMG-B13·HCl) and LCL596 (1-O-DMG-B13·HCl) and di-DMG-B13, LCL521 (1,3-O, O-DMG-B13·2HCl) conjugates, were designed and synthesized through N,N-dimethyl glycine (DMG) esterification of the hydroxyl groups of B13. In MCF7 cells, DMG-B13 prodrugs were efficiently metabolized to B13. The early inhibitory effect of DMG-B13 prodrugs on cellular ceramidases was ACDase specific by their lysosomal targeting. The corresponding dramatic decrease of cellular Sph (80-97% Control/1h) by DMG-B13 prodrugs was mainly from the inhibition of the lysosomal ACDase. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Design choices made by target users for a pay-for-performance program in primary care: an action research approach

    Directory of Open Access Journals (Sweden)

    Kirschner Kirsten

    2012-03-01

    Full Text Available Abstract Background International interest in pay-for-performance (P4P initiatives to improve quality of health care is growing. Current programs vary in the methods of performance measurement, appraisal and reimbursement. One may assume that involvement of health care professionals in the goal setting and methods of quality measurement and subsequent payment schemes may enhance their commitment to and motivation for P4P programs and therefore the impact of these programs. We developed a P4P program in which the target users were involved in decisions about the P4P methods. Methods For the development of the P4P program a framework was used which distinguished three main components: performance measurement, appraisal and reimbursement. Based on this framework design choices were discussed in two panels of target users using an adapted Delphi procedure. The target users were 65 general practices and two health insurance companies in the South of the Netherlands. Results Performance measurement was linked to the Dutch accreditation program based on three domains (clinical care, practice management and patient experience. The general practice was chosen as unit of assessment. Relative standards were set at the 25th percentile of group performance. The incentive for clinical care was set twice as high as the one for practice management and patient experience. Quality scores were to be calculated separately for all three domains, and for both the quality level and the improvement of performance. The incentive for quality level was set thrice as high as the one for the improvement of performance. For reimbursement, quality scores were divided into seven levels. A practice with a quality score in the lowest group was not supposed to receive a bonus. The additional payment grew proportionally for each extra group. The bonus aimed at was on average 5% to 10% of the practice income. Conclusions Designing a P4P program for primary care with involvement of

  8. Design choices made by target users for a pay-for-performance program in primary care: an action research approach

    Science.gov (United States)

    2012-01-01

    Background International interest in pay-for-performance (P4P) initiatives to improve quality of health care is growing. Current programs vary in the methods of performance measurement, appraisal and reimbursement. One may assume that involvement of health care professionals in the goal setting and methods of quality measurement and subsequent payment schemes may enhance their commitment to and motivation for P4P programs and therefore the impact of these programs. We developed a P4P program in which the target users were involved in decisions about the P4P methods. Methods For the development of the P4P program a framework was used which distinguished three main components: performance measurement, appraisal and reimbursement. Based on this framework design choices were discussed in two panels of target users using an adapted Delphi procedure. The target users were 65 general practices and two health insurance companies in the South of the Netherlands. Results Performance measurement was linked to the Dutch accreditation program based on three domains (clinical care, practice management and patient experience). The general practice was chosen as unit of assessment. Relative standards were set at the 25th percentile of group performance. The incentive for clinical care was set twice as high as the one for practice management and patient experience. Quality scores were to be calculated separately for all three domains, and for both the quality level and the improvement of performance. The incentive for quality level was set thrice as high as the one for the improvement of performance. For reimbursement, quality scores were divided into seven levels. A practice with a quality score in the lowest group was not supposed to receive a bonus. The additional payment grew proportionally for each extra group. The bonus aimed at was on average 5% to 10% of the practice income. Conclusions Designing a P4P program for primary care with involvement of the target users gave us an

  9. Recurrence pattern of squamous cell carcinoma in the midthoracic esophagus: implications for the clinical target volume design of postoperative radiotherapy

    Directory of Open Access Journals (Sweden)

    Wang X

    2016-10-01

    Full Text Available Xiaoli Wang,1,2,* Yijun Luo,1,2,* Minghuan Li,2 Hongjiang Yan,2 Mingping Sun,2 Tingyong Fan2 1School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Background: Postoperative radiotherapy has shown positive efficacy in lowering the recurrence rate and improving the survival rate for patients with esophageal squamous cell carcinoma (ESCC. However, controversies still exist about the postoperative prophylactic radiation target volume. This study was designed to analyze the patterns of recurrence and to provide a reference for determination of the postoperative radiotherapy target volume for patients with midthoracic ESCC.Patients and methods: A total of 338 patients with recurrent or metastatic midthoracic ESCC after radical surgery were retrospectively examined. The patterns of recurrence including locoregional and distant metastasis were analyzed for these patients.Results: The rates of lymph node (LN metastasis were 28.4% supraclavicular, 77.2% upper mediastinal, 32.0% middle mediastinal, 50.0% lower mediastinal, and 19.5% abdominal LNs. In subgroup analyses, the rate of abdominal LN metastasis was significantly higher in patients with histological node-positive than that in patients with histological node-negative (P=0.033. Further analysis in patients with histological node-positive demonstrated that patients with three or more positive nodes are more prone to abdominal LN metastasis, compared with patients with one or two positive nodes (χ2=4.367, P=0.037. The length of tumor and histological differentiation were also the high-risk factors for abdominal LN metastasis.Conclusion: For midthoracic ESCC with histological node-negative, or one or two positive nodes, the supraclavicular and

  10. Design, synthesis, and testing of multivalent compounds targeted to melanocortin receptors

    Science.gov (United States)

    Dehigaspitiya, Dilani Chathurika

    Our focus is on developing non-invasive molecular imaging reagents, which target human cancers that presently are difficult to detect, such as melanoma. We wish to apply the multivalency concept to differentiate between healthy cells and melanoma cells. Melanoma cells are known to over-express alpha melanocyte stimulating hormone receptors. A successful multivalent construct should show greater avidity towards melanoma cells than healthy cells due to the synergistic effects arising from multivalency. Both oligomeric and shorter linear constructs bearing the minimum active sequence of melanocyte stimulating hormone, His-DPhe-Arg-Trp-NH2(MSH4), which binds with low micromolar affinity to alpha melanocyte stimulating hormone receptors, were synthesized. Binding affinities of these constructs were evaluated in a competitive binding assay by competing with labeled ligands, Eu-DTPA-PEGO-MSH7 and/or Eu-DTPA-PEGO-NDP-alpha-MSH on the engineered cell line HEK293 CCK2R/hMC4R, which is genetically modified to over-express both the cholecystokinin 2 receptor (CCK2R) and human melanocortin 4 receptor (hMC4R). The oligomers were rapidly assembled using microwave-assisted copper catalyzed azide-alkyne cycloaddition between a dialkyne derivative of MSH4 and a diazide derivative of (Pro-Gly)3 as co-monomers. Three oligomer mixtures were further analyzed based on their degree of oligomerization and the route by which the MSH4 monomers were oligomerized, protected vs deprotected. Completive binding assay against Eu-DTPA-PEGO-MSH7 showed only a statistical enhancement of binding when calculated based on the total MSH4 concentration. However, when the calculation of avidity is based on an estimation of the particles numbers, there was a seven times enhancement of binding compared to a monovalent MSH4 control. The shorter linear multivalent MSH4 constructs were synthesized using ethylene glycol, glycerol, and mannitol as core scaffolds with maximum inter-ligand distances ranging from 27

  11. In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Antony M Latham

    Full Text Available Protein kinases play a central role in tumor progression, regulating fundamental processes such as angiogenesis, proliferation and metastasis. Such enzymes are an increasingly important class of drug target with small molecule kinase inhibitors being a major focus in drug development. However, balancing drug specificity and efficacy is problematic with off-target effects and toxicity issues.We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2 and cyclin-dependent kinase 1 (CDK1. This compound acts by simultaneously inhibiting pro-angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A-mediated signaling response and CDK1-mediated mitotic entry elicits anti-angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis.We deduce that JK-31 reduces the growth of both human endothelial cells and human breast cancer cells in vitro. This novel synthetic molecule has broad implications for development of similar multi-kinase inhibitors with anti-angiogenic and anti-cancer properties. In silico design is an attractive and innovative method to aid such drug discovery.

  12. In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis.

    Science.gov (United States)

    Latham, Antony M; Kankanala, Jayakanth; Fearnley, Gareth W; Gage, Matthew C; Kearney, Mark T; Homer-Vanniasinkam, Shervanthi; Wheatcroft, Stephen B; Fishwick, Colin W G; Ponnambalam, Sreenivasan

    2014-01-01

    Protein kinases play a central role in tumor progression, regulating fundamental processes such as angiogenesis, proliferation and metastasis. Such enzymes are an increasingly important class of drug target with small molecule kinase inhibitors being a major focus in drug development. However, balancing drug specificity and efficacy is problematic with off-target effects and toxicity issues. We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro-angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated signaling response and CDK1-mediated mitotic entry elicits anti-angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis. We deduce that JK-31 reduces the growth of both human endothelial cells and human breast cancer cells in vitro. This novel synthetic molecule has broad implications for development of similar multi-kinase inhibitors with anti-angiogenic and anti-cancer properties. In silico design is an attractive and innovative method to aid such drug discovery.

  13. Design and performance of a clean and economic power supply targeting energy independence and operative security

    Energy Technology Data Exchange (ETDEWEB)

    Mushtaha, Mohammed

    2012-07-01

    Stand alone wind-diesel power systems address the major issues for the supply of remotely located consumers or the provision of enhanced energy independence. The specific configuration considered here comprises a prior wind turbine driven induction generator and a supplementary synchronous generator driven by a combustion engine, the latter caring for frequency control and reactive power balance. An accumulator-bank and a hydrogen storage path consisting of an electrolyzer and a hydrogen storage tank are added as short-term and long-term storage devices - respectively - in order to adjust volatile wind generation and varying load demand. The hydrogen re-conversion to electricity is achieved by design of the drive of the synchronous generator as a dual-fuel engine, fed with stored hydrogen primarily, and with diesel oil in case of the rare event of hydrogen storage emptiness. An elementary waste heat recovery from engine cooling water and from exhaust gases makes the system even more energy efficient and environment friendly. For proper sizing of the particular system components under minimization of the life cycle cost - which are composed of the initial installation cost, the replacement cost, the operation and maintenance cost as well as the remaining fuel cost - the meta-heuristic computational method of Particle Swarm Optimization (PSO) was applied. The crucial task of intelligently managing the energy storage strategy depending on their actual states of charge and the current excess power under a given load profile was solved by a fuzzy system and a subsequent time scheduler, the latter providing definite set-point steps for definite periods of time to the electrolyzer in order to achieve smooth and conservative operation. The concrete design and performance of the proposed system structure is shown with the two relevant application examples of independent electricity supply of the main hospital in Gaza-Strip, Palestine, and a remotely located dairy farm. For

  14. Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future.

