WorldWideScience

Sample records for ads target design

  1. Windowless target: Design of the XT-ADS spallation target

    International Nuclear Information System (INIS)

    The design of the XT-ADS spallation target is performed within the European integrated project EUROTRANS (FP6 Contract FI6W-516520) that has started in April 2005. At the current status of the spallation target design process, the boundary conditions for the spallation target loop with respect to the XT-ADS performance requirements and the design of the subcritical core and primary system have been established. The next steps will concentrate on further development of the spallation target nozzle, the vacuum and spallation product confinement system and the pumping, LIDAR (LIght Detection And Ranging) and cooling system

  2. Design and thermal-hydraulic transient analysis of helium-cooled solid target for ADS

    International Nuclear Information System (INIS)

    The Accelerator Driven Sucritial Reactor System (ADS) is a kind of nuclear reactor which can burn minor actinide waste products produced from conventional reactors with inherent safety features. Because of the characteristics of a sub-critical reaction process, the fission chain reaction is maintained by additional neutrons generated in spallation target induced by proton beams. In this paper, a helium-cooled solid target was designed for a 10 MW helium-cooled prismatic-type experimental ADS. Tungsten is choosen as the spallation target material and is modeled into the honeycomb structure. High pressure helium, which flows in honeycomb holes, removes heat deposited by the proton beam in the target. FLUENT code was used to calculate the temperature distribution of target under steady condition, with UDF solving the flow of helium in channels. In order to analyze the transient characteristics of spallation target cooling system, a RELAP5-3DTarget coupling model for cooling system was established. A simplified method was developed to simulate the heat transfer in target. The method avoids fine grid and gets a solution quickly. The simulated results indicate that the peak temperature in the target is lower than the limiting value under operating state as well as three typical transient scenarios with protected system. (and others)

  3. Physical Design of Critical Experiment Facility for Verifying Characteristics and Effects of Coupling Between Reactor and Spallation Target of ADS

    Institute of Scientific and Technical Information of China (English)

    YIN; Sheng-gui; ZHOU; Qi; LI; Yan

    2013-01-01

    For the purpose of studying and verifying characteristics and effects of coupling between reactor and spallation target of ADS,based on the critical experimental facility design criteria and the availableexperiment condition,physical design of a critical experiment facility with lead coolant is completed,using critical calculation code MONK-9A.The contents of physical designs mainly include nuclear fuel,array of fuel rods,neutron source

  4. Design of a molten heavy-metal coolant and target for fast-thermal accelerator driven sub-critical system (ADS)

    International Nuclear Information System (INIS)

    Reactor physics design of a 750 MWth one way coupled fast-thermal ADS was evolved in BARC earlier. This indicated that a fairly large thermal power output was possible with a proton beam of 1 GeV and current 2-3 mA. We also carried out preliminary studies on the molten Pb/Pb-Bi coolant and spallation-target system in the fast zone of this ADS. The thermal power in this zone was estimated to be about 109 MW. In these studies, analyses related to thermal hydraulics have been carried out for a buoyancy driven system to determine the coolant parameters for both lead as well as lead-bismuth eutectic. This design is similar to the passive lead coolant system design of CERN-EA. Appropriate equations for buoyancy pressure head, pressure drop in the reactor core; coolant velocity, heat transport etc. have been solved for different coolant inlet and outlet temperatures, fuel-pin pitch distances, fuel-power densities etc. The analyses show that coolant height required for generating buoyancy pressure head is a very strong function of power density of the fuel-pin and ΔT (difference between outlet and inlet temperature) of the coolant. Main advantage of lead-bismuth eutectic comes from the inlet temperature that can be significantly lower than that of lead; thus larger ΔT can be obtained which in turn will reduce required coolant height. This will result in saving of coolant inventory and cost. In this paper, preliminary engineering design of coolant and target for the 109 MW fast reactor zone is presented. In addition, the proposed Indian programmes to study thermal-hydraulics and materials for the technology development are discussed. (author)

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

    Science.gov (United States)

    Androulaki, Elli; Bellovin, Steven M.

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

  6. Designing added functions in engineered cementitious composites

    Science.gov (United States)

    Yang, En-Hua

    In this dissertation, a new and systematic material design approach is developed for ECC with added functions through material microstructures linkage to composite macroscopic behavior. The thesis research embodies theoretical development by building on previous ECC micromechanical models, and experimental investigations into three specific new versions of ECC with added functions aimed at addressing societal demands of our built infrastructure. Specifically, the theoretical study includes three important ECC modeling elements: Steady-state crack propagation analyses and simulation, predictive accuracy of the fiber bridging constitutive model, and development of the rate-dependent strain-hardening criteria. The first element establishes the steady-state cracking criterion as a fundamental requirement for multiple cracking behavior in brittle matrix composites. The second element improves the accuracy of crack-width prediction in ECC. The third element establishes the micromechanics basis for impact-resistant ECC design. Three new ECCs with added functions were developed and experimentally verified in this thesis research through the enhanced theoretical framework. A green ECC incorporating a large volume of industrial waste was demonstrated to possess reduced crack width and drying shrinkage. The self-healing ECC designed with tight crack width was demonstrated to recover transport and mechanical properties after microcrack damage when exposed to wet and dry cycles. The impact-resistant ECC was demonstrated to retain tensile ductility with increased strength under moderately high strain-rate loading. These new versions of ECC with added functions are expected to contribute greatly to enhancing the sustainability, durability, and safety of civil infrastructure built with ECC. This research establishes the effectiveness of micromechanics-based design and material ingredient tailoring for ECC with added new attributes but without losing its basic tensile ductile

  7. Investigation of the Compatibility Between ADS Target Material With Coolant

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    At present, the program of the compatibility study on ADS project of China Institute of Atomic Energy is focused on the compatibility tests for the tungsten with water and sodium. An ADS verification facility is proposed in next phase of ADS project, an existent swimming pool reactor will be repack as the subcritical reactor system, and tungsten will be used as the target. On the other hand, our CEFR is being constructed now, it may be one of the options as the subcritical reactor system of ADS, thus, it is necessary to understand the compatibility characteristics of tungsten with sodium and water.

  8. Production Target Design Report

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-28

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

  9. Adding Users to the Website Design Process

    Science.gov (United States)

    Tomeo, Megan L.

    2012-01-01

    Alden Library began redesigning its website over a year ago. Throughout the redesign process the students, faculty, and staff that make up the user base were added to the conversation by utilizing several usability test methods. This article focuses on the usability testing conducted at Alden Library and delves into future usability testing, which…

  10. Heavy density liquid metal spallation target studies for Indian ADS programme

    Indian Academy of Sciences (India)

    P Sathamurthy; L M Gantayet; A K Ray

    2007-02-01

    Department of Atomic Energy, India has taken up the development of ADS in view of many attractive features like inherent safety, capability to transmute large quantities of nuclear waste, better utilization of thorium etc. A roadmap has been finalized for the development of ADS. One of the key components of the ADS is the spallation target. Considering the neutron yield, thermal-hydraulics and radiation damage issues, we are proposing to develop spallation target based on heavy density liquid metals like lead and lead-bismuth-eutectic (LBE). Both window and windowless target configurations are presently being studied. In view of the various advantages we are also studying liquid metal flow circulation based on gas lift mechanism. An R&D programme has been initiated to address various physics and technology issues of ADS target. Under this programme, mercury and LBE experimental facilities are presently being set up. Along with these facilities, computational tools related to spallation physics (FLUKA) and CFD are being developed, and the existing ones are utilized to design the entire target loop as well as sub-systems. In this presentation the details of these activities are presented.

  11. Heavy density liquid metal spallation target studies for Indian ADS programme

    Science.gov (United States)

    Satyamurthy, P.; Gantayet, L. M.; Ray, A. K.

    2007-02-01

    Department of Atomic Energy, India has taken up the development of ADS in view of many attractive features like inherent safety, capability to transmute large quantities of nuclear waste, better utilization of thorium etc. A roadmap has been finalized for the development of ADS. One of the key components of the ADS is the spallation target. Considering the neutron yield, thermal-hydraulics and radiation damage issues, we are proposing to develop spallation target based on heavy density liquid metals like lead and lead{bismuth{eutectic (LBE). Both window and windowless target configurations are presently being studied. In view of the various advantages we are also studying liquid metal flow circulation based on gas lift mechanism. An R&D programme has been initiated to address various physics and technology issues of ADS target. Under this programme, mercury and LBE experimental facilities are presently being set up. Along with these facilities, computational tools related to spallation physics (FLUKA) and CFD are being developed, and the existing ones are utilized to design the entire target loop as well as sub-systems. In this presentation the details of these activities are presented.

  12. Study on ADS Pb (Pb/Bi) spallation target

    International Nuclear Information System (INIS)

    The neutron yield and double differential cross section of outgoing neutron produced in p+Pb spallation reaction up to 1.6 GeV have been investigated by some theoretical. Residual radioactivity, energy deposition and radiation damage of the Pb target were studied as well. A verification facility commented of a swimming pool reactor driven by a pulsed low energy high current accelerator (150-300 MeV/3mA) is planned in the next phase of our project. Pb-Bi eutectic is one of the options as the target material in the facility. In order to investigate the material compatibility and the thermohydraulics of Pb-Bi eutectic, a simplified small-scale loop is under designing. (author)

  13. Broadcast design in cognitive radio ad hoc networks

    CERN Document Server

    Song, Yi

    2014-01-01

    This SpringerBrief investigates the special challenges of broadcast design in cognitive radio (CR) ad hoc networks. It introduces two broadcast protocols in CR ad hoc networks: a quality-of-service based broadcast protocol under blind information and a fully-distributed broadcast protocol with collision avoidance. A novel unified analytical model is also presented to analyze the performance of the broadcast protocols. This is the first book dedicated to the unique broadcast design challenges in CR ad hoc networks. The authors also discuss the recent research on the performance analysis of broa

  14. Reducing Youth Exposure to Alcohol Ads: Targeting Public Transit

    OpenAIRE

    Simon, Michele

    2008-01-01

    Underage drinking is a major public health problem. Youth drink more heavily than adults and are more vulnerable to the adverse effects of alcohol. Previous research has demonstrated the connection between alcohol advertising and underage drinking. Restricting outdoor advertising in general and transit ads in particular, represents an important opportunity to reduce youth exposure. To address this problem, the Marin Institute, an alcohol industry watchdog group in Northern California, conduct...

  15. Neutronics of LBE target-cooled ADS for MA transmutation: Japan

    International Nuclear Information System (INIS)

    Purpose and goal: JAEA's reference design of ADS is a tank type 800 MWth subcritical reactor to transmute about 250 kg of minor actinides annually. A lead-bismuth eutectic (LBE) is used as both the primary coolant and the spallation target. A superconducting linear accelerator (SC-LINAC), whose proton energy and maximum current are 1.5 GeV and 20 mA (30 MW), is connected to produce spallation neutrons. The (MA, Pu) N fuel diluted by ZrN is used in the subcritical core. Because the relatively high power peaking factor will be observed at the burnup stage of low HII value, where the influence of the spallation neutrons is strong, Pu is added at the beginning of the first burnup cycle to mitigate the rapid increase of the burnup reactivity

  16. Efficient target tracking with an ad-hoc network of omni-directional sensors

    Science.gov (United States)

    Atanassov, Kalin

    2015-05-01

    Ad-hoc networks of omni-directional sensors provide an efficient means to obtain low-cost, easily deployed, reliable target tracking systems. To remove target position dependency on the target power, a transformation to another coordinate system is introduced. It can be shown that the problem of sensing target position with omni-directional sensors can be adapted to the conventional Kalman filter framework. To validate the proposed methodology, first an analysis is conducted to show that by converting to log-ratio space and at the same time reducing the number of parameters to track, no information about target position is lost. The analysis is done by deriving the CRLBs for the position estimation error in both original and transformed spaces and showing that they are the same. Second, to show how the traditional Kalman filter framework performs, a particle filter that works off the transformed coordinates is designed. The number of particles is selected to be sufficiently large and the result is used as ground truth to compare with the performance of the Kalman tracker. The comparisons are done for different target movement speeds and sensor density modes. The results provide an insight into Kalman tracker performance in different situations.

  17. A Guide to Microsoft Active Directory (AD) Design

    Energy Technology Data Exchange (ETDEWEB)

    Dias, J

    2002-04-29

    The goal of this paper is to facilitate the design process for those DOE sites that are currently engaged in designing their Active Directory (AD) network. It is a roadmap to enable analysis of the complicated design tradeoffs associated with Active Directory Design. By providing discussion of Active Directory design elements which are permanent and costly to change once deployed, the hope is to minimize the risks of sponsoring failed designs, or joining existing infrastructures not suitable to programmatic needs. Specifically, most Active Directory structures will fall under one of three common designs: Single Domain, Single Forest with Multiple Domains, or Multiple Forests. Each has benefits and concerns, depending on programmatic and organizational structures. The comparison of these three approaches will facilitate almost any Active Directory design effort. Finally, this paper describes some best practices to consider when designing Active Directory based on three years of research and experience.

  18. Synthesis of a Potent Vinblastine: Rationally Designed Added Benign Complexity.

    Science.gov (United States)

    Allemann, Oliver; Brutsch, Manuela; Lukesh, John C; Brody, Daniel M; Boger, Dale L

    2016-07-13

    Many natural products, including vinblastine, have not been easily subjected to simplifications in their structures by synthetic means or modifications by late-stage semisynthetic derivatization in ways that enhance their biological potency. Herein, we detail a synthetic vinblastine that incorporates added benign complexity (ABC), which improves activity 10-fold, and is now accessible as a result of advances in the total synthesis of the natural product. The compound incorporates designed added molecular complexity but no new functional groups and maintains all existing structural and conformational features of the natural product. It constitutes a member of an analogue class presently inaccessible by semisynthetic derivatization of the natural product, by its late-stage functionalization, or by biosynthetic means. Rather, it was accessed by synthetic means, using an appropriately modified powerful penultimate single-step vindoline-catharanthine coupling strategy that proceeds with a higher diastereoselectivity than found for the natural product itself. PMID:27356080

  19. The FLUKA study of the secondary particles fluence in the AD-Antiproton Decelerator target area

    CERN Document Server

    Calviani, M

    2014-01-01

    In this paper we present Monte Carlo FLUKA simulations [1, 2] carried out to investigate the secondary particles fluence emerging from the antiproton production target and their spatial distribution in the AD target area. The detailed quantitative analysis has been performed for different positions along the magnet dog-leg as well as after the main collimator. These results allow tuning the position of the new beam current transformers (BCT) in the target area, in order to have a precise pulse-by-pulse evaluation of the intensity of negative particles injected in the AD-ring before the deceleration phase.

  20. Mechanism of ad5 vaccine immunity and toxicity: fiber shaft targeting of dendritic cells.

    Directory of Open Access Journals (Sweden)

    Cheng Cheng

    2007-02-01

    Full Text Available Recombinant adenoviral (rAd vectors elicit potent cellular and humoral immune responses and show promise as vaccines for HIV-1, Ebola virus, tuberculosis, malaria, and other infections. These vectors are now widely used and have been generally well tolerated in vaccine and gene therapy clinical trials, with many thousands of people exposed. At the same time, dose-limiting adverse responses have been observed, including transient low-grade fevers and a prior human gene therapy fatality, after systemic high-dose recombinant adenovirus serotype 5 (rAd5 vector administration in a human gene therapy trial. The mechanism responsible for these effects is poorly understood. Here, we define the mechanism by which Ad5 targets immune cells that stimulate adaptive immunity. rAd5 tropism for dendritic cells (DCs was independent of the coxsackievirus and adenovirus receptor (CAR, its primary receptor or the secondary integrin RGD receptor, and was mediated instead by a heparin-sensitive receptor recognized by a distinct segment of the Ad5 fiber, the shaft. rAd vectors with CAR and RGD mutations did not infect a variety of epithelial and fibroblast cell types but retained their ability to transfect several DC types and stimulated adaptive immune responses in mice. Notably, the pyrogenic response to the administration of rAd5 also localized to the shaft region, suggesting that this interaction elicits both protective immunity and vector-induced fevers. The ability of replication-defective rAd5 viruses to elicit potent immune responses is mediated by a heparin-sensitive receptor that interacts with the Ad5 fiber shaft. Mutant CAR and RGD rAd vectors target several DC and mononuclear subsets and induce both adaptive immunity and toxicity. Understanding of these interactions facilitates the development of vectors that target DCs through alternative receptors that can improve safety while retaining the immunogenicity of rAd vaccines.

  1. Effect of Target Configuration on the Neutronic Performance of the Gas-Cooled ADS

    CERN Document Server

    Biss, K; Shetty, N; Nabbi, R

    2013-01-01

    With the utilization of nuclear energy transuranic elements like Pu, Am and Cm are produced causing high, long term radioactivity and radio toxicity, respectively. To reduce the radiological impact on the environment and to the repository Partitioning and Transmutation is considered as an efficient way. In this respect comprehensive research works are performed at different research institutes worldwide. The results show that the transmutation of TRU is achieved with fast neutrons due to the higher fission probability. Based on Accelerator Driven Systems (ADS) those neutrons are used in a particular system, in which mainly liquid metal eutectic (lead bismuth) is used as coolant. The neutronic performance of an ADS system based on gas cooling was studied in this work by using the simulation tool MCNPX. The usage of the Monte-Carlo method in MCNPX allows the simulation of the physical processes in a 3D-model of the core. In dependence of the spallation target material and design several parameters like the mult...

  2. Design Optimization of ADS Target Based on Numerical Simulations of Flow Field%基于流场数值模拟的ADS靶件结构的设计优化

    Institute of Scientific and Technical Information of China (English)

    徐长江; 陈海燕

    2003-01-01

    采用通用的计算流体力学(CFD)软件PHOENICS 3.3和BFC计算网格生成技术,对加速器驱动次临界系统(ADS)靶件的流场进行数值模拟计算.结果表明:束窗下方导流板起引导流体沿束窗表面流动的作用,消除了束窗两侧下方较大的旋涡,对于改善束窗附近流体的流动结构、提高束窗表面及散裂靶的换热,效果显著.

  3. Hydraulic analysis of the heavy liquid metal free surface in the windowless XT-ADS spallation target

    International Nuclear Information System (INIS)

    A windowless spallation target is currently developed within the EUROpean Research Programme for the TRANSmutation of High Level Nuclear Waste in Accelerator Driven System (EUROTRANS). The target couples an Accelerator Driven Systems (ADS) to a subcritical reactor core. In ADS heavy liquid metal (HLM) can be used as coolant and spallation target. Within EUROTRANS, the first advanced design of an approximately 50 to 100 MWth eXperimental facility demonstrating the technical feasibility of Transmutation in an Accelerator Driven System (XT-ADS) is extensively investigated. In the target, HLM is flowing downwards through a concentric feeder surrounding the beam tube and forms a conical free surface, which is subjected to a beam current. Above the free surface vacuum is desired. This requires that the incoming flow out of feeder to the spallation region should be at a pressure near the cavitation pressure. The thermal-hydraulics of the target must ensure that heat deposited into the HLM can be safely removed. This necessitates minimizing the resulting recirculation near the spallation region where high heat is deposited. The proposed target geometry is based on earlier numerical and experimental studies. In this article, hydraulic analysis of the proposed target is presented. The investigations are carried out using the Star-CD and Star-CCM codes. Different computational domains and flow conditions are investigated. The analysis show that the proposed target geometry results in a stable free surface which fulfills the flow characteristics in the target. Consequently, sufficient thermal performance of the target is expected for the investigated flow conditions. (author)

  4. Design of the next generation cognitive mobile ad hoc networks

    Science.gov (United States)

    Amjad, Ali; Wang, Huiqiang; Chen, Xiaoming

    Cognition capability has been seen by researchers as the way forward for the design of next generation of Mobile Ad Hoc Networks (MANETs). The reason why a cognitive paradigm would be more suited to a MANET is because MANETs are highly dynamic networks. The topology may change very frequently during the operation of a MANET. Traffic patterns in MANETs can vary from time to time depending on the need of the users. The size of a MANET and node density is also very dynamic and may change without any predictable pattern. In a MANET environment, most of these parameters may change very rapidly and keeping track of them manually would be very difficult. Previous studies have shown that the performance of a certain routing approach in MANETs is dependent on the size of the network and node density. The choice of whether to use a reactive or proactive routing approach comes down to the network size parameter. Static or offline approaches to fine tune a MANET to achieve certain performance goals is hence not very productive as a lot of these parameters keep changing during the course of operation of MANETs. Similarly, the performance of MANETs would improve greatly if the MAC layer entity could operate in a more flexible manner. In this paper we propose a cognitive MANET design that will ensure that all these dynamic parameters are automatically monitored and decisions are based on the current status of these parameters.

  5. 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.

  6. Technical Design Report, Second Target Station

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-01-01

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

  7. Targeted Social Distancing Designs for Pandemic Influenza

    OpenAIRE

    Glass, Robert J.; Glass, Laura M; Walter E. Beyeler; Min, H. Jason

    2006-01-01

    Targeted social distancing to mitigate pandemic influenza can be designed through simulation of influenza's spread within local community social contact networks. We demonstrate this design for a stylized community representative of a small town in the United States. The critical importance of children and teenagers in transmission of influenza is first identified and targeted. For influenza as infectious as 1957–58 Asian flu (≈50% infected), closing schools and keeping children and teenagers...

  8. Design of the NIF Cryogenic Target System

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-06-10

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

  9. Ultrapotent vinblastines in which added molecular complexity further disrupts the target tubulin dimer-dimer interface.

    Science.gov (United States)

    Carney, Daniel W; Lukesh, John C; Brody, Daniel M; Brütsch, Manuela M; Boger, Dale L

    2016-08-30

    Approaches to improving the biological properties of natural products typically strive to modify their structures to identify the essential pharmacophore, or make functional group changes to improve biological target affinity or functional activity, change physical properties, enhance stability, or introduce conformational constraints. Aside from accessible semisynthetic modifications of existing functional groups, rarely does one consider using chemical synthesis to add molecular complexity to the natural product. In part, this may be attributed to the added challenge intrinsic in the synthesis of an even more complex compound. Herein, we report synthetically derived, structurally more complex vinblastines inaccessible from the natural product itself that are a stunning 100-fold more active (IC50 values, 50-75 pM vs. 7 nM; HCT116), and that are now accessible because of advances in the total synthesis of the natural product. The newly discovered ultrapotent vinblastines, which may look highly unusual upon first inspection, bind tubulin with much higher affinity and likely further disrupt the tubulin head-to-tail α/β dimer-dimer interaction by virtue of the strategic placement of an added conformationally well-defined, rigid, and extended C20' urea along the adjacent continuing protein-protein interface. In this case, the added molecular complexity was used to markedly enhance target binding and functional biological activity (100-fold), and likely represents a general approach to improving the properties of other natural products targeting a protein-protein interaction. PMID:27512044

  10. The Effect of Beam Intensity on Temperature Distribution in ADS Windowless Lead-Bismuth Eutectic Spallation Target

    Directory of Open Access Journals (Sweden)

    Jie Liu

    2014-01-01

    Full Text Available The spallation target is the component coupling the accelerator and the reactor and is regarded as the “heart” of the accelerator driven system (ADS. Heavy liquid metal lead-bismuth eutectic (LBE is served as core coolant and spallation material to carry away heat deposition of spallation reaction and produce high flux neutron. So it is very important to study the heat transfer process in the target. In this paper, the steady-state flow pattern has been numerically obtained and taken as the input for the nuclear physics calculation, and then the distribution of the extreme large power density of the heat load is imported back to the computational fluid dynamics as the source term in the energy equation. Through the coupling, the transient and steady-state temperature distribution in the windowless spallation target is obtained and analyzed based on the flow process and heat transfer. Comparison of the temperature distribution with the different beam intensity shows that its shape is the same as broken wing of the butterfly. Nevertheless, the maximum temperature as well as the temperature gradient is different. The results play an important role and can be applied to the further design and optimization of the ADS windowless spallation target.

  11. 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.

  12. Designing divertor targets for uniform power load

    Science.gov (United States)

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

    2015-08-01

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

  13. Gossip Based Routing Protocol Design for Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Toqeer Mahmood

    2012-01-01

    Full Text Available A spontaneously mannered decentralized network with no formal infrastructure and limited in temporal and spatial extent where each node communicate with each other over a wireless channel and is willing to forward data for other nodes is called as Wireless Ad Hoc network. In this research study, we proposed a routing strategy based on gossip based routing approach that follows the proactive routing with some treatment for wireless Ad Hoc network. The analytical verification of our proposed idea shows that it is a better approach based on gossip routing.

  14. 29 mm Diameter Test Target Design Report

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-15

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

  15. 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 ...

  16. Adding diverse noncanonical backbones to rosetta: enabling peptidomimetic design.

    Directory of Open Access Journals (Sweden)

    Kevin Drew

    Full Text Available Peptidomimetics are classes of molecules that mimic structural and functional attributes of polypeptides. Peptidomimetic oligomers can frequently be synthesized using efficient solid phase synthesis procedures similar to peptide synthesis. Conformationally ordered peptidomimetic oligomers are finding broad applications for molecular recognition and for inhibiting protein-protein interactions. One critical limitation is the limited set of design tools for identifying oligomer sequences that can adopt desired conformations. Here, we present expansions to the ROSETTA platform that enable structure prediction and design of five non-peptidic oligomer scaffolds (noncanonical backbones, oligooxopiperazines, oligo-peptoids, [Formula: see text]-peptides, hydrogen bond surrogate helices and oligosaccharides. This work is complementary to prior additions to model noncanonical protein side chains in ROSETTA. The main purpose of our manuscript is to give a detailed description to current and future developers of how each of these noncanonical backbones was implemented. Furthermore, we provide a general outline for implementation of new backbone types not discussed here. To illustrate the utility of this approach, we describe the first tests of the ROSETTA molecular mechanics energy function in the context of oligooxopiperazines, using quantum mechanical calculations as comparison points, scanning through backbone and side chain torsion angles for a model peptidomimetic. Finally, as an example of a novel design application, we describe the automated design of an oligooxopiperazine that inhibits the p53-MDM2 protein-protein interaction. For the general biological and bioengineering community, several noncanonical backbones have been incorporated into web applications that allow users to freely and rapidly test the presented protocols (http://rosie.rosettacommons.org. This work helps address the peptidomimetic community's need for an automated and expandable

  17. Designing a gas cooled ADS for enhanced waste transmutation. The PDS-XADS European Project contribution

    Energy Technology Data Exchange (ETDEWEB)

    Rimpault, G. [Commissariat a l' Energie Atomique, CEA, 31-33, rue de la Federation, 75752 Paris cedex (France); Sunderland, R. [AMEC NNC Limited, Booths Hall, Chelford Road, Knutsford, Cheshire, WA16 8QZ (United Kingdom); Mueller, A.C. [CNRS IN2P3 IPN, F-0 91906 Cedex Orsay (France)

    2006-07-01

    objective of accelerator driven systems (ADS) is for nuclear waste transmutation in order to reduce the radio-toxicity of the spent fuel in final storage disposal. Achieving this goal requires other technologies associated with an advanced fuel cycle with uranium-free fuel heavily loaded with minor actinides and associated fabrication and reprocessing capabilities. The primary or reference option for the advanced fuels for the ADS is based on the (Pu,MA)-O{sub 2} material: a composite with Mo92 (CERMET) or MgO (CERCER). The size of the plant for a given fuel technology is of significant importance to achieve net MA consumption. The larger the size, the smaller amount of Plutonium is needed to achieve the requested reactivity level, and the greater amount of Minor Actinide (MA) can be provided and will, in the end, be burnt. A good compromise for a Helium cooled ADT core with roughened steel pin cladding leads to a volume power of 44 W/cm{sup 3} and an installed power of 400 MWth. The design of this core takes advantage of previous studies by keeping the pressure drop over the core height below 0.5 bar hence preserving the decay removal capabilities and decreasing the pin diameter (7.71 mm) in order to keep the linear power below 152 W/cm. The 6. EUROTRANS Integrated Project will be targeting an European Transmutation Demonstrator (ETD) primarily with lead coolant but also with helium coolant (ETD/EFIT of several hundred MWth, EFIT for European Facility on Industrial scale Transmuter) able to transmute Nuclear Waste on a industrial scale with the full set of constraints taken into account. (authors)

  18. Physics Design of Water Moderator Criticality Assembly in Experimental Research About ADS

    Institute of Scientific and Technical Information of China (English)

    LV; Niu

    2013-01-01

    In order to meet the experimental demand of ADS research,we need to design a suitable criticality assembly.The key problem of the design work is the core design,we design a criticality assembly with the water moderator according to available nuclear material(Fig.1).The theoretical calculation have been

  19. Investigation of IFMIF target assembly structure design

    International Nuclear Information System (INIS)

    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. Designing Multi-Targeted Therapeutics for the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Orhan, Ilkay Erdogan; Senol, F Sezer

    2016-01-01

    Due to multi-faceted pathology of AD; no drug can seize the progress of the disease, whereas only the symptomatic treatment is available at the moment. Several drug classes to treat AD are available in clinical use, AChEIs being the most prescribed. In addition to AChEIs, secretase enzymes and iron chelators have turned out to be the focus of research and the popular targets in drug discovery against AD. The latest approaches such as immunotherapy, multi-targeted drug ligand design, AChE inhibitors, antioxidants, metal chelators, monoamine oxidase (MAO) inhibitors, antiinflammatory drugs, and N-methyl-D-aspartate (NMDA) inhibitors are currently in use to cure this disease to some extent. But, there is a certain need to develop new drugs to fight with AD, particularly acting on multi-targets or with dual mechanisms of action. In this review, a particular emphasis will be focused on multitargets aiming at AD to design new drug molecules with respect to treatment strategies and preventive measures. Since the underlying pathogenesis of AD is complicated and still under investigation, the attempts to design highly selective and potent agents to treat AD are quite intensively continuing. In this respect, designing novel drugs with dual/multi-acting mechanisms seems to be more rational.

  1. 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.

  2. Design of targeted B cell killing agents.

    Directory of Open Access Journals (Sweden)

    Alexey V Stepanov

    Full Text Available B cells play an important role in the pathogenesis of both systemic and organ-specific autoimmune diseases. Autoreactive B cells not only produce autoantibodies, but also are capable to efficiently present specific autoantigens to T cells. Furthermore, B cells can secrete proinflammatory cytokines and amplify the vicious process of self-destruction. B cell-directed therapy is a potentially important approach for treatment of various autoimmune diseases. The depletion of B cells by anti-CD20/19 monoclonal antibody Retuximab® used in autoimmune diseases therapy leads to systemic side effects and should be significantly improved. In this study we designed a repertoire of genetically engineered B cell killers that specifically affected one kind of cells carrying a respective B cell receptor. We constructed immunotoxins (ITs, fused with c-myc epitope as a model targeting sequence, based on barnase, Pseudomonas toxin, Shiga-like toxin E.coli and Fc domain of human antibody IgGγ1. C-MYC hybridoma cell line producing anti-c-myc IgG was chosen as a model for targeted cell depletion. C-myc sequence fused with toxins provided addressed delivery of the toxic agent to the target cells. We demonstrated functional activity of designed ITs in vitro and showed recognition of the fusion molecules by antibodies produced by targeted hybridoma. To study specificity of the proposed B cells killing molecules, we tested a set of created ITs ex vivo, using C-MYC and irrelevant hybridoma cell lines. Pseudomonas-containing IT showed one of the highest cytotoxic effects on the model cells, however, possessed promiscuous specificity. Shiga-like toxin construct demonstrated mild both cytotoxicity and specificity. Barnase and Fc-containing ITs revealed excellent balance between their legibility and toxic properties. Moreover, barnase and Fc molecules fused with c-myc epitope were able to selectively deplete c-myc-specific B cells and decrease production of anti

  3. Using Ad Hoc Transient Communities to Strengthen Social Capital: Design Considerations

    NARCIS (Netherlands)

    Fetter, Sibren; Berlanga, Adriana; Sloep, Peter

    2010-01-01

    Fetter, S., Berlanga, A. J., & Sloep, P. B. (2010, 3-4 May). Using Ad Hoc Transient Communities to Strengthen Social Capital: Design Considerations. Presented at the 7th International Conference on Networked Learning (NLC-2010), Aalborg, Denmark.

  4. Optimal design of nanomagnets for targeted hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Mamiya, Hiroaki, E-mail: MAMIYA.Hiroaki@nims.go.j [National Institute for Materials Science, Tsukuba 305-0047 (Japan); Jeyadevan, Balachandran [University of Shiga Prefecture, Hikone 522-8533 (Japan)

    2011-05-15

    We have numerically simulated the dynamic response of single-domain nanomagnets to alternating magnetic fields and discuss nanometer-sized thermal seeds suitable for selectively targeted magnetic hyperthermia. When we assign priority to the easy delivery and biological safety of these fields, the maximum heating power is obtained by the irradiation of a weak field at a medium frequency ({approx}1 MHz) on almost spherical magnetite nanomagnets with a diameter of approximately 20 nm. On the other hand, the irradiation of the amplified field at a low frequency ({approx}100 kHz) is more effective if the neural stimulation is allowable. - Research Highlights: Simulation of the dynamic response of single-domain nanomagnets. Exposure limits for alternating magnetic fields. Size- and shape-controlled magnetite nanomagnets. Optimal design for maximum specific energy absorption rate.

  5. VisitSense: Sensing Place Visit Patterns from Ambient Radio on Smartphones for Targeted Mobile Ads in Shopping Malls

    OpenAIRE

    Byoungjip Kim; Seungwoo Kang; Jin-Young Ha; Junehwa Song

    2015-01-01

    In this paper, we introduce a novel smartphone framework called VisitSense that automatically detects and predicts a smartphone user’s place visits from ambient radio to enable behavioral targeting for mobile ads in large shopping malls. VisitSense enables mobile app developers to adopt visit-pattern-aware mobile advertising for shopping mall visitors in their apps. It also benefits mobile users by allowing them to receive highly relevant mobile ads that are aware of their place visit pattern...

  6. Key Targets for Multi-Target Ligands Designed to Combat Neurodegeneration.

    Science.gov (United States)

    Ramsay, Rona R; Majekova, Magdalena; Medina, Milagros; Valoti, Massimo

    2016-01-01

    HIGHLIGHTS Compounds that interact with multiple targets but minimally with the cytochrome P450 system (CYP) address the many factors leading to neurodegeneration.Acetyl- and Butyryl-cholineEsterases (AChE, BChE) and Monoamine Oxidases A/B (MAO A, MAO B) are targets for Multi-Target Designed Ligands (MTDL).ASS234 is an irreversible inhibitor of MAO A >MAO B and has micromolar potency against the cholinesterases.ASS234 is a poor CYP substrate in human liver, yielding the depropargylated metabolite.SMe1EC2, a stobadine derivative, showed high radical scavenging property, in vitro and in vivo giving protection in head trauma and diabetic damage of endothelium.Control of mitochondrial function and morphology by manipulating fission and fusion is emerging as a target area for therapeutic strategies to decrease the pathological outcome of neurodegenerative diseases. Growing evidence supports the view that neurodegenerative diseases have multiple and common mechanisms in their aetiologies. These multifactorial aspects have changed the broadly common assumption that selective drugs are superior to "dirty drugs" for use in therapy. This drives the research in studies of novel compounds that might have multiple action mechanisms. In neurodegeneration, loss of neuronal signaling is a major cause of the symptoms, so preservation of neurotransmitters by inhibiting the breakdown enzymes is a first approach. Acetylcholinesterase (AChE) inhibitors are the drugs preferentially used in AD and that one of these, rivastigmine, is licensed also for PD. Several studies have shown that monoamine oxidase (MAO) B, located mainly in glial cells, increases with age and is elevated in Alzheimer (AD) and Parkinson's Disease's (PD). Deprenyl, a MAO B inhibitor, significantly delays the initiation of levodopa treatment in PD patients. These indications underline that AChE and MAO are considered a necessary part of multi-target designed ligands (MTDL). However, both of these targets are simply

  7. Key Targets for Multi-Target Ligands Designed to Combat Neurodegeneration

    Science.gov (United States)

    Ramsay, Rona R.; Majekova, Magdalena; Medina, Milagros; Valoti, Massimo

    2016-01-01

    HIGHLIGHTS Compounds that interact with multiple targets but minimally with the cytochrome P450 system (CYP) address the many factors leading to neurodegeneration.Acetyl- and Butyryl-cholineEsterases (AChE, BChE) and Monoamine Oxidases A/B (MAO A, MAO B) are targets for Multi-Target Designed Ligands (MTDL).ASS234 is an irreversible inhibitor of MAO A >MAO B and has micromolar potency against the cholinesterases.ASS234 is a poor CYP substrate in human liver, yielding the depropargylated metabolite.SMe1EC2, a stobadine derivative, showed high radical scavenging property, in vitro and in vivo giving protection in head trauma and diabetic damage of endothelium.Control of mitochondrial function and morphology by manipulating fission and fusion is emerging as a target area for therapeutic strategies to decrease the pathological outcome of neurodegenerative diseases. Growing evidence supports the view that neurodegenerative diseases have multiple and common mechanisms in their aetiologies. These multifactorial aspects have changed the broadly common assumption that selective drugs are superior to “dirty drugs” for use in therapy. This drives the research in studies of novel compounds that might have multiple action mechanisms. In neurodegeneration, loss of neuronal signaling is a major cause of the symptoms, so preservation of neurotransmitters by inhibiting the breakdown enzymes is a first approach. Acetylcholinesterase (AChE) inhibitors are the drugs preferentially used in AD and that one of these, rivastigmine, is licensed also for PD. Several studies have shown that monoamine oxidase (MAO) B, located mainly in glial cells, increases with age and is elevated in Alzheimer (AD) and Parkinson's Disease's (PD). Deprenyl, a MAO B inhibitor, significantly delays the initiation of levodopa treatment in PD patients. These indications underline that AChE and MAO are considered a necessary part of multi-target designed ligands (MTDL). However, both of these targets are

  8. Antagonistic molecular interactions of photosynthetic pigments with molecular disease targets: a new approach to treat AD and ALS.

    Science.gov (United States)

    Krishnaraj, R Navanietha; Kumari, S S Sreeja; Mukhopadhyay, Sudit Sekhar

    2016-01-01

    Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are progressive neurodegenerative diseases that affect the neurons in the brain and the spinal cord. Neuroinflamation and apoptosis are key players in the progressive damage of the neurons in AD and ALS. Currently, there is no drug to offer complete cure for both these diseases. Riluzole is the only available drug that can prolong the life time of the ALS patients for nearly 3 months. Molecules that offer good HIT to the molecular targets of ALS will help to treat AD and ALS patients. P53 kinase receptor (4AT3), EphA4 (3CKH) and histone deacetylase (3SFF) are the promising disease targets of AD and ALS. This paper discusses on a new approach to combat neurodegenerative diseases using photosynthetic pigments. The docking studies were performed with the Autodock Vina algorithm to predict the binding of the natural pigments such as β carotene, chlorophyll a, chlorophyll b, phycoerythrin and phycocyanin on these targets. The β carotene, phycoerythrin and phycocyanin had higher binding energies indicating the antagonistic activity to the disease targets. These pigments serve as a potential therapeutic molecule to treat neuroinflammation and apoptosis in the AD and ALS patients. PMID:26053508

  9. Building for a better hospital. Value-adding management & design of healthcare real estate

    Directory of Open Access Journals (Sweden)

    Johan van der Zwart

    2014-09-01

    that links nine types of added value (Table 2
to the interests and needs of the stakeholders by four perspectives on real estate: strategic, financial, functional and physical. The value-impact-matrix was developed to support the alignment between the organisation’s key issues for success, the
added values of real estate and stakeholders different perspectives of real estate. This instrument makes it possible to highlight the added values of real estate from different perspectives on real estate (strategic, financial, functional and physical. Table 4 shows an example of possible connections between one of the values – patient satisfaction and healing environment – to four different perspectives.Hospital real estate design assessmentOnly those design decisions that are incorporated into the final design contribute
to achieving the objectives set, so the translation of accommodation targets into
the architectural design is a crucial step in achieving added value by real estate. In addition to defining these values in advance, applying added value as a framework also requires an assessment to measure these values in the design and use phase. Different analytical drawing techniques used in this part of the research show how the attainment of these values in the architectural design can be tested for different aspects of patient satisfaction. Pre-set values are visualised and different design solutions compared. In particular techniques that come from space syntax provide opportunities to study aspects of user-value in the architectural design drawings. The results are promising, despite the fact that PART 4 of the study is a first exploration of the possibilities of design-assessment. The graphs that can be produced seem to give good insight into the consequences of spatial design, although the analyses are still indicative and as yet unvalidated. More validating research is needed to examine the extent to which the results of the analyses are representative

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

    CERN Document Server

    Torregrosa, C; Calviani, M

    2015-01-01

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

  11. Design and Implementation of SCSI Target Emulator

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

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

  12. Design of liposomal formulations for cell targeting

    OpenAIRE

    Nogueira, E.; Gomes, Andreia C.; Preto, Ana; Cavaco-Paulo, Artur

    2015-01-01

    Liposomes have gained extensive attention as carriers for a wide range of drugs due to being both nontoxic and biodegradable as they are composed of substances naturally occurring in biological membranes. Active targeting for cells has explored specific modification of the liposome surface by functionalizing it with specific targeting ligands in order to increase accumulation and intracellular uptake into target cells. None of the Food and Drug Administration-licensed liposomes or lipid nanop...

  13. Comparative experimental and numerical analysis of the hydraulic behaviour of free-surface flow in the water experiment of the XT-ADS windowless spallation target

    International Nuclear Information System (INIS)

    If the long-living actinides contained in nuclear waste are subjected to an intense neutron flux, nuclear reactions convert them into less toxic short living actinides. This process, called transmutation, may be accomplished by Accelerator Driven Systems (ADS). The required neutron flux is generated by bombarding a spallation target with high energy protons emerging from an accelerator. In the windowless target currently developed in the Integrated Project EUROTRANS of the European Community the target material is HLM (heavy liquid metal). The HLM flows downwards through a concentric nozzle surrounding the beam tube and forms a conical free surface which is subjected to the beam current. The thermal-hydraulics of the target must ensure that the high amount of heat deposited into the HLM can be safely removed. The current target design was developed by a close interaction of numerical and experimental studies resulting in a profound understanding of the hydraulic behavior. The water experiment built at UCL (Belgium)) has similar geometry and dimensions as the XT-ADS spallation target. The experimental results are used to validate the numerical methods that will be used in the analysis of the real HLM target. In the current paper the experimental results obtained from the water experiment are compared to numerical results obtained by applying Volume of Fluid methods in combination with cavitation models. The comparison covers the nominal flow case corresponding to a flow rate of 10 l/s and sensitivity study of free surface level to various flow rates and outlet conditions. Numerical results where obtained from the Computational Fluid Dynamics code STAR-CD. This code is selected for its capability to predict sharper free surfaces compared to other CFD codes implemented in the target study. Numerical and experimental results show good agreement, so that the numerical model is considered validated. The results demonstrate that the hydraulic behaviour of the target

  14. Study of Un-added Allowance of Draping-Planar Designing Garment Prototype for Young Ladies

    Institute of Scientific and Technical Information of China (English)

    李兴刚; 李元虹; 苏同岳

    2003-01-01

    As for the theory and method in garment structural design according to human figures,a principle for garment design,i.e.body-fitting without added allowance,and a combination of draping and planar design (DPD hereunder) for young ladies has been put forward,and,also,a DPD garment prototype for them has been established.And the applied formulae for extensively-practicing operation have been set up,which proves to be,with actual samples,a systematic and practical garment structural designing theory and approach.

  15. Nanogel Carrier Design for Targeted Drug Delivery

    OpenAIRE

    Eckmann, D.M.; Composto, R. J.; Tsourkas, A; Muzykantov, V. R.

    2014-01-01

    Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanoge...

  16. Optimization studies of photo-neutron production in high- metallic targets using high energy electron beam for ADS and transmutation

    Indian Academy of Sciences (India)

    V C Petwal; V K Senecha; K V Subbaiah; H C Soni; S Kotaiah

    2007-02-01

    Monte Carlo calculations have been performed using MCNP code to study the optimization of photo-neutron yield for different electron beam energies impinging on Pb, W and Ta cylindrical targets of varying thickness. It is noticed that photo-neutron yield can be increased for electron beam energies ≥ 100 MeV for appropriate thickness of the target. It is also noticed that it can be maximized by further increasing the thickness of the target. Further, at higher electron beam energy heat gradient in the target decreases, which facilitates easier heat removal from the target. This can help in developing a photo-neutron source based on electron LINAC by choosing appropriate electron beam energy and target thickness to optimize the neutron flux for ADS, transmutation studies and as high energy neutron source etc. Photo-neutron yield for different targets, optimum target thickness and photo-neutron energy spectrum and heat deposition by electron beam for different incident energy is presented.

  17. Experimental and numerical study on the flow pattern of the ADS windowless spallation target with a second free surface downstream using model fluid water

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Zhenqin, E-mail: zqxiong@sjtu.edu.cn; Gu, Hanyang; Gong, Shenjie

    2015-09-15

    Highlights: • A windowless spallation target with a buffer tank is tested. • Shape of the main free surface is recorded. • Streamline is obtained with the planar laser induced fluorescence method. • Stability of free surface is improved by the buffer tank. • Flow structure is simulated using RNG k-e turbulence model and VOF model. - Abstract: The windowless spallation targets are a promising design solution for accelerator driven system (ADS) due to their extended life compared to the spallation targets with a window. Keeping the stability of the free surface and reducing the recirculation zone is one of the key tasks for the design of a windowless spallation target. A windowless spallation target with a second free surface downstream (which is a buffer used to stabilize the main free surface of the flow) is studied experimentally and numerically using water at atmospheric pressure. By using planar laser induced fluorescence technique (LIF), the flow pattern inside the target zone is visualized for Reynolds numbers varying between 3.5 × 10{sup 4} and 7.0 × 10{sup 4} and pressure differences from 100 to 804 Pa. The experimental results reveal that the stability of the free surface is improved by adding a buffer in the downstream thus making it easier to control the height of the surface. The effect of the pressure difference between the void above the second free surface (high pressure side) and beam pipe (low pressure side) on the flow pattern is analyzed, as well as the inlet flow rate. The height of the surface length decreases with an increase in the pressure difference. The formation of the spallation zone is simulated with Fluent using the LES turbulence model and VOF model. The interface predicted agrees well with the experimental results.

  18. Experimental and numerical study on the flow pattern of the ADS windowless spallation target with a second free surface downstream using model fluid water

    International Nuclear Information System (INIS)

    Highlights: • A windowless spallation target with a buffer tank is tested. • Shape of the main free surface is recorded. • Streamline is obtained with the planar laser induced fluorescence method. • Stability of free surface is improved by the buffer tank. • Flow structure is simulated using RNG k-e turbulence model and VOF model. - Abstract: The windowless spallation targets are a promising design solution for accelerator driven system (ADS) due to their extended life compared to the spallation targets with a window. Keeping the stability of the free surface and reducing the recirculation zone is one of the key tasks for the design of a windowless spallation target. A windowless spallation target with a second free surface downstream (which is a buffer used to stabilize the main free surface of the flow) is studied experimentally and numerically using water at atmospheric pressure. By using planar laser induced fluorescence technique (LIF), the flow pattern inside the target zone is visualized for Reynolds numbers varying between 3.5 × 104 and 7.0 × 104 and pressure differences from 100 to 804 Pa. The experimental results reveal that the stability of the free surface is improved by adding a buffer in the downstream thus making it easier to control the height of the surface. The effect of the pressure difference between the void above the second free surface (high pressure side) and beam pipe (low pressure side) on the flow pattern is analyzed, as well as the inlet flow rate. The height of the surface length decreases with an increase in the pressure difference. The formation of the spallation zone is simulated with Fluent using the LES turbulence model and VOF model. The interface predicted agrees well with the experimental results

  19. Overall Design of the ADS Injector I Cryogenic System in China

    Science.gov (United States)

    Li, Shaopeng; Ge, Rui; Zhang, Zhuo; Liu, Yaping; Sang, Minjing; Bian, Lin; Han, Ruixiong; Zhang, Jiehao; Sun, Liangrui; Xu, Miaofu; Ye, Rui; Zhang, Jianqin

    The accelerator driven sub-critical system (ADS) in China is a kind of transmutation machine to minimize nuclear waste. As one of the important parts in ADS, injector will be built at IHEP,CAS. Injector I needs two cryomodules operating at 2K cryogenic environment to realize a 10MeVproton beam energy. Each cryomodule includes seven spoke cavities and sevensuperconducting magnets. This paper describes the overall design of the cryogenic system, including the cooling flow chart, heat loads estimation, the structure of the operation cryomodule and some of the key components.

  20. Design of the Next Generation Spallation Target

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-13

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

  1. This Ad is for You: Targeting and the Effect of Alcohol Advertising on Youth Drinking.

    Science.gov (United States)

    Molloy, Eamon

    2016-02-01

    Endogenous targeting of alcohol advertisements presents a challenge for empirically identifying a causal effect of advertising on drinking. Drinkers prefer a particular media; firms recognize this and target alcohol advertising at these media. This paper overcomes this challenge by utilizing novel data with detailed individual measures of media viewing and alcohol consumption and three separate empirical techniques, which represent significant improvements over previous methods. First, controls for the average audience characteristics of the media an individual views account for attributes of magazines and television programs alcohol firms may consider when deciding where to target advertising. A second specification directly controls for each television program and magazine a person views. The third method exploits variation in advertising exposure due to a 2003 change in an industry-wide rule that governs where firms may advertise. Although the unconditional correlation between advertising and drinking by youth (ages 18-24) is strong, models that include simple controls for targeting imply, at most, a modest advertising effect. Although the coefficients are estimated less precisely, estimates with models including more rigorous controls for targeting indicate no significant effect of advertising on youth drinking.

  2. This Ad is for You: Targeting and the Effect of Alcohol Advertising on Youth Drinking.

    Science.gov (United States)

    Molloy, Eamon

    2016-02-01

    Endogenous targeting of alcohol advertisements presents a challenge for empirically identifying a causal effect of advertising on drinking. Drinkers prefer a particular media; firms recognize this and target alcohol advertising at these media. This paper overcomes this challenge by utilizing novel data with detailed individual measures of media viewing and alcohol consumption and three separate empirical techniques, which represent significant improvements over previous methods. First, controls for the average audience characteristics of the media an individual views account for attributes of magazines and television programs alcohol firms may consider when deciding where to target advertising. A second specification directly controls for each television program and magazine a person views. The third method exploits variation in advertising exposure due to a 2003 change in an industry-wide rule that governs where firms may advertise. Although the unconditional correlation between advertising and drinking by youth (ages 18-24) is strong, models that include simple controls for targeting imply, at most, a modest advertising effect. Although the coefficients are estimated less precisely, estimates with models including more rigorous controls for targeting indicate no significant effect of advertising on youth drinking. PMID:25580931

  3. Using a 'value-added' approach for contextual design of geographic information.

    Science.gov (United States)

    May, Andrew J

    2013-11-01

    The aim of this article is to demonstrate how a 'value-added' approach can be used for user-centred design of geographic information. An information science perspective was used, with value being the difference in outcomes arising from alternative information sets. Sixteen drivers navigated a complex, unfamiliar urban route, using visual and verbal instructions representing the distance-to-turn and junction layout information presented by typical satellite navigation systems. Data measuring driving errors, navigation errors and driver confidence were collected throughout the trial. The results show how driver performance varied considerably according to the geographic context at specific locations, and that there are specific opportunities to add value with enhanced geographical information. The conclusions are that a value-added approach facilitates a more explicit focus on 'desired' (and feasible) levels of end user performance with different information sets, and is a potentially effective approach to user-centred design of geographic information.

  4. Interface Design between AD7656 and TMS320F2812%AD7656与TMS320F2812的接口设计研究

    Institute of Scientific and Technical Information of China (English)

    韩露

    2015-01-01

    In order to meet the requirment of high-precision data collection ,a system based on digital singal processor TMS320F2812 and communications with 16-bit A/D converter AD7656 through CPLD was designed. Interfacing AD7656 to TMS320F2812 and the key programming was given in this paper ,as well as the attentions of using AD7656 was discussed.%为了满足高精度数据采集的需要,业内设计了一种基于TMS320F2812 DSP芯片并通过CPLD与16位模数转换芯片AD7656通讯的数据采集系统。文章给出了AD7656与TMS320F2812的接口设计与关键编程,并讨论了AD7656使用中需要注意的事项。

  5. 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.

  6. TRAP: using TaRgeted Ads to unveil Google personal Profiles

    OpenAIRE

    Cozza, Vittoria; Petrocchi, Marinella; Spognardi, Angelo; Conti, Mauro

    2015-01-01

    In the last decade, the advertisement market spread significantly in the web and mobile app system. Its effectiveness is also due thanks to the possibility to target the advertisement on the specific interests of the actual user, other than on the content of the website hosting the advertisement. In this scenario, became of great value services that collect and hence can provide information about the browsing user, like Facebook and Google. In this paper, we show how to maliciously exploit th...

  7. Eyelid conditioning to a target amplitude: adding how much to whether and when.

    Science.gov (United States)

    Kreider, Joy C; Mauk, Michael D

    2010-10-20

    Conceptual and practical advantages of pavlovian eyelid conditioning facilitate analysis of cerebellar computation and learning. Even so, eyelid conditioning procedures are unrealistic in an important way. The error signal to the olivocerebellar system does not decrease as learning adapts response amplitude or gain. This inherently limits the utility of eyelid conditioning for studies investigating how cerebellar learning mechanisms acquire and store an adaptive response amplitude. We report the development and characterization of a training procedure in which conditioned response amplitude is brought under experimental control with contingencies that more closely parallel natural conditions. In this procedure, the delivery of the unconditioned stimulus (US) is made contingent on conditioned response amplitude: the US is delivered for responses that fail to reach a specified target amplitude and is omitted for responses that meet or exceed the target. We find that rabbits trained with either a tone or with mossy fiber stimulation as the conditioned stimulus learn responses that approach target amplitudes ranging from 2 to 5 mm. Inactivating the interpositus nucleus with muscimol infusions abolished these conditioned responses, indicating that cerebellar involvement in eyelid conditioning is not tied explicitly to the use of pavlovian procedures. Together with previous studies, these data suggest that response amplitude is learned and encoded in the cerebellum during eyelid conditioning. As such, these results provide a foundation for systematic and controlled investigations of the cerebellar mechanisms that learn and encode the proper amplitude of adaptive movements.

  8. Design of a liquid hydrogen target system

    International Nuclear Information System (INIS)

    An internal liquid hydrogen target is described for use with intermediate energy light ion beams. As a result, certain safety features are required to prevent a possible hydrogen explosion within the beamline or cyclotron. These safety features include an acoustical delay line which slows the hydrogen gas shock wave and a fast closing valve which shuts before any large volume of escaping gas reaches it. Other safety devices which reduce the changes of cell breakage and quickly shut off various ignition sources are discussed. Also described is a device involving a variable heat load which is coupled directly to the cryocondenser and is used to continually monitor and stabilize the pressure and temperature of the liquid hydrogen. (orig.)

  9. Ignition target design for the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-06-01

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

  10. Beryllium ignition target design for indirect drive NIF experiments

    Science.gov (United States)

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

    2016-03-01

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

  11. Wideband Waveform Design for Robust Target Detection

    OpenAIRE

    Panahi, Ashkan; Ström, Marie; Viberg, Mats

    2014-01-01

    Future radar systems are expected to use waveforms of a high bandwidth, where the main advantage is an improved range resolution. In this paper, a technique to design robust wideband waveforms for a Multiple-Input-Single-Output system is developed. The context is optimal detection of a single object with partially unknown parameters. The waveforms are robust in the sense that, for a single transmission, detection capability is maintained over an interval of time-delay and time-scaling (Dopple...

  12. Nyquist AD Converters, Sensor Interfaces, and Robustness Advances in Analog Circuit Design, 2012

    CERN Document Server

    Baschirotto, Andrea; Steyaert, Michiel

    2013-01-01

    This book is based on the presentations during the 21st workshop on Advances in Analog Circuit Design.  Expert designers provide readers with information about a variety of topics at the frontier of analog circuit design, including Nyquist analog-to-digital converters, capacitive sensor interfaces, reliability, variability, and connectivity.  This book serves as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development.  Provides a state-of-the-art reference in analog circuit design, written by experts from industry and academia; Presents material in a tutorial-based format; Includes coverage of Nyquist A/D converters, capacitive sensor interfaces, reliability, variability, and connectivity.

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-07-27

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

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

    Science.gov (United States)

    Duncan, Gregg A; Bevan, Michael A

    2015-10-01

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

  16. Design of the Helium Purifier for IHEP-ADS Helium Purification System

    OpenAIRE

    Jianqin, Zhang; Shaopeng, Li; Zhuo, Zhang; Rui, Ge

    2015-01-01

    Helium Purification System is an important sub-system in the Accelerator Driven Subcritical System of the Institute of High Energy Physics(IHEP ADS). The purifier is designed to work at the temperature of 77K. The purifier will work in a flow rate of 5g/s at 20MPa in continuous operation of 12 hours. The oil and moisture are removed by coalescing filters and a dryer, while nitrogen and oxygen are condensed by a phase separator and then adsorbed in several activated carbon adsorption cylinders...

  17. Design of the Helium Purifier for IHEP-ADS Helium Purification System

    CERN Document Server

    Jianqin, Zhang; Zhuo, Zhang; Rui, Ge

    2015-01-01

    Helium Purification System is an important sub-system in the Accelerator Driven Subcritical System of the Institute of High Energy Physics(IHEP ADS). The purifier is designed to work at the temperature of 77K. The purifier will work in a flow rate of 5g/s at 20MPa in continuous operation of 12 hours. The oil and moisture are removed by coalescing filters and a dryer, while nitrogen and oxygen are condensed by a phase separator and then adsorbed in several activated carbon adsorption cylinders. After purification, the purified helium has an impurity content of less than 5ppm.

  18. Design Study of Full Scale Accelerator Driven System (ADS, for Transmuting High Level Waste of MA/Pu

    Directory of Open Access Journals (Sweden)

    Marsodi

    2008-07-01

    Full Text Available The ADS system used in this study consisting of a high intensity proton linear accelerator, a spallation target, and a sub-critical reactor core. The Pb-Bi spallation target is bombarded by high intensity protons coming from the accelerator. The fast neutrons generated from the spallation reaction were used to drive the sub-critical reactor core. In this ADS system, the neutron source is in the center of reactor core region, so that the neutron distribution was concentrated in the center of core region. In this case, the B/T of MA/Pu could be performed effectively in the center of core region. The neutron energy in the outer region of reactor core was decreased due to the moderation of fuel and coolant materials. Such condition gives a chance to perform Burning and/or Transmutation of LLFPs.The basic parameters of this system are shown in the form of neutronic design, neutron spectrum and B/T rate, including other aspects related to the safety operation system. Furthermore, the analysis of the ADS system was accomplished using ATRAS computer code of the Japan Atomic Energy Research Institute, JAERI[1]. Due to the complexity of the reactor calculation codes, the author has carried out only those calculations needed for analyzing the neutronics system and some parameters related to the safety system. Design study of the transmutation system was a full-scale power level system of 657.53 MWt sub-critical reactor for an accelerator-driven transmutation system. The liquid Pb-Bi was used together as the spallation target materials and coolant of the system, because of some advantages of Pb-Bi in the system concerning the comparison with the sodium coolant. Moreover, they have a possibility to achieve a hard neutron energy spectrum, avoid a positive void reactivity coefficient, allow much lower system operating temperatures, and are favorable for safety in the event of coolant leakage. The multiplication factor of sub-critical core design was adjusted

  19. Design of the Q Meter Based on AD633 Analog Phase Detection%基于AD633模拟鉴相的Q表设计

    Institute of Scientific and Technical Information of China (English)

    葛维亮; 奚大顺; 庹先国; 王洪辉; 李怀良; 张赓; 宋茜茜

    2011-01-01

    In order to solve the problem that the multimeters are unable to measure the parameters of Q, D, etc., the Q meter based on AD633 analog phase detection has been designed. In the instrument, the sine energizing signal and reference signal are generated by the DDS chip AD9851, and phase detection of the signal is implemented by using highly integrated analog multiplier AD633. The single end output signal of phase detection is then converted into differential signal by the differential converter AD8138; and the differential signal is converted into digital and processed by the self-contained ADC of C8051F060. This instrument offers the functions of automatic range changeover, LCD real-time display; and features of compact, low cost as well an meets the measurement demands in engineering projects, teaching and research areas.%为解决万用表无法测量Q、D等参数的问题,设计了基于A1D633模拟鉴相的Q表.该测量仪采用DDS芯片AD9851产生正弦激励信号和基准信号,利用高集成度模拟乘法器AD633对信号进行模拟鉴相,并采用差分转换器AD8138对鉴相输出信号进行单端转差分变换,由C8051F060内部自带的ADC对差分信号进行模数转换和数据处理.Q表具有多量程自动切换和LCD实时显示等功能,且体积小、成本低,能满足工程、教学科研测量的需要.

  20. Delta-Sigma AD-Converters Practical Design for Communication Systems

    CERN Document Server

    Gaggl, Richard

    2013-01-01

    The emphasis of this book is on practical design aspects for broadband A/D converters for communication systems. The embedded designs are employed for transceivers in the field of ADSL solutions and WLAN applications. An area- and power-efficient realization of a converter is mandatory to remain competitive in the market. The right choice for the converter topology and architecture needs to be done very carefully to result in a competitive FOM. The book begins with a brief overview of basic concepts about ADSL and WLAN to understand the ADC requirements. At architectural level, issues on different modulator topologies are discussed employing the provided technology node. The design issues are pointed out in detail for modern digital CMOS technologies, beginning with 180nm followed by 130nm and going down to 65nm feature size. Beside practical aspects, challenges to mixed-signal design level are addressed to optimize the converters in terms of consumed chip area, power consumption and design for high yield in ...

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

    Science.gov (United States)

    Duncan, Gregg A.; Bevan, Michael A.

    2015-09-01

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

  2. VisitSense: Sensing Place Visit Patterns from Ambient Radio on Smartphones for Targeted Mobile Ads in Shopping Malls.

    Science.gov (United States)

    Kim, Byoungjip; Kang, Seungwoo; Ha, Jin-Young; Song, Junehwa

    2015-01-01

    In this paper, we introduce a novel smartphone framework called VisitSense that automatically detects and predicts a smartphone user's place visits from ambient radio to enable behavioral targeting for mobile ads in large shopping malls. VisitSense enables mobile app developers to adopt visit-pattern-aware mobile advertising for shopping mall visitors in their apps. It also benefits mobile users by allowing them to receive highly relevant mobile ads that are aware of their place visit patterns in shopping malls. To achieve the goal, VisitSense employs accurate visit detection and prediction methods. For accurate visit detection, we develop a change-based detection method to take into consideration the stability change of ambient radio and the mobility change of users. It performs well in large shopping malls where ambient radio is quite noisy and causes existing algorithms to easily fail. In addition, we proposed a causality-based visit prediction model to capture the causality in the sequential visit patterns for effective prediction. We have developed a VisitSense prototype system, and a visit-pattern-aware mobile advertising application that is based on it. Furthermore, we deploy the system in the COEX Mall, one of the largest shopping malls in Korea, and conduct diverse experiments to show the effectiveness of VisitSense. PMID:26193275

  3. VisitSense: Sensing Place Visit Patterns from Ambient Radio on Smartphones for Targeted Mobile Ads in Shopping Malls

    Directory of Open Access Journals (Sweden)

    Byoungjip Kim

    2015-07-01

    Full Text Available In this paper, we introduce a novel smartphone framework called VisitSense that automatically detects and predicts a smartphone user’s place visits from ambient radio to enable behavioral targeting for mobile ads in large shopping malls. VisitSense enables mobile app developers to adopt visit-pattern-aware mobile advertising for shopping mall visitors in their apps. It also benefits mobile users by allowing them to receive highly relevant mobile ads that are aware of their place visit patterns in shopping malls. To achieve the goal, VisitSense employs accurate visit detection and prediction methods. For accurate visit detection, we develop a change-based detection method to take into consideration the stability change of ambient radio and the mobility change of users. It performs well in large shopping malls where ambient radio is quite noisy and causes existing algorithms to easily fail. In addition, we proposed a causality-based visit prediction model to capture the causality in the sequential visit patterns for effective prediction. We have developed a VisitSense prototype system, and a visit-pattern-aware mobile advertising application that is based on it. Furthermore, we deploy the system in the COEX Mall, one of the largest shopping malls in Korea, and conduct diverse experiments to show the effectiveness of VisitSense.

  4. 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.

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

    International Nuclear Information System (INIS)

    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)

  6. 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.

  7. TMS320F28335与串行A/D转换器ADS7863的接口设计%Design of Interface Between TMS320F28335 and Serial AD Converter ADS7863

    Institute of Scientific and Technical Information of China (English)

    高瑛

    2011-01-01

    为了实现DSP芯片与串行A/D芯片的多信号通信,设计了TMS320F28335的多通道缓冲串口(McBSP)与串行A/D转换器ADS7863的硬件与软件接口.该设计中A/D转换器与McBSP串口直接相连,不需要占用并行数据总线,避免了总线冲突.通过在CCS环境下编程、调试,得到了满意的实验结果,验证了该接口设计的正确性.%The hardware and software interface between TMS320F28335 McBSP and ADS7863 was designed for the realization of multi-signal communication between DSP and serial A/D converter. In this design, the A/D converter is directly connected to the serial port McBSP without occupying DSP s parallel data bus. The solution avoids the bus impact. By programming and debugging under CCS environment, the satisfied experimental result is achieved, and the correctness of the interface design is verified.

  8. Design target accuracies, data uncertainties and sensitivity studies

    International Nuclear Information System (INIS)

    The aim of this course is to give an overview of the general problem of design parameter target accuracy assessment, the related data needs and the uncertainty analysis techniques which provide the tools for these studies. Concerning target accuracy assessment, this paper is essentially based on a paper, related to LMFBR's. Data needs will be illustrated by the example of fission data needs, in all the fields of core design and fuel cycle. Uncertainty analysis is a general notion which covers different fields. In this paper we will essentially describe the so-called data adjustment aspect. Finally, the sensitivity methods, based on perturbation theory will be described for different type of applications

  9. Design and RF test of MEBT buncher cavities for C-ADS Injector II at IMP

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Shichun; Jia, Huan [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Niu, Haihua [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); He, Yuan, E-mail: hey@impcas.ac.cn [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Zhang, Shenghu; Yuan, Chenzhang [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Wang, Jing [Lanzhou University of Technology, Lanzhou 730050 (China); Zhang, Shengxue; Chang, Wei; Zhang, Peng; Zhao, Hongwei; Xia, Jiawen [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China)

    2015-11-01

    Abstracts: To match the beam from the Radio Frequency Quadrupole (RFQ) accelerator to the Superconducting Half-wave Resonator (HWR) Linac, two room temperature (RT) double-gap Quarter-wave Resonator (QWR) bunchers are designed to be located in the Medium Energy Beam Transport Line (MEBT) for the C-ADS Injector II at IMP. Both cavities work at 162.5 MHz, with β=0.067 and a beam aperture diameter of 40 mm. The effective voltage of these two cavities needs to reach 135 kV in Continuous Wave (CW) mode. In this paper, the RF design and thermal analysis of the cavities will be presented, along with the tuners and coupler consideration. The measured frequencies, R{sub sh}/Q{sub 0}, Q{sub 0} and voltage of the cavities agree well with the simulation result. Details of the RF test results including the full power tests of the cavities will be shown. - Highlights: • High bunching voltage for this type of cavity with limited longitudinal length in MEBT line. • Using copper-plated stainless technique for cavity outer conductor. • Spiral cooling channel design for stem cooling.

  10. 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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

    There is a need for greater understanding of the health impact of various design elements in neonatal intensive care units (NICUs) as well as cost-benefit information to make informed decisions about the long-term value of design decisions. This is particularly evident when design teams are considering the transition from open-bay NICUs to single-family-room (SFR) units. This paper introduces the guiding principles behind target value design (TVD)-a price-led design methodology that is gaining acceptance in healthcare facility design within the Lean construction methodology. The paper also discusses the role that set-based design plays in TVD and its application to NICUs. PMID:23224803

  13. Design of Nanoparticle-Based Carriers for Targeted Drug Delivery

    OpenAIRE

    Xiaojiao Yu; Ian Trase; Muqing Ren; Kayla Duval; Xing Guo; Zi Chen

    2016-01-01

    Nanoparticles have shown promise as both drug delivery vehicles and direct antitumor systems, but they must be properly designed in order to maximize efficacy. Computational modeling is often used both to design new nanoparticles and to better understand existing ones. Modeled processes include the release of drugs at the tumor site and the physical interaction between the nanoparticle and cancer cells. In this paper, we provide an overview of three different targeted drug delivery methods (p...

  14. 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 ...

  15. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-06-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

  18. Optimizing the design of oligonucleotides for homology directed gene targeting.

    Directory of Open Access Journals (Sweden)

    Judith Miné-Hattab

    Full Text Available BACKGROUND: Gene targeting depends on the ability of cells to use homologous recombination to integrate exogenous DNA into their own genome. A robust mechanistic model of homologous recombination is necessary to fully exploit gene targeting for therapeutic benefit. METHODOLOGY/PRINCIPAL FINDINGS: In this work, our recently developed numerical simulation model for homology search is employed to develop rules for the design of oligonucleotides used in gene targeting. A Metropolis Monte-Carlo algorithm is used to predict the pairing dynamics of an oligonucleotide with the target double-stranded DNA. The model calculates the base-alignment between a long, target double-stranded DNA and a probe nucleoprotein filament comprised of homologous recombination proteins (Rad51 or RecA polymerized on a single strand DNA. In this study, we considered different sizes of oligonucleotides containing 1 or 3 base heterologies with the target; different positions on the probe were tested to investigate the effect of the mismatch position on the pairing dynamics and stability. We show that the optimal design is a compromise between the mean time to reach a perfect alignment between the two molecules and the stability of the complex. CONCLUSION AND SIGNIFICANCE: A single heterology can be placed anywhere without significantly affecting the stability of the triplex. In the case of three consecutive heterologies, our modeling recommends using long oligonucleotides (at least 35 bases in which the heterologous sequences are positioned at an intermediate position. Oligonucleotides should not contain more than 10% consecutive heterologies to guarantee a stable pairing with the target dsDNA. Theoretical modeling cannot replace experiments, but we believe that our model can considerably accelerate optimization of oligonucleotides for gene therapy by predicting their pairing dynamics with the target dsDNA.

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

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

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

  20. 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.

  1. 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...

  2. A Design of a FPGA-based Controller of ADS1256%基于FPGA的ADS1256芯片控制器设计

    Institute of Scientific and Technical Information of China (English)

    颜丽

    2012-01-01

    This article introduces a design of a FPGA-based controller of ADS1256, which is a chip of Analog-digital conversion, and uses hardware description language Verilog HDL to design the internal functional modules. The synthesis and simulation are completed in advance. The results show that the controller not only completes requirements of all function, but also simplifies the structure by primitives, which reduces the use of hardware resources.%本文针对数据转换芯片ADS1256提出一种基于FPGA的控制器方案,并利用硬件描述语言VerilogHDL详细设计了其内部各功能模块。进一步完成了综合和仿真验证,结果表明此控制器不仅能够完成总体的设计要求,而且利用原语设计简化了设计结构、减少了硬件资源的使用。

  3. Design considerations for foil windows for PET radioisotope targets

    International Nuclear Information System (INIS)

    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 N2 gas target for 15O 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

  4. Thermal hydraulic design of the mercury target vessel

    International Nuclear Information System (INIS)

    Japan Atomic Energy Agency (JAEA) has completed the mercury target system as the pulsed spallation neutron source of J-PARC project, which has the highest level power of 1MW in the world. The basic design of the flow channel and structure of the mercury target vessel, which is the core of the neutron source, was carried out by JAEA, and the detail design, parts fabrication and assembling have been carried out by the vendor from 2003. Taking these fabrication designs and assembling conditions into consideration, the final performance evaluation of the mercury target vessel was carried out from the viewpoint of thermal hydraulics. The general thermal hydraulic analyses code, STAR-CD, was used, and the thermal hydraulic analyses were carried out for the mercury flow in the mercury vessel and the heavy water flow in the safety hull, taking the nuclear heating and the heat transportation into consideration. The analytical model was three dimensional. The total cell number of the mercury vessel and mercury was 1.78 x 106 and that of the safety hull was 2.39 x 106. The standard k-ε model and MARS were adopted as the basic combination of the turbulence model and the differential scheme, but other combinations, such as RNG k-ε model and UD were also used as a reference. Comparing these analytical results, it was confirmed that the mercury target vessel fulfills the design requirements such as the fluid inlet velocity, the maximum temperature of fluid, the maximum temperature of the vessel, the pressure drop of fluid, etc. The influence of the welding deformation of the mercury target vessel was also evaluated. Mercury flow and heavy water flow are affected a little, but they do not much extend the required condition, and the structural integrity was confirmed. (author)

  5. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation.

    Science.gov (United States)

    Kamaly, Nazila; Xiao, Zeyu; Valencia, Pedro M; Radovic-Moreno, Aleksandar F; Farokhzad, Omid C

    2012-04-01

    Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development

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

    CERN Document Server

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

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

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

    Science.gov (United States)

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

    2016-01-01

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

  8. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

  10. Auto Target Tracking Robot Design Based on Smartphone

    OpenAIRE

    Shuen De Wu; Kei-Siang You

    2016-01-01

    This paper describes a robot tracking control design based on a smartphone using a commercial microprocessor. The system hardware consists of four major parts: an Android smartphone with an embedded camera, a Microchip microprocessor, a motor driver circuit and an Attacknid robot. First, an image of the surrounding environment is captured by the high definition camera embedded in the smartphone. The target is then recognized from the image using an algorithm developed in Android OS and OpenCV...

  11. Shielding design calculations for ESS activated target system

    International Nuclear Information System (INIS)

    Full text of publication follows: The European Spallation Source (ESS) is a European common effort in designing and building a next generation large-scale user facility for studies of the structure and dynamics of materials. The ESS target, moderators and reflectors system through interactions with 5 MW proton beam (2.5 GeV, 20 Hz) will produce long pulse (2.8 ms width) neutrons in sub-thermal and thermal energy range. These neutrons are further transported to a variety of neutron scattering instruments. The aim of this work is to assess the strategy to be used for the safe handling and shipping of the ESS target and associated shaft. For safe maintenance, during operation as well as handling, transport and storage of the components of the ESS target station after their lifetime, detailed knowledge is required about the activation induced by the impinging protons and secondary radiation fields. The Monte Carlo transport code MCNPX2.6.0 was coupled with CINDER90 version 07.4 to calculate the residual nuclide production in the target wheel and associated shaft. Dose equivalent rates due to the residual radiation were further calculated with the MICROSHIELD and MCNPX codes using photon sources resulting from CINDER. Various decay times after ceasing operation of the target components were considered. The activation and decay heat density distributions of the target system together with the derived dose rates were analysed to assess the best strategy to be used for their safe removal and transport to a hot cell, eventual dismantling, storage on-site and shipping off-site as intermediate level waste packages. The derived photon sources were used afterwards to design the shielded exchange flasks that are needed to remove and transport the target after its lifespan to a hot cell. Design of a multipurpose cask able to accommodate the different highly activated components of the ESS target station and ship them to external conditioning facility is intended to be developed

  12. Target Station Design for the Mu2e Experiment

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-01

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

  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. 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.

  15. Fostering a Durable Relationship between a Radioactive Waste Management Facility and its Host Community. Adding Value through Design and Process. 2015 Edition

    International Nuclear Information System (INIS)

    In the field of long-term radioactive waste management, repository projects last from decades to centuries. Such projects will inevitably have an effect on the host community from the planning stage to the end of construction and beyond. The key to a long-lasting and positive relationship between a facility and its host community is ensuring that solutions are reached together throughout the entire process. The sustainability of radioactive waste management solutions can potentially be achieved through design and implementation of a facility that provides added cultural and amenity value, as well as economic opportunities, to the local community. This edition of Fostering a Durable Relationship between a Waste Management Facility and its Host Community: Adding Value through Design and Process highlights new innovations in siting processes and in facility design - functional, cultural and physical - from different countries, which could be of added value to host communities and their sites in the short to long term. These new features are examined from the perspective of sustainability, with a focus on increasing the likelihood that people will both understand the facility and its functions, and remember over very long timescales what is located at the site. This 2015 update by the NEA Forum on Stakeholder Confidence will be beneficial in designing paths forward for local or regional communities, as well as for national radioactive waste management programmes. Section 2 of this report summarises the value of developing a sustainable relationship between a community and a radioactive waste management facility through added cultural and amenity value. In Section 3, the report identifies design considerations - functional, cultural and physical - that may help facilities to fit into the community in a sustainable manner. Each design feature is illustrated with examples. Section 4 discusses the benefits that may be gained from the very process of planning radioactive

  16. Nuclear data requirements for the ADS conceptual design EFIT: Uncertainty and sensitivity study

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Herranz, N., E-mail: nuria@din.upm.e [Departamento de Ingenieria Nuclear, Universidad Politecnica de Madrid (Spain); Instituto de Fusion Nuclear, Universidad Politecnica de Madrid (Spain); Cabellos, O. [Departamento de Ingenieria Nuclear, Universidad Politecnica de Madrid (Spain); Instituto de Fusion Nuclear, Universidad Politecnica de Madrid (Spain); Alvarez-Velarde, F. [CIEMAT (Spain); Sanz, J. [Instituto de Fusion Nuclear, Universidad Politecnica de Madrid (Spain); Departamento de Ingenieria Energetica, UNED (Spain); Gonzalez-Romero, E.M. [CIEMAT (Spain); Juan, J. [Laboratorio de Estadistica, Universidad Politecnica de Madrid (Spain)

    2010-11-15

    In this paper, we assess the impact of activation cross-section uncertainties on relevant fuel cycle parameters for a conceptual design of a modular European Facility for Industrial Transmutation (EFIT) with a 'double strata' fuel cycle. Next, the nuclear data requirements are evaluated so that the parameters can meet the assigned design target accuracies. Different discharge burn-up levels are considered: a low burn-up, corresponding to the equilibrium cycle, and a high burn-up level, simulating the effects on the fuel of the multi-recycling scenario. In order to perform this study, we propose a methodology in two steps. Firstly, we compute the uncertainties on the system parameters by using a Monte Carlo simulation, as it is considered the most reliable approach to address this problem. Secondly, the analysis of the results is performed by a sensitivity technique, in order to identify the relevant reaction channels and prioritize the data improvement needs. Cross-section uncertainties are taken from the EAF-2007/UN library since it includes data for all the actinides potentially present in the irradiated fuel. Relevant uncertainties in some of the fuel cycle parameters have been obtained, and we conclude with recommendations for future nuclear data measurement programs, beyond the specific results obtained with the present nuclear data files and the limited available covariance information. A comparison with the uncertainty and accuracy analysis recently published by the WPEC-Subgroup26 of the OECD using BOLNA covariance matrices is performed. Despite the differences in the transmuter reactor used for the analysis, some conclusions obtained by Subgroup26 are qualitatively corroborated, and improvements for additional cross sections are suggested.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-09-01

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

  18. Design and Implementation of Anycast Services in Ad Hoc Networks Connected to IPv6 Networks

    Directory of Open Access Journals (Sweden)

    Xiaonan Wang

    2010-04-01

    Full Text Available The paper proposes a communication model of implementing an Anycast service in an Ad Hoc network which is connected to IPv6 networks where IPv6 nodes can obtain the Anycast service provided by the Ad hoc network. In this model when an Anycast mobile member in an Ad hoc network moves it can keep the existing communications with its corresponding nodes to continue providing the Anycast services with good quality of service to IPv6 nodes. This model creates a new kind of IPv6 address auto-configuration scheme which does not need the address duplication detection. This paper deeply discusses and analyzes the model and the experimental data prove its validity and efficiency.

  19. Integrated analysis of microRNA and mRNA expression: Adding biological significance to microRNA target predictions

    NARCIS (Netherlands)

    M. van Iterson (Mat); S. Bervoets (Sander); E.J. de Meijer (Emile); H.P. Buermans (Henk); P.A.C. 't Hoen (Peter); R.X. Menezes (Renée); J.M. Boer (Judith)

    2013-01-01

    textabstractCurrent microRNA target predictions are based on sequence information and empirically derived rules but do not make use of the expression of microRNAs and their targets. This study aimed to improve microRNA target predictions in a given biological context, using in silico predictions, mi

  20. Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core.

    Science.gov (United States)

    Clark, Andrew J; Davis, Mark E

    2015-10-01

    Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis. PMID:26392563

  1. Mechanism Design for Multi-slot Ads Auction in Sponsored Search Markets

    Science.gov (United States)

    Deng, Xiaotie; Sun, Yang; Yin, Ming; Zhou, Yunhong

    In this paper, we study pricing models for multi-slot advertisements, where advertisers can bid to place links to their sales webpages at one or multiple slots on a webpage, called the multi-slot AD auction problem. We develop and analyze several important mechanisms, including the VCG mechanism for multi-slot ads auction, the optimal social welfare solution, as well as two weighted GSP-like protocols (mixed and hybrid). Furthermore, we consider that forward-looking Nash equilibrium and prove its existence in the weighted GSP-like pricing protocols.

  2. Cross-layer design for intrusion detection and data security in wireless ad hoc sensor networks

    Science.gov (United States)

    Hortos, William S.

    2007-09-01

    A wireless ad hoc sensor network is a configuration for area surveillance that affords rapid, flexible deployment in arbitrary threat environments. There is no infrastructure support and sensor nodes communicate with each other only when they are in transmission range. The nodes are severely resource-constrained, with limited processing, memory and power capacities and must operate cooperatively to fulfill a common mission in typically unattended modes. In a wireless sensor network (WSN), each sensor at a node can observe locally some underlying physical phenomenon and sends a quantized version of the observation to sink (destination) nodes via wireless links. Since the wireless medium can be easily eavesdropped, links can be compromised by intrusion attacks from nodes that may mount denial-of-service attacks or insert spurious information into routing packets, leading to routing loops, long timeouts, impersonation, and node exhaustion. A cross-layer design based on protocol-layer interactions is proposed for detection and identification of various intrusion attacks on WSN operation. A feature set is formed from selected cross-layer parameters of the WSN protocol to detect and identify security threats due to intrusion attacks. A separate protocol is not constructed from the cross-layer design; instead, security attributes and quantified trust levels at and among nodes established during data exchanges complement customary WSN metrics of energy usage, reliability, route availability, and end-to-end quality-of-service (QoS) provisioning. Statistical pattern recognition algorithms are applied that use observed feature-set patterns observed during network operations, viewed as security audit logs. These algorithms provide the "best" network global performance in the presence of various intrusion attacks. A set of mobile (software) agents distributed at the nodes implement the algorithms, by moving among the layers involved in the network response at each active node

  3. Design and Implementation of Key Techniques for Mobile Ad hoc Network Adaptive QoS Provisioning Framework

    Institute of Scientific and Technical Information of China (English)

    YAOYinxiong; LIUJianxun; TANGXinhuai

    2004-01-01

    MAQF is a newly proposed adaptive QoS provisioning framework for Mobile Ad hoc network (MANET) by the authors. Through modifying the architecture of INSIGNIA and adding some components, MAQF overcomes many disadvantages appearing in related works and supports QoS guarantees for MANET. This paper focuses on the design and implementation of some key techniques in MAQF, including QoS routing, signaling in band, adaptive control mechanism, dynamic resource adaptation algorithm and, etc. Simulation results are presented and have verified the validity of MAQF.

  4. On Energy-Efficient Hierarchical Cross-Layer Design: Joint Power Control and Routing for Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Cristina Comaniciu

    2007-03-01

    Full Text Available A hierarchical cross-layer design approach is proposed to increase energy efficiency in ad hoc networks through joint adaptation of nodes' transmitting powers and route selection. The design maintains the advantages of the classic OSI model, while accounting for the cross-coupling between layers, through information sharing. The proposed joint power control and routing algorithm is shown to increase significantly the overall energy efficiency of the network, at the expense of a moderate increase in complexity. Performance enhancement of the joint design using multiuser detection is also investigated, and it is shown that the use of multiuser detection can increase the capacity of the ad hoc network significantly for a given level of energy consumption.

  5. On Energy-Efficient Hierarchical Cross-Layer Design: Joint Power Control and Routing for Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Poor HVincent

    2007-01-01

    Full Text Available A hierarchical cross-layer design approach is proposed to increase energy efficiency in ad hoc networks through joint adaptation of nodes' transmitting powers and route selection. The design maintains the advantages of the classic OSI model, while accounting for the cross-coupling between layers, through information sharing. The proposed joint power control and routing algorithm is shown to increase significantly the overall energy efficiency of the network, at the expense of a moderate increase in complexity. Performance enhancement of the joint design using multiuser detection is also investigated, and it is shown that the use of multiuser detection can increase the capacity of the ad hoc network significantly for a given level of energy consumption.

  6. On Energy Efficient Hierarchical Cross-Layer Design: Joint Power Control and Routing for Ad Hoc Networks

    CERN Document Server

    Comaniciu, Cristina

    2007-01-01

    In this paper, a hierarchical cross-layer design approach is proposed to increase energy efficiency in ad hoc networks through joint adaptation of nodes' transmitting powers and route selection. The design maintains the advantages of the classic OSI model, while accounting for the cross-coupling between layers, through information sharing. The proposed joint power control and routing algorithm is shown to increase significantly the overall energy efficiency of the network, at the expense of a moderate increase in complexity. Performance enhancement of the joint design using multiuser detection is also investigated, and it is shown that the use of multiuser detection can increase the capacity of the ad hoc network significantly for a given level of energy consumption.

  7. Design of a Smart Antenna for Mobile Ad Hoc Network Applications

    OpenAIRE

    Marco Di Filippo; Leonardo Lucci; Dania Marabissi; Stefano Selleri

    2015-01-01

    Among the mobile ad hoc networks appealing characteristics there are network reconfigurability and flexibility. In this context a smart antenna capable of self-configuring multiple high-directivity beams provides a major advantage in terms of power saving, increased range, and spatial reuse of channels. In this paper a smart antenna made of a cylindrical array of patches suitable for MANETs is presented.

  8. AD7656与ARM芯片的接口设计%The design of the interface of AD7656 and ARM Chip

    Institute of Scientific and Technical Information of China (English)

    夏云非; 杨宝龙

    2013-01-01

      AD7656 is a simultaneous sampling bipolar 16-bit A/D converter,which can work with high accuracy,low energy consumption and high speed.The main characteristic,inner configuration are introduced in this paper.The hardware interface and software program of AD7656 and LPC2194 are also provided.%  AD7656是一款16位、6通道、同步采样的数模转换器,具有高精度、低功耗、高性价比、转换速度快等优点。本文介绍了AD7656主要特性、内部结构,给出了AD7656与ARM芯片LPC2194接口电路及软件编程。

  9. β-Secretase 1’s Targeting Reduces Hyperphosphorilated Tau, Implying Autophagy Actors in 3xTg-AD Mice

    Science.gov (United States)

    Piedrahita, Diego; Castro-Alvarez, John Fredy; Boudreau, Ryan L.; Villegas-Lanau, Andres; Kosik, Kenneth S.; Gallego-Gomez, Juan Carlos; Cardona-Gómez, Gloria Patricia

    2016-01-01

    β-site APP cleaving enzyme 1 (BACE1) initiates APP cleavage, which has been reported to be an inducer of tau pathology by altering proteasome functions in Alzheimer’s disease (AD). However, the exact relationship between BACE1 and PHF (Paired Helical Filaments) formation is not clear. In this study, we confirm that BACE1 and Hsc70 are upregulated in the brains of AD patients, and we demonstrate that both proteins show enhanced expression in lipid rafts from AD-affected triple transgenic mouse brains. BACE1 targeting increased Hsc70 levels in the membrane and cytoplasm fractions and downregulated Hsp90 and CHIP in the nucleus in the hippocampi of 3xTg-AD mice. However, these observations occurred in a proteasome-independent manner in vitro. The BACE1miR-induced reduction of soluble hyperphosphorylated tau was associated with a decrease in MAPK activity. However, the BACE1 RNAi-mediated reduction of hyperphosphorylated tau was only blocked by 3-MA (3-methyladenine) in vitro, and it resulted in the increase of Hsc70 and LAMP2 in lipid rafts from hippocampi of 3xTg-AD mice, and upregulation of survival and homeostasis signaling. In summary, our findings suggest that BACE1 silencing neuroprotects reducing soluble hyperphosphorylated tau, modulating certain autophagy-related proteins in aged 3xTg-AD mice. PMID:26778963

  10. HIERARCHICAL DESIGN BASED INTRUSION DETECTION SYSTEM FOR WIRELESS AD HOC SENSOR NETWORK

    OpenAIRE

    Mohammad Saiful Islam Mamun; A.F.M. Sultanul Kabir

    2010-01-01

    In recent years, wireless ad hoc sensor network becomes popular both in civil and military jobs.However, security is one of the significant challenges for sensor network because of their deploymentin open and unprotected environment. As cryptographic mechanism is not enough to protect sensornetwork from external attacks, intrusion detection system needs to be introduced. Though intrusionprevention mechanism is one of the major and efficient methods against attacks, but there might besome atta...

  11. Hierarchical Design Based Intrusion Detection System For Wireless Ad hoc Network

    OpenAIRE

    Mamun, Mohammad Saiful Islam; Kabir, A. F. M Sultanul

    2012-01-01

    In recent years, wireless ad hoc sensor network becomes popular both in civil and military jobs. However, security is one of the significant challenges for sensor network because of their deployment in open and unprotected environment. As cryptographic mechanism is not enough to protect sensor network from external attacks, intrusion detection system needs to be introduced. Though intrusion prevention mechanism is one of the major and efficient methods against attacks, but there might be some...

  12. Design of a Smart Antenna for Mobile Ad Hoc Network Applications

    Directory of Open Access Journals (Sweden)

    Marco Di Filippo

    2015-01-01

    Full Text Available Among the mobile ad hoc networks appealing characteristics there are network reconfigurability and flexibility. In this context a smart antenna capable of self-configuring multiple high-directivity beams provides a major advantage in terms of power saving, increased range, and spatial reuse of channels. In this paper a smart antenna made of a cylindrical array of patches suitable for MANETs is presented.

  13. Adding a design perspective to study learning environments in higher professional education

    NARCIS (Netherlands)

    Zitter, I.I.; De Bruijn, E.E.J.; Simons, P.R.J.; ten Cate, Th.J.

    2010-01-01

    How to design learning environments leading to learning-, thinking, collaboration- and regulation skills which can be applied to transferable, knowledge oriented learning outcomes is still controversial. We studied the designs of learning environments in innovative higher professional education more

  14. Adding a factor in the course of a design space characterization

    NARCIS (Netherlands)

    Schoen, E.D.; Voort Maarschalk, K. van der

    2012-01-01

    Introduction: An early decision on the design space of a pharmaceutical could imply that some process parameter is to be held fixed during production. Therefore, the effect of such a parameter is not studied in the exploration of the design space with statistically designed experiments. Later decisi

  15. Adding a Factor in the Course of a Design Space Characterization

    NARCIS (Netherlands)

    Schoen, Eric D.; Maarschalk, Kees van der Voort

    2012-01-01

    Introduction An early decision on the design space of a pharmaceutical could imply that some process parameter is to be held fixed during production. Therefore, the effect of such a parameter is not studied in the exploration of the design space with statistically designed experiments. Later decisio

  16. Adding Soft-Skills to the Hard Target of Adequacy: The Case for Rearticulation Based on a Multifocal Analysis

    Science.gov (United States)

    Knoeppel, Robert C.; Brewer, Curtis A.; Lindle, Jane Clark; First, Patricia F.

    2009-01-01

    The purpose of this study is to expand the definition of adequacy by adding soft skills as a measure of school productivity. The singular focus on academic standards inherent in education policy has prevented scholars from seeing the concept of adequacy through myriad perspectives and has contributed to a resegregation of schools. Education policy…

  17. Auto Target Tracking Robot Design Based on Smartphone

    Directory of Open Access Journals (Sweden)

    Shuen De Wu

    2016-03-01

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

  18. Adding Timing Requirements to the CODARTS Real-Time Software Design Method

    DEFF Research Database (Denmark)

    Bach, K.R.

    The CODARTS software design method consideres how concurrent, distributed and real-time applications can be designed. Although accounting for the important issues of task and communication, the method does not provide means for expressing the timeliness of the tasks and communication directly...... in the design as is otherwise the case with tasks and communication specifics. In this paper we propose an extension scheme which will enable for speifyinbg timing requirements for tasks and communications within the CODARTS model...

  19. K-targeted metabolomic analysis extends chemical subtraction to DESIGNER extracts: selective depletion of extracts of hops (Humulus lupulus).

    Science.gov (United States)

    Ramos Alvarenga, René F; Friesen, J Brent; Nikolić, Dejan; Simmler, Charlotte; Napolitano, José G; van Breemen, Richard; Lankin, David C; McAlpine, James B; Pauli, Guido F; Chen, Shao-Nong

    2014-12-26

    This study introduces a flexible and compound targeted approach to Deplete and Enrich Select Ingredients to Generate Normalized Extract Resources, generating DESIGNER extracts, by means of chemical subtraction or augmentation of metabolites. Targeting metabolites based on their liquid-liquid partition coefficients (K values), K targeting uses countercurrent separation methodology to remove single or multiple compounds from a chemically complex mixture, according to the following equation: DESIGNER extract = total extract ± target compound(s). Expanding the scope of the recently reported depletion of extracts by immunoaffinity or solid phase liquid chromatography, the present approach allows a more flexible, single- or multi-targeted removal of constituents from complex extracts such as botanicals. Chemical subtraction enables both chemical and biological characterization, including detection of synergism/antagonism by both the subtracted targets and the remaining metabolite mixture, as well as definition of the residual complexity of all fractions. The feasibility of the DESIGNER concept is shown by K-targeted subtraction of four bioactive prenylated phenols, isoxanthohumol (1), 8-prenylnaringenin (2), 6-prenylnaringenin (3), and xanthohumol (4), from a standardized hops (Humulus lupulus L.) extract using specific solvent systems. Conversely, adding K-targeted isolates allows enrichment of the original extract and hence provides an augmented DESIGNER material. Multiple countercurrent separation steps were used to purify each of the four compounds, and four DESIGNER extracts with varying depletions were prepared. The DESIGNER approach innovates the characterization of chemically complex extracts through integration of enabling technologies such as countercurrent separation, K-by-bioactivity, the residual complexity concepts, as well as quantitative analysis by (1)H NMR, LC-MS, and HiFSA-based NMR fingerprinting. PMID:25437744

  20. Berberine target key enzymes and amino acid inibitiors in AD treatment-----creation from berberine-based structure screening

    Directory of Open Access Journals (Sweden)

    Yau Lam

    2014-07-01

    Full Text Available The main components of berberine from coptis have a variety of pharmacological activity include the treatment of neurodegenerative diseases, Alzheimer’s disease (AD. The principle of berberine is inhibiting the lower activity of enzyme and amino acid to prevent (AD. Enzyme like acetylcholinesterase enzyme (AchE, butyrylcholinesterase enzyme (BchE and monoamine oxidase (MAO; Amino acid like beta-amyloid (Aβ. Unfortunately, the single chemical structures of berberine is no significance to regulation effect. As a part of our consideration, the review paper studies on chemically modified and synthesis from berberine-derivatives. Results show that the structures of (23, (10, (86, (52, and (61 have a potential effect for AchE, BuChE and Aβ-amyloid inhibitors for the first time. Especially in (23 and (52 also has better than two western medicine were compared.