    Science.gov (United States)

    Hol, Wim G J

    2015-05-01

    Parasitic protozoa cause a range of diseases which threaten billions of human beings. They are responsible for tremendous mortality and morbidity in the least-developed areas of the world. Presented here is an overview of the evolution over the last three to four decades of structure-guided design of inhibitors, leads and drug candidates aiming at targets from parasitic protozoa. Target selection is a crucial and multi-faceted aspect of structure-guided drug design. The major impact of advances in molecular biology, genome sequencing and high-throughput screening is touched upon. The most advanced crystallographic techniques, including XFEL, have already been applied to structure determinations of drug targets from parasitic protozoa. Even cryo-electron microscopy is contributing to our understanding of the mode of binding of inhibitors to parasite ribosomes. A number of projects have been selected to illustrate how structural information has assisted in arriving at promising compounds that are currently being evaluated by pharmacological, pharmacodynamic and safety tests to assess their suitability as pharmaceutical agents. Structure-guided approaches are also applied to incorporate properties into compounds such that they are less likely to become the victim of resistance mechanisms. A great increase in the number of novel antiparasitic compounds will be needed in the future. These should then be combined into various multi-compound therapeutics to circumvent the diverse resistance mechanisms that render single-compound, or even multi-compound, drugs ineffective. The future should also see (i) an increase in the number of projects with a tight integration of structural biology, medicinal chemistry, parasitology and pharmaceutical sciences; (ii) the education of more `medicinal structural biologists' who are familiar with the properties that compounds need to have for a high probability of success in the later steps of the drug-development process; and (iii) the

  15. Culturally sensitive strategies designed to target the silent epidemic of hepatitis B in a Filipino community.

    Science.gov (United States)

    Marineau, Michelle; Tice, Alan D; Taylor-Garcia, David; Akinaka, Kenneth T; Lusk, Heather; Ona, Fernando

    2007-06-01

    Hepatitis B is frequent in the Philippines. A high rate of immigration to the United States has brought many Filipinos with infections who are asymptomatic yet will go on to develop liver cancer and cirrhosis unless diagnose and evaluated. Interventions are necessary to educate this ethnic community, identify those infected, and offer therapy. In an effort to reach this high risk population in Hawai'i an intervention program was designed to address the silent epidemic of hepatitis. Ethnic barriers were crossed through involvement of trusted, key stakeholders and individuals within the Filipino health care and church communities, along with groups that had joint missions to address viral hepatitis. After extensive planning and meetings with faith-based organizations and health care providers in the Filipino community, it was decided to hold a community health fair in the Filipino community to provide culturally appropriate health information and services. More than 500 individuals attended the health fair; 167 participated in a survey and were tested for hepatitis B. Significant knowledge gaps were found in relation to risk factors, prevention strategies, and transmission. Five individuals tested positive; all were immigrants and did not know of their disease. The objective to educate people and test them for hepatitis was successful through utilizing ethnic community leaders, religious organizations, health care professionals, and a collaborative health fair.

  16. Design, synthesis and activity of BBI608 derivatives targeting on stem cells.

    Science.gov (United States)

    Zhou, Qifan; Peng, Chen; Du, Fangyu; Zhou, Linbo; Shi, Yajie; Du, Yang; Liu, Dongdong; Sun, Wenjiao; Zhang, Meixia; Chen, Guoliang

    2018-05-10

    STAT3 plays a vital role in maintaining the self-renewal of tumor stem cells. BBI608, a small molecule identified by its ability to inhibit gene transcription driven by STAT3 and cancer stemness properties, can inhibit stemness gene expression and kill stemness-high cancer cells isolated from a variety of cancer types. In order to improve the pharmacokinetic properties of BBI608 and the antitumor activity, a series of BBI608 derivatives were designed and synthesized here. Most of these compounds were more potent than BBI608 on HepG2 cells, compound LD-8 had the most potent inhibitory activity among them and was 5.4-fold more potent than BBI608 (IC 50  = 11.2 μM), but had considerable activity on normal liver cells L-02. Compounds LD-17 (IC 50  = 3.5 μM) and LD-19 (IC 50  = 2.9 μM) were found to possess significant inhibitory activities and good selectivity. The results showed that compound LD-19 was worthy to investigate further as a lead compound according to its potent inhibitory activity, ideal ClogP value and better water solubility. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. Designing Targets for Elective Nodal Irradiation in Lung Cancer Radiotherapy: A Planning Study

    International Nuclear Information System (INIS)

    Kepka, Lucyna; Tatro, Daniel; Moran, Jean M.; Quint, Leslie E.; Hayman, James A.; Ten Haken, Randall K.; Kong Fengming

    2009-01-01

    Purpose: To assess doses received by mediastinal and hilar lymph node stations (LNS) delineated according to published recommendations when 'standard' two-dimensional (2D) elective fields are applied and to assess doses to critical structures when fields are designed using 2D and three-dimensional (3D) treatment planning for elective irradiation. Methods and Materials: LNS were delineated on axial CT scans according to existing recommendations. For each case and tumor location, 2D anteroposterior-posteroanterior (AP-PA) elective fields were applied using the AP-PA CT topograms. From the 2D portal fields, 3D dose distributions were then calculated to particular LNS. Next, 3D plans were prepared for elective nodal irradiation for tumors of different lobes. Doses for critical structures were compared for 2D and 3D plans. Results: LNS 1/2R, 1/2L, 3A, 3P, 5, 6, and 8 were not adequately covered in a substantial part of plans by standard 2D portals when guidelines for delineation were strictly followed. The magnitude of the lack of coverage increased with margin application. There was a trend for a higher yet probably still safe dose delivered to lung for 3D plans compared with 2D plans with a prescription dose of 45 Gy. Conclusions: 2D fields did not entirely cover LNS delineated according to the recommendations for 3D techniques. A strict adherence to these guidelines may lead to larger portals than traditionally constructed using 2D methods. Some modifications for clinical implementation are discussed.

  18. A new drug design targeting the adenosinergic system for Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Nai-Kuei Huang

    Full Text Available BACKGROUND: Huntington's disease (HD is a neurodegenerative disease caused by a CAG trinucleotide expansion in the Huntingtin (Htt gene. The expanded CAG repeats are translated into polyglutamine (polyQ, causing aberrant functions as well as aggregate formation of mutant Htt. Effective treatments for HD are yet to be developed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a novel dual-function compound, N(6-(4-hydroxybenzyladenine riboside (designated T1-11 which activates the A(2AR and a major adenosine transporter (ENT1. T1-11 was originally isolated from a Chinese medicinal herb. Molecular modeling analyses showed that T1-11 binds to the adenosine pockets of the A(2AR and ENT1. Introduction of T1-11 into the striatum significantly enhanced the level of striatal adenosine as determined by a microdialysis technique, demonstrating that T1-11 inhibited adenosine uptake in vivo. A single intraperitoneal injection of T1-11 in wildtype mice, but not in A(2AR knockout mice, increased cAMP level in the brain. Thus, T1-11 enters the brain and elevates cAMP via activation of the A(2AR in vivo. Most importantly, addition of T1-11 (0.05 mg/ml to the drinking water of a transgenic mouse model of HD (R6/2 ameliorated the progressive deterioration in motor coordination, reduced the formation of striatal Htt aggregates, elevated proteasome activity, and increased the level of an important neurotrophic factor (brain derived neurotrophic factor in the brain. These results demonstrate the therapeutic potential of T1-11 for treating HD. CONCLUSIONS/SIGNIFICANCE: The dual functions of T1-11 enable T1-11 to effectively activate the adenosinergic system and subsequently delay the progression of HD. This is a novel therapeutic strategy for HD. Similar dual-function drugs aimed at a particular neurotransmitter system as proposed herein may be applicable to other neurotransmitter systems (e.g., the dopamine receptor/dopamine transporter and the serotonin receptor

  19. Development of a methodology for defining whole-building energy design targets for commercial buildings: Phase 2, Development Concept Stage Report

    Energy Technology Data Exchange (ETDEWEB)

    McKay, H.N. (Illuminating Engineering Society of North America, New York, NY (USA)); Deringer, J.J. (American Inst. of Architects, Washington, DC (USA)); Jones, J.W. (American Society of Heating, Refrigerating and Air-Conditioning Engineers, Inc., Atlanta, GA (USA)); Hall, J.D. (Deringer Group, Riva, MD (USA))

    1990-09-01

    This report documents eight tasks performed as part of the Whole-Building Energy Design Targets project, in which detailed conceptual approaches were produced for each element of the proposed Targets model. The eight task reports together describe the important modules proposed for inclusion in the Targets model: input module, energy module, characteristic development moduel, building cost module, analysis control module, energy cost module, search routines module, and economic analysis module. 16 refs., 16 figs., 5 tabs.

  20. Design risk analysis comparison between low-activation composite and aluminum alloy target chamber for the National Ignition Facility

    International Nuclear Information System (INIS)

    Streckert, H.H.; Schleicher, R.W.

    1997-01-01

    The baseline design for the target chamber for the National Ignition Facility (NIF) consists of an aluminum alloy spherical shell. A low-activation composite chamber (e.g., carbon fiber/epoxy) has important advantages such as enhanced environmental and safety characteristics, improved chamber accessibility due to reduced neutron-induced radioactivity, and elimination of the concrete shield. However, it is critical to determine the design and manufacturing risk for the first application. The replacement of such a critical component requires a detailed development risk assessment. A semiquantitative approach to risk assessment has been applied to this problem based on failure modes, effects, and criticality analysis. This analysis consists of a systematic method for organizing the collective judgment of the designers to identify failure modes, estimate probabilities, judge the severity of the consequence, and illustrate risk in a matrix representation. The results of the analyses indicate that the composite chamber has a reasonably high probability of success in the NIF application. The aluminum alloy chamber, however, represents a lower risk, partially based on a more mature technology. 8 refs., 4 figs., 5 tabs

  1. The flush-mounted rail Langmuir probe array designed for the Alcator C-Mod vertical target plate divertor

    Science.gov (United States)

    Kuang, A. Q.; Brunner, D.; LaBombard, B.; Leccacorvi, R.; Vieira, R.