  1. ADS National Programmes: Netherlands

    International Nuclear Information System (INIS)

    The ADS related activities within the Netherlands are concentrated at NRG. From 2000 to 2006, NRG supported SCK•CEN in their development of MYRRHA. The support was mainly devoted to Computational Fluid Dynamics (CFD) simulations for the windowless target option. This collaboration was prolonged within the framework of the EU FP6 EUROTRANS project. Eventually this lead to a solution strategy for the hydraulic (without heat transfer) evaluation of a windowless target with one free surface using an Eulerian-Eulerian modeling approach. As a second free surface was added to the target design later, this approach would need to be revisited. The developed approach was applied to an assess the feasibility of a three feeder windowless target design. This preliminary assessment confirmed that there were no serious show stoppers for a three feeder design. Another study undertaken using related to the windowless target was a preliminary assessment of the risk of lead-bismuth splashing in case of a sudden heat deposition by the beam, e.g. at beam startup or beam interuptions. Within the framework of the EU FP7 CDT project, a window target is currently being assessed thermalhydraulicly in collaboration with SCK•CEN. Within the EU FP5 ASCHLIM project, the state of the art with regard to turbulence modelling for CFD approaches was determined. It was concluded that accurate simulation of heat transport in HLM was not feasible, especially in natural or mixed convection regimes. Within the EU FP7 THINS project this issue is currently being treated. NRG assists the commercial CFD code vendor CD adapco in implementing and testing a promising, academically tested, algebraic heat flux model

  2. HIERARCHICAL DESIGN BASED INTRUSION DETECTION SYSTEM FOR WIRELESS AD HOC SENSOR NETWORK

    Directory of Open Access Journals (Sweden)

    Mohammad Saiful Islam Mamun

    2010-07-01

    Full Text Available In recent years, wireless ad hoc sensor network becomes popular both in civil and military jobs.However, security is one of the significant challenges for sensor network because of their deploymentin open and unprotected environment. As cryptographic mechanism is not enough to protect sensornetwork from external attacks, intrusion detection system needs to be introduced. Though intrusionprevention mechanism is one of the major and efficient methods against attacks, but there might besome attacks for which prevention method is not known. Besides preventing the system from someknown attacks, intrusion detection system gather necessary information related to attack technique andhelp in the development of intrusion prevention system. In addition to reviewing the present attacksavailable in wireless sensor network this paper examines the current efforts to intrusion detectionsystem against wireless sensor network. In this paper we propose a hierarchical architectural designbased intrusion detection system that fits the current demands and restrictions of wireless ad hocsensor network. In this proposed intrusion detection system architecture we followed clusteringmechanism to build a four level hierarchical network which enhances network scalability to largegeographical area and use both anomaly and misuse detection techniques for intrusion detection. Weintroduce policy based detection mechanism as well as intrusion response together with GSM cellconcept for intrusion detection architecture.

  3. Efficient Resource Conservation Design in Mobile Ad hoc Networks Using Reactive Routing Protocol

    Directory of Open Access Journals (Sweden)

    R.Sujitha

    2013-04-01

    Full Text Available Mobile Ad hoc Network is a compilation of wireless mobile terminals that are in contact with each other in the absence of a permanent infrastructure network. This gives a irregular formation. Many resources like power, energy, reliable data delivery and end to end delay plays a significant role in the network. But due to the dynamic movement of nodes, power management and energy conservation stands as a critical area. This is also due to the limited battery power and the maximum utilization of power by the nodes in the network .The responsibility of saving power has increased and it is possible byminimizing the consumption during the routing process. It is done in order to expand the lifetime of the network. In view of such a vital position, we introduce a new algorithm using an MAODV( Modified AdHoc On-Demand Distance Vector Routing Protocol protocol which exactly concentrates on power awareness at the time of route selection. Power status of each and every node is observed to avoid excess consumption. It also makes sure that there is a rise in the speed of route selection and discovery process. Route Patch-Up scheme used in this algorithm results in optimum utilization of power using an Modified AODV (MAODV protocol. Thus the idea proposed provides better performance through simulation over NS2.

  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. Design of Digital Synthesis Filters for Hybrid Filter Bank A/D Converters Using Semidefinite Programming

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2014-05-01

    Full Text Available Hybrid filter bank (HFB analog-to-digital systems permit wideband, high frequency conversion. This paper presents mixed norm optimal design of digital synthesis filters of a HFB. The mixed norm is a convex combination of the 2-norm and the Chebyshev norm with a weighting parameter. Robust HFB design method based on worst-case ellipsoidal uncertainty in analog filters errors is also proposed. Both the problems can be solved using semidefinite programming. The proposed mixed norm method allows designers to select the best suitable filters among a family of synthesis filters for specific applications, and the robust design method is more insensitive to analog filters errors than the nominal minimax design

  6. European project of PDS XADS: preliminary study of the XADS design; El proyecto europeo PDS Xads: Estudios prelimiares de diseno de un sistema accionado por acelerador (ADS)

    Energy Technology Data Exchange (ETDEWEB)

    Jardi, X.; Carluec, B.

    2003-07-01

    The demonstration of the practicability of transmutation on an industrial scale requires to perata at a industrialscale requires to operate at a European level, an experimental ADS (XADS) which will demonstrate the coupling of the accelerator, the neutron spallation target and the subcritical core. Complementary to the demonstration of the basic phenomena involved in the ADS technlogies, the preliminary engineering design studies of the XADS have to be performed in order to select the most promising technical concpets, to address the critical points of the whole system, to identify the research and development (R & D) in support, to define the safety and licensing issues, to preliminary assess the cost of the installation, and, then, to consolidate the roadmap of the XADS development. The assessment and comparison studies of the different concpetual designs of the main systems will allow to identify the most promising solutions which could be studied in detail in the next phases, and eventually realised. The PDS-XADS project is presented in this article. (Author)

  7. Designer interface peptide grafts target estrogen receptor alpha dimerization.

    Science.gov (United States)

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

    2016-09-01

    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. PMID:27462021

  8. Use of the PHM Framework to Create Safe-Sex Ads Targeted to Mature Women 50 and Older.

    Science.gov (United States)

    Morton, Cynthia R; Kim, Hyojin

    2015-01-01

    This research applies the Witte's persuasive health message (PHM) framework to the development of creative concepts that promote sexual health strategies to senior-aged women. The PHM framework proposes an integrated approach to improving message effectiveness and maximizing persuasion in health communication campaigns. A focus group method was used to explore two research questions focused on message effectiveness and persuasion. The findings suggest the PHM framework can be a useful starting point for ensuring that health communicators identify the criteria most relevant to successful ad promotions. PMID:26075543

  9. Use of the PHM Framework to Create Safe-Sex Ads Targeted to Mature Women 50 and Older.

    Science.gov (United States)

    Morton, Cynthia R; Kim, Hyojin

    2015-01-01

    This research applies the Witte's persuasive health message (PHM) framework to the development of creative concepts that promote sexual health strategies to senior-aged women. The PHM framework proposes an integrated approach to improving message effectiveness and maximizing persuasion in health communication campaigns. A focus group method was used to explore two research questions focused on message effectiveness and persuasion. The findings suggest the PHM framework can be a useful starting point for ensuring that health communicators identify the criteria most relevant to successful ad promotions.

  10. A Design Methodology for Power-efficient Continuous-time Sigma-Delta A/D Converters

    DEFF Research Database (Denmark)

    Nielsen, Jannik Hammel; Bruun, Erik

    2003-01-01

    In this paper we present a design methodology for optimizing the power consumption of continuous-time (CT) ΣΔ A/D converters. A method for performance prediction for ΣΔ A/D converters is presented. Estimation of analog and digital power consumption is derived and employed to predict the most power...... efficient configuration of a CT single-loop ΣΔ ADC. Finally, a 10 bit prototype converter is optimized and simulated using a 0.35 μm CMOS technology. The simulation results of the prototype 1.8 V converter show a SNR better than 65 dB and a spurious-free dynamic range of more than 63dB, consistent with 10...

  11. Complete determination of neutron yield from 62 MeV protons on 9Be for the design of a low – power ADS

    Directory of Open Access Journals (Sweden)

    Schillaci Maria

    2014-03-01

    Full Text Available Within the European Partitioning & Transmutation research programs, infrastructures specifically dedicated to the study of fundamental reactor physics of future fast neutron-based reactors are very important. In this respect, an Accelerator Driven System low-power prototype, based on a 70 MeV proton beam impinging on a thick Beryllium converter, was recently proposed and designed within the INFN-E project. The world data on neutron yield from Be target are scarce in this proton energy range. This lack of data calls for a dedicated measurement which was performed at INFN Laboratori Nazionali del Sud, covering a wide angular range, from 0 to 150 degrees, and an almost complete neutron energy interval, from thermal up to the beam energy. In this contribution the results are discussed together with the description of the proposed ADS facility.

  12. Tailoring nanoparticle designs to target cancer based on tumor pathophysiology

    Science.gov (United States)

    Sykes, Edward A.; Dai, Qin; Sarsons, Christopher D.; Chen, Juan; Rocheleau, Jonathan V.; Hwang, David M.; Zheng, Gang; Cramb, David T.; Rinker, Kristina D.; Chan, Warren C. W.

    2016-03-01

    Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient's disease state to achieve optimal diagnostic and therapeutic outcomes.

  13. 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.

  14. Design & Implementation of Cognitive Ad Hoc Network Testbed under Linux%Linux下基于认知Ad Hoc网络的实验床的设计与实现

    Institute of Scientific and Technical Information of China (English)

    王礼鑫; 张勇; 戴超

    2011-01-01

    本文在传统Ad Hoc网络中引入认知网络的思想,设计新型的认知Ad Hoc网络架构,并且结合现有软硬件设备,设计并实现了多终端认知Ad Hoc网络实验平台。该平台包括节点认知学习、信息传输与分析、感知信息动态显示以及多策略执行等模块。该实验平台在动态展示当前Ad Hoc网络认知信息及路由信息之外,还可用于新型Ad Hoc网络路由协议以及新型认知决策行为的实物验证。%This paper introduced the idea of cognitive networks intraditional Ad Hoc networks, and designed new cognitive Ad Hoc network architecture .Combined with existing hardware and software,this paper designed and implemented new cognitive Ad Hoc Networks testbed. This testbed includes node cognitive learning, information transmission and analysis, dynamic information display and multi-policy enforcement modules. The testbed is not only used for a dynamic display of the current Ad Hoc Networks, but also for verifying the new Ad Hoc Network routing protocols and new types of cognitive decision-making behavior.

  15. Design and analysis of a network coding algorithm for ad hoc networks

    Institute of Scientific and Technical Information of China (English)

    王远; 徐华; 贾培发

    2015-01-01

    Network coding is proved to have advantages in both wireline and wireless networks. Especially, appropriate network coding schemes are programmed for underlined networks. Considering the feature of strong node mobility in aviation communication networks, a hop-by-hop network coding algorithm based on ad hoc networks was proposed. Compared with COPE-like network coding algorithms, the proposed algorithm does not require overhearing from other nodes, which meets confidentiality requirements of aviation communication networks. Meanwhile, it does save resource consumption and promise less processing delay. To analyze the performance of the network coding algorithm in scalable networks with different traffic models, a typical network was built in a network simulator, through which receiving accuracy rate and receiving delay were both examined. The simulation results indicate that, by virtue of network coding, the proposed algorithm works well and improves performance significantly. More specifically, it has better performance in enhancing receiving accuracy rate and reducing receiving delay, as compared with any of the traditional networks without coding. It was applied to both symmetric and asymmetric traffic flows and, in particular, it achieves much better performance when the network scale becomes larger. Therefore, this algorithm has great potentials in large-scale multi-hop aviation communication networks.

  16. Application of the CBR method for adding the technological process designing

    Science.gov (United States)

    Ociepka, P.; Herbuś, K.

    2016-08-01

    The manufacturing process is a very important step in the process of new products creating. The market trends cause that the process must be very flexible to facilitate fast and cost-effective adaptation to changing market conditions. Commonly used CNC machine tools, grouped in flexible production systems significantly facilitate fast production adjusting to these dynamic changes. The programs for CNC machine tools could be easily modified or generated in the CAM class programs. It remains, however, the technological process, which should be planned and continuously optimized with respect to new details being produced. In this paper is proposed the method basing on the engineering knowledge and experience for adding the process of production preparation. The method, developed by authors, is based on the CBR (Case Based Reasoning) technique. CBR is a method of problems solving. It bases on seeking an analogy (similarity) between the task currently being solved, and the earlier tasks that had already been solved. The article presents an algorithm and formalized description of the developed method.

  17. A conceptual high flux reactor design with scope for use in ADS applications

    Indian Academy of Sciences (India)

    Usha Pal; V Jagannathan

    2007-02-01

    A 100 MWt reactor design has been conceived to support flux level of the order of 1015 n/cm2/s in selected flux trap zones. The physics design considers high enriched metallic alloy fuel in the form of annular plates placed in a D2O moderator tank in a hexagonal lattice arrangement. By choosing a tight lattice pitch in the central region and double the lattice pitch in the outer region, it is possible to have both high fast flux and thermal flux trap zones. By design the flux level in the seed fuel has been kept lower than in the high flux trap zones so that the burning rate of the seed is reduced. Another important objective of the design is to maximize the time interval of refueling. As against a typical refueling interval of a few weeks in such high flux reactor cores, it is desired to maximize this period to as much as six months or even one year. This is possible to achieve by eliminating the conventional control absorbers and replacing them with a suitable amount of fertile material loading in the reactor. Requisite number of seedless thorium–aluminum alloy plates are placed at regular lattice locations vacated by seed fuel in alternate fuel layers. It is seen that these thorium plates are capable of acquiring asymptotic fissile content of 14 g/kg in about 100 days of irradiation at a flux level of 8 × 1014 n/cm2 /s. In summary, the core has a relatively higher fast flux in the central region and high thermal flux in the outer region. The present physics design envisages a flat core excess reactivity for the longest possible cycle length of 6 months to one year. It is also possible to modify the design for constant subcriticality for about the same period or longer duration by considering neutron spallation source at the centre and curtailing the power density in the inner core region by shielding it with a layer of thoria fuel loading.

  18. Human anti-Aβ IgGs target conformational epitopes on synthetic dimer assemblies and the AD brain-derived peptide.

    Directory of Open Access Journals (Sweden)

    Alfred T Welzel

    Full Text Available Soluble non-fibrillar assemblies of amyloid-beta (Aβ and aggregated tau protein are the proximate synaptotoxic species associated with Alzheimer's disease (AD. Anti-Aβ immunotherapy is a promising and advanced therapeutic strategy, but the precise Aβ species to target is not yet known. Previously, we and others have shown that natural human IgGs (NAbs target diverse Aβ conformers and have therapeutic potential. We now demonstrate that these antibodies bound with nM avidity to conformational epitopes on plate-immobilized synthetic Aβ dimer assemblies, including synaptotoxic protofibrils, and targeted these conformers in solution. Importantly, NAbs also recognized Aβ extracted from the water-soluble phase of human AD brain, including species that migrated on denaturing PAGE as SDS-stable dimers. The critical reliance on Aβ's conformational state for NAb binding, and not a linear sequence epitope, was confirmed by the antibody's nM reactivity with plate-immobilized protofibrills, and weak uM binding to synthetic Aβ monomers and peptide fragments. The antibody's lack of reactivity against a linear sequence epitope was confirmed by our ability to isolate anti-Aβ NAbs from intravenous immunoglobulin using affinity matrices, immunoglobulin light chain fibrils and Cibacron blue, which had no sequence similarity with the peptide. These findings suggest that further investigations on the molecular basis and the therapeutic/diagnostic potential of anti-Aβ NAbs are warranted.

  19. Human anti-Aβ IgGs target conformational epitopes on synthetic dimer assemblies and the AD brain-derived peptide.

    Science.gov (United States)

    Welzel, Alfred T; Williams, Angela D; McWilliams-Koeppen, Helen P; Acero, Luis; Weber, Alfred; Blinder, Veronika; Mably, Alex; Bunk, Sebastian; Hermann, Corinna; Farrell, Michael A; Ehrlich, Hartmut J; Schwarz, Hans P; Walsh, Dominic M; Solomon, Alan; O'Nuallain, Brian

    2012-01-01

    Soluble non-fibrillar assemblies of amyloid-beta (Aβ) and aggregated tau protein are the proximate synaptotoxic species associated with Alzheimer's disease (AD). Anti-Aβ immunotherapy is a promising and advanced therapeutic strategy, but the precise Aβ species to target is not yet known. Previously, we and others have shown that natural human IgGs (NAbs) target diverse Aβ conformers and have therapeutic potential. We now demonstrate that these antibodies bound with nM avidity to conformational epitopes on plate-immobilized synthetic Aβ dimer assemblies, including synaptotoxic protofibrils, and targeted these conformers in solution. Importantly, NAbs also recognized Aβ extracted from the water-soluble phase of human AD brain, including species that migrated on denaturing PAGE as SDS-stable dimers. The critical reliance on Aβ's conformational state for NAb binding, and not a linear sequence epitope, was confirmed by the antibody's nM reactivity with plate-immobilized protofibrills, and weak uM binding to synthetic Aβ monomers and peptide fragments. The antibody's lack of reactivity against a linear sequence epitope was confirmed by our ability to isolate anti-Aβ NAbs from intravenous immunoglobulin using affinity matrices, immunoglobulin light chain fibrils and Cibacron blue, which had no sequence similarity with the peptide. These findings suggest that further investigations on the molecular basis and the therapeutic/diagnostic potential of anti-Aβ NAbs are warranted.

  20. Full Custom Design of a 8-bit Subranging Flash A/D Convertor

    Directory of Open Access Journals (Sweden)

    J. Sevenhans

    1993-07-01

    Full Text Available This paper describes the design of a Nonius Flash Analog to Digital Convertor for video-applications. The conversion is split up in two stages: the MSB and the LSB conversion stage. In the LSB conversion stage, the reference-voltage for the comparators is shifted up and down as a nonius of a vernier gauge, according to the MSB conversion obtained in the first half clock cycle. The MSB's and LSB's are simultaneously available at the output to make a 8-bit representation of the analog signal. Using the subranging mechanism, the number of comparators is reduced from 256 to 32 and the Nonius approach results in a very simple configuration for the subranging switches. The design has been simulated with HSPICE in ES2 1. 5 CMOS technology.

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

    Science.gov (United States)

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

    2016-05-01

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

  2. Deregulation of miRNA-181c potentially contributes to the pathogenesis of AD by targeting collapsin response mediator protein 2 in mice.

    Science.gov (United States)

    Zhou, Huimin; Zhang, Rui; Lu, Kang; Yu, Wenjun; Xie, Bing; Cui, Dongsheng; Jiang, Lei; Zhang, Qingfu; Xu, Shunjiang

    2016-08-15

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is usually accompanied by abnormal gene expression. The 20 to 25 nucleotide (nt) tiny regulators, known as micro ribonucleic acids (miRNAs), have been found to play important roles in the etiology and pathogenesis of various biological processes. The purpose of the current study was to identify the aberrant expression of microRNAs in the hippocampus of an AD mouse model and to investigate its potential role during the progression of AD. The results from microarray analysis showed that several miRNAs were deregulated in the hippocampus tissue of SAMP8 mice compared to SAMR1 mice. Among the deregulated miRNAs, a significant decrease in miR-181c was validated by quantitative real-time PCR. Bioinformatic analysis revealed that miR-181c might be involved in the regulation of axon guidance, MAPK signaling, dorso-ventral axis formation and long-term depression. Moreover, the results of a luciferase activity assay, western blot analysis and immunofluorescent staining showed that over-expression of miR-181c targets the 3'-untranslated region (3'-UTR) of collapsin response mediator protein 2 (crmp2) through its binding sites and down-regulates crmp2 protein abundance at the post-transcriptional level. Taken together, these findings suggested that crmp2 is a target of miR-181c and that the abnormally low expression of miR-181c in the hippocampus of SAMP8 mice could lead to an increase of the crmp2 protein level in AD mice, which might potentially play a role in the pathogenesis of Alzheimer's disease. PMID:27423553

  3. 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).

  4. Design Method Based on Routing Tree for Topology Update in Ad Hoc Network

    Institute of Scientific and Technical Information of China (English)

    WEI Zheng-xi; ZHANG Hong; WANG Xiao-ling

    2006-01-01

    A design method based on the tree-model structure for topology update is presented. The routing tree of every node in network is built by defining the data structure and is used to save the topology information of neighbor nodes. The node topology update is accomplished by exchanging their routing trees. For saving the precious wireless bandwidth, the routing tree is sparsely shaped before sending by pruning the redundant routing information. Then, the node topology update is implemented by using algorithms of inserting and deleting routing sub-trees.

  5. Enhanced Intelligent Risk Divination Using Added Quality Attributes Injected ATAM and Design Patterns

    Directory of Open Access Journals (Sweden)

    N.Sankar Ram

    2008-04-01

    Full Text Available Architectural Tradeoff Analysis Method is a method for evaluation of architecture-level designs and identifies trade-off points between attributes, facilitates communication between stakeholders. ATAM has got the limitations like not a predictor of quality achievement, not deals more quality attributes, Efficiency always depends on the expertise and potential of stakeholders. In this paper we have proposed a system which uses ATAM to predict the risk analysis, with more possible quality attributes. We have used artificial intelligence to predict the risk of the SA based on the Knowledge base of the Stakeholder Experts.

  6. Design and Implementation of AMRP for Multi hop wireless Mobile ad hoc Networks

    Directory of Open Access Journals (Sweden)

    Dr.R.Balakrishna

    2013-01-01

    Full Text Available In this paper have analyzed the interruption concert of a multi-hop wireless network in which the routes between resource-objective pairs are fixed. It has developed a new queue grouping technique to handle the complex correlations of the service process resulting from the multi-hop nature of the flows and their mutual sharing of the wireless medium. A general set based interfering model is assumed that imposes constraints on links that can be served simultaneously at any given time. These interference constraints are used to obtain a fundamental lower bound on the interruption concert of any scheduling policy for the system. It presents a systematic methodology to derive such lower bounds. For a special wireless system, namely the clique, it design a policy that is sample path interruption is finest. For the cycle queue network, where the interruption finest policy is known, the expected interruption of the optimal policy numerically coincides with the lower bound. The lower bound analysis provides useful insights into the design and analysis of optimal or nearly optimal scheduling policies.

  7. The Design and Implementation of a Novel Skew Scenario Model in Mobile Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    N. Vetrivelan

    2010-01-01

    Full Text Available Problem statement: In this research, it had been presented a novel Skew Scenario Model that has been developed and implemented for mobile ad hoc networks. There exist several mobility patterns that try to capture the behavior of the mobile devices under different circumstances, whereas in our work, the direction movement of the nodes is significantly specified horizontally, vertically and diagonally in the simulation area. Approach: Our novel Skew Scenario Model and the impact of mobility on MANET protocols had been compared and analyzed. The performance of DSDV and DSR under SSM in terms of packet delivery fraction, routing load and latency for varying source and destination traffic from 10, 20, 30, 40 and 50 under 100 nodes environment had been analyzed. Apart from this, our SSM with the existing waypoint model in 100 nodes environment had been compared. A suitable algorithm for SSM has also been developed. Results: Our simulation result showed that the functioning of our SSM had greatly influenced the performance of routing protocols in MANET environment. Simulation experiments confirm that for DSR under SSM, the PDF is highest between 93.56-99.43%, routing load is lowest between 1.005-1.068 and Latency is very less between 0.0163-0.049 sec, in the case of DSDV under SSM, the PDF is 63.22-79.104%, routing load is 1.20-1.58 and latency is 0.018-0.050 sec. The result revealed the fact that the reactive routing protocol DSR outperforms much more than the Proactive routing protocol DSDV. Our Novel Model has performed well when we compared it with existing waypoint mobility model while setting many source-destination connections. In DSR under SSM and waypoint model, PDF is between 93.56-99.43% in SSM and in waypoint 94.20-98.88%. Routing load in SSM is 1.0056-1.068, waypoint 1.01-1.06 seconds. Latency is between 0.026-0.063 in SSM and in waypoint 0.026-0.1235 sec. Conclusion: This study revealed the fact that the DSR discovers new routes faster

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

    International Nuclear Information System (INIS)

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

  9. Water-cooled pyrolytic graphite targets at LAMPF: design and operation

    International Nuclear Information System (INIS)

    Design considerations and actual operating experience are reported for water-cooled pyrolytic graphite targets at the Clinton P. Anderson Meson Physics Facility (LAMPF). Emphasis is placed on the use of finite element computer calculations to determine target temperatures and stresses, which can then be evaluated to judge the usefulness of a particular design. Consideration is also given to the swelling of the target following irradiation, and to the measures taken to prolong target lifetime

  10. ADS National Programmes: Belgium

    International Nuclear Information System (INIS)

    The Belgian activities in the field of Accelerator Driven Systems (ADS) are mainly related to the MYRRHA project development. MYRRHA is an accelerator driven, multi purpose fast neutron spectrum facility for R&D, cooled by a lead-bismuth eutectic. SCK•CEN has started the MYRRHA project as a national programme with several national & international bilateral collaboration agreements; the project has now evolved as an European integrated project in the frame of the IPEUROTRANS (European Commission, Sixth Framework Programme). The MYRRHA ‘Draft-2’ predesign file (completed in the early 2005) has been proposed to the partners as a basis for the XT-ADS machine. After a detailed investigation of potential alternatives, the MYRRHA concept (for the subcritical core, the primary coolant system, the accommodation of experimental rigs, the reactor vessel and the spallation target) has been kept with some modifications to achieve the XT-ADS objectives. The most recent version of the XT-ADS design was presented in the 2007 TWG meeting

  11. 基于AD9928A的CCD摄像机的AFE设计%AFE design of CCD sensor based on AD9928A

    Institute of Scientific and Technical Information of China (English)

    张扣香

    2014-01-01

    选用ADI公司的AD9928A芯片进行CCD图像传感器的AFE模拟前端设计,包含对AFE模拟前端硬件设计以及驱动时序的研究.主要应用于安防道路智能分析,具有图像分辨率高、噪声小,帧率高、色彩真实鲜亮、超高动态范围等优点,适合基于CCD摄像机的智能分析和图像识别系统.

  12. Based on the AD9850 signal generator design%基于AD9850的信号发生器的设计

    Institute of Scientific and Technical Information of China (English)

    祝敏; 曾德志; 廖小新

    2007-01-01

    直接数字合成(DDS)是一种重要的频率合成技术,具有分辨率高、频率变换快等优点,在雷达及通信等领域有着广泛的应用前景.系统采用AD9850(DDS)与AT89S52单片机相结合的方法,以AD9850为频率合成器,以单片机为进程控制和任务调度的核心,设计了一个信号发生器.实现了输出频率在10Hz~1MHz范围可调,输出信号频率稳定度优于10-3的正弦波、方波和三角波信号.正弦波信号的电压峰峰值Vopp能在0~5V范围内步进调节,步进间隔达到0.1V,所有输出信号无明显失真,且带负载能力强.

  13. Numerical Model Simulation of Free Surface Behavior in Spallation Target of ADS%ADS散裂靶件内部自由界面形态的数值模型分析

    Institute of Scientific and Technical Information of China (English)

    柴翔; 苏冠宇; 程旭

    2012-01-01

    加速器驱动的次临界系统( ADS)内部的散裂靶件通过加速器装置耦合次临界堆芯.无窗靶件的设计需保证自由界面有着稳定且理想的形状,以避免液态重金属局部过热.为研究无窗靶件内部自由界面的形态,本工作基于开源CFD计算平台OpenFOAM,使用VOF(volume of fluid)方法追踪自由界面,对无窗靶件内部自由界面的形态和特性进行数值模拟,并将结果与商用软件FLUENT计算结果和实验结果进行对比.同时比较多种湍流模型对计算的影响,推荐出较合适的湍流模型.%The spallation target in accelerator driven sub-critical system (ADS) couples the subcritical reactor core with accelerator. The design of a windowless target has to ensure the formation of a stable free surface with desirable shape, to avoid local overheating of the heavy liquid metal (HLM). To investigate the free surface behavior of the spallation target, OpenFOAM, an opened CFD software platform, was used to simulate the formation and features of the free surface in the windowless target. VOF method was utilized as the interface-capturing methodology. The numerical results were compared to experimental data and numerical results obtained with FLUENT code. The effects of turbulence models were studied and recommendations were made related to application of turbulence models.

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

    CERN Document Server

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

  16. 基于AD9269的中频数字处理模块的设计%The Design of Intermediate Frequency Digital Processing Module Built on AD9269

    Institute of Scientific and Technical Information of China (English)

    李梅

    2012-01-01

    中频数字化是软件无线电中的一项核心技术.基于软件无线电技术的短波电台的中频数字处理模块,对输入信号进行了中频数字化处理,进而在数字域内完成数字信号处理.在整个数字处理模块中,A/D和D/A起着关键作用,通常要求A/D转换器有足够的工作带宽(2 GHz以上)和较高的采样速率(一般在60 MHz以上),同时应有较高的A/D转换位数以提高动态范围.AD公司推出的新一代A/D转换器AD9269可以满足其要求.论文阐述了基于AD9269的中频数字处理模块的硬件设计,并说明了中频数字处理模块及接口的设计.%Digital Intermediate Frequency ( DIF) is the key technology in software radio area. The DIF processing module of shortwave base on software radio technology has DIF processing to input signal, then complete Digital signal processing in digital area. In the DIF processing module, A/D and D/A are very important. It asks the A/D converter have enough working bandwidth (more than 2 GHz) and higher sampling velocity (60 MHz) , and higher conversion digit to improve dynamic range. The new A/D converter AD9269 can meet the needs. The paper introduces the design of DIF processing module built on AD9269, and explains the interface design of DIF processing module.

  17. Advances in conceptual design of a gas-cooled accelerator driven system (ADS) transmutation devices to sustainable nuclear energy development

    International Nuclear Information System (INIS)

    The possibilities of a nuclear energy development are considerably increasing with the world energetic demand increment. However, the management of nuclear waste from conventional nuclear power plants and its inventory minimization are the most important issues that should be addressed. Fast reactors and Accelerator Driven Systems (ADS) are the main options to reduce the long-lived radioactive waste inventory. Pebble Bed Very High Temperature advanced systems have great perspectives to assume the future nuclear energy development challenges. The conceptual design of a Transmutation Advanced Device for Sustainable Energy Applications (TADSEA) has been made in preliminary studies. The TADSEA is an ADS cooled by helium and moderated by graphite that uses as fuel small amounts of transuranic elements in the form of TRISO particles, confined in 3 cm radius graphite pebbles forming a pebble bed configuration. It would be used for nuclear waste transmutation and energy production. In this paper, the results of a method for calculating the number of whole pebbles fitting in a volume according to its size are showed. From these results, the packing fraction influence on the TADSEAs main work parameters is studied. In addition, a redesign of the previous configuration, according to the established conditions in the preliminary design, i.e. the exit thermal power, is made. On the other hand, the heterogeneity of the TRISO particles inside the pebbles can not be negligible. In this paper, a study of the power density distribution inside the pebbles by means of a detailed simulation of the TRISO fuel particles and using an homogeneous composition of the fuel is addressed. (author)

  18. 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.

  19. 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.

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

    International Nuclear Information System (INIS)

    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

  1. Separation of no-carrier-added {sup 66,67}Ga produced in heavy ion-induced cobalt target using alginate biopolymers

    Energy Technology Data Exchange (ETDEWEB)

    Nayak, Dalia [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata-700064 (India); Banerjee, Anupam [University of Calcutta, 35 Ballygunge Circular Road, Kolkata-700019 (India); Lahiri, Susanta [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata-700064 (India)]. E-mail: susanta.lahiri@saha.ac.in

    2007-08-15

    Heavy ion activation of natural cobalt foil with 84 MeV {sup 12}C results in the formation of no-carrier-added (nca) {sup 66,67}As radionuclides, along with their corresponding decay products, {sup 66,67}Ge and {sup 66,67}Ga, in the matrix. Because arsenic and germanium radionuclides are short-lived, after a cooling period of 10 h only nca gallium radionuclides remain in the matrix. We attempted to separate the nca gallium radionuclides from the target matrix cobalt by biopolymeric calcium alginate (CA) and Fe-doped calcium alginate (Fe-CA) beads. A complete separation has been achieved by adsorbing {sup 66,67}Ga and a lesser amount of bulk cobalt at pH 3 on Fe-CA beads, followed by desorbing cobalt from the beads with 0.4 M NaNO{sub 2}.

  2. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation†

    OpenAIRE

    Kamaly, Nazila; Xiao, Zeyu; Valencia, Pedro M.; Radovic-Moreno, Aleksandar F.; Farokhzad, Omid C.

    2012-01-01

    Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newe...

  3. Design strategies for self-assembly of discrete targets

    International Nuclear Information System (INIS)

    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

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

    DEFF Research Database (Denmark)

    Heller, Alfred; Gianniou, Panagiota; Katsigiannis, Emmanouil;

    2014-01-01

    Designing cities from an overall energy optimization system point of view, demands changes in engineering procedures. Traditionally the design was driven independently between the involved domains and energy system components. By modelling the whole energy system in one, it is expected...... capacities of buildings that enable shifting energy demand for heating and cooling over periods of hours? While the availability of these capacities is a topic of current research, the consequences for building design are obvious. While we in the past could focus on energy optimization, we now have to design...... our buildings to its context, offering flexibility to the surrounding energy system. No final answers are given due to the fact that this is the edge of current research in this field, while a first concept draft is presented here....

  5. ADS无窗散裂靶件水模拟实验研究%Studies on Free Surface Flow in ADS Windowless Spallation Target

    Institute of Scientific and Technical Information of China (English)

    强成文; 赵强; 李龙; 王飞; 杨伟峰; 张学智; 张雪荧

    2015-01-01

    As the coupling component between accelerator and subcritical core, the spallation target is of crucial importance to the operation safety of the whole system. Hence, the spallation target is one of the most important parts in ADS corresponding researches. Due to lifetime limitation of material, the windowless target which has a stable free surface attracts more and more attention. The present paper deals with the experimental investigation on the free surface behavior in an approximately 1:1 size windowless target model using water as test fluid. We can get the flow and pressure conditions of windowless spallation target water simulation experiment from the platform. The free surface and field visualization were obtained by particle imaging velocimetry. The results show that the position and flow pattern of the free surface depend on experimental pressure, flow velocity and geometry of the target.%散裂靶件作为加速器和次临界堆芯的耦合部件,是ADS系统相关研究最主要的组成部分之一。无窗靶巧妙地利用了液体的自由液面特性,避免了质子束对结构材料直接轰击,是一种很有前景的散裂靶靶件形式。采用水作为实验工质搭建了一套无窗散裂靶水模拟实验台架,该实验系统覆盖了无窗散裂靶水模拟实验所需的流量及压力条件,采用粒子图像测速仪(PIV)对自由界面的流场进行可视化观察与分析,得到了自由界面的基本表征参数之间关系和可视化界面的流场信息。结果表明,无窗靶自由液面的位置和形状受到回路整体流量、压力和靶件几何尺寸的影响。

  6. 基于AD8369的数字音频广播传输系统的研究与实现%Design of Digital Audio Broadcasting Power Amplifier System Based on AD8369

    Institute of Scientific and Technical Information of China (English)

    陆明莹; 刘石; 王国裕; 张红升

    2012-01-01

    This paper introduces in detail the structure and theory of AD8369,it functions inside as a digitally controlled variable gain amplifier,Digital Audio Broadcasting Transmitting System based on A8369 was designed.The system used digitally controlled variable gain amplifier device AD8369 fills the power amplifier in the original Digital Audio Broadcasting system.It presents the block of the structure of system,the hardware structure,the software flow chart,timing control chart,testing and certification and descripes in detail the operational principle and process of the system.%该文详细地介绍了具有内部可控功能的数字可控增益放大器件AD8369的结构与工作原理,设计了基于AD8369的数字音频广播传输系统。本系统采用的数字可控增益放大器件AD8369填补了原数字音频广播系统中没有输出功放的空白。该文给出了系统的结构框图、硬件结构框图、软件流程图和时序控制图及测试和验证,详细介绍了系统工作的原理和流程。

  7. TRPV1: A Target for Rational Drug Design.

    Science.gov (United States)

    Carnevale, Vincenzo; Rohacs, Tibor

    2016-01-01

    Transient Receptor Potential Vanilloid 1 (TRPV1) is a non-selective, Ca(2+) 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. PMID:27563913

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

    Science.gov (United States)

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

    2010-12-01

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

  9. Designing Nonlinear Turbo Codes with a Target Ones Density

    CERN Document Server

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

    2011-01-01

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

  10. 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…

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

    International Nuclear Information System (INIS)

    Neutrino oscillations are now well acknowledged, the purpose of the Opera experiment is to show how ντ appear in a νμ beam. The νμ 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.)

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

    International Nuclear Information System (INIS)

    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

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

    DEFF Research Database (Denmark)

    L. Gargalo, Carina; Gani, Rafiqul

    2015-01-01

    This study focuses on uncertainty analysis of environmental indicators used to support sustainable process design efforts. To this end, the Life Cycle Assessment methodology is extended with a comprehensive uncertainty analysis to propagate the uncertainties in input LCA data to the environmental...... extended LCA procedure is flexible and generic and can handle various sources of uncertainties in environmental impact analysis. This is expected to contribute to more reliable calculation of impact categories and robust sustainable process design....... from algae biomass is used as a case study. The results indicate there are considerable uncertainties in the calculated environmental indicators as revealed by CDFs. The underlying sources of these uncertainties are indeed the significant variation in the databases used for the LCA analysis. The...

  14. Hubble Space Telescope Star Tracker ad Two-Gyro Control Law Design, Implementation, and On-Orbit Performance. Part 2

    Science.gov (United States)

    VanArsdall, John C.

    2005-01-01

    The Hubble Space Telescope (HST) normally requires three gyroscopes for three-axis rate control. The loss of the Space Shuttle Columbia on STS-107 resulted in the cancellation of a shuttle-based HST Servicing Mission 4. Therefore, HST must operate using the on-board hardware until an alternate means of servicing can be accomplished. The probability of gyro failure indicates that fewer than three gyros will be operable before any servicing mission can be performe& To mitigate this, and to extend the HST life expectancy, a rate estimation and control algorithm was developed that requires two gyros to measure rate about two axes, with the remaining axis rate estimated using one of three alternate sensors. Three-axis magnetometers (MSS) are used for coarse rate estimation during large maneuvers and during occultations of other sensors. Fixed-Head Star Trackers (FHSTs) are used for rate estimation during safe mode recovery and during transition to science operations. Fine rate estimation during science operations is performed using the Fine Guidance Sensors (FGSs). The FHST mode (T2G) relies on star vectors as measured by the FHSTs to estimate vehicle rate about the axis not measured by the gyros. Since the FHSTs were not designed to estimate body rate, this method involves a unique set of problems that had to be overcome in the final design, such as the effect of FHST break tracks and moving targets on rate estimation. The solutions to these problems, as well as a detailed description of the design and implementation of the rate estimation are presented Also included are the time domain and frequency domain analysis of the T2G control law. A high fidelity HST simulator (HSTSIM) was used to verify T2G performance prior to on-orbit use. Results of these simulations are also presented. Finally, analysis of actual T2G on-orbit test results is presented for design validation.

  15. Targeting B cell responses in universal influenza vaccine design

    Science.gov (United States)

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

    2011-01-01

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

  16. NIF target area design support. Final summary report

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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

  18. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

  1. Hairy AdS Solitons

    CERN Document Server

    Anabalon, Andres; Choque, David

    2016-01-01

    We construct exact hairy AdS soliton solutions in Einstein-dilaton gravity theory. We discuss the role of these solutions for the existence of first order phase transitions for planar hairy black holes within these theories.

  2. Design of wide-spectrum inhibitors targeting coronavirus main proteases.

    Directory of Open Access Journals (Sweden)

    Haitao Yang

    2005-10-01

    Full Text Available The genus Coronavirus contains about 25 species of coronaviruses (CoVs, which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens, and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pros, which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of Mpro-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pros, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.

  3. IFMIF target and test cell-Conceptual designs, boundary condition definitions and current status of preliminary engineering design

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Kuo, E-mail: kuo.tian@kit.ed [Institut fuer Neutronenphysik und Reaktortechnik, Karlsruhe Institute of Technology (KIT), Campus Nord, Karlsruhe (Germany); Eilert, Dirk [Institut fuer Foerdertechnik und Logistiksysteme, Karlsruhe Institute of Technology (KIT), Campus Sued (Germany); Heupel, Tobias; Ihli, Thomas; Lang, Karlheinz [Institut fuer Neutronenphysik und Reaktortechnik, Karlsruhe Institute of Technology (KIT), Campus Nord, Karlsruhe (Germany); Mittwollen, Martin [Institut fuer Foerdertechnik und Logistiksysteme, Karlsruhe Institute of Technology (KIT), Campus Sued (Germany); Moeslang, Anton [Institut fuer Material- und Festkoerperforschung, Karlsruhe Institute of Technology (KIT), Campus Nord, Karlsruhe (Germany); Scheel, Nicola; Stratmanns, Erwin [Institut fuer Neutronenphysik und Reaktortechnik, Karlsruhe Institute of Technology (KIT), Campus Nord, Karlsruhe (Germany)

    2010-12-15

    The reference design of the IFMIF target and test cell (TTC) which is summarized in the comprehensive design report (CDR) is reviewed and evaluated. Improved TTC conceptual designs, as well as a revision of the reference design, have been proposed in order to qualify precise and flexible positioning of test modules against the backplate in the TTC. As the result of evaluations on the existing design concepts, a referential table which addresses the design requirements and guidelines has been released and is outlined in this paper. Based on the referential table and the existing design concepts a modular TTC concept is introduced, developed, and improved aimed on providing variable in-cell operation environments, flexible accessibility for remote handling, and accurate and reliable positioning for the test modules. The current status of the preliminary engineering design based on the modular TTC concept is represented.

  4. Design and activity evaluation of deoxyribozymes specifically targeting hepatitis C virus RNA

    Institute of Scientific and Technical Information of China (English)

    于乐成; 王宇明; 王升启; 顾长海; 毛青; 陈忠斌; 刘鸿凌

    2003-01-01

    Objective: To explore the cleaving and inhibitory activity of hepatitis C virus (HCV)-specific deoxyribozymes (DRz) at both molecular and transgeneic cellular levels. Methods: According to the secondary structure of HCV 5′-noncoding region (5′-NCR) and the sites characterized with 5′…Y↓R...3′(Y=A/G,R=U/C), HCV-specific naive deoxyribozymes were designed and named DRz-232, DRz-127, DRz-84, DRz1, and the phosphorothioate deoxyribozymes (PSDRz) and mutated phosphorothioate deoxyribozymes (MPSDRz) were also designed. HCV RNA 5′-NCR was transcribed in vitro from linearized plasmid pHCV-neo and radiolabelled at its 5′-end. DRz, PSDRz or MPSDRz was respectively mixed with the substrate RNA and incubated under appropriate conditions, the cleaved products were displayed by 8% denaturated polyacrylamide gel electrophoresis (PAGE) and autoradiography, and the optical density of each band was measured to calculate cleavage rates. After that, every kind of DRz was added respectively to the cultured transgeneic HepG2 cells containing luciferase gene controlled by HCV 5′-NCR. The cells were lysed at intended time points and the activity of luciferase was measured with chemiluminescence method for calculating inhibition rates. Results: After incubated for 90 min in vitro, the cleavage rates of DRz-127, PSDRz-127, DRz1 and PSDRz1 reached 32.6%, 30.8%, 24.3% and 21.5%, respectively. No cleavage product was observed in any MPSDRz. DRz-127, PSDRz-127, DRz1 and PSDRz1 had an inhibitory rate of 53.2%, 50.6%, 44.7% and 43.3% respectively in transgeneic HepG2 cells in the first 24 h when the final dose of the DRz was 0.5 μmol/L, higher than that of the corresponding MPSDRz. There was no significant difference between the inhibitory effect of each DRz and its PSDRz in HepG2 cells, but the inhibitory rate of DRz decreased more rapidly than that of the latter with the elapse of time. The results from transfection groups were significantly better than those of non

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-15

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

  6. Design of ignition targets for the National Ignition Facility (IFSA 1999)

    Science.gov (United States)

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

    2016-10-01

    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 in imploding capsule, done in 3D on a 70° by 70° 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.

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

    CERN Document Server

    Thomas, Chris; Jago, Stephen

    2005-01-01

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

  8. RobOKoD: microbial strain design for (overproduction of target compounds

    Directory of Open Access Journals (Sweden)

    Natalie Jane Stanford

    2015-03-01

    Full Text Available 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 focussing 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 favourable 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 optimised strain design.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-28

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

  10. Enhanced tumour uptake and in vitro radiotoxicity of no-carrier-added [131I]meta-iodobenzylguanidine: implications for the targeted radiotherapy of neuroblastoma

    International Nuclear Information System (INIS)

    In vitro and in vivo neuroblastoma models were used to determine whether improvements in tumour targeting in vivo and therapeutic efficacy in vitro could result from the use of no-carrier-added (n.c.a.) [131I]MIBG. Results were compared with use of the conventional therapy MIBG preparation (ex.[131I]MIBG)of lower specific activity which is produced by iodide exchange reaction. The efficacy of n.c.a. [131I]MIBG was compared with that of [131I]MIBG over a range of specific activities by the assessment of neuroblastoma spheroid growth delay. Whereas n.c.a. [131I]MIBG at a radioactivity concentration of 2 MBq/ml prevented the regrowth of 84% of spheroids, toxicity was significantly reduced by the addition of non-radiolabelled MIBG to the incubation medium. The time-dependent biodistribution of n.c.a. [131I]MIBG in nude mice bearing human neuroblastoma xenografts was compared with that of the conventional therapy radiopharmaceutical. The n.c.a. agent gave improved tumour uptake but also significantly greater accumulation in normal tissues known to accumulate MIBG such as heart, adrenal and skin. However, uptake and retention in the blood was unaltered. For all tissues examined, the 3-day cumulative tumour to normal tissue radiation dose ratio was greater for n.c.a. [131I]MIBG. Theoretical calculations were undertaken to predict organ to tumour dose ratios which would result in human neuroblastoma patients with each of the [131I]MIBG preparations. These results suggest that significant therapeutic gain may be achieved by the use of n.c.a. [131I]MIBG as a treatment agent in neuroblastoma. (Author)

  11. Design of 5 .8GHz Circular Microstrip Rectenna Based on ADS%基于 ADS 的5.8GHz 圆形微带整流天线仿真设计

    Institute of Scientific and Technical Information of China (English)

    耿凯峰; 刘丽; 漆世锴

    2016-01-01

    Rectenna is one of the critical components of wireless power transmission(WPT ) .Common rectangle patch microstrip antenna have its shortages which include oversize area ,high-cost ,difficult integration and so on .According to the design theory of circular microstrip antenna and a source of feed cavity model theory ,a novel 5 .8GHz circular microstrip re-ctenna is designed .Optimizing the designed circular microstrip rectenna using ADS2008 software ,which makes this receiving antenna area of circular microstrip rectenna nearly 4 times smaller than the same kind rectangle patch microstrip antenna .It not only greatly reduces the production cost ,but also is easy to be integrated and conformal ,more suitable to make up anten-na array .Experimental results show that power transmission efficiency of this rectenna system is above 70% ,which indirect-ly demonstrates the simulation and optimization of this microstrip rectenna availability using ADS2008 software .%整流天线是无线能量传输的关键部件之一。常用的矩形微带天线存在面积大、成本高、不易集成等不足。根据圆形微带天线设计理论和有馈源的空腔模型理论,设计了一种工作在5.8GHz 的新型圆形微带整流天线。经过ADS2008软件仿真优化使得该圆形微带整流天线的接收天线面积比同类矩形微带天线将近小4倍左右,这不仅大大降低了生产成本,而且易集成和共形,更适合组成天线阵。实验结果表明,该整流天线系统的输能效率可达到70%以上,间接说明了利用 ADS2008仿真优化该微带整流天线的可行性。

  12. Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study

    DEFF Research Database (Denmark)

    Hørslev-Petersen, Kim; Hetland, Merete Lund; Junker, Peter;

    2014-01-01

    OBJECTIVES: An investigator-initiated, double-blinded, placebo-controlled, treat-to-target protocol (Clinical Trials:NCT00660647) studied whether adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment in early rheumatoid arthritis (ERA) increased the frequency......-label biologics after 6-9 months. Efficacy was assessed primarily on the proportion of patients who reached treatment target (DAS28CRP

  13. Design of new EEG acquisition front-end based on the ADS1298%基于ADS1298的新型脑电信号采集前端设计

    Institute of Scientific and Technical Information of China (English)

    谢宏; 颜林; 姚楠; 夏斌; 董洋洋

    2013-01-01

    ADS1298转换器为基础,通过将高精度模数转换与数字降噪处理技术结合来简化信号调理硬件电路设计,利用芯片内部集成的右腿驱动模块设计了右腿驱动信号电路,实现一种精度高、体积小、低功耗的多通道脑电信号采集前端,并讨论了实现更多通道脑电信号采集的多芯片级联技术,可广泛应用于便携式多通道脑电信号采集设备.%In this paper, a chip based on a TI company's highly integrated ADS 1298 dedicated to handling biological signals, combined with high-precision analog-to-digital conversion and digital noise reduction processing technology to simplify the design of the signal conditioning hardware circuit, the use of chip integrates right leg drive module design the right leg drive signal circuit to achieve a high accuracy、small in size、low power multi-channel EEG acquisition front-end, and discuss more channel EEG acquisition of multi-chip cascade technology can be widely used in portable multi - channel EEG acquisition equipment.

  14. Design of high speed data acquisition system based on S3C2440 and AD9248%基于S3C2440和AD9248的高速采集系统的设计

    Institute of Scientific and Technical Information of China (English)

    张自嘉; 徐向明

    2011-01-01

    A high speed data acquisition system is designed based on a high-speed A/D, FIFO and the ARM9. ARM9 is used to control A/D's conversion and FIFO's read and write, and large-capacity onboard data storage, as well as to achieve longer continuous acquisition. At the same time the design of network interface and USB interface to the preservation and transmission of data, GPS timing module interface to achieve data acquirement multiple sites at the same time.%设计了一个利用高速A/D、FIFO以及ARM9实现的高速数据采集系统.通过ARM9控制高速A/D转换和FIFO的读写,并采用大容量的板载数据存储器,可以实现较长时间的连续采集.设计了网络接口和USB接口实现数据的保存和传输,并设计了GPS授时模块接口以实现多个站点的同时数据采集.

  15. Driver and Receiver Circuit Design of Ultrasound Transducer Based on AD9850%基于AD9850超声换能器的驱动和接收电路设计*

    Institute of Scientific and Technical Information of China (English)

    魏俊益; 龙建军; 李赶先

    2013-01-01

    In order to improve the measurement accuracy of ultrasonic testing on submarine acoustic measurements, this paper used the DDS chip AD9850 as a high-precision signal source,and designed the driver and receiver circuits of ultrasonic transducer. Some methods such as,frequency division,phase shift,optical isolation,power amplification and impedance matching,etc,were designed to drive the transducer,and then the reception signal was processed by charge amplifier and band-pass filter. Finally,experiment shows that the circuits not only were in good condition,but also met the measurement requirements.%  为了提高超声检测在海底声学测量中的测量精度,利用DDS芯片AD9850作为高精度信号源,并设计了超生换能器的驱动和接收电路。采用分频移相、光电隔离、功率放大的和阻抗匹配的方法对换能器进行驱动;用电荷放大器和带通滤波器对接收信号进行处理。实验结果表明,电路性能良好,满足测量要求。

  16. 浮选自动加药控制系统的设计%Design of Flotation Auto Chemical Adding Control System

    Institute of Scientific and Technical Information of China (English)

    赵平胜; 王然风

    2011-01-01

    The author studied the existing problems in the flotation auto chemical adding system and proposed the solutions. A new flotation auto chemical adding system was worked out through rational design and model selection, which could meet the serious environment in coal preparation plants.%论述了现有浮选自动加药系统存在的问题,提出了解决这些问题的解决方案,通过合理的设计和选型,设计了能够应对恶劣选煤厂环境的新型浮选加药系统。

  17. Design and rationale for RE-VERSE AD : A phase 3 study of idarucizumab, a specific reversal agent for dabigatran

    NARCIS (Netherlands)

    Pollack, Charles V.; Reilly, Paul A.; Bernstein, Richard; Dubiel, Robert; Eikelboom, John; Glund, Stephan; Huisman, Menno V.; Hylek, Elaine; Kam, Chak-Wah; Kamphuisen, Pieter W.; Kreuzer, Joerg; Levy, Jerrold H.; Sellke, Frank; Stangier, Joachim; Steiner, Thorsten; Wang, Bushi; Weitz, Jeffrey I.

    2015-01-01

    Idarucizumab, a Fab fragment directed against dabigatran, produced rapid and complete reversal of the anticoagulation effect of dabigatran in animals and in healthy volunteers. The Study of the REVERSal Effects of Idarucizumab in Patients on Active Dabigatran (RE-VERSE AD (TM)) is a global phase 3 p

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

    Science.gov (United States)

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

    2016-06-17

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

  19. 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.

  20. Added Sugars

    Science.gov (United States)

    ... Restaurant Deciphering the Menu Ordering Your Meal Eating Fast Food Dining Out Tips by Cuisine Physical Activity Fitness ... Learn more about reading food labels . Limit your consumption of foods with high amounts of added sugars, ...

  1. 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.

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

    Institute of Scientific and Technical Information of China (English)

    YANG Chonglin; YAO Lan

    2002-01-01

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

  3. 基于FPGA的A/D转换采集控制模块设计%Design of A/D Convertion Sampling Control Module Based on FPGA

    Institute of Scientific and Technical Information of China (English)

    黄容兰; 万德焕

    2009-01-01

    The FPGA device EP1C3T144C8N is used to control the A/D converter AD7714 in this paper.The whole design is based on the Quartus Ⅱ platform.The process is described by the Verilog language to realize the correct sequence controlling process of AD7714 converter and storage the sampling data to processe.It can be widely used in the feebleness data sampling and the real-time supervisory control.Simulation result shows that the module has the advantages of stable performance,high reliability and convenient usage.%采用FPGA器件EP1C3T144C8N处理器,对A/D转换芯片AD7714进行采样控制.整个设计在Quartus I平台下进行软件编程,采用Verilog语言描述,实现正确的AD7714转换的工作时序控制过程,并将采样的数据存储起来进行处理.本设计可用于微弱信号采集和实时监控方面,仿真结果显示该模块工作性能稳定、可靠性高、使用方便.

  4. Value Adding Management

    DEFF Research Database (Denmark)

    Jensen, Per Anker; Katchamart, Akarapong

    2011-01-01

    Purpose: To investigate how Facilities Management (FM) can add value and develop a management concept that can assist facilities managers in implementing value adding strategies and practices. Theory: The study is based on the management model for FM included in the European FM standards, recent...... theories on added value of FM and real estate and the related concept of Value Management from building projects. The study is related to the EuroFM research group on The Added Value of FM. Design/methodology/approach: The study outlines a preliminary theoretical based management concept, which...... the relevance of the basic concept and provides an important example of how Value Adding Management can be implemented and added value measured. Originality/value: The study develops a concept of Value Adding Management, which is new in FM literature. It is expected to increase the awareness of the impacts...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-08-11

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

  7. Creating value-added cereal-based baked products: marketplace offer, laboratory-designed goods, and revisited local products

    OpenAIRE

    Conte, Paola

    2016-01-01

    In recent years, the growing interest in well-being and healthy lifestyle, the increasing awareness of the relationship between non-communicable diseases and unhealthy diet, as well as the increasing prevalence of food intolerances have boosted the production of an increasing number of novel goods in both gluten-containing and gluten-free products market. The overall objective of this thesis was to create cereal-based baked products with added value with respect to those currently available o...

  8. Design and Implementation of Multi-channel Data Acquisition System Based on CPLD and AD7865%基于CPLD和AD7865的多通道数据采集系统的设计与实现

    Institute of Scientific and Technical Information of China (English)

    刘静; 姜恒; 石晓原; 郑善军

    2012-01-01

    介绍了一种基于PC104总线的多通道高速同步数据采集系统的设计方法,在硬件设计上采用四通道模数转换芯片AD7865组成模数转换模块,利用CPLD组成功能电路模块进行逻辑控制与数据传输的实现,简化了硬件电路,同时也提高了其设计的灵活性,具有采集数据速率快,准确率高的优点.%A multi-channel and high-speed synchronous data acquisition system based on PC104 bus is introduced. The analog and data signal conversion module performed by 4 passageway conversion chip AD7865 ,the data transmission and the control logics performed by CPLD in hardware simplify the cirOcuit greatly. It has the advantage of flexible design, high accuracy and high speed.

  9. Interventional targeting administration of Ad-p53 combined with ultrasound irradiation in rabbit models of hepatic VX2 tumors%介入导入Ad-p53基因联合超声辐照治疗兔VX2肝癌

    Institute of Scientific and Technical Information of China (English)

    齐劲松; 杨瑞民; 赵鹏; 张铭秋; 崔红凯

    2013-01-01

    Objective To observe the effect of interventional targeting administration of Ad-p53 combined with ultrasound irradiation in rabbit models of hepatic VX2 tumors, as well as its impact on VEGF and MMP2. Methods Forty-two Chinchilla rabbits were collected and VX2 cancer cells were injected into the left lobe of liver on the observation in rabbits. The growth of cancer was monitored by ultrasound. Thirty rabbit models were successfully made and divided into 3 groups (each n=10) randomly. Fourteen days after transplantation of cancer cells, Ad-p53 was administrated through hepatic artery (in Ad-p53 group) or combined with ultrasound wave irradiation (in Ad-p53 + US group), while the same amount of saline was given for rabbits in control group. Three days later, the tumor size was observed with ultrasound, and then all rabbits were sacrificed, the serum VEGF level was measured by ELISA, the hepatic tissue expression of p53, MMP2 and VEGF were detected respectively by immunohistochemistry, and expression level of wild type p53 was measured using Western blot. Results No difference of tumor size was found between 3 groups before therapy. All tumor sizes increased, but the tumors in Ad-p53 + US group were relatively smaller. The efficiency of Ad-p53 transfection was improved in Ad-p53 group compared with control group, which was the highest in Ad-p53 + US group. Furthermore, the serum VEGF level decreased in Ad-p53 + US group, so did the expression of MMP2 and VEGF in Ad-p53 group and Ad-p53 + US group, more obviously in Ad-p53 + US group. Conclusion Ad-p53 can suppress the growth of hepatic VX2 tumors in rabbit models. The therapeutic efficacy of Ad-p53 can be improved by interventional targeting administration combining with ultrasound irradiation.%目的 探讨介入导向下联合超声辐照对兔VX2肝癌模型Ad-p53转染效率及该基因对VEGF、MMP2的影响.方法 青紫蓝兔42只,直视下手术,将VX2肿瘤细胞种植于肝左叶,以超声检测

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

    International Nuclear Information System (INIS)

    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

  11. Wormholes in AdS

    OpenAIRE

    Maldacena, Juan; Maoz, Liat

    2004-01-01

    We construct a few Euclidean supergravity solutions with multiple boundaries. We consider examples where the corresponding boundary field theory is well defined on each boundary. We point out that these configurations are puzzling from the AdS/CFT point of view. A proper understanding of the AdS/CFT dictionary for these cases might yield some information about the physics of closed universes.

  12. Design of spectrally versatile forward-looking ground-penetrating radar for detection of concealed targets

    Science.gov (United States)

    Phelan, Brian R.; Ressler, Marc A.; Mazzaro, Gregory J.; Sherbondy, Kelly D.; Narayanan, Ram M.

    2013-05-01

    The design of high-resolution radars which can operate in theater involves a careful consideration of the radar's radiated spectrum. While a wide bandwidth yields better target detectability and classification, it can also interfere with other devices and/or violate federal and international communication laws. Under the Army Research Laboratory (ARL) Partnerships in Research Transition (PIRT) program, we are developing a Stepped-Frequency Radar (SFR) which allows for manipulation of the radiated spectrum, while still maintaining an effective ultra-wide bandwidth for achieving good range resolution. The SFR is a forward-looking, ultra-wideband (UWB) imaging radar capable of detecting concealed targets. This paper presents the research and analysis undertaken during the design of the SFR which will eventually complement an existing ARL system, the Synchronous Impulse REconstruction (SIRE) radar. The SFR is capable of excising prohibited frequency bands, while maintaining the down-range resolution capability of the original SIRE radar. The SFR has two transmit antennas and a 16-element receive antenna array, and this configuration achieves suitable cross-range resolution for target detection. The SFR, like the SIRE radar, is a vehicle mounted, forward-looking, ground penetrating radar (GPR) capable of using synthetic aperture radar (SAR) technology for the detection of subsurface targets via 3D imaging. Many contradicting design considerations are analyzed in this paper. The selection of system bandwidth, antenna types, number of antennas, frequency synthesizers, digitizers, receive amplifiers, wideband splitters, and many other components are critical to the design of the SFR. Leveraging commercial components and SIRE sub-systems were design factors offering an expedited time to the initial implementation of the radar while reducing overall costs. This SFR design will result in an ARL asset to support obscured target detection such as improvised explosive devices

  13. Design and modeling of spectral-thermal unmixing targets for airborne hyperspectral imagery

    Science.gov (United States)

    Clare, Phil

    2006-05-01

    Techniques to determine the proportions of constituent materials within a single pixel spectrum are well documented in the reflective (0.4-2.5μm) domain. The same capability is also desirable for the thermal (7-14μm) domain, but is complicated by the thermal contributions to the measured spectral radiance. Atmospheric compensation schemes for the thermal domain have been described along with methods for estimating the spectral emissivity from a spectral radiance measurement and hence the next stage to be tackled is the unmixing of thermal spectral signatures. In order to pursue this goal it is necessary to collect data of well-calibrated targets which will expose the limits of the available techniques and enable more robust methods to be designed. This paper describes the design of a set of ground targets for an airborne hyperspectral imager, which will test the effectiveness of available methods. The set of targets include panels to explore a number of difficult scenarios such as isothermal (different materials at identical temperature), isochromal (identical materials, but at differing temperatures), thermal adjacency and thermal point sources. Practical fabrication issues for heated targets and selection of appropriate materials are described. Mathematical modelling of the experiments has enabled prediction of at-sensor measured radiances which are used to assess the design parameters. Finally, a number of useful lessons learned during the fielding of these actual targets are presented to assist those planning future trials of thermal hyperspectral sensors.

  14. Point design targets, specifications, and requirements for the 2010 ignition campaign on the National Ignition Facility

    International Nuclear Information System (INIS)

    Point design targets have been specified for the initial ignition campaign on the National Ignition Facility [G. H. Miller, E. I. Moses, and C. R. Wuest, Opt. Eng. 443, 2841 (2004)]. The targets contain D-T fusion fuel in an ablator of either CH with Ge doping, or Be with Cu. These shells are imploded in a U or Au hohlraum with a peak radiation temperature set between 270 and 300 eV. Considerations determining the point design include laser-plasma interactions, hydrodynamic instabilities, laser operations, and target fabrication. Simulations were used to evaluate choices, and to define requirements and specifications. Simulation techniques and their experimental validation are summarized. Simulations were used to estimate the sensitivity of target performance to uncertainties and variations in experimental conditions. A formalism is described that evaluates margin for ignition, summarized in a parameter the Ignition Threshold Factor (ITF). Uncertainty and shot-to-shot variability in ITF are evaluated, and sensitivity of the margin to characteristics of the experiment. The formalism is used to estimate probability of ignition. The ignition experiment will be preceded with an experimental campaign that determines features of the design that cannot be defined with simulations alone. The requirements for this campaign are summarized. Requirements are summarized for the laser and target fabrication.

  15. Flash在计算机中的设计与实现%Design and Implementation of Flash Public Service Ads in Computer

    Institute of Scientific and Technical Information of China (English)

    史耀进

    2012-01-01

    本文将广告理论与Flash广告相结合,介绍了Flash公益广告的设计与实现,并通过实例分析了Flash公益广告的特色.%This paper introduced the design and implementation of Flash public service advertising combined with the Flash ads and theory of the traditional advertising, and analyzed the characteristics of Flash public service advertising through the case.

  16. Adding Ajax

    CERN Document Server

    Powers, Shelley

    2007-01-01

    Ajax can bring many advantages to an existing web application without forcing you to redo the whole thing. This book explains how you can add Ajax to enhance, rather than replace, the way your application works. For instance, if you have a traditional web application based on submitting a form to update a table, you can enhance it by adding the capability to update the table with changes to the form fields, without actually having to submit the form. That's just one example.Adding Ajax is for those of you more interested in extending existing applications than in creating Rich Internet Applica

  17. Trypanothione Reductase: A Viable Chemotherapeutic Target for Antitrypanosomal and Antileishmanial Drug Design

    Directory of Open Access Journals (Sweden)

    M. Omar F. Khan

    2007-01-01

    Full Text Available Trypanosomiasis and leishmaniasis are two debilitating disease groups caused by parasites of Trypanosoma and Leishmania spp. and affecting millions of people worldwide. A brief outline of the potential targets for rational drug design against these diseases are presented, with an emphasis placed on the enzyme trypanothione reductase. Trypanothione reductase was identified as unique to parasites and proposed to be an effective target against trypanosomiasis and leishmaniasis. The biochemical basis of selecting this enzyme as a target, with reference to the simile and contrast to human analogous enzyme glutathione reductase, and the structural aspects of its active site are presented. The process of designing selective inhibitors for the enzyme trypanothione reductase has been discussed. An overview of the different chemical classes of inhibitors of trypanothione reductase with their inhibitory activities against the parasites and their prospects as future chemotherapeutic agents are briefl y revealed.

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

    International Nuclear Information System (INIS)

    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)

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

    Science.gov (United States)

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

    2016-04-14

    As a central regulator of metabolism, the AMP-activated protein kinase (AMPK) is an established therapeutic target for metabolic diseases. Beyond the metabolic area, the number of medical fields that involve AMPK grows continuously, expanding the potential applications for AMPK modulators. Even though indirect AMPK activators are used in the clinics for their beneficial metabolic outcome, the few described direct agonists all failed to reach the market to date, which leaves options open for novel targeting methods. As AMPK is not actually a single molecule and has different roles depending on its isoform composition, the opportunity for isoform-specific targeting has notably come forward, but the currently available modulators fall short of expectations. In this review, we argue that with the amount of available structural and ligand data, computer-based drug design offers a number of opportunities to undertake novel and isoform-specific targeting of AMPK. PMID:26510622

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

    Science.gov (United States)

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

    2016-07-01

    Target DNA enrichment combined with high-throughput sequencing technologies is a powerful approach to probing a large number of loci in genomes of interest. However, software algorithms that explicitly consider nucleotide sequence information of target loci in multiple reference species for optimizing design of target enrichment baits to be applicable across a wide range of species have not been developed. Here we present an algorithm that infers target DNA enrichment baits from multiple nucleotide sequence alignments. By applying clustering methods and the combinatorial 1-center sequence optimization to bait design, we are able to minimize the total number of baits required to efficiently probe target loci in multiple species. Consequently, more loci can be probed across species with a given number of baits. Using transcript sequences of 24 apoid wasps (Hymenoptera: Crabronidae, Sphecidae) from the 1KITE project and the gene models of Nasonia vitripennis, we inferred 57,650, 120-bp-long baits for capturing 378 coding sequence sections of 282 genes in apoid wasps. Illumina reduced-representation library sequencing confirmed successful enrichment of the target DNA when applying these baits to DNA of various apoid wasps. The designed baits furthermore enriched a major fraction of the target DNA in distantly related Hymenoptera, such as Formicidae and Chalcidoidea, highlighting the baits' broad taxonomic applicability. The availability of baits with broad taxonomic applicability is of major interest in numerous disciplines, ranging from phylogenetics to biodiversity monitoring. We implemented our new approach in a software package, called BaitFisher, which is open source and freely available at https://github.com/cmayer/BaitFisher-package.git. PMID:27009209

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

    Science.gov (United States)

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

    2011-10-01

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

  2. Between generative prototyping and work of synthesis in design: Interplay and adding value in the early concept development

    DEFF Research Database (Denmark)

    Cramer-Petersen, Claus Lundgaard

    2013-01-01

    The paper analyzes a case in which generative prototypes are applied as part of a participatory design methodology to elicit insights from practitioners, and how these insights are translated and represented, to inform the following work of synthesis in design. In literature, arguments are made...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-06-01

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

  4. Design of High-Specificity Nanocarriers by Exploiting Non-Equilibrium Effects in Cancer Cell Targeting.

    Directory of Open Access Journals (Sweden)

    Konstantinos Tsekouras

    Full Text Available Although targeting of cancer cells using drug-delivering nanocarriers holds promise for improving therapeutic agent specificity, the strategy of maximizing ligand affinity for receptors overexpressed on cancer cells is suboptimal. To determine design principles that maximize nanocarrier specificity for cancer cells, we studied a generalized kinetics-based theoretical model of nanocarriers with one or more ligands that specifically bind these overexpressed receptors. We show that kinetics inherent to the system play an important role in determining specificity and can in fact be exploited to attain orders of magnitude improvement in specificity. In contrast to the current trend of therapeutic design, we show that these specificity increases can generally be achieved by a combination of low rates of endocytosis and nanocarriers with multiple low-affinity ligands. These results are broadly robust across endocytosis mechanisms and drug-delivery protocols, suggesting the need for a paradigm shift in receptor-targeted drug-delivery design.

  5. ADS specific accelerator developments: Status in India

    International Nuclear Information System (INIS)

    Since India envisages the application as thorium–uranium breeder, the ADS must be operated with high beam power to maximize breeding potential. Since the thermalhydraulics issue in spallation target may restrict ~1 GeV proton beam current to ~10 mA on a single target module, an ADS core design is visualized with 3 or more spallation targets that would also help suppress the neutron flux peaking. With this assumption, the R&D objective is to realize a proton accelerator of 30 mA beam current (cw/average) within as short time as feasible. Of the two alternative accelerator types, cyclotron and LINAC, basic indigenous technological know-how, up to limited extent, exists for both

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

    Science.gov (United States)

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

    2016-05-01

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

  7. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Wang Haitao; Shi Lei; Wang Youlin; Ben De

    2013-01-01

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

  9. A Combination Regimen Design Program Based on Pharmacodynamic Target Setting for Childhood Tuberculosis: Design Rules for the Playground

    Science.gov (United States)

    Srivastava, Shashikant; Deshpande, Devyani; Pasipanodya, Jotam G.; Thomas, Tania; Swaminathan, Soumya; Nuermberger, Eric; Gumbo, Tawanda

    2016-01-01

    Children with tuberculosis are treated with drug regimens copied from adults despite significant differences in antibiotic pharmacokinetics, pathology, and the microbial burden between childhood and adult tuberculosis. We sought to develop a new and effective oral treatment regimen specific to children of different ages. We investigated and validated the concept that target drug concentrations associated with therapy failure and death in children are different from those of adults. On that basis, we proposed a 4-step program to rapidly develop treatment regimens for children. First, target drug concentrations for optimal efficacy are derived from preclinical models of disseminated tuberculosis that recapitulate pediatric pharmacokinetics, starting with monotherapy. Second, 2-drug combinations were examined for zones of synergy, antagonism, and additivity based on a whole exposure–response surface. Exposures associated with additivity or synergy were then combined and the regimen was compared to standard therapy. Third, several exposures of the third drug were added, and a 3-drug regimen was identified based on kill slopes in comparison to standard therapy. Fourth, computer-aided clinical trial simulations are used to identify clinical doses that achieve these kill rates in children in different age groups. The proposed program led to the development of a 3-drug combination regimen for children from scratch, independent of adult regimens, in <2 years. The regimens and doses can be tested in animal models and in clinical trials. PMID:27742637

  10. Rationale and design of the AdRem study : Evaluating the effects of blood pressure lowering and intensive glucose control on vascular retinal disorders in patients with type 2 diabetes mellitus

    NARCIS (Netherlands)

    Stolk, Ronald P.; Vingerling, Johannes R.; Cruickshank, J. Kennedy; Hughes, Alun D.; Stanton, Alice; Lu Juming, [No Value; Patel, Anushka; Thom, Simon A. McG.; Grobbee, Diederick E.; Lu, J.M.

    2007-01-01

    The ADVANCE Retinal Measurements (AdRem) Study is a large intervention study evaluating the effects of target driven intensive glucose control and placebo controlled blood pressure lowering on retinal vascular changes. AdRem is a sub-study of the ADVANCE Study (Action in Diabetes and Vascular diseas

  11. Statistical assessment and targets. Contribution to the PIARC XIXth World Road Congress, Ad hoc Group IV : road safety, Marrakesh, Morocco, 22-28 September 1991.

    OpenAIRE

    Wegman, F.C.M.

    1992-01-01

    The intention of this paper was to ensure that road safety would be assigned a more prominent place in the decision making process over a period of years. Among other things, attention is paid to: (1) realistic and quantitative targets; (2) specification of targets; (3) quality of road safety data; (4) strategies for preventive measures; and (5) organisational aspects.

  12. Design of the Fifth-Generation Target-Moderator-Reflector-Shield Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Nowicki, Suzanne Florence [Los Alamos National Lab. (LANL), Los Alamos, NM (United Sta; Mocko, Michal [Los Alamos National Lab. (LANL), Los Alamos, NM (United Sta

    2015-11-16

    The facilities at the Los Alamos Neutron Science Center are described first. The target is being redesigned so that the Flight Paths (FP) in the upper tier provide a higher intensity in the epithermal and medium energy range. It is found that a 3-piece design looks promising: intensity in epithermal and medium energy range in upper tier is an order of magnitude higher than current Mark III, and intensity in the thermal energy range is higher in the lower tier than current Mark III. Time emission spectra show a bump due to the scattering of fast neutrons. Other investigations such as the addition of wings around the upper target will be conducted.

  13. 基于AD7745的数字式油品检测传感器设计%Design of digital sensor for oil quality detection based on AD7745

    Institute of Scientific and Technical Information of China (English)

    刘海仓; 滕召胜; 刘静波; 熊海涛; 罗彬

    2011-01-01

    植物油掺伪后难以检测,根据不同油品具有不同介电常数的特性,设计了通过电容值进行检测的数字式油品传感器,建立了传感器等效电路,分析了传感器结构对电容检测的影响.传感器为插杆状结构,平板电容极板为敏感元件,检测时不同油品介质引起的电容量变化经AD7745转换成相应的数字量通过I2C串行总线口输出.实验结果表明:数字式油品传感器能够对掺伪3%以上的植物油进行快速有效鉴别,重复性优于0.2%.%It's difficult to detect whether the edible vegetable oil is adulteration. According to the characteristics that one kind of oil's permittivity is different from others,a capacitive sensor is designed for oil quality detection. The equivalent circuit of the sensor is established to analyze the impact of sensor structure on capacitance detection. The sensor is rod-shaped, and the probe of plate capacitor is sensing unit. The AD7745 chip is used to detect the capacitance change due to different oil quality acting as medium. The detecting result of the sensor is displayed digitally,and is output through the I2C serial bus port. Experiment shows that the sensor can distinguish quickly whether the oil contain adulteration or not to above 3 % edible vegetable oil,and its repeatability is prior to 0.2%.

  14. Conceptual design of target station and neutron scattering spectrometers for the Chinese spallation neutron source

    International Nuclear Information System (INIS)

    The authors report the recent progress on the conceptual design of the target station and neutron scattering spectrometers for the Chinese Spallation Neutron Source (CSNS). The CSNS target station will be constructed with three parts: tungsten targets cooled by heavy water, Be/Fe reflectors and Fe/high-density-iron-aggregate-concrete shields. there will be 3 WING moderators: water (300 K), liquid methane (100 K) and liquid hydrogen (20 K), and 18 horizontal neutron channels for neutron scattering spectrometers. The Monte Carlo simulation shows that the optimized ratio of height to width of the target cross-section is ∼1:2.5. With a nuclear power of 100 kW, the pulsed neutron flux is 2.4 x 1016 cm-2·s-1 for a 40 mm x 100 mm x 10 mm x 40 target stack. The emitted heat is about 47 kJ/s, the target temperature is somewhat higher than 90 degree C with a normal cooling efficiency, and the strain should be lower than 0.2 mm. Initially 5 typical spectrometers are chosen to be constructed, including a high intensity powder diffractometer, a high resolution powder diffractometer, a small angle scattering spectrometer, a reflectometer and a direct geometry inelastic neutron scattering spectrometer. These spectrometers can cover more than 80% of the neutron scattering applications. (authors)

  15. ADS National Programmes: India

    International Nuclear Information System (INIS)

    Initial preliminary studies in India on ADS concepts were aimed toward applications such as, one way coupled booster reactor concept, thorium burner concept, enhancement of breeding rate of thorium– fueled fast reactors, and to incinerate Pu and minor actinides discharged from heavy water and fast reactors. These studies led to a roadmap on development of ADS subsystems in India, which was chalked out initially in June 2001. It was realized in these studies that the most challenging subsystem in terms of technology development and capital investment for ADS in India would be the high intensity proton accelerator, and that it must be accomplished in phased manner. Of the two alternative accelerator types, viz. the cyclotron and linear accelerator (linac), it is concluded that only linac would provide the necessary intense beam current for ADS applications. The energy amplifier (EA) scheme, with lead (45.5%) bismuth (55.5%) eutectic (LBE) as target & coolant, which was proposed in the early nineties would be one of the desired configurations of ADS for Indian applications. Additionally, subcritical reactor core of Indian Advanced Heavy Water Reactor (AHWR), with advantages of its low fission power density, and neutron economy is also a candidate among various ADS reactor configurations. These options of ADS configurations for thorium utilization are based on the neutronic properties of 233U isotope as fissile fuel, which are more or less similar in thermal and in moderately fast neutron spectra

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

    International Nuclear Information System (INIS)

    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.

  17. Adding a strategic edge to human factors/ergonomics: principles for the management of uncertainty as cornerstones for system design.

    Science.gov (United States)

    Grote, Gudela

    2014-01-01

    It is frequently lamented that human factors and ergonomics knowledge does not receive the attention and consideration that it deserves. In this paper I argue that in order to change this situation human factors/ergonomics based system design needs to be positioned as a strategic task within a conceptual framework that incorporates both business and design concerns. The management of uncertainty is presented as a viable candidate for such a framework. A case is described where human factors/ergonomics experts in a railway company have used the management of uncertainty perspective to address strategic concerns at firm level. Furthermore, system design is discussed in view of the relationship between organization and technology more broadly. System designers need to be supported in better understanding this relationship in order to cope with the uncertainties this relationship brings to the design process itself. Finally, the emphasis on uncertainty embedded in the recent surge of introducing risk management across all business sectors is suggested as another opportunity for bringing human factors and ergonomics expertise to the fore.

  18. Design and recognition of three dimensional calibration target based on coded marker

    Science.gov (United States)

    Zhai, You; Xiong, Wei; Zeng, Luan; Gu, Dalong

    2015-08-01

    Traditional three-dimensional (3D) calibration targets consist of two or three mutual orthogonal planes (each of the planes contains several control points constituted by corners or circular points) that cannot be captured simultaneously by cameras in front view. Therefore, large perspective distortions exist in the images of the calibration targets resulting in inaccurate image coordinate detection of the control points. Besides, in order to eliminate mismatches, recognition of the control points usually needs manual intervention consuming large amount of time. A new design of 3D calibration target is presented for automatic and accurate camera calibration. The target employs two parallel planes instead of orthogonal planes to reduce perspective distortion, which can be captured simultaneously by cameras in front view. Control points of the target are constituted by carefully designed circular coded markers, which can be used to realize automatic recognition without manual intervention. Due to perspective projection, projections of the circular coded markers' centers deviate from the centers of their corresponding imaging ellipses. Colinearity of the control points is used to correct perspective distortions of the imaging ellipses. Experiment results show that the calibration target can be automatically and correctly recognized under large illumination and viewpoint change. The image extraction errors of the control points are under 0.1 pixels. When applied to binocular cameras calibration, the mean reprojection errors are less than 0.15 pixels and the 3D measurement errors are less than 0.2mm in x and y axis and 0.5mm in z axis respectively.

  19. Target selection and comparison of mission design for space debris removal by DLR's advanced study group

    Science.gov (United States)

    van der Pas, Niels; Lousada, Joao; Terhes, Claudia; Bernabeu, Marc; Bauer, Waldemar

    2014-09-01

    Space debris is a growing problem. Models show that the Kessler syndrome, the exponential growth of debris due to collisions, has become unavoidable unless an active debris removal program is initiated. The debris population in LEO with inclination between 60° and 95° is considered as the most critical zone. In order to stabilize the debris population in orbit, especially in LEO, 5 to 10 objects will need to be removed every year. The unique circumstances of such a mission could require that several objects are removed with a single launch. This will require a mission to rendezvous with a multitude of objects orbiting on different altitudes, inclinations and planes. Removal models have assumed that the top priority targets will be removed first. However this will lead to a suboptimal mission design and increase the ΔV-budget. Since there is a multitude of targets to choose from, the targets can be selected for an optimal mission design. In order to select a group of targets for a removal mission the orbital parameters and political constraints should also be taken into account. Within this paper a number of the target selection criteria are presented. The possible mission targets and their order of retrieval is dependent on the mission architecture. A comparison between several global mission architectures is given. Under consideration are 3 global missions of which a number of parameters are varied. The first mission launches multiple separate deorbit kits. The second launches a mother craft with deorbit kits. The third launches an orbital tug which pulls the debris in a lower orbit, after which a deorbit kit performs the final deorbit burn. A RoM mass and cost comparison is presented. The research described in this paper has been conducted as part of an active debris removal study by the Advanced Study Group (ASG). The ASG is an interdisciplinary student group working at the DLR, analyzing existing technologies and developing new ideas into preliminary

  20. Design, manufacture and testing of the IFMIF lithium target bayonet concept

    Energy Technology Data Exchange (ETDEWEB)

    Micciche, G. [ENEA CR Brasimone, via bacino del Brasimone, I-40035 Camugnano, Bo (Italy)]. E-mail: gioacchino.micciche@brasimone.enea.it; Riccardi, B. [Associazione EURATOM ENEA sulla Fusione, I-00044 Frascati, Rome (Italy)

    2005-11-15

    In the frame of the IFMIF R and D activities program a prototype of a replaceable backplate, based on the so called ' bayonet concept', has been developed, manufactured and tested. This concept allows the backplate replacement inside the target assembly while working laterally to the target, using a set of dedicated devices. The prototype design utilises an innovative closing and tightening system. The feasibility of the bayonet concept has been assessed and the remote handling trials carried out during 2003 have successfully demonstrated the maintainability requirements and procedures specification. This paper focuses on the design and manufacturing of the bayonet concept prototype and on the related remote handling trials carried out. The overall results of the activities are also reported.

  1. Computational and Pharmacological Target of Neurovascular Unit for Drug Design and Delivery

    Directory of Open Access Journals (Sweden)

    Md. Mirazul Islam

    2015-01-01

    Full Text Available The blood-brain barrier (BBB is a dynamic and highly selective permeable interface between central nervous system (CNS and periphery that regulates the brain homeostasis. Increasing evidences of neurological disorders and restricted drug delivery process in brain make BBB as special target for further study. At present, neurovascular unit (NVU is a great interest and highlighted topic of pharmaceutical companies for CNS drug design and delivery approaches. Some recent advancement of pharmacology and computational biology makes it convenient to develop drugs within limited time and affordable cost. In this review, we briefly introduce current understanding of the NVU, including molecular and cellular composition, physiology, and regulatory function. We also discuss the recent technology and interaction of pharmacogenomics and bioinformatics for drug design and step towards personalized medicine. Additionally, we develop gene network due to understand NVU associated transporter proteins interactions that might be effective for understanding aetiology of neurological disorders and new target base protective therapies development and delivery.

  2. Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site.

    Science.gov (United States)

    Kanekiyo, Masaru; Bu, Wei; Joyce, M Gordon; Meng, Geng; Whittle, James R R; Baxa, Ulrich; Yamamoto, Takuya; Narpala, Sandeep; Todd, John-Paul; Rao, Srinivas S; McDermott, Adrian B; Koup, Richard A; Rossmann, Michael G; Mascola, John R; Graham, Barney S; Cohen, Jeffrey I; Nabel, Gary J

    2015-08-27

    Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and ∼200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The structurally designed nanoparticle vaccine increased neutralization 10- to 100-fold compared to soluble gp350 by targeting a functionally conserved site of vulnerability, improving vaccine-induced protection in a mouse model. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by arrayed presentation of a conserved viral entry domain, a strategy that can be applied to other viruses.

  3. RAS GTPase AS THE DRUG TARGET FOR ANTI-CANCER DESIGNING OF DRUG FROM TEMPLATE

    Directory of Open Access Journals (Sweden)

    A.S. Krishnapriya and P.K. Krishnan Namboori*

    2013-11-01

    Full Text Available Ras proteins in association with GTP and GDP act as a bio-molecular switch for signaling cell growth, cell survival and signal transduction. The presence of mutated Ras proteins is found to vary in different cancer types and the highest occurrence of about 90% is observed in pancreatic cancer. The Ras GTPase binding site is mainly involved in signal cell proliferation. Hence, this binding site has been considered as a major target. At the same time, targeting a specific protein and designing the drug molecule with respect to that is practically of no use as the target proteins are fast mutating. In this scenario, designing the template from the hot spot of proteins and fitting the template for all the target protein molecules seem to be a promising technique. The templates are initially screened on the basis of pharmacokinetic and pharmacodynamic requirements. Six templates are found to be satisfying conditions like IC50, lipophilic efficiency, ligand efficiency etc. and their efficiencies are compared with standard reference molecules. The computed enrichment factors support these templates to be leads for effective anti-cancer drugs subject to further in vitro and in vivo evaluation.

  4. Design of Student Information Management Database Application System for Office and Departmental Target Responsibility System

    Science.gov (United States)

    Zhou, Hui

    It is the inevitable outcome of higher education reform to carry out office and departmental target responsibility system, in which statistical processing of student's information is an important part of student's performance review. On the basis of the analysis of the student's evaluation, the student information management database application system is designed by using relational database management system software in this paper. In order to implement the function of student information management, the functional requirement, overall structure, data sheets and fields, data sheet Association and software codes are designed in details.

  5. Design and cancer-targeting potential of antibody-based molecules directed against carcinoembryonic antigen.

    OpenAIRE

    Huhalov, A.

    2004-01-01

    This thesis examines the use of protein engineering to create antibody-based molecules for cancer treatment. The targeting unit used for these molecules was the single chain Fv antibody fragment MFE-23, which is directed against the tumour-associated marker carcinoembryonic antigen (CEA). It was hypothesised that implementation of molecular design features such as humanisation, high affinity, multivalency and mannose glycosylation to accelerate systemic clearance would result in the favourabl...

  6. Design of nanodrugs for miRNA targeting in tumor cells.

    Science.gov (United States)

    Yoo, Byunghee; Ghosh, Subrata K; Kumar, Mohanraja; Moore, Anna; Yigit, Mehmet V; Medarova, Zdravka

    2014-06-01

    The delivery of oligonucleotide antagonists to cytosolic RNA targets such as microRNA represents an avenue for the post-transcriptional control of cellular phenotype. In tumor cells, oncogenic miRNAs, termed oncomirs, are tightly linked to processes that ultimately determine cancer initiation, progression, and response to therapy. Therefore, the capacity to redirect tumor cell fate towards therapeutically beneficial phenotypes holds promise in a future clinical scenario. Previously, we have designed "nanodrugs" for the specific inhibition of oncogenic microRNAs in tumor cells. The basic design of these nanodrugs includes dextran coated iron oxide nanoparticles, conjugated to a tumor-targeting peptide, and a locked nucleic acid (LNA)-modified antisense oligonucleotide that stably binds and inhibits the complementary mature miRNA. Here, we focus on elucidating an optimal nanodrug design for effective miRNA inhibition in tumor cells. Specifically, we investigate the choice of chemical linker for the conjugation of the oligonucleotide to the nanoparticles and evaluate the contribution of tumor-cell targeting to nanodrug uptake and functionality. We find that short labile linkers (SPDP; N-Succinimidyl 3-(2-pyridyldithio)-propionate) are superior to non-labile short linkers (GMBS; N-(gamma-Maleimidobutyryloxy)succinimide ester) or non-labile long linkers (PEG24; Succinimidyl-([N-maleimidopropionamido]-24ethyleneglycol)ester) in terms of their capacity to gain access to the cytosolic cellular compartment and to engage their cognate miRNA. Furthermore, using the nanodrug design that incorporates SPDP as a linker, we establish that the addition of tumor-cell targeting through functionalization of the nanodrug with the alphavbeta3-specific cyclic RGDfK-PEG peptide does not confer an advantage in vitro at long incubation times required for inhibition. PMID:24749405

  7. Preconceptual design of liquid metal targets with diaphragm for accelerator-based systems

    International Nuclear Information System (INIS)

    Preconceptual design of liquid lead-bismuth targets has been carried out for proton beam power 1-25 MW. The experience gained by SSCRF-IPPE and RDB 'Gidropress' in design, fabrication and exploitation of NNP with lead-bismuth was used in this design. The design of heat exchange equipment was developed in the form of integrated units including primary pumps, heat exchangers with Fild tubes, volume compensator. The comparative design was carried out with lead instead of lead-bismuth. This cause the diaphragm temperature 150 deg C higher than the one for lead-bismuth. The use of lead will require a lot of additional investigations of corrosion, mass transfer and coolant technology. Some results of thermohydraulic calculations are presented for velocity and temperature fields in the diaphragm area. These data were obtained using the SIMAX code, newly developed. The main technical parameters of liquid metal target for power 10 and 20 MW are presented. 2 refs., 3 figs., 1 tab

  8. Optimal marker-strategy clinical trial design to detect predictive markers for targeted therapy.

    Science.gov (United States)

    Zang, Yong; Liu, Suyu; Yuan, Ying

    2016-07-01

    In developing targeted therapy, the marker-strategy design (MSD) provides an important approach to evaluate the predictive marker effect. This design first randomizes patients into non-marker-based or marker-based strategies. Patients allocated to the non-marker-based strategy are then further randomized to receive either the standard or targeted treatments, while patients allocated to the marker-based strategy receive treatments based on their marker statuses. Little research has been done on the statistical properties of the MSD, which has led to some widespread misconceptions and placed clinical researchers at high risk of using inefficient designs. In this article, we show that the commonly used between-strategy comparison has low power to detect the predictive effect and is valid only under a restrictive condition that the randomization ratio within the non-marker-based strategy matches the marker prevalence. We propose a Wald test that is generally valid and also uniformly more powerful than the between-strategy comparison. Based on that, we derive an optimal MSD that maximizes the power to detect the predictive marker effect by choosing the optimal randomization ratios between the two strategies and treatments. Our numerical study shows that using the proposed optimal designs can substantially improve the power of the MSD to detect the predictive marker effect. We use a lung cancer trial to illustrate the proposed optimal designs.

  9. Design and Implementation of a Fibre Channel Target Driver Supporting SCSI

    Institute of Scientific and Technical Information of China (English)

    WU Hao; SHU Jiwu; WEN Dongchan; ZHENG Weimin

    2005-01-01

    Fibre channel storage area networks (FC-SAN) are effective solutions to address storage management problems caused by very large volumes of data. But the expense of fibre channel devices limits FC-SAN applications. The use of IP networks instead of fibre channel networks will reduce SAN cost, but will also reduce the performance. Therefore, small computer system interface (SCSI) devices were considered to replace FC disks to reduce the SAN cost. A driver for the FC network adapter and the FC target, designed and implemented to support this structure, obeys the SCSI protocol and works in target mode with 200 MB/s bandwidth. The FC target architecture and implementation were compared with the FC initiator. The SCSI command transfer process in the FC layer was described. The performance test results show that the maximum I/O throughput reachs 167 MB/s for read requests and 196 MB/s for write requests (FC bandwidth is 200 MB/s), verifying that the FC target is very efficient. The modularization, efficiency, and low cost of the FC target will enable SAN and fibre channel to be more widely used in applications.

  10. Design of the EURISOL multi-MW target assembly: radiation and safety issues

    CERN Document Server

    Felcini, M; Kadi, Y; Otto, T; Tecchio, L; Otto, Th.

    2006-01-01

    The multi-MW target proposed for the EURISOL facility will be based on fission of uranium (or thorium) compounds to produce rare isotopes far from stability. A two-step process is used for the isotope production. First, neutrons are generated in a liquid mercury target, irradiated by the 1 GeV proton or deuteron beam, provided by the EURISOL linac driver. Then, the neutrons induce fission in a surrounding assembly of uranium carbide. R&D projects on several aspects of the target assembly are ongoing. Key criteria for the target design are a maximum beam power capability of 4 MW, a remote handling system with minimum downtime and maximum reliability, as well as radiation safety, minimization of hazards and the classification of the facility. In the framework of the ongoing radiation characterization and safety studies, radiation transport simulations have been performed to calculate the prompt radiation dose in the target and surrounding materials, as well as to determine shielding material and angle-depen...