    2018-04-01

    An array of flush-mounted and toroidally elongated Langmuir probes (henceforth called rail probes) have been specifically designed for the Alcator C-Mod's vertical target plate divertor and operated over multiple campaigns. The "flush" geometry enables the tungsten electrodes to survive high heat flux conditions in which traditional "proud" tungsten electrodes suffer damage from melting. The toroidally elongated rail-like geometry reduces the influence of sheath expansion, which is an important effect to consider in the design and interpretation of flush-mounted Langmuir probes. The new rail probes successfully operated during C-Mod's FY2015 and FY2016 experimental campaigns with no evidence of damage, despite being regularly subjected to heat flux densities parallel to the magnetic field exceeding ˜1 GW m-2 for short periods of time. A comparison between rail and proud probe data indicates that sheath expansion effects were successfully mitigated by the rail design, extending the use of these Langmuir probes to incident magnetic field line angles as low as 0.5°.

  2. Computation-based virtual screening for designing novel antimalarial drugs by targeting falcipain-III: a structure-based drug designing approach.

    Science.gov (United States)

    Kesharwani, Rajesh Kumar; Singh, Durg Vijay; Misra, Krishna

    2013-01-01

    Cysteine proteases (falcipains), a papain-family of enzymes of Plasmodium falciparum, are responsible for haemoglobin degradation and thus necessary for its survival during asexual life cycle phase inside the human red blood cells while remaining non-functional for the human body. Therefore, these can act as potential targets for designing antimalarial drugs. The P. falciparum cysteine proteases, falcipain-II and falcipain- III are the enzymes which initiate the haemoglobin degradation, therefore, have been selected as targets. In the present study, we have designed new leupeptin analogues and subjected to virtual screening using Glide at the active site cavity of falcipain-II and falcipain-III to select the best docked analogues on the basis of Glide score and also compare with the result of AutoDock. The proposed analogues can be synthesized and tested in vivo as future potent antimalarial drugs. Protein falcipain-II and falcipain-III together with bounds inhibitors epoxysuccinate E64 (E64) and leupeptin respectively were retrieved from protein data bank (PDB) and latter leupeptin was used as lead molecule to design new analogues by using Ligbuilder software and refined the molecules on the basis of Lipinski rule of five and fitness score parameters. All the designed leupeptin analogues were screened via docking simulation at the active site cavity of falcipain-II and falcipain-III by using Glide software and AutoDock. The 104 new leupeptin-based antimalarial ligands were designed using structure-based drug designing approach with the help of Ligbuilder and subjected for virtual screening via docking simulation method against falcipain-II and falcipain-III receptor proteins. The Glide docking results suggest that the ligands namely result_037 shows good binding and other two, result_044 and result_042 show nearly similar binding than naturally occurring PDB bound ligand E64 against falcipain-II and in case of falcipain-III, 15 designed leupeptin analogues having

  3. Design, simulation and manufacture of a multi leaf collimator to confirm the target volumes in intensity modulated radiation therapy

    International Nuclear Information System (INIS)

    Kamali-Asl, A.; Batooli, A. H.; Harriri, S.; Salman-Rezaee, F.; Shahmardan, F.; Yavari, L.

    2010-01-01

    Intensity modulated radiation therapy is one of the cancer treatment methods. It is important to selectively aim at the target in this way, which can be performed using a multi leaf collimator. Materials and Methods: In order to specifically irradiate the target volume in radiotherapy to reduce the patient absorbed dose, the use of multi leaf collimator has been investigated in this work. Design and simulation of an multi leaf collimator was performed by a Monte Carlo method and the optimum material for manufacturing the leaves was determined using MCNP4C. After image processing (CT or MRI) in this system, the tumor configuration is determined. Then the linear accelerator is switched on and the beam irradiates the cancerous cells. When the multi leaf collimator leaves receive a command from the micro controller, they start to move and absorb the radiation and modulate its intensity. Consequently, the tumor receives maximum intensity of radiation but minimum intensity is delivered to healthy tissues. Results: According to the simulations and calculations, the best material to manufacture the leaves from is tungsten alloy containing copper and nickel which absorbs a large amount of the radiation; by using a 8.65 cm thickness of alloy, 10.55% of radiation will transmit through the leaves. Discussion and Conclusion: Lead blocks are conventionally used in radiotherapy. However, they have some problems like cost, storage and manufacture for every patient. Certainly, the multi leaf collimator is the most efficient device to specifically irradiate the tumor in Intensity modulated radiation therapy. Furthermore, it facilitates treating the target in different views by rotation around the patient. Thus the patient's absorbed dose will decrease and the tumor will receive maximum dose.

  4. Design and Generation of Humanized Single-chain Fv Derived from Mouse Hybridoma for Potential Targeting Application.

    Science.gov (United States)

    Khantasup, Kannika; Chantima, Warangkana; Sangma, Chak; Poomputsa, Kanokwan; Dharakul, Tararaj

    2015-12-01

    Single-chain variable antibody fragments (scFvs) are attractive candidates for targeted immunotherapy in several human diseases. In this study, a concise humanization strategy combined with an optimized production method for humanizing scFvs was successfully employed. Two antibody clones, one directed against the hemagglutinin of H5N1 influenza virus, the other against EpCAM, a cancer biomarker, were used to demonstrate the validity of the method. Heavy chain (VH) and light chain (VL) variable regions of immunoglobulin genes from mouse hybridoma cells were sequenced and subjected to the construction of mouse scFv 3-D structure. Based on in silico modeling, the humanized version of the scFv was designed via complementarity-determining region (CDR) grafting with the retention of mouse framework region (FR) residues identified by primary sequence analysis. Root-mean-square deviation (RMSD) value between mouse and humanized scFv structures was calculated to evaluate the preservation of CDR conformation. Mouse and humanized scFv genes were then constructed and expressed in Escherichia coli. Using this method, we successfully generated humanized scFvs that retained the targeting activity of their respective mouse scFv counterparts. In addition, the humanized scFvs were engineered with a C-terminal cysteine residue (hscFv-C) for site-directed conjugation for use in future targeting applications. The hscFv-C expression was extensively optimized to improve protein production yield. The protocol yielded a 20-fold increase in production of hscFv-Cs in E. coli periplasm. The strategy described in this study may be applicable in the humanization of other antibodies derived from mouse hybridoma.

  5. Designing the Sniper: Improving Targeted Human Cytolytic Fusion Proteins for Anti-Cancer Therapy via Molecular Simulation

    Directory of Open Access Journals (Sweden)

    Anna Bochicchio

    2017-02-01

    Full Text Available Targeted human cytolytic fusion proteins (hCFPs are humanized immunotoxins for selective treatment of different diseases including cancer. They are composed of a ligand specifically binding to target cells genetically linked to a human apoptosis-inducing enzyme. hCFPs target cancer cells via an antibody or derivative (scFv specifically binding to e.g., tumor associated antigens (TAAs. After internalization and translocation of the enzyme from endocytosed endosomes, the human enzymes introduced into the cytosol are efficiently inducing apoptosis. Under in vivo conditions such enzymes are subject to tight regulation by native inhibitors in order to prevent inappropriate induction of cell death in healthy cells. Tumor cells are known to upregulate these inhibitors as a survival mechanism resulting in escape of malignant cells from elimination by immune effector cells. Cytosolic inhibitors of Granzyme B and Angiogenin (Serpin P9 and RNH1, respectively, reduce the efficacy of hCFPs with these enzymes as effector domains, requiring detrimentally high doses in order to saturate inhibitor binding and rescue cytolytic activity. Variants of Granzyme B and Angiogenin might feature reduced affinity for their respective inhibitors, while retaining or even enhancing their catalytic activity. A powerful tool to design hCFPs mutants with improved potency is given by in silico methods. These include molecular dynamics (MD simulations and enhanced sampling methods (ESM. MD and ESM allow predicting the enzyme-protein inhibitor binding stability and the associated conformational changes, provided that structural information is available. Such “high-resolution” detailed description enables the elucidation of interaction domains and the identification of sites where particular point mutations may modify those interactions. This review discusses recent advances in the use of MD and ESM for hCFP development from the viewpoints of scientists involved in both fields.

  6. Design of multifunctional magnetic iron oxide nanoparticles/mitoxantrone-loaded liposomes for both magnetic resonance imaging and targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    He Y

    2014-08-01

    Full Text Available Yingna He,1 Linhua Zhang,2 Dunwan Zhu,2 Cunxian Song2 1Laboratory of Chinese Medicine Pharmacology, College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China; 2Key Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People’s Republic of China Abstract: Tumor-targeting multifunctional liposomes simultaneously loaded with magnetic iron oxide nanoparticles (MIONs as a magnetic resonance imaging (MRI contrast agent and anticancer drug, mitoxantrone (Mit, were developed for targeted cancer therapy and ultrasensitive MRI. The gonadorelin-functionalized MION/Mit-loaded liposome (Mit-GML showed significantly increased uptake in luteinizing hormone–releasing hormone (LHRH receptor overexpressing MCF-7 (Michigan Cancer Foundation-7 breast cancer cells over a gonadorelin-free MION/Mit-loaded liposome (Mit-ML control, as well as in an LHRH receptor low-expressing Sloan-Kettering HER2 3+ Ovarian Cancer (SK-OV-3 cell control, thereby leading to high cytotoxicity against the MCF-7 human breast tumor cell line. The Mit-GML formulation was more effective and less toxic than equimolar doses of free Mit or Mit-ML in the treatment of LHRH receptors overexpressing MCF-7 breast cancer xenografts in mice. Furthermore, the Mit-GML demonstrated much higher T2 enhancement than did Mit-ML controls in vivo. Collectively, the study indicates that the integrated diagnostic and therapeutic design of Mit-GML nanomedicine potentially allows for the image-guided, target-specific treatment of cancer. Keywords: multifunctional liposome, magnetic resonance imaging, theranostic nanomedicine, mitoxantrone, gonadorelin

  7. Implosion scaling and hydro dynamically equivalent target design - Strategy for proof of principle of high gain inertial fusion

    International Nuclear Information System (INIS)

    Murakami, M.; Nishihara, K.; Azechi, H.; Nakatsuka, M.; Kanabe, T.; Miyanaga, N.