  11. Design of the EURISOL multi-MW target assembly radiation and safety issues

    CERN Document Server

    Felcini, Marta; Kadi, Yacine; Otto, Thomas; Tecchio, L

    2006-01-01

    The multi-MW target proposed for the EURISOL facility will be based on fission of uranium (or thorium) compounds to produce rare isotopes far from stability. A two-step process is used for the isotope production. First, neutrons are generated in a liquid mercury target, irradiated by the 1 GeV proton or deuteron beam, provided by the EURISOL linac driver. Then, the neutrons induce fission in a surrounding assembly of uranium carbide. R&D projects on several aspects of the target assembly are ongoing. Key criteria for the target design are a maximum beam power capability of 4 MW, a remote handling system with minimum downtime and maximum reliability, as well as radiation safety, minimization of hazards and the classification of the facility. In the framework of the ongoing radiation characterization and safety studies, radiation transport simulations have been performed to calculate the prompt radiation dose in the target and surrounding materials, as well as to determine shielding material and angle-depen...

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

    Science.gov (United States)

    Simakov, Andrei N.; Wilson, Douglas C.; Yi, Sunghwan A.; Kline, John L.; Clark, Daniel S.; Milovich, Jose L.; Salmonson, Jay D.; Batha, Steven H.

    2014-02-01

    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.

  13. EFFECT OF CLUSTERING IN DESIGNING A FUZZY BASED HYBRID INTRUSION DETECTION SYSTEM FOR MOBILE AD HOC NETWORKS

    Directory of Open Access Journals (Sweden)

    D. Vydeki

    2013-01-01

    Full Text Available Intrusion Detection System (IDS provides additional security for the most vulnerable Mobile Adhoc Networks (MANET. Use of Fuzzy Inference System (FIS in the design of IDS is proven to be efficient in detecting routing attacks in MANETs. Clustering is a vital means in the detection process of FIS based hybrid IDS. This study describes the design of such a system to detect black hole attack in MANET that uses Adhoc On-Demand Distance Vector (AODV routing protocol. It analyses the effect of two clustering algorithms and also prescribes the suitable clustering algorithm for the above-mentioned IDS. MANETs with various traffic scenarios were simulated and the data set required for the IDS is extracted. A hybrid IDS is designed using Sugeno type-2 FIS to detect black hole attack. From the experimental results, it is derived that the subtractive clustering algorithm produces 97% efficient detection while FCM offers 91%. It has been found that the subtractive clustering algorithm is more fit and efficient than the Fuzzy C-Means clustering (FCM for the FIS based detection system.

  14. Application of CellDesigner to the Selection of Anticancer Drug Targets: Test Case using P53

    OpenAIRE

    Isea, Raul; Hoebeke, Johan; Mayo, Rafael; Alvarez, Fernando; Holmes, David S.

    2013-01-01

    Cancer is a disease involving many genes, consequently it has been difficult to design anticancer drugs that are efficacious over a broad range of cancers. The robustness of cellular responses to gene knockout and the need to reduce undesirable side effects also contribute to the problem of effective anti-cancer drug design. To promote the successful selection of drug targets, each potential target should be subjected to a systems biology scrutiny to locate effective and specific targets whil...

  15. The design of log amplifier of broad band high dynamic range based on AD8306%基于AD8306的宽带大动态范围对数放大器设计

    Institute of Scientific and Technical Information of China (English)

    袁乙木; 马尚昌

    2016-01-01

    Log amplifier is actually a log converter, it is a amplifying circuit that the relationship between the output signal amplitude and the input signal amplitude is a log function. In the field of electronic measurement, some signals have very high dynamic range, such as in the radar system, sonar system and so on, the signal dynamic range in the front of the receiver can be more than 120dB. Linear amplifier cannot handle such a wide dynamic range. In order to measure and analyze these signals expediently, modern measurement receiver used to adopt a design of large dynamic range log amplifier. This paper introduced a design of large dynamic range log amplifier based on AD8306, with 90 dB of dynamic range. Making use of this method, the log amplifier dynamic range is very large, and besides, this circuit is very simple and effective. If we use more than one chips, we can achieve larger dynamic range. This practical applications show that the design method is valid and practical.%对数放大器实实质上就是一种对数变换器,是指输出信号幅值与输入信号幅值呈对数函数关系的基本放大电路。在电子测量技术领域之中,某些信号的电压具有比较宽的动态范围,例如在雷达、声纳等无线电接受系统中,接收机前端信号动态范围可以达到120dB甚至更高。一般的线性放大器不能处理这样宽的动态范围,为了更加方便的测试和分析这些信号,在线代测量接收机的设计中,采用大动态范围对数放大器设计技术。本文介绍了一种核心器件为AD8306的大动态范围对数放大器的设计,实现了90dB的动态范围,宽带频率,灵敏度高。采用该方法实现的对数放大器动态范围大,电路简单易于实现,如果采用多片芯片级联还可以实现更大动态范围的对数放大器。实际应用表明,本文给出的设计方法合理有效,具有很高的使用价值。

  16. Inhibitor designing, virtual screening, and docking studies for methyltransferase: A potential target against dengue virus

    Science.gov (United States)

    Singh, Jagbir; Kumar, Mahesh; Mansuri, Rani; Sahoo, Ganesh Chandra; Deep, Aakash

    2016-01-01

    Aim: Aim of this work was to design and identify some S-adenosyl-L-homocysteine (SAH) analogs as inhibitors of S-adenosyl-L-methionine-dependent methyltransferase (MTase) protein using computational approaches. Introduction: According to the current scenario the dengue has been a global burden. The people are being killed by dengue virus in an abundant number. Despite of lot of research being going on dengue worldwide, there is no single drug which can kill its virus. This creates an urge for new drug target identification and designing. MTase has been reported as an effective target against dengue virus as it catalyzes an essential step in methylation and capping of viral RNA for viral replication. Materials and Methods: The crystal structure of MTase in complex with SAH was used for designing new analogs of SAH. SAH analogs designed were analyzed on the basis of docking, ADMET, and toxicity analysis done using Discovery Studio 3.5. Results: Seventeen analogs found noncarcinogenic, nonmutagenic, as well as good ADMET properties and good drug-like profile. Conclusion: These SAH analogs, inhibitors of MTase may act as drugs against dengue virus. Further synthesis and biological testing against dengue virus is under observation. PMID:27413346

  17. Research and Design of a Trust Management Model in Ad Hoc Networks%一种Ad Hoc网络中信任管理模型的研究与设计

    Institute of Scientific and Technical Information of China (English)

    张大雷

    2011-01-01

    Ad Hoc网络的安全性是当前网络安全问题的研究热点,建立合理的信任管理模型是Ad Hoc网络安全的首要问题.文章分析了Ad Hoc网络的特点和它所面临的安全挑战,引入信任管理的概念,给出了一种新颖的基于主观信任的Ad Hoc网络信任管理模型,为建立安全的Ad Hoc网络提供了新的解决方法.

  18. Metabolic engineering of an industrial polyoxin producer for the targeted overproduction of designer nucleoside antibiotics.

    Science.gov (United States)

    Qi, Jianzhao; Liu, Jin; Wan, Dan; Cai, You-Sheng; Wang, Yinghu; Li, Shunying; Wu, Pan; Feng, Xuan; Qiu, Guofu; Yang, Sheng-Ping; Chen, Wenqing; Deng, Zixin

    2015-09-01

    Polyoxin and nikkomycin are naturally occurring peptidyl nucleoside antibiotics with potent antifungal bioactivity. Both exhibit similar structural features, having a nucleoside skeleton and one or two peptidyl moieties. Combining the refactoring of the polyoxin producer Streptomyces aureochromogenes with import of the hydroxypyridylhomothreonine pathway of nikkomycin allows the targeted production of three designer nucleoside antibiotics designated as nikkoxin E, F, and G. These structures were determined by NMR and/or high resolution mass spectrometry. Remarkably, the introduction of an extra copy of the nikS gene encoding an ATP-dependent ligase significantly enhanced the production of the designer antibiotics. Moreover, all three nikkoxins displayed improved bioactivity against several pathogenic fungi as compared with the naturally-occurring antibiotics. These data provide a feasible model for high efficiency generation of nucleoside antibiotics related to polyoxins and nikkomycins in a polyoxin cell factory via synthetic biology strategy.

  19. C-LOAD POWER CONTROL PROTOCOL-CROSS-LAYER DESIGN OF A NETWORK LAYER LOAD POWER CONTROL PROTOCOL IN WIRELESS AD HOC NETWORKS

    Directory of Open Access Journals (Sweden)

    A. Arivoli

    2014-01-01

    Full Text Available In wireless ad hoc network scenario, Cross-layer design is emerging, important in wireless ad hoc network and the power control methods. Power control is the intelligent selection of transmit power in a communication to achieve the better performance within the system. Cross-layer is used to sharing the information between the layers. Physical to Transport layer information are shared in this protocol, due to this cross-layering is designed to optimize the power control. CLD using LOADPOWER (LOADPOW control protocol is reduce the overall end-end delay and the energy consumption using transmission power. The novelty of this work deals with both low and high transmission power control methodologies. So many power control schemes are dealt in MAC layer but this work, Power control protocol was done in network layer and it plays a vital role. A MAC approach to power control only does a local optimization whereas network layer is capable of global optimization. Simulation was done in NS-2 simulator with the performance metrics as improved throughput, energy consumption and end-end delay. The key concept is to improve the throughput, saves energy by sending all the packets with optimal transmission power according to the network load. A comparison of few protocols with Load Power Control Protocol (LPCP was implemented and got the better performances using NS-2 simulator.

  20. The Design and Synthesis of a New Class of RTK/HDAC Dual-Targeted Inhibitors

    Directory of Open Access Journals (Sweden)

    Wei Lu

    2013-06-01

    Full Text Available Over the years, the development of targeted medicines has made significant achievements. As a typical example, receptor tyrosine kinases (RTK inhibitors have become important chemotherapy drugs for a variety of cancers. However, the effectiveness of these agents is always hindered by poor response rates and acquired drug resistance. In order to overcome these limitations, several dual-targeted inhibitors with quinazoline core were designed and synthesized. Though these compounds can simultaneously inhibit histone deacetylases (HDAC as well as RTK, the structure-activity relationship (SAR is still not clear enough. To further explore this type of dual-targeted inhibitors, a new class of quinazoline derivatives were designed and synthesized. Their activity evaluations include in vitro inhibitory activity of HDAC, epidermal growth factor receptor (EGFR and human epidermal growth factor receptor 2 (HER2. The SAR study indicated that the introduction of polar group such as hydroxamate on the 4-position of the quinazoline core is more likely to provide a potent HDACi/HER2i hybrid rather than HDACi/EGFRi molecule.

  1. 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...

  2. Development of TMTP-1 targeted designer biopolymers for gene delivery to prostate cancer.

    Science.gov (United States)

    McBride, John W; Massey, Ashley S; McCaffrey, J; McCrudden, Cian M; Coulter, Jonathan A; Dunne, Nicholas J; Robson, Tracy; McCarthy, Helen O

    2016-03-16

    Designer biopolymers (DBPs) represent state of the art genetically engineered biomacromolecules designed to condense plasmid DNA, and overcome intra- and extra- cellular barriers to gene delivery. Three DBPs were synthesized, each with the tumor molecular targeting peptide-1 (TMTP-1) motif to specifically target metastases. Each DBP was complexed with a pEGFP-N1 reporter plasmid to permit physiochemical and biological assay analysis. Results indicated that two of the biopolymers (RMHT and RM3GT) effectively condensed pEGFP-N1 into cationic nanoparticles <100 nm and were capable of transfecting PC-3 metastatic prostate cancer cells. Conversely the anionic RMGT DBP nanoparticles could not transfect PC-3 cells. RMHT and RM3GT nanoparticles were stable in the presence of serum and protected the cargo from degradation. Additionally it was concluded that cell viability could recover post-transfection with these DBPs, which were less toxic than the commercially available transfection reagent Lipofectamine(®) 2000. With both DBPs, a higher transfection efficacy was observed in PC-3 cells than in the moderately metastatic, DU145, and normal, PNT2-C2, cell lines. Blocking of the TMTP-1 receptors inhibited gene transfer indicating internalization via this receptor. In conclusion RMHT and RM3GT are fully functional DBPs that address major obstacles to gene delivery and target metastatic cells expressing the TMTP-1 receptor.

  3. Design of functional small interfering RNAs targeting amyotrophic lateral sclerosis-associated mutant alleles

    Institute of Scientific and Technical Information of China (English)

    GENG Chang-ming; DING Hong-liu

    2011-01-01

    Background RNA interference (RNAi) is a potential cure for amyotrophic lateral sclerosis (ALS) caused by dominant,gain-of-function superoxide dismutase 1 (SOD1) mutations. The success of such therapy relies on the functional small interfering RNAs (siRNAs) that can effectively deliver RNAi. This study aimed to design the functional siRNAs targeting ALS-associated mutant alleles.Methods A modified dual luciferase system containing human SOD1 mRNA target was established to quantify siRNA efficacy. Coupled with validated siRNAs identified in the literature, we analyzed the rationale of siRNA design and subsequently developed an asymmetry rule-based strategy for designing siRNA. We then further tested the effectiveness of this design strategy in converting a naturally symmetric siRNA into functional siRNAs with favorable asymmetry for gene silencing of SOD1 alleles.Results The efficacies of siRNAs could vary tremendously by one base-pair position change. Functional siRNAs could target the whole span of SOD1 mRNA coding sequence as well as non-coding region. While there is no distinguishable pattern of the distribution of nucleobases in these validated siRNAs, the high percent of GC count at the last two positions of siRNAs (P18 and P19) indicated a strong effect of asymmetry rule. Introducing a mismatch at position 1 of the 5' of antisense strand of siRNA successfully converted the inactive siRNA into functional siRNAs that silence SOD1 with desired efficacy.Conclusions Asymmetry rule-based strategy that incorporates a mismatch into siRNA most consistently enhances RNAi efficacy and guarantees producing functional siRNAs that successfully silence ALS-associated SOD1 mutant alleles regardless target positions. This strategy could also be useful to design siRNAs for silencing other disease-associated dominant, gain-of-function mutant genes.

  4. ADS specific accelerator developments: Status in Japan

    International Nuclear Information System (INIS)

    In Japan, JAEA proposes an ADS which consists of a high power proton LINAC, a spallation target of lead-bismuth eutectic (LBE) and a subcritical core. In this proposal, the energy and beam power of the high power proton LINAC are 1.5 GeV and 20–30 MW, respectively. Other specifications of the high power proton linac are described in [4.28]. An important technical aspect that is considered in the JAEA work is the negative impact of very frequent beam trips as experienced in existing intense accelerator facilities. Frequent beam trips cause thermal fatigue problems for ADS components materials, leading to degradation of their structural integrity and reduction of their lifetime. They can also badly erode the availability or the capacity of ADS, resulting in poor economics. In the development of accelerators for ADS, it is vitally important to establish the technologies to achieve a very high degree of reliability. On the other hand, JAEA considers that it is also important in the development of ADS to design structural components to withstand possible thermal fatigues and a power conversion system less sensitive to beam trips. The purpose of the JAEA study is the comparison of beam trip frequencies between requirement from ADS transient analyses and estimation from current experimental data of accelerators

  5. Design of a modular protein-based MRI contrast agent for targeted application.

    Directory of Open Access Journals (Sweden)

    Daniel Grum

    Full Text Available Magnetic resonance imaging (MRI offers a non-radioactive alternative for the non-invasive detection of tumours. Low molecular weight MRI contrast agents currently in clinical use suffer either from a lack of specificity for tumour tissue or from low relaxivity and thus low contrast amplification. In this study, we present the newly designed two domain fusion protein Zarvin, which is able to bind to therapeutic IgG antibodies suitable for targeting, while facilitating contrast enhancement through high affinity binding sites for Gd(3+. We show that the Zarvin fold is stable under serum conditions, specifically targets a cancer cell-line when bound to the Cetuximab IgG, and allows for imaging with high relaxivity, a property that would be advantageous for the detection of small tumours and metastases at 1.5 or 3 T.

  6. 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.

  7. Triplex formation at single-stranded nucleic acid target sites of unrestricted sequence by two added strands of oligonucleotides: A proposed model

    Energy Technology Data Exchange (ETDEWEB)

    Trapane, T.L.; Ts' o, P.O.P. (John Hopkins Univ., Baltimore, MD (United States))

    1994-11-16

    By using the standard purine nucleosides, guanosine and adenosine, and the pyrimidine C-nucleosides, pseudoisocytidine and pseudouridine, as complements on a probe strand, it is possible to construct a regular Watson-Crick helix with a single-stranded target sequence having any arrangement of the four naturally-occurring bases found in nucleic acids. The major groove of this helix will have a unique configuration of hydrogen-bonding sites on the probe strand for each of these four base pairs. By using this duplex as a framework, an ensemble of recognition patterns composed of base triads may be constructed. In these patterns, either a homopyrimidine or homopurine third strand binds in the major groove of the duplex formed by the target and probe strands. Ten distinct geometries, or motifs, are shown, each one consisting of four isomorphic base triads built upon recognition of C, G, A, or U(T) residues in the target strand. In order to maintain specific hydrogen bonding and to construct isomorphous triads, the use of several nonstandard bases is proposed. 33 refs., 9 figs., 3 tabs.

  8. Size Matters: Developing Design Rules to Engineer Nanoparticles for Solid Tumour Targeting

    Science.gov (United States)

    Sykes, Edward Alexander

    Nanotechnology enables the design of highly customizable platforms for producing minimally invasive and programmable strategies for cancer diagnosis and treatment. Advances in this field have demonstrated that nanoparticles can enhance specificity of anti-cancer agents, respond to tumour-specific cues, and direct the visualization of biological targets in vivo. . Nanoparticles can be synthesized within the 1 to 100 nm range to achieve different electromagnetic properties and specifically interact with biological tissues by tuning their size, shape, and surface chemistry. However, it remains unclear which physicochemical parameters are critical for delivering nanomaterials to the tumour site. With less than 5% of administered nanoparticles reaching the tumour, engineering of nanoparticles for effective delivery to solid tumours remains a critical challenge to cancer nanomedicine. A more comprehensive understanding of the interplay between the nanomaterial physicochemical properties and biological systems is necessary to enhance the efficacy of nanoparticle tumour targeting. This thesis explores how nanoparticle size and functionalization with cancer cell specific agents impact nanoparticle delivery to tumours. Furthermore, this doctoral work (i) discusses how tumour structure evolves with growth, (ii) elucidates how such changes modulate nanoparticle accumulation, and (iii) identifies how the skin serves as a significant off-target site for nanoparticle uptake. This thesis also demonstrates the utility of empirically-derived parametric models, Monte Carlo simulations, and decision matrices for mechanistically understanding and predicting the impact of nanomaterial features and tumour biology on nanoparticle fate in vivo. These topics establish key design considerations to tailor nanoparticles for enhanced tumour targeting. Collectively, the concepts presented herein form a fundamental framework for the development of personalized nanomedicine and nano

  9. Optical system design of solar-blind UV target simulator with long focal length

    Science.gov (United States)

    Chen, Yu; Huo, Furong; Zheng, Liqin

    2014-11-01

    Ultraviolet (UV) radiation of 200nm-300nm waveband from the sun is absorbed by atmosphere, which is often referred to the solar-blind region of the solar spectrum. Solar-blind characteristics of this waveband have important application value, especially in military fields. The application of solar-blind waveband has developed very rapidly, which is receiving more and more attention. Sometimes, to test the performance of a UV optical system, a standard solar-blind UV target simulator is needed as the UV light source. In this paper, an optical system of a solar-blind UV target simulator is designed with waveband 240nm-280nm. To simulate a far UV target, the focal length of this UV optical system needs to be long. Besides, different field of view (FOV) of the system should meet aplanatic condition. The optional materials are very few for UV optical systems, in which only CaF2 and JGS1 are commonly used. Various aberrations are difficult to be corrected. To save production cost and enhance the precision of fabrication and test, aspheric surfaces and binary elements are not adopted in the system. Moreover, doublet or triplet cannot be used in UV optical system considering possible cracking for different thermal expansion coefficients of different materials. After optimization, the system is composed of 4 lenses with focal length 500mm. MTF curves of different FOV coincide together. The maximum RMS radius of the optimized system has almost the same size as Airy disk, which proves the good image quality after system optimization. The aplanatic condition is met very well in this system. In the spot diagram, root mean square (RMS) radius changes from 3 microns to 3.6 microns, which has similar size with Airy disk and meets aplanatic condition very well. This optical system of solar-blind UV target simulator also has relatively loose tolerance data, which can prove the system is designed in an optimal state.

  10. 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)

  11. Optimal design and validation of antiviral siRNA for targeting hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Jie FU; Zhong-ming TANG; Xin GAO; Fan ZHAO; Hui ZHONG; Mao-rong WEN; Xiao SUN; Hai-feng SONG; Xiao-hong QIAN

    2008-01-01

    Aim: Optimal design of antiviral short-interfering RNA (siRNA) targeting highly divergent hepatitis B virus (HBV) was validated by quantitative structure-activity relationship (QSAR) analysis. Methods: The potency of 23 synthetic siRNAs targeting 23 sites throughout HBV pregenomic RNA were evaluated at 10 nmol/L by determining the inhibition on the expression of S/P/pregenomic mRNA and hepatitis B surface antigen (HBsAg) quantitatively in HepG2.2.15 cells. Genotype homology within HBV genomes was identified through plentiful computational analysis and the multiple linear regression analysis was made to validate the relationship between the functional siRNAs and primary characteristics. Based on the preliminary results, relationships between different determined endpoints [S/P mRNA, HBsAg, C/P mRNA, hepatitis B e antigen (HBeAg) and viral DNA load] and siRNA efficacy evaluation were investigated. Results: Genotype homology, open reading frame (ORF) S/E X and C had tight correlation with the ability of siRNAs on inhibiting the expression of S/P/Pregenomic mRNA and HBsAg (P<0.01), of which, ORF C was negatively correlated with the siRNA potency (P<0.05). Further study showed that siRNA potency evaluation was influenced by different determined endpoints. P-target siRNAs showed significant inhibition on the S mRNA and HBsAg expression. S-target siRNAs inhibited the expression of S mRNA and HBsAg strongly. X-target siRNAs played active roles in inhibiting all 5 determined endpoints. C-target siRNAs blocked the expression of C mRNA, HBeAg and viral DNA load significantly. Conclusion: The antiviral potency of siRNA was relevant to its primary characteristics and determined endpoints were important for siRNA efficacy evaluation for complex genome with overlapping ORF, which was helpful for siRNA optimal design.

  12. Design of Targeted Inhibitors of Polo-like Kinase 1 (Plk1)

    Science.gov (United States)

    Dalafave, D. S.

    2011-03-01

    Computational design of small molecule inhibitors of Polo-like Kinase 1 (Plk1) is presented. Plk1, which regulates cell cycle, is often overexpressed in cancers. Its downregulation was shown to inhibit cancer progression. Most inhibitors of kinases' interact with the highly conserved ATP binding site. This makes the development of Plk1-specific inhibitors challenging, since different kinases have similar ATP sites. However, Plk1 also contains the polo-box domain (PBD), which is absent from other kinases. In this study, the PBD site was used as a target for designed Plk1 inhibitors. Common structural features of experimentally known Plk1 ligands were first identified. The information was used to design putative small molecules that specifically bonded Plk1. Druglikeness and possible toxicities of the designed molecules were determined. Molecules with no implied toxicities and optimal druglikeness were used for docking studies. The docking studies identified several molecules that made stable complexes with the Plk1 PBD site. Possible utilization of the designed molecules in drugs against cancers with overexpressed Plk1 is discussed.

  13. ADS National Programmes: Italy

    International Nuclear Information System (INIS)

    Following a preliminary design developed in 1998, based on the Energy Amplifier concept proposed by CERN, a first configuration of a lead-bismuth Eutectic cooled Experimental ADS (LBE-XADS) was worked out in the period 1999–2001, under the aegis of MURST, by a group of Italian organizations led by Ansado Nucleare, with the aim of assessing the feasibility of a small sized (80 MWth) ADS. At the end of 1997 a joint effort of ENEA (National Agency for New Technology, Energy and the Environment) and INFN (National Institute for Nuclear Physics) led to the approval of a national programme by MURST (Minister for University and Scientific and Technological Research) named TRASCO (TRAsmutazione SCOrie) aiming at the study of physics and technologies needed to design an ADS for radioactive waste transmutation. The programme consisted of research subprogrammes on accelerator, neutronics, thermalhydraulics analysis, beam window technology, and material technology and compatibility with Pb and Pb-Bi. At now, most of the activities in support to the ADS development carried out at national level are part of EU-funded Projects. These activities are complemented by the programme agreement (AdP -Accordo di programma), signed between ENEA and the Ministry of Economic Development, which provides in general a range of activities aimed at the development of sustainable nuclear fission systems. Several universities and the national industry are involved, besides ENEA, in the activities

  14. AD HOC TEAMWORK BEHAVIORS FOR INFLUENCING A FLOCK

    OpenAIRE

    Katie Genter; Peter Stone

    2016-01-01

    Ad hoc teamwork refers to the challenge of designing agents that can influence the behavior of a team, without prior coordination with its teammates. This paper considers influencing a flock of simple robotic agents to adopt a desired behavior within the context of ad hoc teamwork. Specifically, we examine how the ad hoc agents should behave in order to orient a flock towards a target heading as quickly as possible when given knowledge of, but no direct control over, the behavior of the flock...

  15. “建筑广告”设计布局研究%A Study on the Design Layout of “Ads on Building”

    Institute of Scientific and Technical Information of China (English)

    钟砚涛

    2015-01-01

    With economic development and the requirement for advertising,we are now living in cities with mixture of buildings and advertising messages.We can call these phenomena “Ads on Building”.The real meaning of“Ads on Building”is not as simple and narrow as the commercial advertisement signboards that we see everyday,it has a higher demand of combining buildings and advertisements together in meaningful ways.To achieve this,prop-er design layouts need to be used to produce “Ads on Buildings”,such as Subject -Object Swapping,Fiction -Reality Hiding/Highlighting,Dislocation Binding,Assembling/Combining,Static /Dynamic Harmonizing,etc.%经济的发展,广告宣传的需要,使我们生活在一个由建筑与众多广告信息所拼贴出来的城市里。这些广告现象我们可称之为“建筑广告”。真正的“建筑广告”并不是日常所见的商业广告招牌那么简单、狭义,而是将广告与建筑两者融为一体的更高要求。达到这一要求需要用合理的设计布局来制作“建筑广告”,如主宾互换、虚实藏露、错位拼合、拼接融合、动静相宜等设计布局。

  16. Design of vehicular multimedia AD player based on embedded Linux%基于嵌入式Linux的车载多媒体广告机设计

    Institute of Scientific and Technical Information of China (English)

    郑继亭; 王润民; 张楠

    2014-01-01

    Aiming at the limitation of traditional vehicular multimedia AD player, a design method of vehicular multimedia AD player based on embedded Linux and Qt/Embedded is proposed. S3C6410 is adopted as the central processor in the hardware and the software platform uses Embedded Linux operating system. Additionally, the interface is developed by Qt, which is a type of open source graphical user interface library. The system adopts MPlayer as its media player. After experimental veriifcation, the AD player has the characteristic of low cost, user-friendly, quick reaction, and has a signiifcant improvement in cross-platform and scalability.%针对传统车载多媒体广告机的局限性,提出了一种基于嵌入式Liunx与Qt/Embedded的车载多媒体广告机的设计方案。该方案采用以ARM处理器S3C6410为核心的硬件平台和以嵌入式Linux系统为核心的软件平台,并在此基础上采用开放源代码的图形界面库Qt开发广告机界面,同时利用开源播放软件MPlayer作为播放器。经实验验证,该多媒体广告机具有成本较低、界面友好、反应灵敏等特点,并在跨平台性、可扩展性等方面比传统方案有显著改善。

  17. Neutronic Design and Measured Performance of the Low Energy Neutron Source (LENS) Target Moderator Reflector Assembly

    CERN Document Server

    Lavelle, C M; Bogdanov, A; Derenchuk, V P; Kaiser, H; Leuschner, M B; Lone, M A; Lozowski, W; Nann, H; Von Przewoski, B; Remmes, N; Rinckel, T; Shin, Y; Snow, W M; Sokol, P E

    2008-01-01

    The Low Energy Neutron Source (LENS) is an accelerator-based pulsed cold neutron facility under construction at the Indiana University Cyclotron Facility (IUCF). The idea behind LENS is to produce pulsed cold neutron beams starting with ~MeV neutrons from (p,n) reactions in Be which are moderated to meV energies and extracted from a small solid angle for use in neutron instruments which can operate efficiently with relatively broad (~1 msec) neutron pulse widths. Although the combination of the features and operating parameters of this source is unique at present, the neutronic design possesses several features similar to those envisioned for future neutron facilities such as long-pulsed spallation sources (LPSS) and very cold neutron (VCN) sources. We describe the underlying ideas and design details of the target/moderator/reflector system (TMR) and compare measurements of its brightness, energy spectrum, and emission time distribution under different moderator configurations with MCNP simulations. Brightnes...

  18. Designing of Anti Dengue Drug Molecule against Insilico Modeled Target DC-Sign (CD-209

    Directory of Open Access Journals (Sweden)

    Prashantha C.N

    2013-09-01

    Full Text Available The C-type lectin DC-SIGN (CD209 plays a major role in receptor on human dendritic cells, it binds to several glycoproteins of viruses that facilitate disease progression. In dengue fever, the disease targets of arbovirus infection, show dendritic and reticuloendothelial cells that may affect immune system. The phytochemical extracts of Bosenbergia rotunda (BR have been effectively used as potential small molecular inhibitors to inhibit DC-SIGN (CD209 function. Using rational drug designing the training sets include Panduratin-A and 4-hydroxypanduratin is designed from BR derivatives could be an effective inhibitor of a DC-SIGN (CD209 binding towards the drug discovery/ therapy against dengue fever.

  19. Discussion on Added Function of Packaging Design for Children Products%儿童产品包装设计的附加功能之探讨

    Institute of Scientific and Technical Information of China (English)

    张佳宁; 谭一

    2012-01-01

    从儿童产品包装的角度出发,探索包装附加功能的设计方法。首先从分析儿童的心理和需求特点入手,进而探讨儿童的消费特点。结合以上分析,提出了儿童产品包装设计的拓展思路和方式方法,并将创意性思维与包装设计结合,力求设计出适合儿童的安全、方便、趣味、环保的包装。最后总结分析了研究包装附加功能的社会及经济价值,并希望借设计之臂推动包装的可持续发展。%It discussed the design methodology of added function of product package from the perspective of children product packaging. Starting from children' s psychological and essential requirement, then it further discussed about children product consuming characteristics. Based on above analysis, it proposed the way of children's product packaging design developing ideas and methods, and integrated creative thinking and packaging design, and strived to design children' s product package with safety, convenience, interest and environmental friendly feature. In the end, it summarized the social and economic value of research on additional function of product packaging design, and hope to push forward the sustainable development of package via design.

  20. Fuel performance evaluation for ADS MYRRHA

    International Nuclear Information System (INIS)

    MYRRHA is an Accelerator Driven System (ADS) under development at Mol in Belgium and aiming to serve as a basis for the European experimental ADS to provide protons and neutrons for various applications. It consists of a proton accelerator delivering a 350 MeV*5 mA proton beam to a liquid Pb-Bi spallation target that in turn couples to a Pb-Bi cooled, subcritical fast core. A preliminary design of the experimental fuel rods and analysis of their performance under typical ADS conditions is a first step of the fuel development program. Different designs are to be studied and different kinds of fuels are expected to be tested. In the current design, (U,Pu)O2 MOX fuel with the enrichment of 20-30 wt.% of Pu is considered to be a basis of the subcritical core, whereas different sorts of experimental fuel rods should be tested in the experimental channels to study minor actinides and low-lived fission products transmutation. In a later phase, a part of the MOX fuel in the subcritical core will be replaced with non-uranium fuels with transuranium elements. In the present report some result of modelling of the behaviour of two experimental rods (one with MOX and another with IMF) in the hottest fuel assembly of the ADS MYRRHA - are presented. (author)

  1. Is anti-doping analysis so far from clinical, legal or forensic targets?: The added value of close relationships between related disciplines.

    Science.gov (United States)

    Segura, Jordi

    2009-11-01

    There are many areas of common interest between anti-doping laboratories and those working in the clinical, legal and forensic fields. In addition to methodological similarities, there are aspects of the findings in sport drug testing that overlap with other fields in such a way that sport drug testing and clinical, legal or forensic work may benefit from mutual interaction. Three recent examples are presented from the author's experience. Case report 1 concerns the clinical relevance of hCG findings in sport drug testing as potential indicators of the presence of a (testicular) tumour in athletes. Case report 2 refers to difficulties that accredited laboratories can encounter due to differences between national legal systems and the administrative regulation systems of sport authorities. The example involves a network of blood collection for further autologous transfusion. Case report 3 relates to additional forensic-type investigations needed to interpret a situation where intoxication of a whole delegation was responsible for apparent doping cases. Clinical, legal and forensic fields must recognize the added value that some results and developments coming from anti-doping laboratories may have. At the same time anti-doping analysts should be aware of new issues, methodologies and problems appearing in related fields.

  2. 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 ...

  3. MEGAPIE target design and LiSoR experiment — Status report

    Science.gov (United States)

    Auger, T.; Aphecetche, L.; Cadiou, A.; Dai, Y.; Glasbrenner, H.; Gröschel, F.; Kirchner, T.

    2002-09-01

    MEGAPIE is an international project between PSI, CEA, CNRS, ENEA, FZK, JAERI, SCK/CEN, DOE and KAERI to design, build, operate and explore a liquid lead-bismuth spallation target for 1 MW of beam power, taking advantage of the existing spallation neutron facility SINQ at PSI. After a short overview on the MEGAPIE project this paper will concentrate on the material aspects related to the MEGAPIE liquid lead-bismuth target window. The candidate beam window material is a 9Cr-1MoVNb martensitic steel (T91). The LiSoR experiment, being carried out at PSI, simulates severe operating conditions foreseen for future liquid-metal targets such as MEGAPIE in order to validate the material selection relative to irradiation assisted liquid metal corrosion and embrittlement. T91 specimens under stress will be irradiated by 72 MeV protons in flowing liquid lead-bismuth. The experiment will be carried out at the PSI's proton cyclotron INJI. The major goal is to investigate whether corrosion and embrittlement could be enhanced or triggered under representative irradiation conditions.

  4. Design upgrade of the ISOLDE target unit for HIE-ISOLDE

    Science.gov (United States)

    Montaño, J.; Giles, T.; Gottberg, A.

    2013-12-01

    The High Intensity and Energy HIE-ISOLDE project is a major upgrade of the existing ISOLDE and REX-ISOLDE facilities with the objective of increasing the energy and the intensity of the delivered radioactive ion beams (RIB) [1]. In order to accommodate the future increase of primary beam intensity delivered by the new LINAC4 H- driver to the Proton Synchrotron Booster (PSB) [2] and from this to ISOLDE, a major study is being carried out to upgrade the existing designs of the ISOLDE target and its supporting infrastructure. In particular, the extraction optics plays an important role in the initial beam transport and the quality of the beam supplied to the mass separators. Important factors include the emittance of the beam and the beam profile to avoid beam losses. A new double electrode extraction system has been developed for simplifying and improving the interface between the target unit and the frontend (target coupling table). Numerical and experimental studies have been performed in order to define the new extraction geometry, and the coupling table has been adapted to keep the compatibility. An alternative heating system is under study. An electron bombardment heating system is being developed as an option for avoiding the employment of big cross section cables. The results of these studies and the mechanical models developed are presented and discussed.

  5. Tools for the rational design of bivalent microtubule-targeting drugs.

    Science.gov (United States)

    Marangon, Jacopo; Christodoulou, Michael S; Casagrande, Fancesca V M; Tiana, Guido; Dalla Via, Lisa; Aliverti, Alessandro; Passarella, Daniele; Cappelletti, Graziella; Ricagno, Stefano

    2016-10-01

    Microtubule (MT) dynamic behaviour is an attractive drug target for chemotherapy, whose regulation by MT-stabilizing and destabilizing agents has been fruitfully applied in treating several types of cancers. MT-stabilizing agents are also emerging as potential remedies for neurodegenerative conditions, such as Alzheimer's and Parkinson's disease, although single-target drugs are not expected to fully cure these complex pathologies. Drug combination often displays enhanced efficacy with respect to mono-therapies. In particular, MT-targeting bivalent compounds (MTBCs) represent a promising class of molecules; however, surprisingly, the majority of MTBCs reported so far exhibit equal if not less efficacy than their building monomers. In order to shed light on MTBCs poor performance, we characterised through a set of complementary approaches thiocolchine (TH) and two bivalent TH-homodimers as prototype molecules. First, the binding affinities of these three molecules were assessed, then we obtained the crystallographic structure of a tubulin-TH complex. The binding affinities were interpreted in light of structural data and of molecular dynamics simulations. Finally, their effects on MT cytoskeleton and cell survival were validated on HeLa cells. The ensemble of these data provides chemical and structural considerations on how a successful rational design of MTBCs should be conceived.

  6. 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

  7. 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.

  8. Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site.

    Science.gov (United States)

    Kanekiyo, Masaru; Bu, Wei; Joyce, M Gordon; Meng, Geng; Whittle, James R R; Baxa, Ulrich; Yamamoto, Takuya; Narpala, Sandeep; Todd, John-Paul; Rao, Srinivas S; McDermott, Adrian B; Koup, Richard A; Rossmann, Michael G; Mascola, John R; Graham, Barney S; Cohen, Jeffrey I; Nabel, Gary J

    2015-08-27

    Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and ∼200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The structurally designed nanoparticle vaccine increased neutralization 10- to 100-fold compared to soluble gp350 by targeting a functionally conserved site of vulnerability, improving vaccine-induced protection in a mouse model. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by arrayed presentation of a conserved viral entry domain, a strategy that can be applied to other viruses. PMID:26279189

  9. 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.

  10. 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. PMID:27112322

  11. Analysis of variance of designed chromatographic data sets: The analysis of variance-target projection approach.

    Science.gov (United States)

    Marini, Federico; de Beer, Dalene; Joubert, Elizabeth; Walczak, Beata

    2015-07-31

    Direct application of popular approaches, e.g., Principal Component Analysis (PCA) or Partial Least Squares (PLS) to chromatographic data originating from a well-designed experimental study including more than one factor is not recommended. In the case of a well-designed experiment involving two or more factors (crossed or nested), data are usually decomposed into the contributions associated with the studied factors (and with their interactions), and the individual effect matrices are then analyzed using, e.g., PCA, as in the case of ASCA (analysis of variance combined with simultaneous component analysis). As an alternative to the ASCA method, we propose the application of PLS followed by target projection (TP), which allows a one-factor representation of the model for each column in the design dummy matrix. PLS application follows after proper deflation of the experimental matrix, i.e., to what are called the residuals under the reduced ANOVA model. The proposed approach (ANOVA-TP) is well suited for the study of designed chromatographic data of complex samples. It allows testing of statistical significance of the studied effects, 'biomarker' identification, and enables straightforward visualization and accurate estimation of between- and within-class variance. The proposed approach has been successfully applied to a case study aimed at evaluating the effect of pasteurization on the concentrations of various phenolic constituents of rooibos tea of different quality grades and its outcomes have been compared to those of ASCA.

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

    International Nuclear Information System (INIS)

    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-cateninS45F-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

  13. 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.

  14. Preliminary design studies of a 100 MeV H-/H+ LINAC as injector for SNS synchrotron/ADS LINAC

    Indian Academy of Sciences (India)

    S A Pande; Moonooku Prasad; Nita Kulkarni; P R Hannurkar

    2002-11-01

    It is proposed to construct a spallation neutron source (SNS) at Centre for Advanced Technology (CAT) based on a 1 GeV proton synchrotron with 100 MeV H- LINAC as injector. Additionally, the LINAC can form the first 100 MeV part of a 1 GeV proton LINAC to be built in future for accelerator driven system (ADS) applications. We are exploring a configuration of the 100 MeV LINAC which will consist of an H- ion source, a 4–6 MeV RFQ followed either by a 20 MeV drift tube LINAC (DTL) and 100 MeV separated function drift tube LINAC (SDTL) or a coupled cavity drift tube LINAC (CCDTL) structure. In this paper, we present the results of our preliminary physics design studies of the RFQ–SDTL, RFQ–CCDTL and RFQ–DTL–SDTL configurations. The design of the 4.5 MeV RFQ is discussed along with the matching sections between the RFQ–SDTL/DTL and RFQ–CCDTL. The choice of the accelerator configuration and that of various parameters of the individual accelerator structures under consideration are discussed. The design objectives are to arrive at a configuration which eases heat removal for CW operation and which is less prone to halo formation in order to reduce the beam loss at higher energies.

  15. Challenges in the design of clinically useful brain-targeted drug nanocarriers.

    Science.gov (United States)

    Costantino, L; Boraschi, D; Eaton, M

    2014-01-01

    Nowadays, the delivery of drugs by means of intravenously administered nanosized drug carriers - polymerdrug conjugates, liposomes and micelles, is technically possible. These delivery systems are mainly designed for tumour therapy, and accumulate passively into tumours by means of the well known EPR effect. Targeted nanocarriers, that additionally contain ligands for receptors expressed on cell surfaces, are also widely studied but products of this kind are not marketed, and only a few are in clinical trial. Polymeric nanoparticles (Np) able to deliver drugs to the CNS were pioneered in 1995; a number of papers have been published dealing with brain-targeted drug delivery using polymeric Np able to cross the BBB, mainly for the treatment of brain tumours. At present, however, the translation potential of these Np seems to have been exceeded by targeted liposomes, a platform based on a proven technology. This drug delivery system entered clinical trials soon after its discovery, while the challenges in formulation, characterization and manufacturing of brain-targeted polymeric Np and the cost/benefit ratio could be the factors that have prevented their development. A key issue is that it is virtually impossible to define the in vivo fate of polymers, especially in the brain, which is a regulatory requirement; perhaps this is why no progress has been made. The most advanced Np for brain tumours treatment will be compared here with the published data available for those in clinical trial for tumours outside the CNS, to highlight the knowledge gaps that still penalise these delivery systems. At present, new approaches for brain tumours are emerging, such as lipid Np or the use of monoclonal antibody (mAb)-drug conjugates, which avoid polymers. The success or failure in the approval of the polymeric Np currently in clinical trials will certainly affect the field. At present, the chances of their approval appear to be very low.

  16. The AdMit Package

    NARCIS (Netherlands)

    D. David (David); L.F. Hoogerheide (Lennart); H.K. van Dijk (Herman)

    2008-01-01

    textabstractThis short note presents the R package AdMit which provides flexible functions to approximate a certain target distribution and it provides an efficient sample of random draws from it, given only a kernel of the target density function. The estimation procedure is fully automatic and thu

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

    NARCIS (Netherlands)

    Mandal, S.; Bakeine, G.J.; Krol, S.; Ferrari, C.; Clerici, A.M.; Zonta, C.; Cansolino, L.; Ballarini, F.; Bortolussi, S.; Stella, S.; Protti, N.; Bruschi, P.; Altieri, S.

    2011-01-01

    The aim of this study is to optimize targeted boron delivery to cancer cells and its tracking down to the cellular level. To this end, we describe the design and synthesis of novel nanovectors that double as targeted boron delivery agents and fluorescent imaging probes. Gold nanoparticles were coate

  18. 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.

  19. Characterization of a multi-component anthrax vaccine designed to target the initial stages of infection as well as toxaemia

    OpenAIRE

    Cote, C. K.; Kaatz, L.; Reinhardt, J.; Bozue, J.; Tobery, S. A.; Bassett, A. D.; Sanz, P; Darnell, S C; Alem, F.; O’Brien, A.D.; Welkos, S. L.

    2012-01-01

    Current vaccine approaches to combat anthrax are effective; however, they target only a single protein [the protective antigen (PA) toxin component] that is produced after spore germination. PA production is subsequently increased during later vegetative cell proliferation. Accordingly, several aspects of the vaccine strategy could be improved. The inclusion of spore-specific antigens with PA could potentially induce protection to initial stages of the disease. Moreover, adding other epitopes...

  20. AD HOC TEAMWORK BEHAVIORS FOR INFLUENCING A FLOCK

    Directory of Open Access Journals (Sweden)

    Katie Genter

    2016-02-01

    Full Text Available Ad hoc teamwork refers to the challenge of designing agents that can influence the behavior of a team, without prior coordination with its teammates. This paper considers influencing a flock of simple robotic agents to adopt a desired behavior within the context of ad hoc teamwork. Specifically, we examine how the ad hoc agents should behave in order to orient a flock towards a target heading as quickly as possible when given knowledge of, but no direct control over, the behavior of the flock. We introduce three algorithms which the ad hoc agents can use to influence the flock, and we examine the relative importance of coordinating the ad hoc agents versus planning farther ahead when given fixed computational resources. We present detailed experimental results for each of these algorithms, concluding that in this setting, inter-agent coordination and deeper lookahead planning are no more beneficial than short-term lookahead planning.

  1. LAMOST Spectroscopic Survey of the Galactic Anti-centre (LSS-GAC): target selection and the first release of value-added catalogues

    CERN Document Server

    Yuan, Haibo; Huo, Zhiying; Xiang, Maosheng; Huang, Yang; Chen, Bingqiu; Zhang, Huihua; Sun, Ningchen; Wang, Chun; Zhang, Huawei; Zhao, Yongheng; Luo, Ali; Shi, Jianrong; Li, Guoping; Yuan, Hailong; Dong, Yiqiao; Li, Guangwei; Hou, Yonghui; Zhang, Yong

    2014-01-01

    As a major component of the LAMOST Galactic surveys, the LAMOST Spectroscopic Survey of the Galactic Anti-centre (LSS-GAC) aims to survey a significant volume of the Galactic thin/thick discs and halo for a contiguous sky area of over 3,400 deg$^2$ centred on the Galactic anti-centre ($|b| \\leq 30^{\\circ}$, $150 \\leq l \\leq 210^{\\circ}$), and obtain $\\lambda\\lambda$3700 -- 9000 low resolution ($R \\sim 1,800$) spectra for a statistically complete sample of $\\sim 3$\\,M stars of all colours down to a limiting magnitued of $r$ $\\sim$ 17.8\\,mag (to 18.5\\,mag for limited fields). Together with Gaia, the LSS-GAC will yield a unique dataset to advance our understanding of the structure and assemblage history of the Galaxy, in particular its disk(s). In addition to the main survey, the LSS-GAC will also target hundreds of thousands objects in the vicinity fields of M\\,31 and M\\,33 and survey a significant fraction (over a million) of randomly selected very bright stars (VB; $r \\le 14$ mag) in the northern hemisphere. ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-04-21

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

  3. The Impact of Verification Area Design on Tropical Cyclone Targeted Observations Based on the CNOP Method

    Institute of Scientific and Technical Information of China (English)

    ZHOU Feifan; MU Mu

    2011-01-01

    This study investigated the impact of different verification-area designs on the sensitive areas identified using the conditional nonlinear optimal perturbation (CNOP) method for tropical cyclone targeted observations.The sensitive areas identified using the first singular vector (FSV) method,which is the linear approximation of CNOP,were also investigated for comparison.By analyzing the validity of the sensitive areas,the proper design of a verification area was developed.Tropical cyclone Rananim,which occurred in August 2004 in the northwest Pacific Ocean,was studied.Two sets of verification areas were designed; one changed position,and the other changed both size and position.The CNOP and its identified sensitive areas were found to be less sensitive to small variations of the verification areas than those of the FSV and its sensitive areas.With larger variations of the verification area,the CNOP and the FSV as well as their identified sensitive areas changed substantially.In terms of reducing forecast errors in the verification area,the CNOP-identified sensitive areas were more beneficial than those identified using FSV.The design of the verification area is important for cyclone prediction.The verification area should be designed with a proper size according to the possible locations of the cyclone obtained from the ensemble forecast results.In addition,the development trend of the cyclone analyzed from its dynamic mechanisms was another reference.When the general position of the verification area was determined,a small variation in size or position had little influence on the results of CNOP.