    2003-01-01

    Scaling laws for hydro dynamically similar implosions are derived by applying Lie group analysis to the set of partial differential equations for the hydrodynamic system. Physically this implies that any fluid system belonging to a common similarity group evolves quite in the same manner including hydrodynamic instabilities. The scalings strongly depend on the description of the energy transport, i.e., whether the fluid system is heat conductive or adiabatic. Under a fully specified group transformation including prescriptions on the laser wavelength and the ionization state, the hydrodynamic similarity can still be preserved even when the system is cooperated with such other energy sources as classical laser absorption, hot electrons, local alpha heating, and bremsstrahlung loss. The results are expected to give the basis of target design and diagnostics for scaled high gain experiments in future. (author)

  8. Design, synthesis, and evaluation of 4,6-diaminonicotinamide derivatives as novel and potent immunomodulators targeting JAK3.

    Science.gov (United States)

    Nakajima, Yutaka; Aoyama, Naohiro; Takahashi, Fumie; Sasaki, Hiroshi; Hatanaka, Keiko; Moritomo, Ayako; Inami, Masamichi; Ito, Misato; Nakamura, Koji; Nakamori, Fumihiro; Inoue, Takayuki; Shirakami, Shohei

    2016-10-01

    In organ transplantation, T cell-mediated immune responses play a key role in the rejection of allografts. Janus kinase 3 (JAK3) is specifically expressed in hematopoietic cells and associated with regulation of T cell development via interleukin-2 signaling pathway. Here, we designed novel 4,6-diaminonicotinamide derivatives as immunomodulators targeting JAK3 for prevention of transplant rejection. Our optimization of C4- and C6-substituents and docking calculations to JAK3 protein confirmed that the 4,6-diaminonicotinamide scaffold resulted in potent inhibition of JAK3. We also investigated avoidance of human ether-a-go-go related gene (hERG) inhibitory activity. Selected compound 28 in combination with tacrolimus prevented allograft rejection in a rat heterotopic cardiac transplantation model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. In silico design of fragment-based drug targeting host processing α-glucosidase i for dengue fever

    Science.gov (United States)

    Toepak, E. P.; Tambunan, U. S. F.

    2017-02-01

    Dengue is a major health problem in the tropical and sub-tropical regions. The development of antiviral that targeting dengue’s host enzyme can be more effective and efficient treatment than the viral enzyme. Host enzyme processing α-glucosidase I has an important role in the maturation process of dengue virus envelope glycoprotein. The inhibition of processing α-glucosidase I can become a promising target for dengue fever treatment. The antiviral approach using in silico fragment-based drug design can generate drug candidates with high binding affinity. In this research, 198.621 compounds were obtained from ZINC15 Biogenic Database. These compounds were screened to find the favorable fragments according to Rules of Three and pharmacological properties. The screening fragments were docked into the active site of processing α-glucosidase I. The potential fragment candidates from the molecular docking simulation were linked with castanospermine (CAST) to generate ligands with a better binding affinity. The Analysis of ligand - enzyme interaction showed ligands with code LRS 22, 28, and 47 have the better binding free energy than the standard ligand. Ligand LRS 28 (N-2-4-methyl-5-((1S,3S,6S,7R,8R,8aR)-1,6,7,8-tetrahydroxyoctahydroindolizin-3-yl) pentyl) indolin-1-yl) propionamide) itself among the other ligands has the lowest binding free energy. Pharmacological properties prediction also showed the ligands LRS 22, 28, and 47 can be promising as the dengue fever drug candidates.

  10. Intranuclear biophotonics by smart design of nuclear-targeting photo-/radio-sensitizers co-loaded upconversion nanoparticles.

    Science.gov (United States)

    Fan, Wenpei; Shen, Bo; Bu, Wenbo; Zheng, Xiangpeng; He, Qianjun; Cui, Zhaowen; Ni, Dalong; Zhao, Kuaile; Zhang, Shengjian; Shi, Jianlin

    2015-11-01

    Biophotonic technology that uses light and ionizing radiation for positioned cancer therapy is a holy grail in the field of biomedicine because it can overcome the systemic toxicity and adverse side effects of conventional chemotherapy. However, the existing biophotonic techniques fail to achieve the satisfactory treatment efficacy, which remains a big challenge for clinical implementation. Herein, we develop a novel theranostic technique of "intranuclear biophotonics" by the smart design of a nuclear-targeting biophotonic system based on photo-/radio-sensitizers covalently co-loaded upconversion nanoparticles. These nuclear-targeting biophotonic agents can not only generate a great deal of multiple cytotoxic reactive oxygen species in the nucleus by making full use of NIR/X-ray irradiation, but also produce greatly enhanced intranuclear synergetic radio-/photodynamic therapeutic effects under the magnetic/luminescent bimodal imaging guidance, which may achieve the optimal efficacy in treating radio-resistant tumors. We anticipate that the highly effective intranuclear biophotonics will contribute significantly to the development of biophotonic techniques and open new perspectives for a variety of cancer theranostic applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin-avidin-specific binding.

    Science.gov (United States)

    Liu, Yongjun; Wu, Xiaoyun; Sun, Xiaohe; Wang, Dan; Zhong, Ying; Jiang, Dandan; Wang, Tianqi; Yu, Dexin; Zhang, Na

    2017-01-01

    Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin-avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P contrast agent and held great potential for molecular diagnosis of tumor.

  12. Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding

    Science.gov (United States)

    Liu, Yongjun; Wu, Xiaoyun; Sun, Xiaohe; Wang, Dan; Zhong, Ying; Jiang, Dandan; Wang, Tianqi; Yu, Dexin; Zhang, Na

    2017-01-01

    Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin–avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P<0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM−1 s−1) was observed compared to Magnevist® (4.9 mM−1 s−1; P<0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor. PMID:28765707

  13. National Ignition Facility subsystem design requirements laser and target area building (LTAB) SSDR 1.2.2.1

    International Nuclear Information System (INIS)

    Kempel, P.; Hands, J.

    1996-01-01

    This Subsystem Design Requirements (SSDR) document establishes the performance, design, and verification requirements for the conventional building systems and subsystems of the Laser and Target Area Building (LTAB), including those that house and support the operation of high-energy laser equipment and the operational flow of personnel and materials throughout the facility. This SSDR addresses the following subsystems associated with the LTAB: Building structural systems for the Target Bay, Switchyards, Diagnostic Building, Decontamination Area, Laser Bays, Capacitor Bays and Operations Support Area, and the necessary space associated with building-support equipment; Architectural building features associated with housing the space and with the operational cleanliness of the functional operation of the facilities; Heating, Ventilating, and Air Conditioning (HVAC) systems for maintaining a clean and thermally stable ambient environment within the facilities; Plumbing systems that provide potable water and sanitary facilities for the occupants, plus stormwater drainage for transporting rainwater; Fire Protection systems that guard against fire damage to the facilities and their contents; Material handling systems for transporting personnel and heavy materials within the building areas; Mechanical process piping systems for liquids and gases that provide cooling and other service to experimental laser equipment and components; Electrical power and grounding systems that provide service and standby power to building and experimental equipment, including lighting distribution and communications systems for the facilities; Instrumentation and control systems that ensure the safe operation of conventional facilities systems, such as those listed above. Detailed requirements for building subsystems that are not addressed in this document (such as specific sizes, locations, or capacities) are included in detail-level NIP Project Interface Control Documents (ICDS)

  14. Designing inhibitors of cytochrome c/cardiolipin peroxidase complexes: mitochondria-targeted imidazole-substituted fatty acids.

    Science.gov (United States)

    Jiang, Jianfei; Bakan, Ahmet; Kapralov, Alexandr A; Silva, K Ishara; Huang, Zhentai; Amoscato, Andrew A; Peterson, James; Garapati, Venkata Krishna; Saxena, Sunil; Bayir, Hülya; Atkinson, Jeffrey; Bahar, Ivet; Kagan, Valerian E

    2014-06-01

    Mitochondria have emerged as the major regulatory platform responsible for the coordination of numerous metabolic reactions as well as cell death processes, whereby the execution of intrinsic apoptosis includes the production of reactive oxygen species fueling oxidation of cardiolipin (CL) catalyzed by cytochrome (Cyt) c. As this oxidation occurs within the peroxidase complex of Cyt c with CL, the latter represents a promising target for the discovery and design of drugs with antiapoptotic mechanisms of action. In this work, we designed and synthesized a new group of mitochondria-targeted imidazole-substituted analogs of stearic acid TPP-n-ISAs with various positions of the attached imidazole group on the fatty acid (n = 6, 8, 10, 13, and 14). By using a combination of absorption spectroscopy and EPR protocols (continuous wave electron paramagnetic resonance and electron spin echo envelope modulation) we demonstrated that TPP-n-ISAs indeed were able to potently suppress CL-induced structural rearrangements in Cyt c, paving the way to its peroxidase competence. TPP-n-ISA analogs preserved the low-spin hexa-coordinated heme-iron state in Cyt c/CL complexes whereby TPP-6-ISA displayed a significantly more effective preservation pattern than TPP-14-ISA. Elucidation of these intermolecular stabilization mechanisms of Cyt c identified TPP-6-ISA as an effective inhibitor of the peroxidase function of Cyt c/CL complexes with a significant antiapoptotic potential realized in mouse embryonic cells exposed to ionizing irradiation. These experimental findings were detailed and supported by all-atom molecular dynamics simulations. Based on the experimental data and computation predictions, we identified TPP-6-ISA as a candidate drug with optimized antiapoptotic potency. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Population Connectivity Measures of Fishery-Targeted Coral Reef Species to Inform Marine Reserve Network Design in Fiji.

    Science.gov (United States)

    Eastwood, Erin K; López, Elora H; Drew, Joshua A

    2016-01-25

    Coral reef fish serve as food sources to coastal communities worldwide, yet are vulnerable to mounting anthropogenic pressures like overfishing and climate change. Marine reserve networks have become important tools for mitigating these pressures, and one of the most critical factors in determining their spatial design is the degree of connectivity among different populations of species prioritized for protection. To help inform the spatial design of an expanded reserve network in Fiji, we used rapidly evolving mitochondrial genes to investigate connectivity patterns of three coral reef species targeted by fisheries in Fiji: Epinephelus merra (Serranidae), Halichoeres trimaculatus (Labridae), and Holothuria atra (Holothuriidae). The two fish species, E. merra and Ha. trimaculatus, exhibited low genetic structuring and high amounts of gene flow, whereas the sea cucumber Ho. atra displayed high genetic partitioning and predominantly westward gene flow. The idiosyncratic patterns observed among these species indicate that patterns of connectivity in Fiji are likely determined by a combination of oceanographic and ecological characteristics. Our data indicate that in the cases of species with high connectivity, other factors such as representation or political availability may dictate where reserves are placed. In low connectivity species, ensuring upstream and downstream connections is critical.

  16. A target field design of open multi-purpose RF coil for musculoskeletal MR imaging at 3T.

    Science.gov (United States)

    Gao, Fei; Zhang, Rui; Zhou, Diange; Wang, Xiaoying; Huang, Kefu; Zhang, Jue

    2016-10-01

    Musculoskeletal MR imaging under multi-angle situations plays an increasingly important role in assessing joint and muscle tissues system. However, there are still limitations due to the closed structures of most conventional RF coils. In this study, a time-harmonic target-field method was employed to design open multi-purpose coil (OMC) for multi-angle musculoskeletal MR imaging. The phantom imaging results suggested that the proposed OMC could achieve homogeneously distributed magnetic field and high signal-to-noise ratio (SNR) of 239.04±0.83 in the region of interest (ROI). The maximum temperature in the heating hazard test was 16°C lower than the standard regulation, which indicated the security of the designed OMC. Furthermore, to demonstrate the effectiveness of the proposed OMC for musculoskeletal MR imaging, especially for multi-angle imaging, a healthy volunteer was examined for MR imaging of elbow, ankle and knee using OMC. The in vivo imaging results showed that the proposed OMC is effective for MR imaging of musculoskeletal tissues at different body parts, with satisfied B1 field homogeneity and SNR. Moreover, the open structure of the OMC could provide a large joint movement region. The proposed open multi-purpose coil is feasible for musculoskeletal MR imaging, and potentially, it is more suitable for the evaluation of musculoskeletal tissues under multi-angle conditions. Copyright © 2016. Published by Elsevier Inc.

  17. Bayesian approach to estimate AUC, partition coefficient and drug targeting index for studies with serial sacrifice design.

    Science.gov (United States)

    Wang, Tianli; Baron, Kyle; Zhong, Wei; Brundage, Richard; Elmquist, William

    2014-03-01

    The current study presents a Bayesian approach to non-compartmental analysis (NCA), which provides the accurate and precise estimate of AUC 0 (∞) and any AUC 0 (∞) -based NCA parameter or derivation. In order to assess the performance of the proposed method, 1,000 simulated datasets were generated in different scenarios. A Bayesian method was used to estimate the tissue and plasma AUC 0 (∞) s and the tissue-to-plasma AUC 0 (∞) ratio. The posterior medians and the coverage of 95% credible intervals for the true parameter values were examined. The method was applied to laboratory data from a mice brain distribution study with serial sacrifice design for illustration. Bayesian NCA approach is accurate and precise in point estimation of the AUC 0 (∞) and the partition coefficient under a serial sacrifice design. It also provides a consistently good variance estimate, even considering the variability of the data and the physiological structure of the pharmacokinetic model. The application in the case study obtained a physiologically reasonable posterior distribution of AUC, with a posterior median close to the value estimated by classic Bailer-type methods. This Bayesian NCA approach for sparse data analysis provides statistical inference on the variability of AUC 0 (∞) -based parameters such as partition coefficient and drug targeting index, so that the comparison of these parameters following destructive sampling becomes statistically feasible.

  18. Design of a TOF-SANS instrument for the proposed long wavelength target station at the spallation neutron source

    International Nuclear Information System (INIS)

    Thiyagarajan, P.; Littrell, K.; Seeger, P.A.

    2001-01-01

    We have designed a versatile high-throughput SANS instrument [Broad Range Intense Multipurpose SANS (BRIMS)] for the proposed Long Wavelength Target Station at the SNS by using acceptance diagrams and the Los Alamos NISP Monte Carlo simulation package. This instrument has been fully optimized to take advantage of the 10 Hz source frequency (broad wavelength bandwidth) and the cold neutron spectrum from a tall coupled solid methane moderator (12 cm x 20 cm). BRIMS has been designed to produce data in a Q range spanning from 0.0025 to 0.7 A -1 in a single measurement by simultaneously using neutrons with wavelengths ranging from 1 to 14.5 A in a time of flight mode. A supermirror guide and bender assembly is employed to separate and redirect the useful portion of the neutron spectrum with λ>1 A, by 2.3deg away from the direct beam containing high energy neutrons and γ rays. The effects of various collimation choices on count rate, resolution and Q min have been characterized using spherical particle and delta function scatterers. The overall performance of BRIMS has been compared with that of the best existing reactor-based SANS instrument D22 at ILL. (author)

  19. Toward the Target Model 2.0. Policy Recommendations for a Sustainable EU Power Market Design. Executive summary

    International Nuclear Information System (INIS)

    Roques, Fabien; Perekhodtsev, Dmitri; Verhaeghe, Charles

    2015-06-01

    One of the 10 key priorities of the new European Commission President Jean-Claude Juncker consists of 'reform(ing) and reorganis(ing) Europe's energy policy into a new European Energy Union'. The Energy Union work programme released on 25 February 2015 suggests that a new electricity market design is needed in order to tackle Europe's chosen policy objectives of de-carbonisation whilst maintaining security of supply. The current regulatory and market framework does not provide a sound basis for the investments needed to maintain security of supply and de-carbonise the power sector at an affordable cost. As policy priorities in favour of de-carbonisation and maintaining security of supply have taken centre stage on the policy agenda in the past decade, the design of liberalised electricity markets has failed to evolve and be reconciled with these new priorities. In addition, the issues of competitiveness and affordability of electricity in Europe remain central in the discussions about the market framework. The objective of this study is to assess the deficiencies and gaps in the current European Target Model and the wider regulatory framework for power generation and to propose a number of policy recommendations for improvement. Recognising the need for 'fresh thinking' on the issue, this study looks outside Europe to learn the lessons from experiences with a range of alternative market designs that exist around the globe. The study provides a comprehensive assessment of the issues with current European electricity markets. The study investigates the lessons from market reforms in North America and in Latin America in the past decade to identify 'out of the box' thinking to fill the gaps in the current European Target model. This report presents some of the research findings and concludes with a set of alternative potential directions for reform of European power markets models in the long term, as well as a number of

  20. Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding

    Directory of Open Access Journals (Sweden)

    Liu YJ

    2017-07-01

    Full Text Available Yongjun Liu,1 Xiaoyun Wu,1 Xiaohe Sun,1 Dan Wang,1 Ying Zhong,1 Dandan Jiang,1 Tianqi Wang,1 Dexin Yu,2 Na Zhang1 1School of Pharmaceutical Science, Shandong University, 2Department of Radiology Medicine, Qilu Hospital, Jinan, People’s Republic of China Abstract: Developing magnetic resonance imaging (MRI contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR-targeted poly (l-lysine (PLL-diethylene triamine pentacetate acid (DTPA-gadolinium (Gd (VEGFR-targeted PLL-DTPA-Gd, VPDG, was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin–avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22% in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG (25.16%±4.71%, P<0.05. In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM-1 s-1 was observed compared to Magnevist® (4.9 mM-1 s-1; P<0.01. Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h. These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor. Keywords: MRI, contrast agent, VEGFR, biotin–avidin reaction, relaxivity

  1. Preconceptual design of a Long-Pulse Spallation Source (LPSS) at the LANSCE Facility: Target system, facility, and material handling considerations

    International Nuclear Information System (INIS)

    Sommer, W.F.

    1995-12-01

    This report provides a summary of a preconceptual design study for the proposed Long-Pulse Spallation. Source (LPSS) at the Los Alamos Neutron Science Center (LANSCE). The LPSS will use a 0.8-MW proton beam to produce neutrons from a tungsten target. This study focuses on the design of the target station and changes to the existing building that would be made to accommodate the LPSS. The LPSS will provide fifteen flight paths to neutron scattering instruments. In addition, options for generating ultracold neutrons, pions, and muons will be available. Flight-energy, forward-scattered neutrons on the downstream side of the target will also be available for autoradiography studies. A Target Test Bed (TTB) is also proposed for full-beam tests of component materials and advanced spallation neutron sources. The design allows for separation of the experiment hall from the beam line, target, and flight paths. The target and moderator systems and the systems/components to be tested in the TTB will be emplaced and removed separately by remotely operated, shielded equipment. Irradiated materials will be transported to a hot cell adjacent to the target chamber for testing by remotely operated instruments. These tests will provide information about how materials properties are affected by proton and neutron beams

  2. Design, synthesis, and validation of a β-turn mimetic library targeting protein-protein and peptide-receptor interactions.

    Science.gov (United States)

    Whitby, Landon R; Ando, Yoshio; Setola, Vincent; Vogt, Peter K; Roth, Bryan L; Boger, Dale L

    2011-07-06

    The design and synthesis of a β-turn mimetic library as a key component of a small-molecule library targeting the major recognition motifs involved in protein-protein interactions is described. Analysis of a geometric characterization of 10,245 β-turns in the protein data bank (PDB) suggested that trans-pyrrolidine-3,4-dicarboxamide could serve as an effective and synthetically accessible library template. This was confirmed by initially screening select compounds against a series of peptide-activated GPCRs that recognize a β-turn structure in their endogenous ligands. This validation study was highlighted by identification of both nonbasic and basic small molecules with high affinities (K(i) = 390 and 23 nM, respectively) for the κ-opioid receptor (KOR). Consistent with the screening capabilities of collaborators and following the design validation, the complete library was assembled as 210 mixtures of 20 compounds, providing a total of 4200 compounds designed to mimic all possible permutations of 3 of the 4 residues in a naturally occurring β-turn. Unique to the design and because of the C(2) symmetry of the template, a typical 20 × 20 × 20-mix (8000 compounds prepared as 400 mixtures of 20 compounds) needed to represent 20 variations in the side chains of three amino acid residues reduces to a 210 × 20-mix, thereby simplifying the library synthesis and subsequent screening. The library was prepared using a solution-phase synthetic protocol with liquid-liquid or liquid-solid extractions for purification and conducted on a scale that insures its long-term availability for screening campaigns. Screening the library against the human opioid receptors (KOR, MOR, and DOR) identified not only the activity of library members expected to mimic the opioid receptor peptide ligands but also additional side-chain combinations that provided enhanced receptor binding selectivities (>100-fold) and affinities (as low as K(i) = 80 nM for KOR). A key insight to emerge from

  3. Implementation of treat-to-target in rheumatoid arthritis through a Learning Collaborative: Rationale and design of the TRACTION trial.