  4. Design of a ribozyme targeting human telomerase reverse transcriptase and cloning of it's gene

    Institute of Scientific and Technical Information of China (English)

    Zhi-Ming Hap; Jin-Yan Luo; Jin Cheng; Quan-Yin Wang; Guang-Xiao Yang

    2003-01-01

    AIM: To design a hammerhead ribozyme targeting humantelomerase reverse transcriptase (hTERT) and clone it's genefor future use in the study of tumor gene therapy.METHODS: Using the software RNAstructure, the secondarystructure of hTERT mRNA was predicted and the cleavagesite of ribozyme was selected. A hammerhead ribozymetargeting this site was designed and bimolecular fold betweenthe ribozyme and hTERT was predicted. The DNA encodingthe ribozyme was synthesized and cloned into pGEMEX-1and the sequence of the ribozyme gene was confirmed byDNA sequencing.RESULTS: Triplet GUC at 1742 of hTERT mRNA was chosenas the cleavage site of the ribozyme. The designed ribozymewas comprised of 22nt catalytic core and 17nt flankingsequence. Computer-aided prediction suggested that theribozyme and hTERT mRNA could cofold into a properconformation. Endonuclease restriction and DNA sequencingconfirmed the correct insertion of the ribozyme gene intothe vector pGEMEX-1.CONCLUSION: This fundamental work of successfuldesigning and cloning of an anti-hTERT hammerheadribozyme has paved the way for further study of inhibitingtumor cell growth by cleaving hTERT mRNA with ribozyme.

  5. Preparation of targets for the gas-filled recoil separator TASCA by electrochemical deposition and design of the TASCA target wheel assembly

    International Nuclear Information System (INIS)

    The Transactinide Separator and Chemistry Apparatus (TASCA) is a recoil separator with maximized transmission designed for performing advanced chemical studies as well as nuclear reaction and structure investigations of the transactinide elements (Z>103) on a one-atom-at-a-time basis. TASCA will provide a very clean transactinide fraction with negligible contamination of lighter elements from nuclear side reactions in the target. For TASCA a new target chamber was designed and built at GSI including the rotating target wheel assembly ARTESIA for beam intensities up to 2 μA (particle). For the production of longer-lived isotopes of neutron-rich heavier actinide and transactinide elements, hot fusion reactions with actinide targets are required. Here, possible target materials range from thorium up to curium or even heavier elements. For the deposition of lanthanide and actinide elements on thin aluminum and titanium backings by means of Molecular Plating (MP), a new deposition cell has been constructed that allows precise temperature control of the organic solvent and stirring of the solution. The electrode geometry ensures homogeneity of the electric field inside the cell. With the new set-up, holmium and gadolinium layers (500 μg/cm2) on 2-5 μm thin titanium backings have been produced with deposition yields of the order of 90%. Systematic investigations are under way to further optimize the deposition conditions for other lanthanide and actinide elements including uranium and plutonium on different backing materials

  6. Capabilities, Design, Construction and Commissioning of New Vibration, Acoustic, and Electromagnetic Capabilities Added to the World's Largest Thermal Vacuum Chamber at NASA's Space Power Facility

    Science.gov (United States)

    Motil, Susan M.; Ludwiczak, Damian R.; Carek, Gerald A.; Sorge, Richard N.; Free, James M.; Cikanek, Harry A., III

    2011-01-01

    NASA s human space exploration plans developed under the Exploration System Architecture Studies in 2005 included a Crew Exploration Vehicle launched on an Ares I launch vehicle. The mass of the Crew Exploration Vehicle and trajectory of the Ares I coupled with the need to be able to abort across a large percentage of the trajectory generated unprecedented testing requirements. A future lunar lander added to projected test requirements. In 2006, the basic test plan for Orion was developed. It included several types of environment tests typical of spacecraft development programs. These included thermal-vacuum, electromagnetic interference, mechanical vibration, and acoustic tests. Because of the size of the vehicle and unprecedented acoustics, NASA conducted an extensive assessment of options for testing, and as result, chose to augment the Space Power Facility at NASA Plum Brook Station, of the John H. Glenn Research Center to provide the needed test capabilities. The augmentation included designing and building the World s highest mass capable vibration table, the highest power large acoustic chamber, and adaptation of the existing World s largest thermal vacuum chamber as a reverberant electromagnetic interference test chamber. These augmentations were accomplished from 2007 through early 2011. Acceptance testing began in Spring 2011 and will be completed in the Fall of 2011. This paper provides an overview of the capabilities, design, construction and acceptance of this extraordinary facility.

  7. 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.

  8. Engineering design and construction of a function Hg – loop & Contribution of IPUL in windowless Hg-target feasibility studies

    CERN Document Server

    J. Freibergs, E. Platacis, K. Kravalis, A. Ziks&I.Platnieks

    Within EURISOL – DS, a liquid metal /LM/ spallation target with a power of several Megawatt is designed to provide neutrons to a fission target. The target station that allows the full intensity of a 4 MW proton beam to be used for RIB production will require new advanced technology. It is a critical component of EURISOL.For a power density above 103 MW/m3 the windowless, free-surface, molten LM-jet is proposed as a target since it avoids the very serious lifetime – shortening damage caused by the power proton beam in any system

  9. 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.

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

    International Nuclear Information System (INIS)

    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 (< 0.5 mm) permits monitoring the pharmacokinetics of labeled gene constructs in vivo in small 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

  11. Design, synthesis and biological evaluation of PSMA/hepsin-targeted heterobivalent ligands.

    Science.gov (United States)

    Subedi, Milan; Minn, Il; Chen, Jianbo; Kim, YunHye; Ok, Kiwon; Jung, Yong Woo; Pomper, Martin G; Byun, Youngjoo

    2016-08-01

    Cell surface biomarkers such as prostate-specific membrane antigen (PSMA) and hepsin have received considerable attention as targets for imaging prostate cancer (PCa) due to their high cell surface expression in such tumors and easy access for imaging probes. Novel amidine-containing indole analogs (13-21) as hepsin inhibitors were designed and synthesized. These compounds showed in vitro inhibitory activity against hepsin with IC50 values from 5.9 to 70 μM. Based on the SAR of amidine-derived analogs, the novel heterobivalent compound 30, targeting both hepsin and PSMA, was synthesized by linking compound 18 with Lys-urea-Glu, the key scaffold for the specific binding to PSMA, followed by the conjugation of the optical dye SulfoCy7. Compound 30 exhibited inhibitory activities against PSMA and hepsin, with IC50 values of 28 nM and 2.8 μM, respectively. In vitro cell uptake and preliminary in vivo optical imaging studies of 30 showed selective binding and retention in both PSMA and hepsin high-expressing PC3/ML-PSMA-HPN cells as compared with low-expressing PC3/ML cells. PMID:27128184

  12. Rational design of small molecule inhibitors targeting the Ras GEF, SOS1

    Science.gov (United States)

    Evelyn, Chris R.; Duan, Xin; Biesiada, Jacek; Seibel, William L.; Meller, Jaroslaw; Zheng, Yi

    2014-01-01

    Summary Ras GTPases regulate intracellular signaling involved in cell proliferation. Elevated Ras signaling activity has been associated with human cancers. Ras activation is catalyzed by guanine-nucleotide exchange factors (GEFs), of which SOS1 is a major member that transduces receptor tyrosine kinase signaling to Ras. We have developed a rational approach coupling virtual screening with experimental screening in identifying small-molecule inhibitors targeting the catalytic site of SOS1 and SOS1-regulated Ras activity. A lead inhibitor, NSC-658497, is found to bind to SOS1, competitively suppresses SOS1-Ras interaction, and dose-dependently inhibits SOS1 GEF activity. Mutagenesis and structure-activity relationship studies map the NSC-658497 site of action to the SOS1 catalytic site, and define the chemical moieties in the inhibitor essential for the activity. NSC-658497 showed dose-dependent efficacy in inhibiting Ras, downstream signaling activities, and associated cell proliferation. These studies establish a proof of principle for rational design of small-molecule inhibitors targeting Ras GEF enzymatic activity. PMID:25455859

  13. Rational design of small molecule inhibitors targeting the Ras GEF, SOS1.

    Science.gov (United States)

    Evelyn, Chris R; Duan, Xin; Biesiada, Jacek; Seibel, William L; Meller, Jaroslaw; Zheng, Yi

    2014-12-18

    Ras GTPases regulate intracellular signaling involved in cell proliferation. Elevated Ras signaling activity has been associated with human cancers. Ras activation is catalyzed by guanine nucleotide exchange factors (GEFs), of which SOS1 is a major member that transduces receptor tyrosine kinase signaling to Ras. We have developed a rational approach coupling virtual screening with experimental screening in identifying small-molecule inhibitors targeting the catalytic site of SOS1 and SOS1-regulated Ras activity. A lead inhibitor, NSC-658497, was found to bind to SOS1, competitively suppress SOS1-Ras interaction, and dose-dependently inhibit SOS1 GEF activity. Mutagenesis and structure-activity relationship studies map the NSC-658497 site of action to the SOS1 catalytic site, and define the chemical moieties in the inhibitor essential for the activity. NSC-658497 showed dose-dependent efficacy in inhibiting Ras, downstream signaling activities, and associated cell proliferation. These studies establish a proof of principle for rational design of small-molecule inhibitors targeting Ras GEF enzymatic activity.

  14. Design of Low Power OTA for High Resolution A/D Converters%用于高精度A/D转换器的低功耗OTA设计

    Institute of Scientific and Technical Information of China (English)

    胡栋柯; 景新幸; 赵荣建

    2012-01-01

    A low-power operational transconductance amplifier (OTA) for high-resolution A/D converter was designed Fully-differential two-stage structure, push-pull output and a switched-capacitor common-mode feedback circuit were adopted in this OTA, which was fabricated with SIMC's 0. 18 μm CMOS mixed-signal process. Results from simulation with Cadence's Spectre showed that the circuit had an open-loop DC gain of 63. 4 dB, a unity-gain bandwidth of 206 MHz, a phase margin of 67°, and a slew rate of 75 V/μs for 2 pF driving load with a total power consumption of 650 μW. The OTA is applicable for high-resolution A/D converter and other portable multi-media devices with low-voltage and low-power requirement.%设计了一种用于高精度A/D转换器的低功耗跨导运算放大器(OTA)电路.采用全差分两级运放结构、推挽式输出及开关电容共模反馈电路.设计基于SIMC 0.18 μm CMOS混合信号工艺,工作电压为1.8V.用Cadence/Spectre仿真器进行仿真,结果表明,负载为2 pF时,OTA直流开环增益为63.4 dB,单位增益带宽206 MHz,相位裕度67°,压摆率75 V/μs,功耗650 μW.适用于高精度A/D转换器及其他便携式多媒体设备的低压低功耗应用.

  15. A cross-layer design and ant-colony optimization based load-balancing routing protocol for ad-hoc networks

    Institute of Scientific and Technical Information of China (English)

    ZHENG Xiangquan; GUO Wei; GE Lijia; LIU Renting

    2007-01-01

    In order to periodically reassess the status of the alternate path route (APR) set and to improve the efficiency of alternate path construction existing in most current alternate path routing protocols,we present a cross-layer design and ant-colony optimization based load-balancing routing protocol for ad-hoc networks (CALRA) in this paper.In CALRA,the APR set maintained in nodes is aged and reassessed by the inherent mechanism of pheromone evaporation of ant-colony optimization algorithm,and load balance of network is achieved by ant-colony optimization combining with cross-layer synthetic optimization.The efficiency of APR set construction is improved by bidirectional and hop-by-hop routing update during routing discovery and routing maintenance process.Moreover,ants in CALRA deposit simulated pheromones as a function of multiple parameters corresponding to the information collected by each layer of each node visited,such as the distance from their source node,the congestion degree of the visited nodes,the current pheromones the nodes possess,the velocity of the nodes,and so on,and provide the information to the visiting nodes to update their pheromone tables by endowing the different parameters corresponding to different information and different weight values,which provides a new method to improve the congestion problem,the shortcut problem,the convergence rate and the heavy overheads commonly existed in existing ant-based routing protocols for ad-hoc networks.The performance of the algorithm is measured by the packet delivery rate,good-put ratio (routing overhead),and end-to-end delay.Simulation results show that CALRA performs well in decreasing the route overheads,balancing traffic load,as well as increasing the packet delivery rate,etc.

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

    International Nuclear Information System (INIS)

    The Accelerator Production of Tritium Target/Blanket (T/B) system is comprised of an assembly of tritium-producing modules supported by safety, heat removal, shielding, and retargeting systems. The T/B assembly produces tritium using a high-energy proton beam, a tungsten/lead spallation neutron source and 3He gas as the tritium-producing feedstock. The supporting heat removal systems remove the heat deposited by the proton beam during both normal and off-normal conditions. The shielding protects workers from ionizing radiation, and the retargeting systems remove and replace components that have reached their end of life. All systems reside within the T/B building, which is located at the end of a linear accelerator. For the nominal production mode, protons are accelerated to an energy of 1030 MeV at a current of 100 mA and are directed onto the T/B assembly. The protons are expanded to a 0.19- x 1.9-m beam spot before striking a centrally located tungsten neutron source. A surrounding lead blanket produces additional neutrons from scattered high-energy particles. A total of 27 neutrons are produced per incident proton. Tritium is produced by neutron capture in 3He gas that is contained in aluminum tubes throughout the blanket. The 3He/tritium mixture is removed on a semi-continuous basis for purification in an adjacent Tritium Separation Facility. Systems and components are designed with safety as a primary consideration to minimize risk to the workers and the public. Materials and component designs were chosen based on the experiences of operating spallation neutron sources that have been designed and built for the neutron science community. An extensive engineering development and demonstration program provides detailed information for the completion of the design

  17. Analysis and Algorithm Design of Wormhole Attacking Mobile Ad Hoc Networks%移动Ad Hoc网络中"虫洞"攻击分析及算法设计

    Institute of Scientific and Technical Information of China (English)

    景劼; 田军舰

    2010-01-01

    阐述了"虫洞"攻击原理,建立了攻击模型和流程图,针对典型路由协议进行了"虫洞"攻击分析及算法设计,并用OPNET软件对"虫洞"攻击进行仿真.仿真结果初步验证了"虫洞"攻击对Ad Hoc网络的危害性.

  18. Design and realization of HART protocol telecommunication module based on A5191HRT and AD421%基于A5191HRT和AD421的HART协议通信模块的设计与实现

    Institute of Scientific and Technical Information of China (English)

    顾伟; 费元春; 周建明

    2004-01-01

    首先叙述HART通信协议的发展和协议的层次结构,针对某现场仪表的HART协议远程通信模块的设计与实现的要求,完成了基于HART调制解调器A5191HRT和电流环数模转换器AD421的HART协议通信模块的软硬件设计.

  19. N=2 supersymmetric sigma-models in AdS

    CERN Document Server

    Butter, Daniel

    2011-01-01

    We construct the most general N=2 supersymmetric nonlinear sigma-model in four-dimensional anti-de Sitter (AdS) space in terms of N=1 chiral superfields. The target space is shown to be a non-compact hyperkahler manifold restricted to possess a special Killing vector field. A remarkable property of the sigma-model constructed is that the algebra of OSp(2|4) transformations is closed off the mass shell.

  20. 基于AD7655的鱼雷声靶数据采集系统设计分析%Analysis for the Design of the Data Acquisition System of Torpedo Acoustics-Drone Based on AD7655

    Institute of Scientific and Technical Information of China (English)

    王楠

    2010-01-01

    为了保证鱼雷声靶工作时的可靠性和稳定性,数据采集系统必须具有多通道和高采样频率的特点,以满足高精度的试验要求.本文在分析鱼雷声靶数据采集系统的总体构成的基础上,介绍了运用高性能模数转换芯片AD7655实现数据采集系统的模数转换过程,说明了利用FPGA产生控制信号实现AD7655模数转换功能,以及AD7655与数字处理器传送数据的接口设计.在实际应用过程中证明,该系统的设计是合理的.

  1. Principle of shielding design for the target cave of a high current medical cyclotron

    International Nuclear Information System (INIS)

    Full text: During routine isotope production regimen at the H-ion Medical Cyclotron of the Radiopharmaceutical Division of ANSTO a thick copper plate electroplated with enriched target material is bombarded with a 30 MeV proton beam at 250μA which results in the production of fast evaporation neutrons with an average energy of 5.1 MeV (Nakamura, T. et al, Nucl Sci Engg, 83: 444-458, 1992). This paper highlights the principle of shielding design using the empirical method (Mukherjee, B. Proc. 14th Int. Conf. on Cyclotrons and their Applications, Cape Town, South Africa, October 1995) for a new target cave proposed to house a solid target irradiation station to be bombarded with a proton beam of 500μA and thereby producing an intense flux of fast neutrons. Important nuclear data such as the neutron and gamma source terms defined as the corresponding dose equivalent rates for lμA proton beam current at 1m from the target as well as the neutron energy distribution required for the shielding calculations were previously estimated experimentally (Mukherjee, B. Proc. 14th Int. Conf. on Cyclotrons and their Applications, Cape Town, South Africa, October 1995). The neutron attenuation coefficients of the 4 legged maze were explicitly evaluated from experiments conducted in the existing cyclotron vault and beam room (Mukherjee, B. et al, Appl Radiat Isot, in print, June 1996). Low sodium content high density (2350 kg.m-3) concrete was used as the shielding material. The optimum lateral thicknesses of the shielding walls (t1 and t2) were calculated to be 2.1 m and 2.5 m and the length of the maze legs (ab, bc, cd, de) were evaluated as 1.2 m, 3.1 m, 1.5 m and 6 m respectively. The dose equivalent (gamma plus neutron) rates at the locations of interest 'P1', 'P2' and 'e' were set at 0.5 μSvh-1, 10 pSvh-1 and 10 μSvh-1 respectively. The neutron shielding calculation method presented in this paper was found to be more suitable than the Monte Carlo code generally used for

  2. 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

  3. Online Ad Assignment with an Ad Exchange

    OpenAIRE

    Dvořák, Wolfgang; Henzinger, Monika

    2016-01-01

    Ad exchanges are becoming an increasingly popular way to sell advertisement slots on the internet. An ad exchange is basically a spot market for ad impressions. A publisher who has already signed contracts reserving advertisement impressions on his pages can choose between assigning a new ad impression for a new page view to a contracted advertiser or to sell it at an ad exchange. This leads to an online revenue maximization problem for the publisher. Given a new impression to sell decide whe...

  4. Marginally igniting direct-drive target designs for the laser Megajoule

    International Nuclear Information System (INIS)

    Direct-drive target designs below self-ignition threshold are proposed for the laser Megajoule in the context of shock ignition. Two distinct initial aspect ratios are considered and laser pulses are shaped following a classical Kidder's law in order to achieve an implosion velocity of 300 km/s, an in-fight adiabatic close to unity and to maximize the peak areal density. The pulse shapes are adjusted to arrange shock timing at the inner side of the DT fuel. The robustness of the laser pulse is addressed by the means of random variations around the initial Kidder's laws. Correlation matrices show no significant correlations between laser parameters. An admissible envelope of laser pulse is given for both designs in order to warrant more than 80% of the best peak areal density. Variations of laser drive power produce variations of implosion velocities in the range 250-370 km/s. Self-ignition threshold is achieved and thermonuclear energy are produced in the range 3 kJ-27 MJ. Finally, the random procedure shows that it is possible to improve the first deterministic optimization and the laser pulses are given. (authors)

  5. Structural investigation of inhibitor designs targeting 3-dehydroquinate dehydratase from the shikimate pathway of Mycobacterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Marcio V.B.; Snee, William C.; Bromfield, Karen M.; Payne, Richard J.; Palaninathan, Satheesh K.; Ciulli, Alessio; Howard, Nigel I.; Abell, Chris; Sacchettini, James C.; Blundell, Tom L. (TAM); (Cambridge)

    2011-09-06

    The shikimate pathway is essential in Mycobacterium tuberculosis and its absence from humans makes the enzymes of this pathway potential drug targets. In the present paper, we provide structural insights into ligand and inhibitor binding to 3-dehydroquinate dehydratase (dehydroquinase) from M. tuberculosis (MtDHQase), the third enzyme of the shikimate pathway. The enzyme has been crystallized in complex with its reaction product, 3-dehydroshikimate, and with six different competitive inhibitors. The inhibitor 2,3-anhydroquinate mimics the flattened enol/enolate reaction intermediate and serves as an anchor molecule for four of the inhibitors investigated. MtDHQase also forms a complex with citrazinic acid, a planar analogue of the reaction product. The structure of MtDHQase in complex with a 2,3-anhydroquinate moiety attached to a biaryl group shows that this group extends to an active-site subpocket inducing significant structural rearrangement. The flexible extensions of inhibitors designed to form {pi}-stacking interactions with the catalytic Tyr{sup 24} have been investigated. The high-resolution crystal structures of the MtDHQase complexes provide structural evidence for the role of the loop residues 19-24 in MtDHQase ligand binding and catalytic mechanism and provide a rationale for the design and efficacy of inhibitors.

  6. 基于ADS的S波段平衡式宽带低噪声放大器设计%Design of S band wideband balance LNA with ADS

    Institute of Scientific and Technical Information of China (English)

    徐晓宁; 胡兆刚

    2012-01-01

    An ADS-based design of S-band balanced-broadband low-noise amplifier (LNA) for broadband radar front-end is presented in this paper. The Spice model of the E-PHEMT is used in the simulation software. After the DC operating point is conformed, the minimum noise figure impedance matching in the input port and the maximum gain impedance matching in the output port were designed while the simulation result and layout was offered. The 2-way 90?wide band power splitter was integrated with the balanced LNA. It is the way which improved the electronical performance of the amplifier much more and reduced the dimension of the entire circuit observably. The schematic-EM-co-simulation was adopted in the circuit design and optimization of LNA, in which an EM analysis was performed on the whole circuit as just one physical model, so that the results can approach the measured results more than that of the schematic simulation. This method can shorten the design period and bring about a high design efficiency.%针对宽带雷达接收前端的应用,基于ADS软件设计了一种S波段平衡式宽带低噪声放大器.在软件仿真中使用晶体管的Spice模型,在确定直流工作点后进行输入端的最小噪声阻抗匹配和输出端的最大增益阻抗匹配,最后给出了仿真结果和版图设计.同时采用新型S波段90°宽带功分器用于平衡式LNA的电路,大大提高了放大器的电性能,显著减小了整个电路的尺寸.在此将原理图-版图联合仿真用于LNA的设计优化,将整个电路作为一个模型进行EM分析,得出了一个可以比原理图仿真更接近实际电路的结果,同时有效提高了产品的研发效率,缩短小了研制周期.

  7. 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 midscale 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

  8. 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

  9. 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.

  10. Influence of molecular design on biodistribution and targeting properties of an Affibody-fused HER2-recognising anticancer toxin.

    Science.gov (United States)

    Altai, Mohamed; Liu, Hao; Orlova, Anna; Tolmachev, Vladimir; Gräslund, Torbjörn

    2016-09-01

    Targeted delivery of toxins is a promising way to treat disseminated cancer. The use of monoclonal antibodies as targeting moiety has provided proof-of-principle for this approach. However, extravasation and tissue penetration rates of antibody-based immunotoxins are limited due to antibody bulkiness. The use of a novel class of targeting probes, Affibody molecules, provides smaller toxin-conjugated constructs, which may improve targeting. Earlier, we have demonstrated that affitoxins containing a HER2-targeting Affibody moiety and a deimmunized and truncated exotoxin A from Pseudomonas aeruginosa, PE38X8, provide highly selective toxicity to HER2-expressing cancer cells. To evaluate the influence of molecular design on targeting and biodistribution properties, a series of novel affitoxins were labelled with the residualizing radionuclide 111In. In this study, we have shown that the novel conjugates are more rapidly internalized compared with the parental affitoxin. The use of a (HE)3 purification tag instead of a hexahistidine tag enabled significant (pmolecular design of scaffold protein based anticancer targeted toxins can appreciably improve their biodistribution and targeting properties.

  11. Adding energy minimization strategy to peptide-design algorithm enables better search for RNA-binding peptides: Redesigned λ N peptide binds boxB RNA.

    Science.gov (United States)

    Xiao, Xingqing; Hung, Michelle E; Leonard, Joshua N; Hall, Carol K

    2016-10-15

    Our previously developed peptide-design algorithm was improved by adding an energy minimization strategy which allows the amino acid sidechains to move in a broad configuration space during sequence evolution. In this work, the new algorithm was used to generate a library of 21-mer peptides which could substitute for λ N peptide in binding to boxB RNA. Six potential peptides were obtained from the algorithm, all of which exhibited good binding capability with boxB RNA. Atomistic molecular dynamics simulations were then conducted to examine the ability of the λ N peptide and three best evolved peptides, viz. Pept01, Pept26, and Pept28, to bind to boxB RNA. Simulation results demonstrated that our evolved peptides are better at binding to boxB RNA than the λ N peptide. Sequence searches using the old (without energy minimization strategy) and new (with energy minimization strategy) algorithms confirm that the new algorithm is more effective at finding good RNA-binding peptides than the old algorithm. © 2016 Wiley Periodicals, Inc.

  12. Logical design of an anti-cancer agent targeting the plant homeodomain in Pygopus2.

    Science.gov (United States)

    Ali, Ferdausi; Yamaguchi, Keiichi; Fukuoka, Mayuko; Elhelaly, Abdelazim Elsayed; Kuwata, Kazuo

    2016-09-01

    Pygopus2 (Pygo2) is a component of the Wnt signaling pathway, which is required for β-catenin mediated transcription. Plant homeodomain (PHD) finger in Pygo2 intercalates the methylated histone 3 (H3K4me) tail and HD1 domain of BCL9 that binds to β-catenin. Thus, PHD finger may be a potential target for the logical design of an anti-cancer drug. Here, we found that Spiro[2H-naphthol[1,2-b]pyran-2,4'-piperidine]-1'ethanol,3,4-dihydro-4-hydroxy-α-(6-methyl-1H-indol-3-yl)) termed JBC117 interacts with D339, A348, R356, V376 and A378 in PHD corresponding to the binding sites with H3K4me and/or HD1, and has strong anti-cancer effects. For colon (HCT116) and lung (A549) cancer cell lines, IC50 values were 2.6 ± 0.16 and 3.3 ± 0.14 μM, respectively, while 33.80 ± 0.15 μM for the normal human fibroblast cells. JBC117 potently antagonized the cellular effects of β-catenin-dependent activity and also inhibited the migration and invasion of cancer cells. In vivo studies showed that the survival time of mice was significantly prolonged by the subcutaneous injection of JBC117 (10 mg/kg/day). In conclusion, JBC117 is a novel anti-cancer lead compound targeting the PHD finger of Pygo2 and has a therapeutic effect against colon and lung cancer.

  13. 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

  14. Design of the signal modulation circuit of roughness tester based on AD698%基于AD698的粗糙度测试仪信号调理电路的设计

    Institute of Scientific and Technical Information of China (English)

    杨涛; 颜德田

    2009-01-01

    LVDT(Linear Variable Differential Transformer,可变差分变送器)是触针式粗糙度测试仪的感测部件.当粗糙度测试仪的触针沿着物件表面滑动时,LVDT将触针的纵向机械位移转变成与之成比例的直流信号,从而感测该位移的大小和方向.以往对LVDT输出信号的处理多采用分立元件电路或AD598集成芯片,采用AD698集成芯片能有效减少由温度导致的激励信号飘移,同时,本文将引入一种高灵敏度设计方案,能在不增加输出噪声的情况下,有效提高灵敏度,从而在整体上提高该调理模块的性能.

  15. ADS National Programmes: France

    International Nuclear Information System (INIS)

    Studies related to nuclear reactors and radioactive waste started at the French National Centre for Scientific research, CNRS, as a result of the French law on radioactive waste that was published in 1991. They were initially organized around the programme PACE (Physique pour l’Aval du Cycle Electronucléaire = physics of the back end of the nuclear fuel cycle), which became PACEN (Physique pour l’Aval du Cycle et production d’Energie Nucléaire = Physics of the back end of the nuclear fuel cycle and production of nuclear energy) in 2006. Research on accelerator driven systems was from the beginning part of this programme. This research is mainly funded by the National Institute for Nuclear end Particle Physics (IN2P3) of CNRS and within the EURATOM European programmes (FP5, 6 and 7). The programme took place in several stages, and covered various scientific fields, benefitting from expertise of CNRS in the field. More specifically, it aimed and still aims to: – Test and verify the feasibility and design of the ADS concept, in terms of neutronics, physics of materials, design of the accelerator and tests of its prototypical components that have been built (or are at present under construction); – Measure and-or improve nuclear data related to radioactive waste transmutation. Today, most of the activities in support to ADS development carried out by CNRS focus on accelerator developments, GUINEVERE (Generator of Uninterrupted Intense NEutron at the lead VEnus REactor) experiment, ADS core studies, deployment scenarios and nuclear data measurements. The CEA R&D programmes on ADS are mainly focused on the European project EUROTRANS of the 6th Framework programme (2005–2010) and continued in the FREYA project of the 7th Framework Programme

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

    International Nuclear Information System (INIS)

    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

  17. Polarised black holes in AdS

    Science.gov (United States)

    Costa, Miguel S.; Greenspan, Lauren; Oliveira, Miguel; Penedones, João; Santos, Jorge E.

    2016-06-01

    We consider solutions in Einstein-Maxwell theory with a negative cosmological constant that asymptote to global AdS 4 with conformal boundary {S}2× {{{R}}}t. At the sphere at infinity we turn on a space-dependent electrostatic potential, which does not destroy the asymptotic AdS behaviour. For simplicity we focus on the case of a dipolar electrostatic potential. We find two new geometries: (i) an AdS soliton that includes the full backreaction of the electric field on the AdS geometry; (ii) a polarised neutral black hole that is deformed by the electric field, accumulating opposite charges in each hemisphere. For both geometries we study boundary data such as the charge density and the stress tensor. For the black hole we also study the horizon charge density and area, and further verify a Smarr formula. Then we consider this system at finite temperature and compute the Gibbs free energy for both AdS soliton and black hole phases. The corresponding phase diagram generalizes the Hawking-Page phase transition. The AdS soliton dominates the low temperature phase and the black hole the high temperature phase, with a critical temperature that decreases as the external electric field increases. Finally, we consider the simple case of a free charged scalar field on {S}2× {{{R}}}t with conformal coupling. For a field in the SU(N ) adjoint representation we compare the phase diagram with the above gravitational system.

  18. Designing Efficient Double RNA trans-Splicing Molecules for Targeted RNA Repair.

    Science.gov (United States)

    Hüttner, Clemens; Murauer, Eva M; Hainzl, Stefan; Kocher, Thomas; Neumayer, Anna; Reichelt, Julia; Bauer, Johann W; Koller, Ulrich

    2016-01-01

    RNA trans-splicing is a promising tool for mRNA modification in a diversity of genetic disorders. In particular, the substitution of internal exons of a gene by combining 3' and 5' RNA trans-splicing seems to be an elegant way to modify especially large pre-mRNAs. Here we discuss a robust method for designing double RNA trans-splicing molecules (dRTM). We demonstrate how the technique can be implemented in an endogenous setting, using COL7A1, the gene encoding type VII collagen, as a target. An RTM screening system was developed with the aim of testing the replacement of two internal COL7A1 exons, harbouring a homozygous mutation, with the wild-type version. The most efficient RTMs from a pool of randomly generated variants were selected via our fluorescence-based screening system and adapted for use in an in vitro disease model system. Transduction of type VII collagen-deficient keratinocytes with the selected dRTM led to accurate replacement of two internal COL7A1 exons resulting in a restored wild-type RNA sequence. This is the first study demonstrating specific exon replacement by double RNA trans-splicing within an endogenous transcript in cultured cells, corroborating the utility of this technology for mRNA repair in a variety of genetic disorders. PMID:27669223

  19. Designing Efficient Double RNA trans-Splicing Molecules for Targeted RNA Repair

    Science.gov (United States)

    Hüttner, Clemens; Murauer, Eva M.; Hainzl, Stefan; Kocher, Thomas; Neumayer, Anna; Reichelt, Julia; Bauer, Johann W.; Koller, Ulrich

    2016-01-01

    RNA trans-splicing is a promising tool for mRNA modification in a diversity of genetic disorders. In particular, the substitution of internal exons of a gene by combining 3′ and 5′ RNA trans-splicing seems to be an elegant way to modify especially large pre-mRNAs. Here we discuss a robust method for designing double RNA trans-splicing molecules (dRTM). We demonstrate how the technique can be implemented in an endogenous setting, using COL7A1, the gene encoding type VII collagen, as a target. An RTM screening system was developed with the aim of testing the replacement of two internal COL7A1 exons, harbouring a homozygous mutation, with the wild-type version. The most efficient RTMs from a pool of randomly generated variants were selected via our fluorescence-based screening system and adapted for use in an in vitro disease model system. Transduction of type VII collagen-deficient keratinocytes with the selected dRTM led to accurate replacement of two internal COL7A1 exons resulting in a restored wild-type RNA sequence. This is the first study demonstrating specific exon replacement by double RNA trans-splicing within an endogenous transcript in cultured cells, corroborating the utility of this technology for mRNA repair in a variety of genetic disorders. PMID:27669223

  20. Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent

    Directory of Open Access Journals (Sweden)

    Ohara Koji

    2011-01-01

    Full Text Available Abstract Background Despite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target. Methods We focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop. Results It was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, and gastric cancer cell lines in vitro. In contrast, Antp-TPR peptide did not affect the viability of normal cells. Moreover, analysis in vivo revealed that Antp-TPR peptide displayed a significant antitumor activity in a xenograft model of human pancreatic cancer in mice. Conclusion These results indicate that Antp-TPR peptide would provide a potent and selective anticancer therapy to cancer patients.

  1. 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.

  2. Design of an Intense Muon Source with a Carbon and Mercury Target

    Energy Technology Data Exchange (ETDEWEB)

    Stratakis, Diktys [Brookhaven; Berg, J. Scott [Brookhaven; Neuffer, David [Fermilab; Ding, Xiaoping [UCLA

    2015-06-01

    In high-intensity sources, muons are produced by firing high energy protons onto a target to produce pions. The pions decay to muons which are captured and accelerated. In the present study, we examine the performance of the channel for two different target scenarios: one based on liquid mercury and another one based on a solid carbon target. We produce distributions with the two different target materials and discuss differences in particle spectrum near the sources. We then propagate the distributions through our capture system and compare the full system performance for the two target types.

  3. 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

  4. Material Developing for ADS Beam Window

    Institute of Scientific and Technical Information of China (English)

    XUYong-li; XUYuan-chao; LIHua-qing; NINGGuang-sheng; WANFa-rong; ZHAOFei

    2003-01-01

    The irradiation damage and the chemical interaction with the coolant for the ADS target and the structure materials are the key issues in ADS engineering. The developing of the materials that are irradiation and corrosion resistance is the important topic in ADS program in many countries. In this case,a topic of the material developing for the beam window has been proposed in our ADS program.

  5. Predicting AD conversion: comparison between prodromal AD guidelines and computer assisted PredictAD tool.

    Directory of Open Access Journals (Sweden)

    Yawu Liu

    Full Text Available To compare the accuracies of predicting AD conversion by using a decision support system (PredictAD tool and current research criteria of prodromal AD as identified by combinations of episodic memory impairment of hippocampal type and visual assessment of medial temporal lobe atrophy (MTA on MRI and CSF biomarkers.Altogether 391 MCI cases (158 AD converters were selected from the ADNI cohort. All the cases had baseline cognitive tests, MRI and/or CSF levels of Aβ1-42 and Tau. Using baseline data, the status of MCI patients (AD or MCI three years later was predicted using current diagnostic research guidelines and the PredictAD software tool designed for supporting clinical diagnostics. The data used were 1 clinical criteria for episodic memory loss of the hippocampal type, 2 visual MTA, 3 positive CSF markers, 4 their combinations, and 5 when the PredictAD tool was applied, automatically computed MRI measures were used instead of the visual MTA results. The accuracies of diagnosis were evaluated with the diagnosis made 3 years later.The PredictAD tool achieved the overall accuracy of 72% (sensitivity 73%, specificity 71% in predicting the AD diagnosis. The corresponding number for a clinician's prediction with the assistance of the PredictAD tool was 71% (sensitivity 75%, specificity 68%. Diagnosis with the PredictAD tool was significantly better than diagnosis by biomarkers alone or the combinations of clinical diagnosis of hippocampal pattern for the memory loss and biomarkers (p≤0.037.With the assistance of PredictAD tool, the clinician can predict AD conversion more accurately than the current diagnostic criteria.

  6. Design and preclinical evaluation of melanoma targeting agents for internal radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chezal, J.M.; Papon, J.; Labarre, P.; Denoyer, D.; Bonnet-Duquennoy, M.; Miot-Noirault, E.; Bayle, M.; Chavignon, O.; Teulade, J.C.; Maublant, J.; Madelmont, J.C.; Moins, N. [Centre Jean Perrin, Inserm-Univ. d' Auvergne, UMR 484, 63 - Clermont Ferrand (France)

    2008-02-15

    Targeted internal radionuclide therapy would be an effective alternative to current therapies for disseminated melanoma treatment. N-(2-diethylaminoethyl)-4-iodo benzamide (B.Z.A.) and compounds of this series exhibit a specific affinity for melanoma tissue giving them a potent application for gamma imaging ({sup 123}I) or radionuclide therapy ({sup 131}I or {sup 125}I).With the aim of internal radionuclide therapy, a pharmaco-chemical study has been carried out in order to select new derivatives with a longer retention time in the tumor of melanoma bearing mice and suitable dosimetry. New molecules synthesized are B.Z.A. analogs differing by (1) the aliphatic side chain, (2) aromatic ring. After the design of compounds, the synthesis, and the labelling with {sup 125}I, a study of their biodistribution was performed in B 16 F0 melanoma bearing C.57 B.L.6 mice after i.v. injection. The radioactivity biodistribution was analysed using an A.M.B.I.S.4000 detector on whole body slices of mice obtained by cryo section. The radioactivity was quantified in different organs including tumor and expressed as percentage of injected dose/g of tissue (% I.D./g). Dosimetry parameters for a {sup 131}I utilization were extrapolated using the M.I.R.D. program. The first selected compound has been further evaluated on different models. S.I.M.S. imaging, metabolism and in vivo anti tumoral activity after {sup 131}I labelling were assessed. For number of the studied molecules, a tumor uptake was observed and at least four compounds exhibited an original pharmacokinetic profile: high, specific and durable tumour concentration with a rapid clearance from non-target organs. The tumour concentration after 72 h was increased up to 16- fold compared to B.Z.A. and in term of dosimetry, for a {sup 131}I labelling, the tumor absorbed dose was increased by more than 6-fold. Such profiles made these compounds promising for an application to internal radionuclide therapy. The first selected

  7. Analyzing target user group¡¦s preferences and product form design specification through web-based 2-dimensinoal design decision tool

    Directory of Open Access Journals (Sweden)

    Jih-Shyong Lin

    2010-12-01

    Full Text Available In the modern market where consumerism is running higher and the product life span is getting shorter, it is one of the challenges for the marketing and design departments in enterprises to know how to get a thorough grasp of the consumer¡¦s preference and potential target user group. With the wide spread and growth of the internet, a web-based survey is not influenced by time and space factors, making it easier for designers to have an in-depth understanding of the consumer¡¦s preferences towards products. Based upon the 2-dimensional image scale, 120 college students from Taiwan and Japan were invited to evaluate 27 pencil sharpener samples in terms of their preferences and intention of purchase. From the survey, competitive portable pencil sharpeners were identified for the references of new product design and development. The results indicated that such a web-based 2-dimensional image survey system could offer real time help in product segmentation and the selection of competition products as well as the target user group with the output systematic diagrams and tables. Furthermore, morphological analysis for product form elements and quantification type I analysis could help designers and marketing managers set up proper policies for product form design for the target user groups in the design and marketing of new product development.

  8. 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

  9. Avoiding Design Fixation: Transformation and Abstraction in Mapping from Source to Target

    Science.gov (United States)

    Goldschmidt, Gabriela

    2011-01-01

    Designers try to "enlist" whatever they can to help themselves arrive at high quality, novel and original designs. When stimuli are used for this purpose, usually provided at the onset of the design process, these stimuli, or sources, may have one of two effects: they may enhance the design search and contribute to a high-quality, creative design,…

  10. Distributed design tools: Mapping targeted design tools onto a Web-based distributed architecture for high-performance computing

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, V.P.; Linebarger, J.M.; Miller, D.J.; Poore, C.A.

    1999-11-30

    Design Tools use a Web-based Java interface to guide a product designer through the design-to-analysis cycle for a specific, well-constrained design problem. When these Design Tools are mapped onto a Web-based distributed architecture for high-performance computing, the result is a family of Distributed Design Tools (DDTs). The software components that enable this mapping consist of a Task Sequencer, a generic Script Execution Service, and the storage of both data and metadata in an active, object-oriented database called the Product Database Operator (PDO). The benefits of DDTs include improved security, reliability, scalability (in both problem size and computing hardware), robustness, and reusability. In addition, access to the PDO unlocks its wide range of services for distributed components, such as lookup and launch capability, persistent shared memory for communication between cooperating services, state management, event notification, and archival of design-to-analysis session data.

  11. Polarised Black Holes in AdS

    CERN Document Server

    Costa, Miguel S; Oliveira, Miguel; Penedones, João; Santos, Jorge E

    2015-01-01

    We consider solutions in Einstein-Maxwell theory with a negative cosmological constant that asymptote to global $AdS_{4}$ with conformal boundary $S^{2}\\times\\mathbb{R}_{t}$. At the sphere at infinity we turn on a space-dependent electrostatic potential, which does not destroy the asymptotic $AdS$ behaviour. For simplicity we focus on the case of a dipolar electrostatic potential. We find two new geometries: (i) an $AdS$ soliton that includes the full backreaction of the electric field on the $AdS$ geometry; (ii) a polarised neutral black hole that is deformed by the electric field, accumulating opposite charges in each hemisphere. For both geometries we study boundary data such as the charge density and the stress tensor. For the black hole we also study the horizon charge density and area, and further verify a Smarr formula. Then we consider this system at finite temperature and compute the Gibbs free energy for both $AdS$ soliton and black hole phases. The corresponding phase diagram generalizes the Hawkin...

  12. High Bandwidth, Multi-Purpose Passive Radar Receiver Design For Aerospace and Geoscience Targets

    Science.gov (United States)

    Vertatschitsch, Laura

    Passive radar permits inexpensive and stealthy detection and tracking of aerospace and geoscience targets. Transmitters of opportunity such as commercial FM broadcast, DTV broadcast, and cell phone towers are already illuminating many populated areas with continuous power. Passive radar receivers can be located at a distance from the transmitter, and can sense this direct transmission as well as any reflections from ground clutter, aircraft, ionospheric turbulence and meteor trails. The 100% duty cycle allows for long coherent integration, increasing the sensitivity of these instruments greatly. Traditional radar receivers employ analog front end downconverters to translate the radio frequency spectrum to an intermediate frequency (IF) for sampling and signal processing. Such downconverters limit the spectrum available for study, and can introduce nonlinearities which limit the detectability of weak signals in the presence of strong signals. With suitably fast digitizers one can bypass the downconversion stage completely. Very fast digitizers may have relatively few bits, but precision is recovered in subsequent signal processing. We present a new passive radar receiver designed to utilize a broad spectrum of commercial transmitters without the use of a front end analog downconverter. The receiver centers around a Reconfigurable Open Architecture Computing Hardware (ROACH) board developed by the Collaboration for Astronomy Signal Processing and Electronics Research (CASPER) group. Fast sampling rates (8-bit samples as fast as 3 GSps) combined with 640 multiply/addition operations on the Virtex-5 FPGA centered on the ROACH allows for coherent processing of broad spectrum and dynamic decision-making on one device all while sharing a single front end, putting this device on the cutting edge of wideband receiver technology. The radar is also designed to support mobile operation. It fits within a 19'' rack, it is equipped with solid state hard drives, and can run off an

  13. Multifunctional gold nanoparticles for targeted imaging of angiotensin converting enzyme design, characterization, and application

    Science.gov (United States)

    Ghann, William Emmanuel

    agent could ultimately be used to monitor the levels of this biomarker in people predisposed to cardiovascular diseases due to genetic biases. It is anticipated that the targeted gold nanoparticle system could be applied in the design of similar multifunctional nanoparticles through the use of other disease-specific imaging nanoprobes.

  14. Impact of first-principles properties of deuterium–tritium on inertial confinement fusion target designs

    International Nuclear Information System (INIS)

    of DT are essential for designing ICF ignition targets. Future work on first-principles studies of ICF ablator materials is also discussed

  15. Importance of polar solvation and configurational entropy for design of antiretroviral drugs targeting HIV-1 protease.

    Science.gov (United States)

    Kar, Parimal; Lipowsky, Reinhard; Knecht, Volker

    2013-05-16

    Both KNI-10033 and KNI-10075 are high affinity preclinical HIV-1 protease (PR) inhibitors with affinities in the picomolar range. In this work, the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method has been used to investigate the potency of these two HIV-1 PR inhibitors against the wild-type and mutated proteases assuming that potency correlates with the affinity of the drugs for the target protein. The decomposition of the binding free energy reveals the origin of binding affinities or mutation-induced affinity changes. Our calculations indicate that the mutation I50V causes drug resistance against both inhibitors. On the other hand, we predict that the mutant I84V causes drug resistance against KNI-10075 while KNI-10033 is more potent against the I84V mutant compared to wild-type protease. Drug resistance arises mainly from unfavorable shifts in van der Waals interactions and configurational entropy. The latter indicates that neglecting changes in configurational entropy in the computation of relative binding affinities as often done is not appropriate in general. For the bound complex PR(I50V)-KNI-10075, an increased polar solvation free energy also contributes to the drug resistance. The importance of polar solvation free energies is revealed when interactions governing the binding of KNI-10033 or KNI-10075 to the wild-type protease are compared to the inhibitors darunavir or GRL-06579A. Although the contributions from intermolecular electrostatic and van der Waals interactions as well as the nonpolar component of the solvation free energy are more favorable for PR-KNI-10033 or PR-KNI-10075 compared to PR-DRV or PR-GRL-06579A, both KNI-10033 and KNI-10075 show a similar affinity as darunavir and a lower binding affinity relative to GRL-06579A. This is because of the polar solvation free energy which is less unfavorable for darunavir or GRL-06579A relative to KNI-10033 or KNI-10075. The importance of the polar solvation as revealed here

  16. A phage-targeting strategy for the design of spatiotemporal drug delivery from grafted matrices

    Directory of Open Access Journals (Sweden)

    Sawada Ritsuko

    2011-02-01

    Full Text Available Abstract Background The natural response to injury is dynamic and normally consists of complex temporal and spatial cellular changes in gene expression, which, when acting in synchrony, result in patent tissue repair and, in some instances, regeneration. However, current therapeutic regiments are static and most rely on matrices, gels and engineered skin tissue. Accordingly, there is a need to design next-generation grafting materials to enable biotherapeutic spatiotemporal targeting from clinically approved matrices. To this end, rather then focus on developing completely new grafting materials, we investigated whether phage display could be deployed onto clinically approved synthetic grafts to identify peptide motifs capable of linking pharmaceutical drugs with differential affinities and eventually, control drug delivery from matrices over both space and time. Methods To test this hypothesis, we biopanned combinatorial peptide libraries onto different formulations of a wound-healing matrix (Integra® and eluted the bound peptides with 1 high salt, 2 collagen and glycosaminoglycan or 3 low pH. After three to six rounds of biopanning, phage recovery and phage amplification of the bound particles, any phage that had acquired a capacity to bind the matrix was sequenced. Results In this first report, we identify distinct classes of matrix-binding peptides which elute differently from the screened matrix and demonstrate that they can be applied in a spatially relevant manner. Conclusions We suggest that further applications of these combinatorial techniques to wound-healing matrices may offer a new way to improve the performance of clinically approved matrices so as to introduce temporal and spatial control over drug delivery.