    Science.gov (United States)

    Solomon, Daniel H; Lee, Sara B; Zak, Agnes; Corrigan, Cassandra; Agosti, Jenifer; Bitton, Asaf; Harrold, Leslie; Losina, Elena; Lu, Bing; Pincus, Ted; Radner, Helga; Smolen, Josef; Katz, Jeffrey N; Fraenkel, Liana

    2016-08-01

    Treat-to-target (TTT) is a recommended strategy in the management of rheumatoid arthritis (RA), but various data sources suggest that its uptake in routine care in the US is suboptimal. Herein, we describe the design of a randomized controlled trial of a Learning Collaborative to facilitate implementation of TTT. We recruited 11 rheumatology sites from across the US and randomized them into the following two groups: one received the Learning Collaborative intervention in Phase 1 (month 1-9) and the second formed a wait-list control group to receive the intervention in Phase 2 (months 10-18). The Learning Collaborative intervention was designed using the Model for Improvement, consisting of a Change Package with corresponding principles and action phases. Phase 1 intervention practices had nine learning sessions, collaborated using a web-based tool, and shared results of plan-do-study-act cycles and monthly improvement metrics collected at each practice. The wait-list control group sites had no intervention during Phase 1. The primary trial outcome is the implementation of TTT as measured by chart review, comparing the differences from baseline to end of Phase 1, between intervention and control sites. All intervention sites remained engaged in the Learning Collaborative throughout Phase 1, with a total of 38 providers participating. The primary trial outcome measures are currently being collected by the study team through medical record review. If the Learning Collaborative is an effective means for improving implementation of TTT, this strategy could serve as a way of implementing disseminating TTT more widely. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Fulfilling the pedestrian protection directive using a long-wavelength infrared camera designed to meet both performance and cost targets

    Science.gov (United States)

    Källhammer, Jan-Erik; Pettersson, Håkan; Eriksson, Dick; Junique, Stéphane; Savage, Susan; Vieider, Christian; Andersson, Jan Y.; Franks, John; Van Nylen, Jan; Vercammen, Hans; Kvisterøy, Terje; Niklaus, Frank; Stemme, Göran

    2006-04-01

    Pedestrian fatalities are around 15% of the traffic fatalities in Europe. A proposed EU regulation requires the automotive industry to develop technologies that will substantially decrease the risk for Vulnerable Road Users when hit by a vehicle. Automatic Brake Assist systems, activated by a suitable sensor, will reduce the speed of the vehicle before the impact, independent of any driver interaction. Long Wavelength Infrared technology is an ideal candidate for such sensors, but requires a significant cost reduction. The target necessary for automotive serial applications are well below the cost of systems available today. Uncooled bolometer arrays are the most mature technology for Long Wave Infrared with low-cost potential. Analyses show that sensor size and production yield along with vacuum packaging and the optical components are the main cost drivers. A project has been started to design a new Long Wave Infrared system with a ten times cost reduction potential, optimized for the pedestrian protection requirement. It will take advantage of the progress in Micro Electro-Mechanical Systems and Long Wave Infrared optics to keep the cost down. Deployable and pre-impact braking systems can become effective alternatives to passive impact protection systems solutions fulfilling the EU pedestrian protection regulation. Low-cost Long Wave Infrared sensors will be an important enabler to make such systems cost competitive, allowing high market penetration.

  5. Targeting EphA2-Sam and Its Interactome: Design and Evaluation of Helical Peptides Enriched in Charged Residues.

    Science.gov (United States)

    Mercurio, Flavia A; Marasco, Daniela; Di Natale, Concetta; Pirone, Luciano; Costantini, Susan; Pedone, Emilia M; Leone, Marilisa

    2016-11-17

    The EphA2 receptor controls diverse physiological and pathological conditions and its levels are often upregulated in cancer. Targeting receptor overexpression, through modulation of endocytosis and consequent degradation, appears to be an appealing strategy for attacking tumor malignancy. In this scenario, the Sam domain of EphA2 plays a pivotal role because it is the site where protein regulators of endocytosis and stability are recruited by means of heterotypic Sam-Sam interactions. Because EphA2-Sam heterotypic complexes are largely based on electrostatic contacts, we have investigated the possibility of attacking these interactions with helical peptides enriched in charged residues. Several peptide sequences with high predicted helical propensities were designed, and detailed conformational analyses were conducted by diverse techniques including NMR, CD, and molecular dynamics (MD) simulations. Interaction studies were also performed by NMR, surface plasmon resonance (SPR), and microscale thermophoresis (MST) and led to the identification of two peptides capable of binding to the first Sam domain of Odin. These molecules represent early candidates for the generation of efficient Sam domain binders and antagonists of Sam-Sam interactions involving EphA2. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Design, synthesis and validation of integrin α2β1-targeted probe for microPET imaging of prostate cancer

    International Nuclear Information System (INIS)

    Huang, Chiun-Wei; Li, Zibo; Cai, Hancheng; Chen, Kai; Shahinian, Tony; Conti, Peter S.

    2011-01-01

    The ability of PET to aid in the diagnosis and management of recurrent and/or disseminated metastatic prostate cancer may be enhanced by the development of novel prognostic imaging probes. Accumulating experimental evidence indicates that overexpression of integrin α 2 β 1 may correlate with progression in human prostate cancer. In this study, 64 Cu-labeled integrin α 2 β 1 -targeted PET probes were designed and evaluated for the imaging of prostate cancer. DGEA peptides conjugated with a bifunctional chelator (BFC) were developed to image integrin α 2 β 1 expression with PET in a subcutaneous PC-3 xenograft model. The microPET images were reconstructed by a two-dimensional ordered subsets expectation maximum algorithm. The average radioactivity accumulation within a tumor or an organ was quantified from the multiple region of interest volumes. The PET tracer demonstrated prominent tumor uptake in the PC-3 xenograft (integrin α 2 β 1 -positive). The receptor specificity was confirmed in a blocking experiment. Moreover, the low tracer uptake in a CWR-22 tumor model (negative control) further confirmed the receptor specificity. The sarcophagine-conjugated DGEA peptide allows noninvasive imaging of tumor-associated α 2 β 1 expression, which may be a useful PET probe for evaluating the metastatic potential of prostate cancer. (orig.)

  7. Modeling and optimization of energy generation and storage systems for thermal conditioning of buildings targeting conceptual building design

    Energy Technology Data Exchange (ETDEWEB)

    Grahovac, Milica

    2012-11-29

    minimal costs, emissions or consumption, while maintaining the quality of the supply and, where specified, achieving the targeted annual solar ratio. Two optimization algorithms, the global bounded Nelder Mead and the Exhaustive search are implemented. Simulation and optimization performance has been evaluated using building and weather data for four cities situated in four different climates. Finally a tool, entitled PROBA, has been proposed by adding a user interface to the mod-els. The major characteristic of the interface is its suitability for non-expert users. This is achieved by, firstly, reducing amount of input data by implementing preset values and, secondly, providing information support. Making this tool available to the architects repre-sents an effective way to consider the primary HVAC during the preliminary design, with-out causing additional cost. Although such a tool can never replace an HVAC engineer, its use can heighten the awareness of architects regarding the significance of building energy consumption and inspire further education in this field.

  8. Modeling and optimization of energy generation and storage systems for thermal conditioning of buildings targeting conceptual building design

    Energy Technology Data Exchange (ETDEWEB)

    Grahovac, Milica

    2012-11-29

    costs, emissions or consumption, while maintaining the quality of the supply and, where specified, achieving the targeted annual solar ratio. Two optimization algorithms, the global bounded Nelder Mead and the Exhaustive search are implemented. Simulation and optimization performance has been evaluated using building and weather data for four cities situated in four different climates. Finally a tool, entitled PROBA, has been proposed by adding a user interface to the mod-els. The major characteristic of the interface is its suitability for non-expert users. This is achieved by, firstly, reducing amount of input data by implementing preset values and, secondly, providing information support. Making this tool available to the architects repre-sents an effective way to consider the primary HVAC during the preliminary design, with-out causing additional cost. Although such a tool can never replace an HVAC engineer, its use can heighten the awareness of architects regarding the significance of building energy consumption and inspire further education in this field.

  9. Synthesis of the studies on fuels and transmutation targets (fabrication, design, irradiation damage and dissolution) realized in the framework of the Bataille law

    International Nuclear Information System (INIS)

    Pillon, S.

    2004-12-01

    This document presents the different studied fuels and targets for the transmutation of the minor actinides and of the long life fission products for PWR/EPR and Fast neutron Reactor/EFR of today technology; the results of studies on the behavior under ions irradiation and in experimental nuclear reactor; the knowledge in terms of design, simulation and sizing; the development in terms of fabrication; the knowledge on the dissolution aptitude of these fuels and targets. (A.L.B.)

  10. Development of lithium target system in engineering validation and engineering design activity of the international fusion materials irradiation facility (IFMIF/EVEDA)

    International Nuclear Information System (INIS)

    Wakai, Eiichi; Kondo, Hiroo; Sugimoto, Masayoshi; Ida, Mizuho; Kanemura, Takuji; Watanabe, Kazuyoshi; Fujishiro, Kouji; Edao, Yuuki; Niitsuma, Shigeto; Kimura, Haruyuki; Fukada, Satoshi; Hiromoto, Tetsushi; Shigeharu, Satoshi; Yagi, Jyuro; Furukawa, Tomohiro; Hirakawa, Yasushi; Suzuki, Akihiro; Terai, Takayuki; Horiike, Hiroshi; Hoashi, Eiji; Suzuki, Sachiko; Yamaoka, Nobuo; Serizawa, Hisashi; Kawahito, Yosuke; Tsuji, Yoshiyuki; Furuya, Kazuyuki; Takeo, Fumio

    2012-01-01

    Engineering validation and engineering design activity (EVEDA) for the international fusion materials irradiation facility (IFMIF) has been conducted since 2007. Research and development of the Lithium target facility is an important part of this activity. We constructed a world largest liquid Lithium test loop with a capacity of 5000 L in 2010 and successfully completed the first stage validation tests (functional tests of components and Lithium flow test (flow velocity 15 m/s at the target). In the present article, recent results of the EVEDA activity for the Lithium target facility and related technologies on liquid Lithium are reviewed. (author)

  11. Superior control of HIV-1 replication by CD8+ T cells targeting conserved epitopes: implications for HIV vaccine design.

    Directory of Open Access Journals (Sweden)

    Pratima Kunwar

    Full Text Available A successful HIV vaccine will likely induce both humoral and cell-mediated immunity, however, the enormous diversity of HIV has hampered the development of a vaccine that effectively elicits both arms of the adaptive immune response. To tackle the problem of viral diversity, T cell-based vaccine approaches have focused on two main strategies (i increasing the breadth of vaccine-induced responses or (ii increasing vaccine-induced responses targeting only conserved regions of the virus. The relative extent to which set-point viremia is impacted by epitope-conservation of CD8(+ T cell responses elicited during early HIV-infection is unknown but has important implications for vaccine design. To address this question, we comprehensively mapped HIV-1 CD8(+ T cell epitope-specificities in 23 ART-naïve individuals during early infection and computed their conservation score (CS by three different methods (prevalence, entropy and conseq on clade-B and group-M sequence alignments. The majority of CD8(+ T cell responses were directed against variable epitopes (p<0.01. Interestingly, increasing breadth of CD8(+ T cell responses specifically recognizing conserved epitopes was associated with lower set-point viremia (r = - 0.65, p = 0.009. Moreover, subjects possessing CD8(+ T cells recognizing at least one conserved epitope had 1.4 log10 lower set-point viremia compared to those recognizing only variable epitopes (p = 0.021. The association between viral control and the breadth of conserved CD8(+ T cell responses may be influenced by the method of CS definition and sequences used to determine conservation levels. Strikingly, targeting variable versus conserved epitopes was independent of HLA type (p = 0.215. The associations with viral control were independent of functional avidity of CD8(+ T cell responses elicited during early infection. Taken together, these data suggest that the next-generation of T-cell based HIV-1 vaccines should focus

  12. Development of a methodology for defining whole-building energy design targets for commercial buildings: Phase 2, Development concept stage report

    Energy Technology Data Exchange (ETDEWEB)

    Jones, J.W. (American Society of Heating, Refrigerating and Air-Conditioning Engineers, Inc., Atlanta, GA (USA)); Deringer, J.J. (Deringer Group, Riva, MD (USA)); Hall, J.D. (American Inst. of Architects, Washington, DC (USA)) (comps.)

    1990-09-01

    The Whole-Building Energy Design Targets project is being conducted for the US Department of Energy (DOE) by the Pacific Northwest Laboratory (PNL). The objective of the project is to develop a flexible methodology for setting energy performance guidelines with which architects, engineers, planners, and owners can assess energy efficiency in commercial building design. This volume, the third in the four-volume report on the Targets project concept stage, contains the minutes of the workshops as well as summaries of the expert's written comments prepared at the close of each workshop. In Section 2, the building energy simulation workshop is summarized. Section 3 provides a summary of the building cost workshop.

  13. CRISPR-DT: designing gRNAs for the CRISPR-Cpf1 system with improved target efficiency and specificity

    OpenAIRE

    Liang, Chun; Zhu, Houxiang

    2018-01-01

    The CRISPR-Cpf1 system has been successfully applied in genome editing. However, target efficiency of the CRISPR-Cpf1 system varies among different gRNA sequences. We reanalyzed the published CRISPR-Cpf1 gRNAs data and found many sequence and structural features related to their target efficiency. Using machine learning technology, a SVM model was created to predict target efficiency for any given gRNAs. We have developed the first web service application, CRISPR-DT (CRISPR DNA Targeting), to...

  14. New design targets and new automated technology for the production of radionuclides with high specificity radioactivity in nuclear research reactors

    International Nuclear Information System (INIS)

    Gerasimov, A.S.; Kiselev, G.V.

    1997-01-01

    Current demands of industry require the application of radionuclides with high specific radioactivity under low consumption of neutrons. To provide this aim staff of ITEP Reactor Department investigated the different type AEs of start targets for the production of the main radionuclides; Co-60, Ir-192 and others. In first turn the targets of Co and Ir without the block-effect of neutron flux (with low absorption of neutrons) were investigated. The following principal results were received for example for Ir-192: block effect is equal 0.086 for diameter of Ir target mm and is equal 0.615 for diameter Ir target 0.5mm. It means average neutron flux for Ir target diameter 0.5mm and therefore the production of Ir-192 will be at 10 times more than for diameter 6.0mm. To provide the automated technology of the manufacture of radioactive sources with radionuclides with high specific radioactivity it was proposed that the compound targets for the irradiation of ones and for the management with the irradiated targets. Different types of compound targets were analyzed. (authors)

  15. Metallochaperone UreG serves as a new target for design of urease inhibitor: A novel strategy for development of antimicrobials.

    Directory of Open Access Journals (Sweden)

    Xinming Yang

    2018-01-01

    Full Text Available Urease as a potential target of antimicrobial drugs has received considerable attention given its versatile roles in microbial infection. Development of effective urease inhibitors, however, is a significant challenge due to the deeply buried active site and highly specific substrate of a bacterial urease. Conventionally, urease inhibitors are designed by either targeting the active site or mimicking substrate of urease, which is not efficient. Up to now, only one effective inhibitor-acetohydroxamic acid (AHA-is clinically available, but it has adverse side effects. Herein, we demonstrate that a clinically used drug, colloidal bismuth subcitrate, utilizes an unusual way to inhibit urease activity, i.e., disruption of urease maturation process via functional perturbation of a metallochaperone, UreG. Similar phenomena were also observed in various pathogenic bacteria, suggesting that UreG may serve as a general target for design of new types of urease inhibitors. Using Helicobacter pylori UreG as a showcase, by virtual screening combined with experimental validation, we show that two compounds targeting UreG also efficiently inhibited urease activity with inhibitory concentration (IC50 values of micromolar level, resulting in attenuated virulence of the pathogen. We further demonstrate the efficacy of the compounds in a mammalian cell infection model. This study opens up a new opportunity for the design of more effective urease inhibitors and clearly indicates that metallochaperones involved in the maturation of important microbial metalloenzymes serve as new targets for devising a new type of antimicrobial drugs.

  16. Metallochaperone UreG serves as a new target for design of urease inhibitor: A novel strategy for development of antimicrobials.

    Science.gov (United States)

    Yang, Xinming; Koohi-Moghadam, Mohamad; Wang, Runming; Chang, Yuen-Yan; Woo, Patrick C Y; Wang, Junwen; Li, Hongyan; Sun, Hongzhe

    2018-01-01

    Urease as a potential target of antimicrobial drugs has received considerable attention given its versatile roles in microbial infection. Development of effective urease inhibitors, however, is a significant challenge due to the deeply buried active site and highly specific substrate of a bacterial urease. Conventionally, urease inhibitors are designed by either targeting the active site or mimicking substrate of urease, which is not efficient. Up to now, only one effective inhibitor-acetohydroxamic acid (AHA)-is clinically available, but it has adverse side effects. Herein, we demonstrate that a clinically used drug, colloidal bismuth subcitrate, utilizes an unusual way to inhibit urease activity, i.e., disruption of urease maturation process via functional perturbation of a metallochaperone, UreG. Similar phenomena were also observed in various pathogenic bacteria, suggesting that UreG may serve as a general target for design of new types of urease inhibitors. Using Helicobacter pylori UreG as a showcase, by virtual screening combined with experimental validation, we show that two compounds targeting UreG also efficiently inhibited urease activity with inhibitory concentration (IC)50 values of micromolar level, resulting in attenuated virulence of the pathogen. We further demonstrate the efficacy of the compounds in a mammalian cell infection model. This study opens up a new opportunity for the design of more effective urease inhibitors and clearly indicates that metallochaperones involved in the maturation of important microbial metalloenzymes serve as new targets for devising a new type of antimicrobial drugs.

  17. Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs.

    Science.gov (United States)

    Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

    2010-09-01

    We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.

  18. One size does not fit all: how the tobacco industry has altered cigarette design to target consumer groups with specific psychological and psychosocial needs.

    Science.gov (United States)

    Cook, Benjamin Lê; Wayne, Geoffrey Ferris; Keithly, Lois; Connolly, Gregory

    2003-11-01

    To identify whether the tobacco industry has targeted cigarette product design towards individuals with varying psychological/psychosocial needs. Internal industry documents were identified through searches of an online archival document research tool database using relevancy criteria of consumer segmentation and needs assessment. The industry segmented consumer markets based on psychological needs (stress relief, behavioral arousal, performance enhancement, obesity reduction) and psychosocial needs (social acceptance, personal image). Associations between these segments and smoking behaviors, brand and design preferences were used to create cigarette brands targeting individuals with these needs. Cigarette brands created to address the psychological/psychosocial needs of smokers may increase the likelihood of smoking initiation and addiction. Awareness of targeted product development will improve smoking cessation and prevention efforts.

  19. Gene design, cloning and protein-expression methods for high-value targets at the Seattle Structural Genomics Center for Infectious Disease

    International Nuclear Information System (INIS)

    Raymond, Amy; Haffner, Taryn; Ng, Nathan; Lorimer, Don; Staker, Bart; Stewart, Lance

    2011-01-01

    An overview of one salvage strategy for high-value SSGCID targets is given. Any structural genomics endeavor, particularly ambitious ones such as the NIAID-funded Seattle Structural Genomics Center for Infectious Disease (SSGCID) and Center for Structural Genomics of Infectious Disease (CSGID), face technical challenges at all points of the production pipeline. One salvage strategy employed by SSGCID is combined gene engineering and structure-guided construct design to overcome challenges at the levels of protein expression and protein crystallization. Multiple constructs of each target are cloned in parallel using Polymerase Incomplete Primer Extension cloning and small-scale expressions of these are rapidly analyzed by capillary electrophoresis. Using the methods reported here, which have proven particularly useful for high-value targets, otherwise intractable targets can be resolved

  20. Design principles, targets and criterions for a Multipurpose Advanced Reactor Inherently Safe (MARS). Evaluation of the total production cost of electric energy

    International Nuclear Information System (INIS)

    Cumo, M.