  17. Design of a flowing heavy metal target with a free surface for an accelerator driven neutron source

    International Nuclear Information System (INIS)

    In the paper the design of the flowing heavy metal target with free surface under proton beam irradiation within 0.8-1.6 GeV energy and the 10-320 mA current range is presented and analyzed. Following data submitted below: - the results of numerical modeling of the heat deposition in the Pb-Bi eutectic flow due to the penetrating through the proton beam; - the numerical investigation of swirling flow with a free surface; - the calculation of the temperature distributions occurring in the flowing heavy metal target because of the proton beam energy deposition; - the main construction parameters of the flowing heavy metal targets for the proton beams within 0.8-1.6 GeV energy and the 10-320 mA current range; - the design and numerical investigations of the supersonic wind shutter which is needed to isolate the vacuum part of the proton line. 3 refs., 10 figs

  18. Recommendations for the design of laboratory studies on non-target arthropods for risk assessment of genetically engineered plants

    Science.gov (United States)

    This paper provides recommendations on experimental design for early-tier laboratory studies used in the risk assessment process to evaluate potential adverse impacts of arthropod-resistant genetically-engineered plants on non-target arthropods. While we rely heavily on the currently used proteins f...

  19. Design, synthesis and evaluation of N-acetyl glucosamine (NAG)-PEG-doxorubicin targeted conjugates for anticancer delivery.

    Science.gov (United States)

    Pawar, Smita K; Badhwar, Archana J; Kharas, Firuza; Khandare, Jayant J; Vavia, Pradeep R

    2012-10-15

    Efficacy of anticancer drug is limited by the severe adverse effects induced by drug; therefore the crux is in designing delivery systems targeted only to cancer cells. Toward this objectives, we propose, synthesis of poly(ethylene glycol) (PEG)-doxorubicin (DOX) prodrug conjugates consisting N-acetyl glucosamine (NAG) as a targeting moiety. Multicomponent system proposed here is characterized by (1)H NMR, UV spectroscopy, and HPLC. The multicomponent system is evaluated for in vitro cellular kinetics and anticancer activity using MCF-7 and MDA-MB-231 cells. Molecular modeling study demonstrated sterically stabilized conformations of polymeric conjugates. Interestingly, PEG-DOX conjugate with NAG ligand showed significantly higher cytotoxicity compared to drug conjugate with DOX. In addition, the polymer drug conjugate with NAG and DOX showed enhanced internalization and retention effect in cancer cells, compared to free DOX. Thus, with enhanced internalization and targeting ability of PEG conjugate of NAG-DOX has implication in targeted anticancer therapy.

  20. A rail system for circular synthetic aperture sonar imaging and acoustic target strength measurements: design/operation/preliminary results.

    Science.gov (United States)

    Kennedy, J L; Marston, T M; Lee, K; Lopes, J L; Lim, R

    2014-01-01

    A 22 m diameter circular rail, outfitted with a mobile sonar tower trolley, was designed, fabricated, instrumented with underwater acoustic transducers, and assembled on a 1.5 m thick sand layer at the bottom of a large freshwater pool to carry out sonar design and target scattering response studies. The mobile sonar tower translates along the rail via a drive motor controlled by customized LabVIEW software. The rail system is modular and assembly consists of separately deploying eight circular arc sections, measuring a nominal center radius of 11 m and 8.64 m arc length each, and having divers connect them together in the underwater environment. The system enables full scale measurements on targets of interest with 0.1° angular resolution over a complete 360° aperture, without disrupting target setup, and affording a level of control over target environment conditions and noise sources unachievable in standard field measurements. In recent use, the mobile cart carrying an instrumented sonar tower was translated along the rail in 720 equal position increments and acoustic backscatter data were acquired at each position. In addition, this system can accommodate both broadband monostatic and bistatic scattering measurements on targets of interest, allowing capture of target signature phenomena under diverse configurations to address current scientific and technical issues encountered in mine countermeasure and unexploded ordnance applications. In the work discussed here, the circular rail apparatus is used for acoustic backscatter testing, but this system also has the capacity to facilitate the acquisition of magnetic and optical sensor data from targets of interest. A brief description of the system design and operation will be presented along with preliminary processed results for data acquired from acoustic measurements conducted at the Naval Surface Warfare Center, Panama City Division Test Pond Facility. [Work Supported by the U.S. Office of Naval Research and

  1. Design of RC frames for pre-selected collapse mechanism and target displacement using energy–balance

    Indian Academy of Sciences (India)

    Onur Merter; Taner Ucar

    2014-06-01

    In earthquake-prone countries, structures may be exposed to several seismic loads in any stage of building’s life. It is expected that the structures designed by engineers will show ductile behaviour under the effect of vertical and lateral loads and remain stable without making a sudden collapse. In consequence of nonlinear behaviour, plastic hinges are expected to form in structural members which are under the effect of external loads. Earthquake input energy is dissipated in plastic hinges, so, structures behave ductile. In this study, total energy of RC frames is calculated and the energy–based base shear force is determined by equating the total internal energy to the work done by external lateral design forces for pre-selected target displacement and collapse mechanism. Sections of RC frames are controlled if they can resist the calculated design lateral loads or not. If the capacity of the sections cannot withstand the external design loads, the design is rearranged and new sections are chosen. Beam and column sections that can resist the design loads securely are accepted as final sections of the energy–based design methodology. Pre-selected target displacement for desired performance level is checked using the results of nonlinear analyses. The results of the presented design methodology in this study are compatible with the results of nonlinear analyses.

  2. 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 whi

  3. Design of a 7Li rotating target for neutron production using a Van de Graaff accelerator

    International Nuclear Information System (INIS)

    We present a rotating target used for the production of monokinetic neutron fluxes. The neutrons are produced from the 7Li(p,n)7Be reaction for fast neutron elastic and inelastic scattering experiments. This target has been operated with a proton beam current of 8 to 10 μA during six consecutive weeks and has given entire satisfaction

  4. Designing a Clustering and Prediction-based Protocol for Target Tracking in Wireless Sensor Networks (WSNs

    Directory of Open Access Journals (Sweden)

    Vahid Hosseini

    2013-07-01

    Full Text Available Target tracking is one of the applications of wireless sensor network which is set up in the areas of field surveillance, habitat monitoring, and intruder tracking. Energy saving is one of the main challenges in target tracking sensor networks. In this paper, we present a Clustering and Prediction-Based Protocol (CPBP for Target Tracking in Wireless Sensor Networks (WSNs. Also, the Base Station (BS was exploited as a cluster formation manager and target movement predictor. Our protocol uses two parameters, distance and energy, for clustering algorithm. For evaluation, the proposed protocol was compared to a number of protocols in terms of network lifetime, number of transmitted packets and number of target miss during network lifetime. Performance of the proposed protocol was compared with cluster size 5 and 7. The simulation results represented desirable performance of the presented protocol.

  5. Ad Hoc网络%Ad Hoc Network

    Institute of Scientific and Technical Information of China (English)

    王海涛

    2005-01-01

    首先介绍了Ad Hoc网络的基本概念、技术特点以及关键技术等,然后较为全面地归纳了Ad Hoc网络的典型应用,最后讨论了Ad Hoc网络的发展趋势和有待解决的问题.

  6. Baby Skyrmions in AdS

    OpenAIRE

    Elliot-Ripley, Matthew; Winyard, Thomas

    2015-01-01

    We study the baby Skyrme model in a pure AdS background without a mass term. The tail decays and scalings of massless radial solutions are demonstrated to take a similar form to those of the massive flat space model, with the AdS curvature playing a similar role to the flat space pion mass. We also numerically find minimal energy solutions for a range of higher topological charges and find that they form concentric ring-like solutions. Popcorn transitions (named in analogy with studies of toy...

  7. 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...

  8. Update on design simulations for NIF ignition targets, and the rollup of all specifications into an error budget

    Science.gov (United States)

    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.

    2007-08-01

    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, SiO2 foam fill, and SiO2 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.

  9. The design and construction of the input and output isolation system for power channel and control rod position in the research reactor SR4 with analog device AD210

    International Nuclear Information System (INIS)

    The design and construction of analog input-output system with device AD210, SR4 (ICS Kartini Reactor) is used as interface and output signal isolation system for power channel meter NLW-2, NP1000 and control measurement with the slave computer system so that the measuring tools and computer operate independently. Device AD210 provides a very compact insulators and economically with highly accurate system performance. It is a DIP chip with 3-port model, input, output and integrated power supply. It can be applied as a multichannel data acquisition, or a single channel and others. Analog Device AD210 is placed between the output channel power measurement and control rod position measurement system / other support tools such as Computer Slave, ADC, multiplexer, and others. The design and construction of Analog Devices AD210 insulator use the input-output mode with the gain of 1, so that pulses or output voltage are equal to the input voltage pulses. The test results in graphs of output versus input are excellent with the linearity close to 100%. The use of this Device AD210 for NLW2 and NP1000 which are a vital instrument for the continuity of the operation of reactor, is expected to increase the Main Time Between Failure (MTBF) of the reactor as a whole. (author)

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

    CERN Document Server

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

    2000-01-01

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

  11. 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

    2012-06-01

    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 effects on responses to stimuli that varied by repetition and target presence, differences related to expectancy by comparing performance in single- and double-blind task designs, and individual differences in skin stimulation and mood. Participants were trained for 1h to detect target objects hidden in a complex virtual environment, while anodal tDCS was applied over RIFC at 0.1 mA or 2.0 mA for the first 30 min. Participants were tested immediately before and after training and again 1h later. Higher tDCS current was associated with increased performance for all test stimuli, but was greatest for repeated test stimuli with the presence of hidden-targets. This finding was replicated in a second set of subjects using a double-blind task design. Accuracy for target detection discrimination sensitivity (d'; Z(hits)-Z(false alarms)) was greater for 2.0 mA current (1.77) compared with 0.1 mA (0.95), with no differences in response bias (β). Taken together, these findings indicate that the enhancement of performance with tDCS is sensitive to stimulus repetition and target presence, but not to changes in expectancy, mood, or type of blinded task design. The implications of these findings for understanding the cognitive mechanisms of tDCS are discussed. PMID:22450198

  12. Eternal Black Holes in AdS

    OpenAIRE

    Maldacena, Juan M.

    2001-01-01

    We propose a dual non-perturbative description for maximally extended Schwarzschild Anti-de-Sitter spacetimes. The description involves two copies of the conformal field theory associated to the AdS spacetime and an initial entangled state. In this context we also discuss a version of the information loss paradox and its resolution.

  13. Current status of AdS instability

    CERN Document Server

    CERN. Geneva

    2016-01-01

    arXiv:1403.6471 and thoroughly developed in arXiv:1407.6273. On the other hand the negative cosmological constant allows for the existence of stable, time-periodic, asymptotically AdS solutions of Einstein equations [arXiv:1303.3186].

  14. AdS braneworld with Backreaction

    CERN Document Server

    Bilic, Neven

    2014-01-01

    We review the tachyon model derived from the dynamics of a 3-brane moving in the AdS5 bulk. The bulk geometry is based on the Randall-Sundrum II model extended to include the radion. The effective tachyon Lagrangian is modified due to the back-reaction of the brane on the bulk geometry.

  15. Design, Synthesis and Bio-evaluation of an EphA2-based Targeted Delivery System

    OpenAIRE

    Barile, Elisa; Wang, Si; Das, Swadesh K.; Noberini, Roberta; Dahl, Russell; Stebbins, John L.; Pasquale, Elena B.; Fisher, Paul B.; Pellecchia, Maurizio

    2014-01-01

    We recently described a new targeted delivery system based on specific EphA2 receptor targeting peptides conjugated with the chemotherapeutic agent paclitaxel. In this manuscript we investigate the chemical determinants responsible for the stability and degradation of these agents in plasma. Introducing modifications in both the peptide and the linker between the peptide and paclitaxel, resulted in drug conjugates that are both long-lived in rat plasma and that markedly reduced tumor size in ...

  16. A Beam-Specific Planning Target Volume (PTV) Design for Proton Therapy to Account for Setup and Range Uncertainties

    International Nuclear Information System (INIS)

    Purpose: To report a method for explicitly designing a planning target volume (PTV) for treatment planning and evaluation in heterogeneous media for passively scattered proton therapy and scanning beam proton therapy using single-field optimization (SFO). Methods and Materials: A beam-specific PTV (bsPTV) for proton beams was derived by ray-tracing and shifting ray lines to account for tissue misalignment in the presence of setup error or organ motion. Range uncertainties resulting from inaccuracies in computed tomography–based range estimation were calculated for proximal and distal surfaces of the target in the beam direction. The bsPTV was then constructed based on local heterogeneity. The bsPTV thus can be used directly as a planning target as if it were in photon therapy. To test the robustness of the bsPTV, we generated a single-field proton plan in a virtual phantom. Intentional setup and range errors were introduced. Dose coverage to the clinical target volume (CTV) under various simulation conditions was compared between plans designed based on the bsPTV and a conventional PTV. Results: The simulated treatment using the bsPTV design performed significantly better than the plan using the conventional PTV in maintaining dose coverage to the CTV. With conventional PTV plans, the minimum coverage to the CTV dropped from 99% to 67% in the presence of setup error, internal motion, and range uncertainty. However, plans using the bsPTV showed minimal drop of target coverage from 99% to 94%. Conclusions: The conventional geometry-based PTV concept used in photon therapy does not work well for proton therapy. We investigated and validated a beam-specific PTV method for designing and evaluating proton plans.

  17. Design and operation strategies of the system for destroying time-sensitive target based on system effectiveness

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    To improve the effect of destroying time-sensitive target (TST), a method of operational effectiveness evaluation is presented and some influential factors are analyzed based on the combat flow of system for destroying TST. Considering the possible operation modes of the system, a waved operation mode and a continuous operation mode are put forward at first. At the same time, some relative formulas are modified. In examples, the influential factors and operation modes are analyzed based on the system effectiveness. From simulation results, some design and operation strategies of the system for destroying time sensitive targets are concluded, which benefit to the improvement of the system effectiveness.

  18. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kaminaga, Masanori; Terada, Atsuhiko; Haga, Katsuhiro; Kinoshita, Hidetaka; Hino, Ryutaro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2001-03-01

    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)

  20. 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.)

  1. 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.

  2. Reasons for Using English or the Local Language in the Genre of Job Advertisements: Insights From Interviews With Dutch Job Ad Designers.

    NARCIS (Netherlands)

    Meurs, W.F.J. van; Planken, B.C.; Gerritsen, M.; Korzilius, H.P.L.M.

    2015-01-01

    Research problem: This study provides insight into practitioners' reasons for choosing a particular language (English versus the local language) in the genre of job ads in countries where English is a foreign language (EFL countries). Scholarly publications and public discourse have suggested reason

  3. A User Study of the Design Issues of PROPIE: A Novel Environment for Enhanced Interaction and Value-Adding of Electronic Documents.

    Science.gov (United States)

    Liew, Chern Li; Foo, Schubert; Chennupati, K. R.

    2001-01-01

    Presents a proposed information environment (PROPIE) for enhanced interaction and value-adding of electronic documents that allows users multiple ways to query intuitively and navigate information in an electronic document. Highlights include user interface technologies; visualization and interactive techniques; query and browsing processes; and…

  4. Overview of PbBi-Cooled Reactor Development and ADS Program in China

    International Nuclear Information System (INIS)

    -ER will be built by 2022. The design parameter of ADS-ER is similar with the MYRRHA project which consists of a LBE cooled reactor, a proton accelerator with 600-1000 MeV/10mA, and a LBE spallation target. The design thermal power of this ADS reactor is about 100 MW. In the third phase, an ADS demonstration reactor named ADS-DEMO will be built by 2032. The ADS-DEMO has a significant capacity for nuclear waste transmutation which consists of a LBE cooled reactor (about 1 GWth), a proton accelerator (1.5 GeV/∼10mA) coupled with windowless LBE spallation target. (author)

  5. Superradiant instability in AdS

    CERN Document Server

    Ganchev, Bogdan

    2016-01-01

    The phenomenon of superradiance in the context of asymptotically global AdS spacetimes is investigated with particular accent on its effect on the stability of the systems under consideration. To this end, the concept of an asymptotically AdS spacetime is explained, together with its implications on the boundary conditions at $\\mathcal{I}$, as well as the Newman-Penrose-Teukolsky formalism, whereby the Teukolsky master equation in a most general form for Kerr-AdS is given. Furthermore, work done in the cases of RN-AdS and Kerr-AdS is laid out in a concise manner, putting emphasis on the important steps taken in determining the endpoint of the superradiant instability in the two configurations. For the former this turns out to be a black hole with reduced charge and a static charged scalar condensate around it, whereas for the latter two of the more probable outcomes are presented, both of which imply a violation of one of the cosmic censorships.

  6. Belarus activity in ADS field

    International Nuclear Information System (INIS)

    Conclusions: • The YALINA facility is a unique installation which was designed as a zero power model of real ADS. • It is intended to study neutronics and kinetics of the sub-critical reactors driven by external neutron sources. • The successful operation of this facility is a scientific contribution from the Republic of Belarus, as well as the international team from EC and USA. • The experimental data are used to benchmark and validate methods and computer codes for designing and licensing ADS

  7. 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.

  8. 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)

  9. 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.

  10. Detection Parameters Design for Compound Survey Seafloor Targets by Multibeam Sonar

    Directory of Open Access Journals (Sweden)

    Li Hong Wu

    2013-08-01

    Full Text Available Swath bathymetry system surveys with wide swath, high location resolution, and is used to detect sea bottom terrain. But the object resolution detected decreases as the depth increasing, its data processing with high mistake, used rarely in sea floor object survey.So GeoSwath, a multibeam sonar does. Although it covers an angular range of -120°to 120 °from the vertical direction, providing high density and high quality bathymetry data along with side scan like amplitude imagery, the data processing is more relied on human intervention to get accurate depth contour and sonar image which prevent its propular use in survey of seafloor targets. The purpose of this article presents survey parameter setting during survey and data processing technique to survey seafloor target by GeoSwath system, which set the proper detect parameters including ping length, ship velocity to increase the points over targets, setting navigation line parallel to the maximum dimension of target during survey, adopting appropriate filter to depth data processing and using TVG control over amplitude data to get accurate depth grid and sonar image of seafloor target. Finally, the way is used to measure the artificial object in harbor and two ship wrecks at sea, compound with the sonar image taken by the forward looking sonar, to search the ship wreck near harbor, to help to recognize the targets and locates its real position. This technology improves GeoSwath survey capability with compound detection and is helpful for make precise map for waterway. Also this work is helpful to achieve detecting seafloor objects fast, accurately, effectively in underwater large scale area during salvation and rescue task.  

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

    Science.gov (United States)

    Shengsong, Xie; Yi, Zhang; Lisheng, Zhang; Guanglei, Li; Changzhi, Zhao; Pan, Ni; Shuhong, Zhao

    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. PMID:26582526

  12. 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.

  13. 多通道A/D转换控制模块的设计与实现%Implementation and Design of Multi-channel A/D Conversion Control Module

    Institute of Scientific and Technical Information of China (English)

    李言武

    2011-01-01

    The implementation and design of Multi-channel A/D Conversion Control module with MC143150 Neuron Chip and ADS7844 is put forward in this paper.The structure and principle of MC143150 Neuron Chip and ADS7844 are also given in detail,including collection,a%提出了利用MC143150 Neuron芯片和Burr-Brown公司生产的12位串行模数转换器ADS7844实现多通道A/D转换控制模块的设计与实现方法。介绍了MC143150 Neuron芯片和12位串行模数转换器ADS7844的硬件结构与工作原理,以及运用Neuron C语言开发多通道A/D转换控制模块,对数据转换结果的采集、分析与处理程序。通过长时间运行测试,该控制模块精度高、性能可靠,给现场自动化控制系统的集成带来较大的灵活性。

  14. Wireless Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Hong-Chuan Yang

    2007-01-01

    Full Text Available We study the energy-efficient configuration of multihop paths with automatic repeat request (ARQ mechanism in wireless ad hoc networks. We adopt a cross-layer design approach and take both the quality of each radio hop and the battery capacity of each transmitting node into consideration. Under certain constraints on the maximum tolerable transmission delay and the required packet delivery ratio, we solve optimization problems to jointly schedule the transmitting power of each transmitting node and the retransmission limit over each hop. Numerical results demonstrate that the path configuration methods can either significantly reduce the average energy consumption per packet delivery or considerably extend the average lifetime of the multihop route.

  15. Instability corners in AdS space

    CERN Document Server

    Dimitrakopoulos, Fotios V; Lippert, Matthew; Yang, I-Sheng

    2014-01-01

    We investigate whether arbitrarily small perturbations in global AdS space are generically unstable and collapse into black holes on the time scale set by gravitational interactions. We argue that current evidence, combined with our analysis, strongly suggests that a set of nonzero measure in the space of initial conditions does not collapse on this time scale. On the other hand, existing results do not provide an equally strong indication whether the unstable solutions also form a set of nonzero measure. We perform an analysis in position space to address this puzzle, and our formalism allows us to directly address the vanishing-amplitude limit. We show that gravitational self-interaction leads to tidal deformations which are equally likely to focus or defocus energy, and we sketch the phase diagram accordingly. We also clarify the connection between gravitational evolution in global AdS and holographic thermalization.

  16. Baby Skyrmions in AdS

    CERN Document Server

    Elliot-Ripley, Matthew

    2015-01-01

    We study the baby Skyrme model in a pure AdS background without a mass term. The tail decays and scalings of massless radial solutions are demonstrated to take a similar form to those of the massive flat space model, with the AdS curvature playing a similar role to the flat space pion mass. We also numerically find minimal energy solutions for a range of higher topological charges and find that they form concentric ring-like solutions. Popcorn transitions (named in analogy with studies of toy models of holographic QCD) from an n layer to an n+1-layer configuration are observed at topological charges 9 and 27 and further popcorn transitions for higher charges are predicted. Finally, a point-particle approximation for the model is derived and used to successfully predict the ring structures and popcorn transitions for higher charge solitons.

  17. Google Advertising Tools Cashing in with AdSense and AdWords

    CERN Document Server

    Davis, Harold

    2010-01-01

    With this book, you'll learn how to take full advantage of Google AdWords and AdSense, the sophisticated online advertising tools used by thousands of large and small businesses. This new edition provides a substantially updated guide to advertising on the Web, including how it works in general, and how Google's advertising programs in particular help you make money. You'll find everything you need to work with AdWords, which lets you generate text ads to accompany specific search term results, and AdSense, which automatically delivers precisely targeted text and image ads to your website.

  18. 无人机自组网系统设计与实现%Designing and Implementing Self-Organized Unmanned Aerial Vehicle(UAV)Ad Hoc Network

    Institute of Scientific and Technical Information of China (English)

    陈旿; 孙凯将; 张力; 肖鑫

    2009-01-01

    文章描述了一个无人机自组网验证系统.基于802.11b/g实现了无人机机载嵌入式Ad Hoc 模块.设计了一个面向小规模、网络拓朴结构快速变化的Ad Hoc网络距离矢量路由协议.优化了UDP协议,以适应将无线遥控信号在无线自组网环境中传输.实现了基于H.264的视频传输系统和基于离线数字证书的安全通信协议.

  19. Efficient Designer Nuclease-Based Homologous Recombination Enables Direct PCR Screening for Footprintless Targeted Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Sylvia Merkert

    2014-01-01

    Full Text Available Genetic engineering of human induced pluripotent stem cells (hiPSCs via customized designer nucleases has been shown to be significantly more efficient than conventional gene targeting, but still typically depends on the introduction of additional genetic selection elements. In our study, we demonstrate the efficient nonviral and selection-independent gene targeting in human pluripotent stem cells (hPSCs. Our high efficiencies of up to 1.6% of gene-targeted hiPSCs, accompanied by a low background of randomly inserted transgenes, eliminated the need for antibiotic or fluorescence-activated cell sorting selection, and allowed the use of short donor oligonucleotides for footprintless gene editing. Gene-targeted hiPSC clones were established simply by direct PCR screening. This optimized approach allows targeted transgene integration into safe harbor sites for more predictable and robust expression and enables the straightforward generation of disease-corrected, patient-derived iPSC lines for research purposes and, ultimately, for future clinical applications.

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

    CERN Document Server

    Aghamousa, Amir; Ahlen, Steve; Alam, Shadab; Allen, Lori E; Prieto, Carlos Allende; Annis, James; Bailey, Stephen; Balland, Christophe; Ballester, Otger; Baltay, Charles; Beaufore, Lucas; Bebek, Chris; Beers, Timothy C; Bell, Eric F; Bernal, José Luis; Besuner, Robert; Beutler, Florian; Blake, Chris; Bleuler, Hannes; Blomqvist, Michael; Blum, Robert; Bolton, Adam S; Briceno, Cesar; Buckley-Geer, Elizabeth; Burden, Angela; Burtin, Etienne; Busca, Nicolas G; Cahn, Robert N; Cai, Yan-Chuan; Carlberg, Raymond G; Carton, Pierre-Henri; Casas, Ricard; Castander, Francisco J; Claybaugh, Todd M; Close, Madeline; Coker, Carl T; Cole, Shaun; Cooper, Andrew P; Cousinou, M -C; Crocce, Martin; Cuby, Jean-Gabriel; Cunningham, Daniel P; Davis, Tamara; Dawson, Kyle S; de la Macorra, Axel; De Vicente, Juan; Delubac, Timothée; Derwent, Mark; Dey, Arjun; Dhungana, Govinda; Ding, Zhejie; Duan, Yutong T; Ealet, Anne; Edelstein, Jerry; Eftekharzadeh, Sarah; Eisenstein, Daniel J; Elliott, Ann; Escoffier, Stephanie; Evatt, Matthew; Fagrelius, Parker; Fan, Xiaohui; Fanning, Kevin; Farahi, Arya; Favole, Ginevra; Feng, Yu; Fernandez, Enrique; Findlay, Joseph R; Finkbeiner, Douglas P; Fitzpatrick, Michael J; Flaugher, Brenna; Flender, Samuel; Font-Ribera, Andreu; Forero-Romero, Jaime E; Fosalba, Pablo; Frenk, Carlos S; Fumagalli, Michele; Garcia-Bellido, Juan; Gaztanaga, Enrique; Gershkovich, Irina; Gillet, Denis; Gonzalez-de-Rivera, Guillermo; Gonzalez-Perez, Violeta; Gott, Shelby; Graur, Or; Gutierrez, Gaston; Guy, Julien; Habib, Salman; Heetderks, Henry; Heetderks, Ian; Heitmann, Katrin; Hellwing, Wojciech A; Herrera, David A; Ho, Shirley; Honscheid, Klaus; Huff, Eric; Hutchinson, Timothy A; Huterer, Dragan; Hwang, Ho Seong; Laguna, Joseph Maria Illa; Ishikawa, Yuzo; Jacobs, Dianna; Jeffrey, Niall; Jelinsky, Patrick; Jiang, Linhua; Jimenez, Jorge; Johnson, Jennifer; Joyce, Richard; Jullo, Eric; Juneau, Stephanie; Kama, Sami; Karcher, Armin; Karkar, Sonia; Kehoe, Robert; Kennamer, Noble; Kent, Stephen; Kilbinger, Martin; Kim, Alex G; Kirkby, David; Kisner, Theodore; Kitanidis, Ellie; Kneib, Jean-Paul; Koposov, Sergey; Kovacs, Eve; Kremin, Anthony; Kron, Richard; Kronig, Luzius; Kueter-Young, Andrea; Lacey, Cedric G; Lafever, Robin; Lahav, Ofer; Lambert, Andrew; Landriau, Martin; Lang, Dustin; Name, Publication; Lauer, Tod R; Goff, Jean-Marc Le; Guillou, Laurent Le; Van Suu, Auguste Le; Lee, Jae Hyeon; Lee, Su-Jeong; Leitner, Daniela; Levi, Michael E; L'Huillier, Benjamin; Li, Baojiu; Liang, Ming; Lin, Huan; Linder, Eric; Loebman, Sarah R; Lukić, Zarija; MacCrann, Niall; Magneville, Christophe; Makarem, Laleh; Manera, Marc; Manser, Christopher J; Marshall, Robert; Martini, Paul; Massey, Richard; Matheson, Thomas; McCauley, Jeremy; McDonald, Patrick; McGreer, Ian D; Meisner, Aaron; Metcalfe, Nigel; Miller, Timothy N; Miquel, Ramon; Moustakas, John; Myers, Adam; Naik, Milind; Newman, Jeffrey; Nichol, Robert C; Nicola, Andrina; da Costa, Luiz Nicolati; Niz, Gustavo; Norberg, Peder; Nord, Brian; Norman, Dara; Nugent, Peter; O'Brien, Thomas; Oh, Minji; Olsen, Knut A G; Padilla, Cristobal; Padmanabhan, Hamsa; Padmanabhan, Nikhil; Palanque-Delabrouille, Nathalie; Palmese, Antonella; Pappalardo, Daniel; Park, Changbom; Patej, Anna; Peacock, John A; Peiris, Hiranya V; Percival, Will J; Perruchot, Sandrine; Pieri, Matthew M; Pogge, Richard; Poppett, Claire; Probst, Ronald G; Rabinowitz, David; Ree, Chang Hee; Refregier, Alexandre; Regal, Xavier; Reid, Beth; Reil, Kevin; Rezaie, Mehdi; Rockosi, Connie; Roe, Natalie; Ronayette, Samuel; Roodman, Aaron; Ross, Ashley J; Ross, Nicholas P; Rossi, Graziano; Rozo, Eduardo; Ruhlmann-Kleider, Vanina; Rykoff, Eli; Sabiu, Cristiano; Samushia, Lado; Sanchez, Javier; Schlegel, David J; Schneider, Michael; Schubnell, Michael; Secroun, Aurélia; Seljak, Uros; Seo, Hee-Jong; Serrano, Santiago; Shafieloo, Arman; Shan, Huanyuan; Sholl, Michael J; Shourt, William V; Silber, Joseph H; Silva, David R; Sirk, Martin M; Slosar, Anze; Smith, Alex; Smoot, George; Som, Debopam; Song, Yong-Seon; Sprayberry, David; Staten, Ryan; Stefanik, Andy; Tarle, Gregory; Tie, Suk Sien; Tinker, Jeremy L; Tojeiro, Rita; Valdes, Francisco; Valenzuela, Octavio; Valluri, Monica; Vargas-Magana, Mariana; Verde, Licia; Walker, Alistair R; Wang, Yuting; Weaver, Benjamin A; Weaverdyck, Curtis; Wechsler, Risa; Weinberg, David H; White, Martin; Yang, Qian; Yeche, Christophe; Zhao, Gong-Bo; Zheng, Yi; Zhu, Yaling; Zou, Hu; Zu, Ying

    2016-01-01

    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 galaxie...

  1. Optimal de novo design of MRM experiments for rapid assay development in targeted proteomics.

    Science.gov (United States)

    Bertsch, Andreas; Jung, Stephan; Zerck, Alexandra; Pfeifer, Nico; Nahnsen, Sven; Henneges, Carsten; Nordheim, Alfred; Kohlbacher, Oliver

    2010-05-01

    Targeted proteomic approaches such as multiple reaction monitoring (MRM) overcome problems associated with classical shotgun mass spectrometry experiments. Developing MRM quantitation assays can be time consuming, because relevant peptide representatives of the proteins must be found and their retention time and the product ions must be determined. Given the transitions, hundreds to thousands of them can be scheduled into one experiment run. However, it is difficult to select which of the transitions should be included into a measurement. We present a novel algorithm that allows the construction of MRM assays from the sequence of the targeted proteins alone. This enables the rapid development of targeted MRM experiments without large libraries of transitions or peptide spectra. The approach relies on combinatorial optimization in combination with machine learning techniques to predict proteotypicity, retention time, and fragmentation of peptides. The resulting potential transitions are scheduled optimally by solving an integer linear program. We demonstrate that fully automated construction of MRM experiments from protein sequences alone is possible and over 80% coverage of the targeted proteins can be achieved without further optimization of the assay. PMID:20201589

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-12-14

    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.

  3. 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.

  4. Green design "bioinspired disassembly-reassembly strategy" applied for improved tumor-targeted anticancer drug delivery.

    Science.gov (United States)

    Wang, Ruoning; Gu, Xiaochen; Zhou, Jianping; Shen, Lingjia; Yin, Lifang; Hua, Peiying; Ding, Yang

    2016-08-10

    In this study, a simple and green approach 'bioinspired disassembly-reassembly strategy' was employed to reconstitute lipoprotein nanoparticles (RLNs) using whole-components of endogenous ones (contained dehydrated human lipids and native apolipoproteins). These RLNs were engineered to mimic the configuration and properties of natural lipoproteins for efficient drug delivery. In testing therapeutic targeting to microtubules, paclitaxel (PTX) was reassembled into RLNs to achieve improved targeted anti-carcinoma treatment and minimize adverse effects, demonstrating ultimately more applicable than HDL-like particles which are based on exogenous lipid sources. We have characterized that apolipoprotein-decoration of PTX-loaded RLNs (RLNs-PTX) led to favoring uniformly dispersed distribution, increasing PTX-encapsulation with a sustained-release pattern, while enhancing biostability during blood circulation. The innate biological RLNs induced efficient intracellular trafficking of cargos in situ via multi-targeting mechanisms, including scavenger receptor class B type I (SR-BI)-mediated direct transmembrane delivery, as well as other lipoprotein-receptors associated endocytic pathways. The resulting anticancer treatment from RLNs-PTX was demonstrated a half-maximal inhibitory concentration of 0.20μg/mL, cell apoptosis of 18.04% 24h post-incubation mainly arresting G2/M cell cycle in vitro, and tumor weight inhibition of 70.51% in vivo. Collectively, green-step assembly-based RLNs provided an efficient strategy for mediating tumor-targeted accumulation of PTX and enhanced anticancer efficacy. PMID:27238442

  5. Design, synthesis and preliminary biological evaluation of brain targeting L-ascorbic acid prodrugs of ibuprofen

    Institute of Scientific and Technical Information of China (English)

    Xue-Ying Wu; Xiao-Cen Li; Jie Mi; Jing You; Li Hai

    2013-01-01

    L-Ascorbic acid (AA,vitamin C) exhibits a high concentration in the brain.The transportation of AA in brain is mainly mediated by the glucose transporter 1 (GLUT1) and the Na+-dependent vitamin C transporter SVCT2.While L-ascorbic acid C6-O conjugation has been investigated as a tool to enhance brain drug delivery,C5-O conjugation and C5-O & C6-O conjugation as brain targeting tools have not been reported.In this letter,ibuprofen was linked directly to C5-O,C6-O and C5-O & C6-O positions of L-ascorbic acid with eater bonds,providing prodrug 1,2 and 3,respectively,to improve their targeting abilities in the brain.Prodrug 1,2 and 3 were synthesized in facile ways with good yields.And the preliminary evaluation in vivo illustrated that prodrug 2 had a better targeting ability than prodrug 1.Moreover,prodrug 3,whose C5-O & C6-O positions were both modified,had good targeting ability for brain which will provide an important evidence for our further study on C5-O-& C6-O-di-derivatives of L-ascorbic acid.

  6. Design of High-Neutron-Yield, Polar-drive targets for diagnostic activation experiments on the NIF

    Energy Technology Data Exchange (ETDEWEB)

    McKenty, P W; Craxton, R S; Marshall, F J; Sangster, T C; Marozas, J A; Cok, A M; Bonino, M J; Harding, D R; Meyerhofer, D D; McCrory, R L [Laboratory for Laser Energetics, University of Rochester, 250 E. River Road, Rochester, NY 14623 (United States); Kilkenny, J D; Nikroo, A; Fooks, J; Hoppe, M L [General Atomics Corporation, La Jolla, CA (United States); Edwards, J M; MacKinnon, A J; Munro, D H; Wallace, R J, E-mail: pmck@lle.rochester.ed [Lawrence Livermore National Laboratory, Livermore, CA (United States)

    2010-08-01

    Polar-drive (PD) target implosions have been designed for neutron diagnostic development on the NIF. These experiments use thin, room-temperature glass shells filled with low pressures of DT. Initial target implosions on the NIF will produce DT yields in the range of a few 10{sup 14} neutrons. The predicted yields are consistent with earlier data (10{sup 14} neutrons at 30 kJ) and recent PD scoping experiments performed on OMEGA. The experiments will use existing x-ray-drive phase plates with judicious repointing and defocusing to drive the implosions as uniformly as possible. These implosions have been modeled with three codes: LILAC, to optimize the 1-D design; SAGE, to optimize the pointing uniformity; and DRACO, to predict the yield from 2-D implosion simulations. Current simulation results indicate that the required yields will be obtained using up to 200-kJ UV light formed into a 1500-ps Gaussian pulse. Large-diameter glass shells ({approx}1500-{mu}m OD) are under development and fabrication at General Atomics. As tritium and environmental conditions evolve, similar target designs, with larger diameters and higher laser energies, are expected to produce thermonuclear yields approaching 10{sup 16} neutrons.

  7. Targeted transcriptional activation of silent oct4 pluripotency gene by combining designer TALEs and inhibition of epigenetic modifiers.

    Science.gov (United States)

    Bultmann, Sebastian; Morbitzer, Robert; Schmidt, Christine S; Thanisch, Katharina; Spada, Fabio; Elsaesser, Janett; Lahaye, Thomas; Leonhardt, Heinrich

    2012-07-01

    Specific control of gene activity is a valuable tool to study and engineer cellular functions. Recent studies uncovered the potential of transcription activator-like effector (TALE) proteins that can be tailored to activate user-defined target genes. It remains however unclear whether and how epigenetic modifications interfere with TALE-mediated transcriptional activation. We studied the activity of five designer TALEs (dTALEs) targeting the oct4 pluripotency gene. In vitro assays showed that the five dTALEs that target distinct sites in the oct4 promoter had the expected DNA specificity and comparable affinities to their corresponding DNA targets. In contrast to their similar in vitro properties, transcriptional activation of oct4 by these distinct dTALEs varied up to 25-fold. While dTALEs efficiently upregulated transcription of the active oct4 promoter in embryonic stem cells (ESCs) they failed to activate the silenced oct4 promoter in ESC-derived neural stem cells (NSCs), indicating that as for endogenous transcription factors also dTALE activity is limited by repressive epigenetic mechanisms. We therefore targeted the activity of epigenetic modulators and found that chemical inhibition of histone deacetylases by valproic acid or DNA methyltransferases by 5-aza-2'-deoxycytidine facilitated dTALE-mediated activation of the epigenetically silenced oct4 promoter in NSCs. Notably, demethylation of the oct4 promoter occurred only if chemical inhibitors and dTALEs were applied together but not upon treatment with inhibitors or dTALEs only. These results show that dTALEs in combination with chemical manipulation of epigenetic modifiers facilitate targeted transcriptional activation of epigenetically silenced target genes.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Defang; Min, Guanghui; Wu, Yan; Yu, Huashun; Zhang, Lin, E-mail: zhanglin2007@sdu.edu.cn

    2015-07-25

    Highlights: • High-purity LaB{sub 6} powder was prepared due to significant reduction of residual B{sub 4}C and effective purification process. • The effects of raw materials ratio on the size, morphology, phase structure and crystalline size of LaB{sub 6} were studied. • The correlation of component between LaB{sub 6} films and boron-rich targets was established. • The variation of densities of LaB{sub 6} targets with sintering time and sintering temperature was investigated. - Abstract: Lanthanum Hexaboride (LaB{sub 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{sub 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{sub 6} powder. As raising the content of La{sub 2}O{sub 3} in reactants, more uniform, finer (2.686 μm) and purer (99.5139 wt%) LaB{sub 6} powder is prepared, with only 0.4434 wt% residual B{sub 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{sub 6} nano-film which is tentatively considered to be composed of LaB{sub 6} nanocrystalline and amorphous microstructure of La and B atoms. The film LaB{sub 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.

  9. AdS solutions through transgression

    Energy Technology Data Exchange (ETDEWEB)

    Donos, A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Gauntlett, J.P. [Imperial College, London (United Kingdom). Blackett Lab.]|[Imperial College, London (United Kingdom). The Institute for Mathematical Sciences; Kim, Nakwoo [Kyung Hee Univ., Seoul (Korea). Dept. of Physics and Research Inst. of Basic Science

    2008-07-15

    We present new classes of explicit supersymmetric AdS{sub 3} solutions of type IIB supergravity with non-vanishing five-form flux and AdS{sub 2} solutions of D=11 supergravity with electric four-form flux. The former are dual to two-dimensional SCFTs with (0,2) supersymmetry and the latter to supersymmetric quantum mechanics with two supercharges. We also investigate more general classes of AdS{sub 3} solutions of type IIB supergravity and AdS{sub 2} solutions of D=11 supergravity which in addition have non-vanishing three-form flux and magnetic four-form flux, respectively. The construction of these more general solutions makes essential use of the Chern-Simons or ''transgression'' terms in the Bianchi identity or the equation of motion of the field strengths in the supergravity theories. We construct infinite new classes of explicit examples and for some of the type IIB solutions determine the central charge of the dual SCFTs. The type IIB solutions with non-vanishing three-form flux that we construct include a two-torus, and after two T-dualities and an S-duality, we obtain new AdS3 solutions with only the NS fields being non-trivial. (orig.)

  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. Application Analysis of Ad Lamp-box Controller

    Institute of Scientific and Technical Information of China (English)

    FANG Yuan; LU Bin

    2014-01-01

    The ad lamp-box controller is designed in consideration that ordinary urban ad lights usually remain lit through the night and a specially assigned staff needs to be on duty to control their switches. It can be automatically controlled with a photo resistance testing the day and night as well as a CD4060 chip controlling the length of time interval between switching the ad lamp-boxes on and off. In this way, both energy and labor can be saved with the controller. It is matching with the target of“constructing a conservation-minded society”in our country and deserves to be promoted in market with its practical signifi-cance.

  12. Using Wikipedia categories for ad hoc search

    NARCIS (Netherlands)

    R. Kaptein; M. Koolen; J. Kamps

    2009-01-01

    In this paper we explore the use of category information for ad hoc retrieval in Wikipedia. We show that techniques for entity ranking exploiting this category information can also be applied to ad hoc topics and lead to significant improvements. Automatically assigned target categories are good sur

  13. Design of antibody-functionalized carbon nanotubes filled with radioactivable metals towards a targeted anticancer therapy

    Science.gov (United States)

    Spinato, Cinzia; Perez Ruiz de Garibay, Aritz; Kierkowicz, Magdalena; Pach, Elzbieta; Martincic, Markus; Klippstein, Rebecca; Bourgognon, Maxime; Wang, Julie Tzu-Wen; Ménard-Moyon, Cécilia; Al-Jamal, Khuloud T.; Ballesteros, Belén; Tobias, Gerard; Bianco, Alberto

    2016-06-01

    In the present work we have devised the synthesis of a novel promising carbon nanotube carrier for the targeted delivery of radioactivity, through a combination of endohedral and exohedral functionalization. Steam-purified single-walled carbon nanotubes (SWCNTs) have been initially filled with radioactive analogues (i.e. metal halides) and sealed by high temperature treatment, affording closed-ended CNTs with the filling material confined in the inner cavity. The external functionalization of these filled CNTs was then achieved by nitrene cycloaddition and followed by the derivatization with a monoclonal antibody (Cetuximab) targeting the epidermal growth factor receptor (EGFR), overexpressed by several cancer cells. The targeting efficiency of the so-obtained conjugate was evaluated by immunostaining with a secondary antibody and by incubation of the CNTs with EGFR positive cells (U87-EGFR+), followed by flow cytometry, confocal microscopy or elemental analyses. We demonstrated that our filled and functionalized CNTs can internalize more efficiently in EGFR positive cancer cells.In the present work we have devised the synthesis of a novel promising carbon nanotube carrier for the targeted delivery of radioactivity, through a combination of endohedral and exohedral functionalization. Steam-purified single-walled carbon nanotubes (SWCNTs) have been initially filled with radioactive analogues (i.e. metal halides) and sealed by high temperature treatment, affording closed-ended CNTs with the filling material confined in the inner cavity. The external functionalization of these filled CNTs was then achieved by nitrene cycloaddition and followed by the derivatization with a monoclonal antibody (Cetuximab) targeting the epidermal growth factor receptor (EGFR), overexpressed by several cancer cells. The targeting efficiency of the so-obtained conjugate was evaluated by immunostaining with a secondary antibody and by incubation of the CNTs with EGFR positive cells (U87

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

    International Nuclear Information System (INIS)

    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)

  15. Design of hypoxia-targeting radiopharmaceuticals: selective uptake of copper-64 complexes in hypoxic cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Dearling, J.L.J.; Lewis, J.S.; Mullen, G.E.D.; Rae, M.T. [Biosciences Dept., University of Kent, Canterbury (United Kingdom); Zweit, J. [Joint Dept of Physics, Institute of Cancer Research, Sutton (United Kingdom); Blower, P.J. [Biosciences Dept., University of Kent, Canterbury (United Kingdom)]|[Nuclear Medicine Dept, Kent and Canterbury Hospital, Canterbury (United Kingdom)

    1998-07-01

    The well-known perfusion tracer CuPTSM, labelled with {sup 62}Cu or {sup 64}Cu, is believed to be trapped in cells non-selectively by a bioreductive mechanism. It is proposed that by modifying the ligand to increase its electron donor strength (for example by adding alkyl functionality or replacing sulphur ligands with oxygen ligands), the copper complexes will become less easily reduced and tracers with selectivity for hypoxic tissues could thus be developed. The aim of this work was to prepare {sup 64}Cu-labelled complexes of two series of ligands, based on the bis(thiosemicarbazone) (13 ligands) and bis(salicylaldimine) (3 ligands) skeletons, and to evaluate the hypoxia dependence of their uptake in cells. The complexes were incubated with Chinese hamster ovary cells under normoxic and hypoxic conditions, and the cells isolated by centrifugation to determine radioactivity uptake at various time points up to 90 min. Several members of both series demonstrated significant (P<0.05) or highly significant (P<0.01) hypoxia selectivity, indicating that both series of complexes offer a basis for development of hypoxia-targeting radiopharmaceuticals for positron emission tomography ({sup 60}Cu, {sup 61}Cu, {sup 62}Cu, {sup 64}Cu) and targeted radiotherapy ({sup 64}Cu, {sup 67}Cu). (orig.) With 5 figs., 1 tab., 10 refs.