    2001-01-01

    To be accepted and to be, sooner or later, extensively utilized, a new technology must respect the nature and its equilibria. For a nuclear power plant, the full respect of nature and of its equilibria means: for normal operation of the plant, guaranteeing a radiological impact comparable to the standard deviation of the radioactive natural background; for worst design plant accidents, guaranteeing an external impact only with the same probability as that of ultra-catastrophic natural events, such as bolide impacts to the earth. In compliance with Prof. A. Weinberg's suggestions, the design of the MARS nuclear plant was conceived according to this philosophy. The main factors which have affected the design development process of the MARS nuclear plant are introduced in the following. They include design principles, design targets and design criteria. These factors will be presented in two groups: the first group refers to the most relevant ones, regarding project fundamentals, as design principles, targets and main criteria (paragraph 1). The second group refers to detailed design criteria adopted for systems, structures and components relevant to safety (paragraph 2). (author)

  1. Design, synthesis and molecular modeling of new 4-phenylcoumarin derivatives as tubulin polymerization inhibitors targeting MCF-7 breast cancer cells.

    Science.gov (United States)

    Batran, Rasha Z; Kassem, Asmaa F; Abbas, Eman M H; Elseginy, Samia A; Mounier, Marwa M

    2018-07-23

    A new set of 4-phenylcoumarin derivatives was designed and synthesized aiming to introduce new tubulin polymerization inhibitors as anti-breast cancer candidates. All the target compounds were evaluated for their cytotoxic effects against MCF-7 cell line, where compounds 2f, 3a, 3b, 3f, 7a and 7b, showed higher cytotoxic effect (IC 50  = 4.3-21.2 μg/mL) than the reference drug doxorubicin (IC 50  = 26.1 μg/mL), additionally, compounds 1 and 6b exhibited the same potency as doxorubicin (IC 50  = 25.2 and 28.0 μg/mL, respectively). The thiazolidinone derivatives 3a, 3b and 3f with potent and selective anticancer effects towards MCF-7 cells (IC 50  = 11.1, 16.7 and 21.2 μg/mL) were further assessed for tubulin polymerization inhibition effects which showed that the three compounds were potent tubulin polymerization suppressors with IC 50 values of 9.37, 2.89 and 6.13 μM, respectively, compared to the reference drug colchicine (IC 50  = 6.93 μM). The mechanistic effects on cell cycle progression and induction of apoptosis in MCF-7 cells were determined for compound 3a due to its potent and selective cytotoxic effects in addition to its promising tubulin polymerization inhibition potency. The results revealed that compound 3a induced cell cycle cessation at G2/M phase and accumulation of cells in pre-G1 phase and prevented its mitotic cycle, in addition to its activation of caspase-7 mediating apoptosis of MCF-7 cells. Molecular modeling studies for compounds 3a, 3b and 3f were carried out on tubulin crystallography, the results indicated that the compounds showed binding mode similar to the co-crystalized ligand; colchicine. Moreover, pharmacophore constructed models and docking studies revealed that thiazolidinone, acetamide and coumarin moieties are crucial for the activity. Molecular dynamics (MD) studies were carried out for the three compounds over 100 ps. MD results of compound 3a showed that it reached the stable state

  2. Design Considerations for mHealth Programs Targeting Smokers Not Yet Ready to Quit: Results of a Sequential Mixed-Methods Study

    OpenAIRE

    McClure, Jennifer B; Heffner, Jaimee; Hohl, Sarah; Klasnja, Predrag; Catz, Sheryl L

    2017-01-01

    Background Mobile health (mHealth) smoking cessation programs are typically designed for smokers who are ready to quit smoking. In contrast, most smokers want to quit someday but are not yet ready to quit. If mHealth apps were designed for these smokers, they could potentially encourage and assist more people to quit smoking. No prior studies have specifically examined the design considerations of mHealth apps targeting smokers who are not yet ready to quit. Objective To inform the user-cente...

  3. Computer-aided design of multi-target ligands at A1R, A2AR and PDE10A, key proteins in neurodegenerative diseases.

    Science.gov (United States)

    Kalash, Leen; Val, Cristina; Azuaje, Jhonny; Loza, María I; Svensson, Fredrik; Zoufir, Azedine; Mervin, Lewis; Ladds, Graham; Brea, José; Glen, Robert; Sotelo, Eddy; Bender, Andreas

    2017-12-30

    Compounds designed to display polypharmacology may have utility in treating complex diseases, where activity at multiple targets is required to produce a clinical effect. In particular, suitable compounds may be useful in treating neurodegenerative diseases by promoting neuronal survival in a synergistic manner via their multi-target activity at the adenosine A 1 and A 2A receptors (A 1 R and A 2A R) and phosphodiesterase 10A (PDE10A), which modulate intracellular cAMP levels. Hence, in this work we describe a computational method for the design of synthetically feasible ligands that bind to A 1 and A 2A receptors and inhibit phosphodiesterase 10A (PDE10A), involving a retrosynthetic approach employing in silico target prediction and docking, which may be generally applicable to multi-target compound design at several target classes. This approach has identified 2-aminopyridine-3-carbonitriles as the first multi-target ligands at A 1 R, A 2A R and PDE10A, by showing agreement between the ligand and structure based predictions at these targets. The series were synthesized via an efficient one-pot scheme and validated pharmacologically as A 1 R/A 2A R-PDE10A ligands, with IC 50 values of 2.4-10.0 μM at PDE10A and K i values of 34-294 nM at A 1 R and/or A 2A R. Furthermore, selectivity profiling of the synthesized 2-amino-pyridin-3-carbonitriles against other subtypes of both protein families showed that the multi-target ligand 8 exhibited a minimum of twofold selectivity over all tested off-targets. In addition, both compounds 8 and 16 exhibited the desired multi-target profile, which could be considered for further functional efficacy assessment, analog modification for the improvement of selectivity towards A 1 R, A 2A R and PDE10A collectively, and evaluation of their potential synergy in modulating cAMP levels.

  4. CRISPR-RT: A web service for designing CRISPR-C2c2 crRNA with improved target specificity

    OpenAIRE

    Zhu, Houxiang; Richmond, Emily; Liang, Chun

    2017-01-01

    CRISPR-Cas systems have been successfully applied in genome editing. Recently, the CRISPR-C2c2 system has been reported as a tool for RNA editing. Here we describe CRISPR-RT (CRISPR RNA-Targeting), the first web service to help biologists design the crRNA with improved target specificity for the CRISPR-C2c2 system. CRISPR-RT allows users to set up a wide range of parameters, making it highly flexible for current and future research in CRISPR-based RNA editing. CRISPR-RT covers major model org...

  5. Designing Ligands for Leishmania, Plasmodium, and Aspergillus N-Myristoyl Transferase with Specificity and Anti-Target-Safe Virtual Libraries.

    Science.gov (United States)

    Garcia-Sosa, Alfonso T

    2018-01-01

    Leishmaniasis, malaria, and fungal diseases are burdens on individuals and populations and can present severe complications. Easily accessible chemical treatments for these diseases are increasingly sought-after. Targeting the parasite N-myristoyl transferase while avoiding the human enzyme and other anti-targets may allow the prospect of compounds with pan-activity against these diseases, which would simplify treatments and costs. Developing chemical libraries, both virtual and physical, that have been filtered and flagged early on in the drug discovery process (before virtual screening) could reduce attrition rates of compounds being developed and failing late in development stages due to problems of side-effects or toxicity. Chemical libraries have been screened against the anti-targets pregnane-X-receptor, sulfotransferase, cytochrome P450 2a6, 2c9, and 3a4 with three different docking programs. Statistically significant differences are observed in their interactions with these enzymes as compared to small molecule drugs and bioactive non-drug datasets. A series of compounds are proposed with the best predicted profiles for inhibition of all parasite targets while sparing the human form and anti-targets. Some of the topranked compounds have confirmed experimental activity against Leishmania, and highlighted are those compounds with best properties for further development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Design of foam-buffered high gain target with Fokker-Planck implosion simulation for thermal insulation and imprint mitigation

    International Nuclear Information System (INIS)

    Takeda, T.; Mima, K.; Norimatsu, T.; Nagatomo, H.; Nishiguchi, A.

    2003-01-01

    It is proposed that a thick foam layer on a plastic capsule of fusion pellet is effective not only for reducing the initial imprint, but also for solving the melting problem of cryogenic deuterium-tritium layer, in a reactor chamber. Investigated are the dependences of gain, thermal insulation for preventing the melting, and imprint mitigation of a foam-buffered target on the foam layer thickness. The imprint mitigation, the Rayleigh-Taylor growth factor and the fusion gain of a foam-buffered target are evaluated by the hydrodynamic implosion code HIMICO [A. Nishiguchi et al., Phys. Fluids B 4, 417 (1992)], which includes a Fokker-Planck transport code. As the result, it is found that high gain can be achieved by the foam-buffered target together with thermal insulation and imprint mitigation

  7. [Optimization study on extraction technology of the seed of Ziziphus jujuba var. spinosa by orthogonal design with multi-targets].

    Science.gov (United States)

    Wang, Xiao-liang; Zhang, Yu-jie; Chen, Ming-xia; Wang, Ze-feng

    2005-05-01

    To optimize extraction technology of the seed of Ziziphus jujuba var. spinosa with the targets of the total saponin, total jujuboside A and B and total flavonoids. In the method of one-way and orthogonal tests, ethanol concentration, amount of ethanol, extraction time and extraction times were the factors in orthogonal test, and each factor with three levels. Ethanol concentration and extraction times had significant effect on all the targets, other factors should be selected in accordance with production practice. The best extraction technology is to extract for three times with 8 fold ethanol solution (60%), and 1.5 h each time.

  8. Impact of tDCS on Performance and Learning of Target Detection: Interaction with Stimulus Characteristics and Experimental Design

    Science.gov (United States)

    Coffman, B. A.; Trumbo, M. C.; Flores, R. A.; Garcia, C. M.; van der Merwe, A. J.; Wassermann, E. M.; Weisend, M. P.; Clark, V. P.

    2012-01-01

    We have previously found that transcranial direct current stimulation (tDCS) over right inferior frontal cortex (RIFC) enhances performance during learning of a difficult visual target detection task (Clark et al., 2012). In order to examine the cognitive mechanisms of tDCS that lead to enhanced performance, here we analyzed its differential…

  9. Design o