  16. Design and Implementation of a Storage Virtualization System Based on SCSI Target Simulator in SAN

    Institute of Scientific and Technical Information of China (English)

    LI Bigang; SHU Jiwu; ZHENG Weimin

    2005-01-01

    The ideal storage virtualization system is compatible with all operating systems in storage area networks (SANs). However, current storage systems on clustered hosts and multiple operating systems are not practical. This paper presents a storage virtualization system based on a SCSI target simulator in a SAN to solve these problems. This storage virtualization system runs in the target hosts of the SAN, dynamically stores the physical information, and uses the mapping table method to modify the SCSI command addresses. The system uses the bitmap technique to manage the free space. The storage virtualization system provides various functions, such as logical volume resizing, data mirroring, and snapshots, and is compatible with clustered hosts and multiple operating systems, such as Windows NT and RedHat.

  17. Validation of a Computer Code for Use in the Mechanical Design of Spallation Neutron Targets

    CERN Document Server

    Montanez, P A

    2000-01-01

    The present work concentrates on comparing a numerical code and a closed-form analytic solution for determining transient stress waves generated by an impinging, high-intensity proton pulse onto a perfectly elastic solid cylindrical target. The comparison of the two methods serves both to benchmark the physics and numerical methods of the codes, and to verify them against analytic expressions that can be established for calculating the response of the target for simple cases of loading and geometry. Additionally, the comparison elucidated the effects of approximations used in the computation of the analytic results. Two load cases have been investigated: (1) an instantaneously uniform thermal loading along the central core, and (2) a ramped and uniform thermal load applied along the central core. In addition, the influence of the approximations applied to the accurate analytic forms has been elucidated. By validating these analytical results, the closed-form solution may be confidently used to "bound" the sol...

  18. Rational Design of Targeted Next-Generation Carriers for Drug and Vaccine Delivery.

    Science.gov (United States)

    Narasimhan, Balaji; Goodman, Jonathan T; Vela Ramirez, Julia E

    2016-07-11

    Pattern recognition receptors on innate immune cells play an important role in guiding how cells interact with the rest of the organism and in determining the direction of the downstream immune response. Recent advances have elucidated the structure and function of these receptors, providing new opportunities for developing targeted drugs and vaccines to treat infections, cancers, and neurological disorders. C-type lectin receptors, Toll-like receptors, and folate receptors have attracted interest for their ability to endocytose their ligands or initiate signaling pathways that influence the immune response. Several novel technologies are being developed to engage these receptors, including recombinant antibodies, adoptive immunotherapy, and chemically modified antigens and drug delivery vehicles. These active targeting technologies will help address current challenges facing drug and vaccine delivery and lead to new tools to treat human diseases.

  19. A design of space robot multi-target capture algorithm based on DSP

    Institute of Scientific and Technical Information of China (English)

    MA Xiao-na; HU Bing-liang; LIU Xue-bin; LIU Hui; LIU Qian-wen

    2009-01-01

    To correctly capture spatial targets from cluttered and motive celestial background, a new Multi-Target Capture algorithm was proposed, which is a comparative difference algorithm based on the combination of centroid extraction and despun registration of efficient points. Moreover, this algorithm was applied in an image processing system based on the DSP featuring high speed and high performance. The procedures of image processing are as follows: first, label efficient points in the frame and extract their centroids; second, make appropriate despun registration, according to the reference rotation angles provided by Space Robot position system; third, translate and register centroid coordinates of efficient points in reference frames and get the registration points according to the principle that there are the most same centroid coordinates of efficient points when completely registered; finally, eliminate the same background points by using comparative difference method. The result shows that this image processing system can meet the needs of the whole system.

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

    OpenAIRE

    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 ...

  1. Design of nanodrugs for miRNA targeting in tumor cells (13-510-R)

    OpenAIRE

    Yoo, Byunghee; Ghosh, Subrata K.; Kumar, Mohanraja; Moore, Anna; Yigit, Mehmet V.; Medarova, Zdravka

    2014-01-01

    The delivery of oligonucleotide antagonists to cytosolic RNA targets such as microRNA represents an avenue for the post-transcriptional control of cellular phenotype. In tumor cells, oncogenic miRNAs, termed oncomirs, are tightly linked to processes that ultimately determine cancer initiation, progression, and response to therapy. Therefore, the capacity to redirect tumor cell fate towards therapeutically beneficial phenotypes holds promise in a future clinical scenario. Previously, we have d...

  2. 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.

  3. GNC architecture for autonomous robotic capture of a non-cooperative target: Preliminary concept design

    Science.gov (United States)

    Jankovic, Marko; Paul, Jan; Kirchner, Frank

    2016-04-01

    Recent studies of the space debris population in low Earth orbit (LEO) have concluded that certain regions have already reached a critical density of objects. This will eventually lead to a cascading process called the Kessler syndrome. The time may have come to seriously consider active debris removal (ADR) missions as the only viable way of preserving the space environment for future generations. Among all objects in the current environment, the SL-8 (Kosmos 3M second stages) rocket bodies (R/Bs) are some of the most suitable targets for future robotic ADR missions. However, to date, an autonomous relative navigation to and capture of an non-cooperative target has never been performed. Therefore, there is a need for more advanced, autonomous and modular systems that can cope with uncontrolled, tumbling objects. The guidance, navigation and control (GNC) system is one of the most critical ones. The main objective of this paper is to present a preliminary concept of a modular GNC architecture that should enable a safe and fuel-efficient capture of a known but uncooperative target, such as Kosmos 3M R/B. In particular, the concept was developed having in mind the most critical part of an ADR mission, i.e. close range proximity operations, and state of the art algorithms in the field of autonomous rendezvous and docking. In the end, a brief description of the hardware in the loop (HIL) testing facility is made, foreseen for the practical evaluation of the developed architecture.

  4. 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.

  5. 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

  6. Refined Holographic Entanglement Entropy for the AdS Solitons and AdS black Holes

    CERN Document Server

    Ishihara, Masafumi; Ning, Bo

    2012-01-01

    We consider the refinement of the holographic entanglement entropy on a disk region for the holographic dual theories to the AdS solitons and AdS black holes, including the corrected ones by the Gauss-Bonnet term. The AdS soliton is dual to a gapped system with an IR fixed-point. The refinement is obtained by extracting the UV-independent piece of the holographic entanglement entropy. We then study the renormalization group (RG) flow of the refinement by tuning the linear size of the chosen disk region. Our main results are (i) the RG flow of the refinement decreases monotonically for most of the cases; (ii) there is no topological entanglement entropy for AdS$_5$ soliton even with Gauss-Bonnet correction; (iii) for the AdS black holes, the refinement obeys the volume law at IR regime, and the transition between UV and IR regimes is a smooth crossover; however, the crossover will turn into phase transition by the Gauss-Bonnet correction; (iv) for the AdS solitons, there are discontinuous phase transitions bet...

  7. Refined holographic entanglement entropy for the AdS solitons and AdS black holes

    International Nuclear Information System (INIS)

    We consider the refinement of the holographic entanglement entropy for the holographic dual theories to the AdS solitons and AdS black holes, including the corrected ones by the Gauss–Bonnet term. The refinement is obtained by extracting the UV-independent piece of the holographic entanglement entropy, the so-called renormalized entanglement entropy which is independent of the choices of UV cutoff. Our main results are: (i) the renormalized entanglement entropies of the AdSd+1 soliton for d=4,5 are neither monotonically decreasing along the RG flow nor positive-definite, especially around the deconfinement/confinement phase transition; (ii) there is no topological entanglement entropy for AdS5 soliton even with Gauss–Bonnet correction; (iii) for the AdS black holes, the renormalized entanglement entropy obeys an expected volume law at IR regime, and the transition between UV and IR regimes is a smooth crossover even with Gauss–Bonnet correction; (iv) based on AdS/MERA conjecture, we postulate that the IR fixed-point state for the non-extremal AdS soliton is a trivial product state

  8. Predicting AD conversion

    DEFF Research Database (Denmark)

    Liu, Yawu; Mattila, Jussi; Ruiz, Miguel �ngel Mu�oz;

    2013-01-01

    To compare the accuracies of predicting AD conversion by using a decision support system (PredictAD tool) and current research criteria of prodromal AD as identified by combinations of episodic memory impairment of hippocampal type and visual assessment of medial temporal lobe atrophy (MTA) on MRI...

  9. A Rational Design Strategy for the Selective Activity Enhancement of a Molecular Chaperone toward a Target Substrate.

    Science.gov (United States)

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

    2015-08-18

    Molecular chaperones facilitate the folding and assembly of proteins and inhibit their aberrant aggregation. They thus offer several opportunities for biomedical and biotechnological applications, as for example they can often prevent protein aggregation more effectively than other therapeutic molecules, including small molecules and antibodies. Here we present a method of designing molecular chaperones with enhanced activity against specific amyloidogenic substrates while leaving unaltered their functions toward other substrates. The method consists of grafting onto a molecular chaperone a peptide designed to bind specifically an epitope in the target substrate. We illustrate this strategy by describing Hsp70 variants with increased affinities for α-synuclein and Aβ42 but otherwise unaltered affinities for other substrates. These designed variants inhibit protein aggregation and disaggregate preformed fibrils significantly more effectively than wild-type Hsp70 indicating that the strategy presented here provides a possible route for tailoring rationally molecular chaperones for specific purposes.

  10. Urokinase-targeted recombinant bacterial protein toxins-a rationally designed and engineered anticancer agent for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Yizhen LIU; Shi-Yan LI

    2009-01-01

    Urokinase-targeted recombinant bacterial protein toxins are a sort of rationally designed and engineered anticancer recombinant fusion proteins representing a novel class of agents for cancer therapy.Bacterial protein toxins have long been known as the primary virulence factor(s) for a variety of pathogenic bacteria and are the most powerful human poisons.On the other hand,it has been well documented that urokinase-type plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR),making up the uPA system,are overexpressed in a variety of human tumors and tumor cell lines.The expression of uPA system is highly correlated with tumor invasion and metastasis.To exploit these characteristics in the design of tumor cell-selective cytotoxins,two prominent bacterial protein toxins,i.e.,the diphtheria toxin and anthrax toxin are deliberately engineered through placing a sequence targeted specifically by the uPA system to form anticancer recombinant fusion proteins.These uPA system-targeted bacterial protein toxins are activated selectively on the surface of uPA systemexpressing tumor cells,thereby killing these cells.This article provides a review on the latest progress in the exploitation of these recombinant fusion proteins as potent tumoricidal agents.It is perceptible that the strategies for cancer therapy are being innovated by this novel therapeutic approach.

  11. Design and conduct of early-phase radiotherapy trials with targeted therapeutics: Lessons from the PRAVO experience

    International Nuclear Information System (INIS)

    New strategies to facilitate the improvement of physical and integrated biological optimization of high-precision treatment protocols are an important priority for modern radiation oncology. From a clinical perspective, as knowledge accumulates from molecular radiobiology, there is a complex and exciting opportunity to investigate novel approaches to rational patient treatment stratification based on actionable tumor targets, together with the appropriate design of next-generation early-phase radiotherapy trials utilizing targeted therapeutics, to formally evaluate relevant clinical and biomarker endpoints. A unique aspect in the development pathway of systemic agents with presumed radiosensitizing activity will also be the need for special attention on patient eligibility and the rigorous definition of radiation dose–volume relationships and potential dose-limiting toxicities. Based on recent experience from systematically investigating histone deacetylase inhibitors as radiosensitizing agents, from initial studies in preclinical tumor models through the conduct of a phase I clinical study to evaluate tumor activity of the targeted agent as well as patient safety and tumor response to the combined treatment modality, this communication will summarize principles relating to early clinical evaluation of combining radiotherapy and targeted therapeutics

  12. Design and Characterization of Novel EphA2 Agonists for Targeted Delivery of Chemotherapy to Cancer Cells.

    Science.gov (United States)

    Wu, Bainan; Wang, Si; De, Surya K; Barile, Elisa; Quinn, Bridget A; Zharkikh, Irina; Purves, Angela; Stebbins, John L; Oshima, Robert G; Fisher, Paul B; Pellecchia, Maurizio

    2015-07-23

    The development of novel, targeted delivery agents for anti-cancer therapies requires the design and optimization of potent and selective tumor-targeting agents that are stable and amenable to conjugation with chemotherapeutic drugs. While short peptides represent potentially an excellent platform for these purposes, they often get degraded and are eliminated too rapidly in vivo. In this study, we used a combination of nuclear magnetic resonance-guided structure-activity relationships along with biochemical and cellular studies to derive a novel tumor-homing agent, named 123B9, targeting the EphA2 tyrosine kinase receptor ligand-binding domain. Conjugating 123B9 to the chemotherapeutic drug paclitaxel (PTX) via a stable linker results in an agent that is significantly more effective than the unconjugated drug in both a pancreatic cancer xenograft model and a melanoma lung colonization and metastases model. Hence, 123B9 could represent a promising strategy for the development of novel targeted therapies for cancer.

  13. Design and Characterization of Novel EphA2 Agonists for Targeted Delivery of Chemotherapy to Cancer Cells.

    Science.gov (United States)

    Wu, Bainan; Wang, Si; De, Surya K; Barile, Elisa; Quinn, Bridget A; Zharkikh, Irina; Purves, Angela; Stebbins, John L; Oshima, Robert G; Fisher, Paul B; Pellecchia, Maurizio

    2015-07-23

    The development of novel, targeted delivery agents for anti-cancer therapies requires the design and optimization of potent and selective tumor-targeting agents that are stable and amenable to conjugation with chemotherapeutic drugs. While short peptides represent potentially an excellent platform for these purposes, they often get degraded and are eliminated too rapidly in vivo. In this study, we used a combination of nuclear magnetic resonance-guided structure-activity relationships along with biochemical and cellular studies to derive a novel tumor-homing agent, named 123B9, targeting the EphA2 tyrosine kinase receptor ligand-binding domain. Conjugating 123B9 to the chemotherapeutic drug paclitaxel (PTX) via a stable linker results in an agent that is significantly more effective than the unconjugated drug in both a pancreatic cancer xenograft model and a melanoma lung colonization and metastases model. Hence, 123B9 could represent a promising strategy for the development of novel targeted therapies for cancer. PMID:26165155

  14. Winding Strings in AdS_3

    CERN Document Server

    Minces, P; Minces, Pablo; Nunez, Carmen

    2006-01-01

    Correlation functions of one-unit spectral flowed states in string theory on AdS_3 are considered. We present a formalism which allows to explicitly find the modified Knizhnik-Zamolodchikov and null vector equations to be satisfied by amplitudes of states in w=1 sectors. We give a precise prescription to solve this system of linear differential equations in cases that are relevant to obtain three and four point functions involving spectral flowed string states. We specifically compute three point functions with two and three one-unit spectral flowed operators and also discuss four point functions.

  15. Design-on-demand or how to create a target-oriented social web-site

    CERN Document Server

    Miszczak, Jarosław Adam

    2010-01-01

    We describe an informal methodology for developing on-line applications, which is, to some extent, complementary to the Web 2.0 aspects of web development. The presented methodology is suitable for developing low-cost and non-cost web sites targeted at medium-sized communities. We present basic building blocks used in the described strategy. To achieve a better understanding of the discussed concepts we comment on their application during the realization of two web projects. We focus on the role of community-driven development, which is crucial for projects of the discussed type.

  16. Biological characteristics of dengue virus and potential targets for drug design

    Institute of Scientific and Technical Information of China (English)

    Rui-feng Qi; Ling Zhang; Cheng-wu Chi

    2008-01-01

    Dengue infection is a major cause of morbidity in tropical and subtropical regions, bringing nearly 40% of the world population at risk and causing more than 20,000 deaths per year. But there is neither a vaccine for dengue disease nor antiviral drugs to treat the infection. In recent years, dengue infection has been particularly prevalent in India, Southeast Asia, Brazil, and Guangdong Province, China. In this article, we present a brief summary of the biological characteristics of dengue virus and associated flaviviruses, and outline the progress on studies of vaccines and drugs based on potential targets of the dengue virus.

  17. OptMAVEn – A New Framework for the de novo Design of Antibody Variable Region Models Targeting Specific Antigen Epitopes

    OpenAIRE

    Li, Tong; Pantazes, Robert J; Maranas, Costas D.

    2014-01-01

    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 method...

  18. Challenges of clinical trial design for targeted agents against pediatric leukemias

    Directory of Open Access Journals (Sweden)

    Francis Jay Mussai

    2015-01-01

    Full Text Available The past 40 years have seen significant improvements in both event-free and overall survival for children with acute lymphoblastic or acute myeloid leukemia (ALL or AML respectively. Serial national and international clinical trials have optimised the use of conventional chemotherapeutic drugs and, along with improvements in supportive care that have enabled the delivery of more intensive regimens, have been responsible for the major improvements in patient outcome seen over the past few decades,. The benefits of dose intensification, however, have likely now been maximised, and over the same period, the identification of new cytotoxic drugs has been limited.As the biology of leukemogenesis has become better understood, key molecules and intracellular pathways have been identified that offer the possibility of targeting directly the leukemia cells whilst sparing normal cells. Consequently, there is now a drive to develop novel leukemia-specific or ‘targeted’ therapies. These new classes of drugs will have mechanisms of action, toxicities and therapeutic indices quite different from conventional cytotoxic drugs previously encountered, thus rendering current clinical trial methodologies inappropriate; clinical trial methods will need to be adapted to accommodate these features of these new classes of drugs. This review will address the challenges and some of the techniques for developing clinical trials for targeted therapies.

  19. Analysis of Reverse Phase Protein Array Data: From Experimental Design towards Targeted Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Astrid Wachter

    2015-11-01

    Full Text Available Mastering the systematic analysis of tumor tissues on a large scale has long been a technical challenge for proteomics. In 2001, reverse phase protein arrays (RPPA were added to the repertoire of existing immunoassays, which, for the first time, allowed a profiling of minute amounts of tumor lysates even after microdissection. A characteristic feature of RPPA is its outstanding sample capacity permitting the analysis of thousands of samples in parallel as a routine task. Until today, the RPPA approach has matured to a robust and highly sensitive high-throughput platform, which is ideally suited for biomarker discovery. Concomitant with technical advancements, new bioinformatic tools were developed for data normalization and data analysis as outlined in detail in this review. Furthermore, biomarker signatures obtained by different RPPA screens were compared with another or with that obtained by other proteomic formats, if possible. Options for overcoming the downside of RPPA, which is the need to steadily validate new antibody batches, will be discussed. Finally, a debate on using RPPA to advance personalized medicine will conclude this article.

  20. 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)

    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

  1. AdCell: Ad Allocation in Cellular Networks

    CERN Document Server

    Alaei, Saeed; Liaghat, Vahid; Pei, Dan; Saha, Barna

    2011-01-01

    With more than four billion usage of cellular phones worldwide, mobile advertising has become an attractive alternative to online advertisements. In this paper, we propose a new targeted advertising policy for Wireless Service Providers (WSPs) via SMS or MMS- namely {\\em AdCell}. In our model, a WSP charges the advertisers for showing their ads. Each advertiser has a valuation for specific types of customers in various times and locations and has a limit on the maximum available budget. Each query is in the form of time and location and is associated with one individual customer. In order to achieve a non-intrusive delivery, only a limited number of ads can be sent to each customer. Recently, new services have been introduced that offer location-based advertising over cellular network that fit in our model (e.g., ShopAlerts by AT&T) . We consider both online and offline version of the AdCell problem and develop approximation algorithms with constant competitive ratio. For the online version, we assume tha...

  2. Development of design of CLA: target lens line-focusing system

    Science.gov (United States)

    Li, Xuechun; Zhu, Jianqiang

    1999-08-01

    In this paper the principle of CLA-target system to obtain focal line with homogenous intensity distribution was described. And tow new structure modal CLA used for improving the homogeneous of focal line was described and the numerical results of the classical CLA and new type CLA was also given. Those result showed that the focal line long-range intensity distribution can be improved greatly by using CLA with optimized unequal cylindrical lens element for beam with Gaussian intensity distribution and by using hybrid element CLA for the case of super-Gaussian distribution. The optimal process was treated by simulated annealing method. The intensity modulation decreased to 0.7 percent for optimized 4-element unequal width CLA system when incident laser with Gaussian section distribution.

  3. Korea's emission trading scheme and policy design issues to achieve market-efficiency and abatement targets

    International Nuclear Information System (INIS)

    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 CO2. • 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

  4. Application of stochastic method to optimum design of energy-efficient induction motors with a target of LCC

    Institute of Scientific and Technical Information of China (English)

    方攸同; 范承志; 叶云岳; 陈永校

    2003-01-01

    For an energy-efficient induction machine, the life-cycle cost (LCC) usually is the most important index to the consumer. With this target, the optimization design of a motor is a complex nonlinear problem with constraints. To solve the problem, the authors introduce a united random algorithm. At first, the problem is divided into two parts, the optimal rotor slots and the optimization of other dimensions. Before optimizing the rotor slots with genetic algorithm (GA), the second part is solved with TABU algorithm to simplify the problem. The numerical results showed that this method is better than the method using a traditional algorithm.

  5. Application of stochastic method to optimum design of energy-efficient induction motors with a target of LCC

    Institute of Scientific and Technical Information of China (English)

    方攸同; 范承志; 叶云岳; 陈永校

    2003-01-01

    For an energy-efficient induction machine, the life-cycle cost (LCC) usually is the most important index to the consumer. With this target, the optimization design of a motor is a complex nonlinear problem with constraints. To solve the problem, the authors introduce a united random algorithm. At first, the problem is divided into two parts, the optimal rotor slots and the optimization of other dimensions. Before optimizing the rotor slots with genetic algorithm ( GA), the second part is solved with TABU algorithm to simplify the problem. The numerical results showed that this method is better than the method using a traditional algorithm.

  6. Synthesis and Biological Evaluation of a Novel Pentagastrin- Toxin Conjugate Designed for a Targeted Prodrug Monotherapy of Cancer

    Directory of Open Access Journals (Sweden)

    Ingrid Schuberth

    2008-05-01

    Full Text Available A novel carbamate prodrug 2 containing a pentagastrin moiety was synthesized. 2 was designed as a detoxified analogue of the highly cytotoxic natural antibiotic duocarmycin SA (1 for the use in a targeted prodrug monotherapy of cancers expressing cholecystokinin (CCK-B/gastrin receptors. The synthesis of prodrug 2 was performed using a palladium-catalyzed carbonylation of bromide 6, followed by a radical cyclisation to give the pharmacophoric unit 10, coupling of 10 to the DNA-binding subunit 15 and transformation of the resulting seco-drug 3b into the carbamate 2 via addition of a pentagastrin moiety.

  7. Personas as a Powerful Methodology to Design Targeted Professional Development Resources

    CERN Document Server

    Madsen, Adrian; Sayre, Eleanor C; Martinuk, Matthew; Bell, Alexander

    2014-01-01

    Scaling and sustaining educational innovations is a common problem in the learning sciences. Professional development resources around educational innovations that are personalized to appeal to the needs and motivations of different types of faculty offer a possible solution. The method of developing personas to represent key types of users is commonly employed in user-interface design and can be used to produce personalized resources. Personas are fictional named archetypes of users encompassing generalizations of their key characteristics and goals that emerge from interviews. This method is especially powerful because personas succinctly package information into the form of a person, who is easily understood and reasoned about. Herein we describe the creation of a set of personas focusing on the needs and motivations of physics faculty around assessment and teaching. We present the personas, a discussion of how they inform our design and how the method can be used more broadly.

  8. 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.

  9. Numerical and Compact Modeling of Embedded Flash Memory Devices Targeted for IC Design

    OpenAIRE

    Garetto, Davide

    2012-01-01

    In a semiconductor market dominated by portable consumer applications, embedded flash memory technology has experienced a rapid diffusion. It is now considered the preferred solid-state memory solution for its non-volatile characteristics, high read and write speeds and scalability properties. As technology scales down in the nanometer range, new accurate physical tools should be made available to circuit designers, to support the development and ...

  10. 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.

  11. Crystals’ added value

    CERN Multimedia

    Antonella Del Rosso

    2012-01-01

    We are becoming used to the many applications that physics transfers to society. They span from vacuum techniques to electronics, and, of course, medicine and biophysics. The EU-supported PICOSEC project, of which CERN is the coordinator, goes beyond the simple spin-off technology and opens the doors of state-of-the-art crystal research to 22 researchers for applications that include calorimetry but also the next generation PET scanners.     Prototypes of crystal matrices developed for medical imaging projects.   The keyword is “multidisciplinary approach”. Developing new detectors for implementation in high-energy physics experiments but also in medical instrumentation requires a very diverse mixture of skills and competencies. Such a mixture does not necessarily come from a specific university faculty but rather from targeted training opportunities that are designed by several stakeholders, each one contributing with its own specificity. The PICOS...

  12. Structure-based drug design targeting the cell membrane receptor GPBAR1: exploiting the bile acid scaffold towards selective agonism

    Science.gov (United States)

    Di Leva, Francesco Saverio; Festa, Carmen; Renga, Barbara; Sepe, Valentina; Novellino, Ettore; Fiorucci, Stefano; Zampella, Angela; Limongelli, Vittorio

    2015-01-01

    Bile acids can regulate nutrient metabolism through the activation of the cell membrane receptor GPBAR1 and the nuclear receptor FXR. Developing an exogenous control over these receptors represents an attractive strategy for the treatment of enterohepatic and metabolic disorders. A number of dual GPBAR1/FXR agonists are known, however their therapeutic use is limited by multiple unwanted effects due to activation of the diverse downstream signals controlled by the two receptors. On the other hand, designing selective GPBAR1 and FXR agonists is challenging since the two proteins share similar structural requisites for ligand binding. Here, taking advantage of our knowledge of the two targets, we have identified through a rational drug design study a series of amine lithocholic acid derivatives as selective GPBAR1 agonists. The presence of the 3α-NH2 group on the steroidal scaffold is responsible for the selectivity over FXR unveiling unprecedented structural insights into bile acid receptors activity modulation. PMID:26567894

  13. Design of a TOF-SANS instrument for the proposed long-wavelength target station at the spallation neutron source

    CERN Document Server

    Littrell, K C; Carpenter, J M; Seeger, P A

    2002-01-01

    We have designed a versatile high-data-rate SANS instrument (broad-range intense multipurpose SANS (BRIMS)) for the proposed long-wavelength target station at the SNS using the Los Alamos NISP Monte Carlo simulation package. BRIMS is designed to produce data spanning a Q range from 0.0025 to 0.7 A sup - sup 1 in a single measurement by simultaneously using neutrons with wavelengths from 1 to 14.5 A in a time-of-flight mode. The effects of various collimation choices, including multiple confocal pinhole apertures, on count rate, resolution, and Q range have been characterized with simulations using spherical particle and delta-function scatterers. We compare the anticipated performance of BRIMS with that of the premier reactor-based SANS instrument, D22, at ILL. (orig.)

  14. Structure-based drug design targeting the cell membrane receptor GPBAR1: exploiting the bile acid scaffold towards selective agonism

    Science.gov (United States)

    di Leva, Francesco Saverio; Festa, Carmen; Renga, Barbara; Sepe, Valentina; Novellino, Ettore; Fiorucci, Stefano; Zampella, Angela; Limongelli, Vittorio

    2015-11-01

    Bile acids can regulate nutrient metabolism through the activation of the cell membrane receptor GPBAR1 and the nuclear receptor FXR. Developing an exogenous control over these receptors represents an attractive strategy for the treatment of enterohepatic and metabolic disorders. A number of dual GPBAR1/FXR agonists are known, however their therapeutic use is limited by multiple unwanted effects due to activation of the diverse downstream signals controlled by the two receptors. On the other hand, designing selective GPBAR1 and FXR agonists is challenging since the two proteins share similar structural requisites for ligand binding. Here, taking advantage of our knowledge of the two targets, we have identified through a rational drug design study a series of amine lithocholic acid derivatives as selective GPBAR1 agonists. The presence of the 3α-NH2 group on the steroidal scaffold is responsible for the selectivity over FXR unveiling unprecedented structural insights into bile acid receptors activity modulation.

  15. AdS3: the NHEK generation

    Science.gov (United States)

    Bena, Iosif; Heurtier, Lucien; Puhm, Andrea

    2016-05-01

    It was argued in [1] that the five-dimensional near-horizon extremal Kerr (NHEK) geometry can be embedded in String Theory as the infrared region of an infinite family of non-supersymmetric geometries that have D1, D5, momentum and KK monopole charges. We show that there exists a method to embed these geometries into asymptotically- {AdS}_3× {S}^3/{{Z}}_N solutions, and hence to obtain infinite families of flows whose infrared is NHEK. This indicates that the CFT dual to the NHEK geometry is the IR fixed point of a Renormalization Group flow from a known local UV CFT and opens the door to its explicit construction.

  16. Twistor methods for AdS$_5$

    CERN Document Server

    Adamo, Tim; Williams, Jack

    2016-01-01

    We consider the application of twistor theory to five-dimensional anti-de Sitter space. The twistor space of AdS$_5$ is the same as the ambitwistor space of the four-dimensional conformal boundary; the geometry of this correspondence is reviewed for both the bulk and boundary. A Penrose transform allows us to describe free bulk fields, with or without mass, in terms of data on twistor space. Explicit representatives for the bulk-to-boundary propagators of scalars and spinors are constructed, along with twistor action functionals for the free theories. Evaluating these twistor actions on bulk-to-boundary propagators is shown to produce the correct two-point functions.

  17. ADS National Programmes: Russian Federation

    International Nuclear Information System (INIS)

    Studies on accelerator driven systems (ADS), which be used as burners of long lived radioactive waste accrued due to operation of thermal reactors, first of all, minor actinides (MA), are carried out in some Russian research institutes (ITEP, SSC RF - IPPE, VNIIEF, JINR, RSC KI, IYaI RAN, OKB ‘GIDROPRESS’, VNIITF etc.). These researches are mainly connected with studying physical processes existing in ADS and their parameters and with design studies and substantiation of experimental ADS facilities. One of the most important directions of researches is the acquirement of quite precise and reliable nuclear data on MA with reference to conditions existing in ADS. Now a coordinated programme of researches on measurement and estimation of nuclear data for 22 isotopes of U, Pu, Np, Am, Cm, Bk and Cf in neutron energy range from 0.05 eV up to 30 MeV has been prepared. Development of different variants of ADS has put a task of comparison of their efficiency as burners of MA

  18. Acid-mediated Lipinski’s second rule: application to drug design and targeting in cancer

    OpenAIRE

    Omran, Ziad; Rauch, Cyril

    2014-01-01

    With a predicted 382.4 per 100,000 people expected to suffer from some form of malignant neoplasm by 2015, and a current death toll of 1 out of 8 deaths worldwide, improving treatment and/or drug design is an essential focus of cancer research. Multi-drug resistance is the leading cause of chemotherapeutic failure, and delivery of anticancer drugs to the inside of cancerous cells is another major challenge. Fifteen years ago, in a completely different field in which improving drug delivery is...

  19. 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.

  20. Amidated pectin/sodium carboxymethylcellulose microspheres as a new carrier for colonic drug targeting: Development and optimization by factorial design.

    Science.gov (United States)

    Gadalla, Hytham H; El-Gibaly, Ibrahim; Soliman, Ghareb M; Mohamed, Fergany A; El-Sayed, Ahmed M

    2016-11-20

    The colon is a promising site for drug targeting owing to its long transit time and mild proteolytic activity. The aim of this study was to prepare new low methoxy amidated pectin/NaCMC microspheres cross-linked by a mixture of Zn(2+) and Al(3+) ions and test their potential for colonic targeting of progesterone. A 2(4) factorial design was carried out to optimize the preparation conditions. High drug entrapment efficiency (82-99%) was obtained and it increased with increasing drug concentration but decreased with increasing polymer concentration. Drug release rate was directly proportional to the microsphere drug content and inversely related to Al(3+) ion concentration. Drug release was minimal during the first 3h but was significantly improved in the presence of 1% rat caecal contents, confirming the microsphere potential for colonic delivery. The microspheres achieved >2.3-fold enhancement of colonic progesterone permeability. These results confirm the viability of the produced microspheres as colon-targeted drug delivery vehicle. PMID:27561525

  1. Novel Heat Transfer Issues Associated with the Design and Safe Operation of the MEGAPIE Spallation Source Target

    Institute of Scientific and Technical Information of China (English)

    Brian L.Smith

    2007-01-01

    Critical heat transfer problems are discussed in the context of the operation of a spallation source target, which represents a first demonstration of the feasibility of an innovative concept for generating energy using a particle accelerator. Within the framework of the umbrella project MEGAPIE, an R&D support group was organized to take responsibility for target cooling. This involved the use of advanced numerical methods - Computational Fluid Dynamics (CFD) and Finite Element Method (FEM) - validated against suitable experimental data, and by means of appropriate benchmarking exercises. The design studies using CFD resulted in an optimum flow configuration being defined for the coolant circulation. Flow visualization tests were undertaken using a glass/water test section, with the velocity field mapped using optical and ultrasonic measuring techniques. These were followed by heat transfer tests, using the actual target materials (lead-bismuth-eutectic coolant and steel confinement). Further CFD/FEM work to analyze operational transients and accident sequences was also carried out, and is described in the paper.

  2. Design and Characterization of Colon Targeted Tegaserod Microspheres by Ionotropic Gelation.

    Directory of Open Access Journals (Sweden)

    Nemade M. S.

    2015-11-01

    Full Text Available The aim of study was to develop and evaluate tegaserod maleate (TM microspheres for colonic drug delivery system. Microspheres of TM were prepared by with little modification in the ionotropic gelation method by using polymer tamarind seed polysaccharide (TSP. These microspheres were evaluated for angle of repose, bulk density, tapped density, particle size, percentage drug entrapment, swelling behavior and in-vitro drug release studies. All the micrometric properties of the microsphere were within the range. The mean particle size of prepared microspheres was found to be in a range of 715.66 - 747.00 μm. Percentage drug entrapment observed in all formulations was between 74.03 - 76.69 %. The % water uptake in the pH 1.2 and pH 7.8 was between 69.66 - 73.33 and 181 - 192 respectively. In-vitro drug release studies showed that the release of tegaserod maleate from the microspheres was mainly influenced by the polymer concentration. Among all the formulations, F1 and F3 shows 94.98 and 88.52% better controlled release at the end of 12 hr respectively. The results indicated that a decrease in release of the drug was observed by increasing the polymer concentration. It is concluded from the present investigation that TM loaded microspheres were promising controlled release carriers for colon targeted delivery.

  3. Hsp60, a novel target for antitumor therapy: structure-function features and prospective drugs design.

    Science.gov (United States)

    Pace, Andrea; Barone, Giampaolo; Lauria, Antonino; Martorana, Annamaria; Piccionello, Antonio Palumbo; Pierro, Paola; Terenzi, Alessio; Almerico, Anna Maria; Buscemi, Silvestre; Campanella, Claudia; Angileri, Francesca; Carini, Francesco; Zummo, Giovanni; de Macario, Everly Conway; Cappello, Francesco; Macario, Alberto J L

    2013-01-01

    Heat shock protein 60 kDa (Hsp60) is a chaperone classically believed to be involved in assisting the correct folding of other mitochondrial proteins. Hsp60 also plays a role in cytoprotection against cell stressors, displaying for example, antiapoptotic potential. Despite the plethora of studies devoted to the mechanism of Hsp60's function, especially in prokaryotes, fundamental issues still remain unexplored, including the definition of its role in cancer. Key questions still unanswered pertain to the differences in structure-function features that might exist between the well-studied prokaryotic GroEL and the largely unexplored eukaryotic Hsp60 proteins. In this article we discuss these differences in sequence, structure, and roles of Hsp60, focusing on the human ortholog with the view of devising compounds to block its ability to favour tumor-cell growth and survival. Compounds currently known to directly or indirectly affect Hsp60 functions, such as protein folding, HIF-1α accumulation, or Hsp60-induced cell proliferation, are discussed along with strategies that might prove effective for developing Hsp60-targeting drugs for anticancer therapy.

  4. Cells by design: a mini-review of targeting cell engineering using DNA microarrays.

    Science.gov (United States)

    Jaluria, Pratik; Chu, Chia; Betenbaugh, Michael; Shiloach, Joseph

    2008-06-01

    Recent studies have demonstrated the utility of DNA microarray technology in engineering cellular properties. For instance, cellular adhesion, the necessity of cells to attach to a surface in order to to proliferate, was examined by comparing two distinct HeLa cell lines. Two genes, one encoding a type II membrane glycosylating sialyltransferase (siat7e) and the other encoding a secreted glycoprotein (lama4), were found to influence adhesion. The expression of siat7e correlated with reduced adhesion, whereas expression of lama4 correlated with increased adhesion, as shown by various assays. In a separate example, a gene encoding a mitochondrial assembly protein (cox15) and a gene encoding a kinase (cdkl3), were found to influence cellular growth. Enhanced expression of either gene resulted in slightly higher specific growth rates and higher maximum cell densities for HeLa, HEK-293, and CHO cell lines. Another investigated property was the adaptation of HEK-293 cells to serum-free media. The genes egr1 and gas6, both with anti-apoptotic properties, were identified as potentially improving adaptability by impacting viability at low serum levels. In trying to control apoptosis, researchers found that by altering the expression levels of four genes faim, fadd, alg-2, and requiem, apoptotic response could be altered. In the present work, these and related studies in microorganisms (prokaryote and eukaryote) are examined in greater detail focusing on the approach of using DNA microarrays to direct cellular behavior by targeting select genes. PMID:18327555

  5. 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

  6. 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

  7. 谈某核电厂附加柴油发电机厂房防火设计%Discussion on the fire protection design of the nuclear power plant adding diesel generator workshop

    Institute of Scientific and Technical Information of China (English)

    赵月

    2016-01-01

    Through analyzing building fire protection design problems of the nuclear power plant adding diesel generator workshop,starting from aspects of fire protection layout,fire protection distribution,safety evacuation and oil tank design,the paper carries out the building fire protec-tion design,which reduces the fire hazards and improves the nuclear power safety performance.%通过分析某核电厂附加柴油发电机厂房建筑防火设计中存在的问题,从防火布置、防火分区、安全疏散、油罐间设计等方面,进行了建筑防火优化设计,降低了火灾危害的发生,提高了核电厂的安全性能。

  8. Design Concept of a Gamma-gamma Higgs Factory Driven by Thin Laser Targets and Energy Recovery Linacs

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuhong [JLAB

    2013-06-01

    A gamma-gamma collider has long been considered an option for a Higgs Factory. Such photon colliders usually rely on Compton back-scattering for generating high energy gamma photons and further Higgs bosons through gamma-gamma collisions. The presently existing proposals or design concepts all have chosen a very thick laser target (i.e., high laser photon intensity) for Compton scatterings. In this paper, we present a new design concept of a gamma-gamma collider utilizing a thin laser target (i.e., relatively low photon density), thus leading to a low electron to gamma photon conversion rate. This new concept eliminates most useless and harmful low energy soft gamma photons from multiple Compton scattering so the detector background is improved. It also greatly relaxes the requirement of the high peak power of the laser, a significant technical challenge. A high luminosity for such a gamma-gamma collider can be achieved through an increase of the bunch repetition rate and current of the driven electron beam. Further, multi-pass recirculating linac could greatly reduce the linac cost and energy recovery is required to reduce the needed RF power.

  9. A New Target Design with a Beryllium Multiplier for a Lead Slowing Down Time Spectrometer (LSDTS) System

    International Nuclear Information System (INIS)

    In order to quantify fissile isotopes in the spent nuclear fuel or the recycled nuclear material, a lead slowing down time spectrometer (LSDTS) system has been investigated and developed. Among several components of LSDTS, a highly intense neutron should be produced in the system to overcome the background neutrons from spontaneous fission in the curium isotopes. Thus a thin and plate target is designed using tantalum based on the successive reactions such as a bremmstrahlung conversion (e,g) and a photoneutron production (g,n). The beam energy of incident electrons is as high as 35 MeV in LSDTS system, which will decrease in the lead medium after interaction with target. It is known that the higher energy than 5 MeV is enough to produce neutrons for light elements such as beryllium and deuterium Beryllium is widely used as a reflector due to its good characteristics of neutron scattering. Above all, a neutron multiplier is a good choice for beryllium especially in a fusion facility based on the following chain reaction, Be-9 + n (>2MeV) -> 2 He-4 + 2n -1.666 MeV and the cross section is as high as about 580 mb. Using the above application, a beryllium plate is installed on back side of tantalum target in order to multiply neutrons emitting from the target. Furthermore, some sensitivity tests are carried out by changing the thickness of beryllium plate. As a computing tool, MCNPX-2.5 code, a popular Monte Carlo three dimensional code, is taken into consideration

  10. A Two-step Design Method for Shaft Work Targeting on Low-temperature Process

    Institute of Scientific and Technical Information of China (English)

    罗祎青; 冯胜科; 孙长江; 袁希钢

    2014-01-01

    In low-temperature processes, there are interactions between heat exchanger network (HEN) and refrig-eration system. The modification on HEN of the chilling train for increasing energy recovery does not always coor-dinate with the minimum shaft work consumption of the corresponding refrigeration system. In this paper, a sys-tematic approach for optimizing low-temperature system is presented through mathematical method and exergy analysis. The possibility of“pockets”, which appears as right nose section in the grand composite curve (EGCC) of the process, is first optimized. The EGCC with the pockets cutting down is designed as a separate part. A case study is used to illustrate the application of the approach for a HEN of a chilling train with propylene and ethylene refrig-erant system in an ethylene production process.

  11. Improved strategies for designing lupus trials with targeted therapies: learning from 65 years of experience.

    Science.gov (United States)

    Wallace, D J

    2016-09-01

    The development of new agents to manage lupus erythematosus has lagged behind other autoimmune rheumatic diseases. This is in large part because lupus is a heterogeneous disorder affecting nine principal domains (organ systems) that are difficult to measure and quantify and can be at variance with each other. Over the last two decades, a variety of guidelines, definitions, candidate surrogate or biomarkers, metrics and composite indices have been presented as benchmarks that can be utilized to assess lupus in clinical trials. Despite this, over 20 agents have failed to achieve their primary outcome measure, some of which are generally believed to be clinically effective. This article presents constructive suggestions and improved strategies in trial design that will hopefully lead to the introduction of new agents for the disease. PMID:27497258

  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)

    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.

  13. K-Targeted Metabolomic Analysis Extends Chemical Subtraction to DESIGNER Extracts: Selective Depletion of Extracts of Hops (Humulus lupulus)⊥

    OpenAIRE

    Ramos Alvarenga, René F.; Friesen, J. Brent; Nikolić, Dejan; Simmler, Charlotte; Napolitano, José G.; van Breemen, Richard; Lankin, David C.; McAlpine, James B.; Pauli, Guido F.; Chen, Shao-Nong

    2014-01-01

    This study introduces a flexible and compound targeted approach to Deplete and Enrich Select Ingredients to Generate Normalized Extract Resources, generating DESIGNER extracts, by means of chemical subtraction or augmentation of metabolites. Targeting metabolites based on their liquid–liquid partition coefficients (K values), K targeting uses countercurrent separation methodology to remove single or multiple compounds from a chemically complex mixture, according to the following equation: DES...

  14. Ad-blocking Games: Monetizing Online Content Under the Threat of Ad Avoidance

    OpenAIRE

    Vratonjic, Nevena; Manshaei, Mohammadhossein; Grossklags, Jens; Hubaux, Jean-Pierre

    2012-01-01

    Much of the Internet economy relies on online advertising for monetizing digital content: Users are expected to accept the presence of online advertisements in exchange for content being free. However, online advertisements have become a serious problem for many Internet users: while some are merely annoyed by the incessant display of distracting ads cluttering Web pages, others are highly concerned about the privacy implications - as ad providers typically track users' behavior for ad target...

  15. Advances in implosion physics, alternative targets design, and neutron effects on heavy ion fusion reactors

    International Nuclear Information System (INIS)

    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 DTx fuel with a small tritium initial content (xe 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 SiC, modify the understanding of the calculation of displacement per atom, dpa, to quantify the collisional damage. An important analysis has been the confirmation, using Molecular Dynamics (MD) with an astonishing agreement, of the experimental evidence of low-temperature amorphization by damage accumulation in SiC, which could modify extensively its viability as a

  16. 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

  17. Structure-driven design of radionuclide tracers for non-invasive imaging of uPAR and targeted radiotherapy. The tale of a synthetic peptide antagonist

    DEFF Research Database (Denmark)

    Ploug, Michael

    2013-01-01

    -function relationships in uPAR has been refined to such a level that a rational design of uPAR function as well as compounds specifically targeting defined functions of uPAR are now realistic options. This knowledge opens new avenues for developing therapeutic intervention regimens targeting uPAR as well...

  18. 基于DSP片内A/D信号检测与调理电路的设计%Design of the signal detection and conditioning circuit based on the DSP chip A/D

    Institute of Scientific and Technical Information of China (English)

    易映萍; 李栋; 肖飞

    2013-01-01

    信号采样与调理电路是整个DSP数字控制系统的重要组成部分,为了实现系统的实时控制和系统的稳定,主电路中的电压量和电流量需要通过有隔离效果的霍尔进行采集,而霍尔输出信号的幅值范围与DSP的片内AD采样的电压范围不能良好匹配,所以需要通过一系列的电路将霍尔的输出信号调理到DSP的片内AD采样的电压范围之内.文中主要介绍了可再生能源并网变流器中DSP片内AD的信号采样与调理电路的设计方法,仿真和实验结果表明所设计的信号采样与调理电路能满足DSP片内AD采样的电压范围,同样适用于带有片内AD的MCU的信号采集系统.%Signal sampling and conditioning circuit is an important part of the whole DSP digital control system, the voltage and current of the main circuit required be sampled by Hall sensor which has the effect of isolation, but the DSP chip AD sampling voltage range of the amplitude can not be a good match with the Hall sensor output signals, so it is necessary to use a series circuit to adjust the output signal of Hall sensor to match with the voltage range of the DSP chip AD sampling. This dissertation introduces the circuit design method of DSP chip AD converter sampling the signal conditioning in the renewable energy grid variable. The simulation and experimental results show that sampling the signal conditioning circuit designed can satisfy sampling voltage range of the DSP chip AD, it is also same applies to the MCU with chip AD signal acquisition system.

  19. The effectiveness of adding cognitive behavioural therapy aimed at changing lifestyle to managed diabetes care for patients with type 2 diabetes: design of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    van Oppen Patricia

    2007-05-01

    Full Text Available Abstract Background In patients with type 2 diabetes, the risk for cardiovascular disease is substantial. To achieve a more favourable risk profile, lifestyle changes on diet, physical activity and smoking status are needed. This will involve changes in behaviour, which is difficult to achieve. Cognitive behavioural therapies focussing on self-management have been shown to be effective. We have developed an intervention combining techniques of Motivational Interviewing (MI and Problem Solving Treatment (PST. The aim of our study is to investigate if adding a combined behavioural intervention to managed care, is effective in achieving changes in lifestyle and cardiovascular risk profile. Methods Patients with type 2 diabetes will be selected from general practices (n = 13, who are participating in a managed diabetes care system. Patients will be randomised into an intervention group receiving cognitive behaviour therapy (CBT in addition to managed care, and a control group that will receive managed care only. The CBT consists of three to six individual sessions of 30 minutes to increase the patient's motivation, by using principles of MI, and ability to change their lifestyle, by using PST. The first session will start with a risk assessment of diabetes complications that will be used to focus the intervention. The primary outcome measure is the difference between intervention and control group in change in cardiovascular risk score. For this purpose blood pressure, HbA1c, total and HDL-cholesterol and smoking status will be assessed. Secondary outcome measures are quality of life, patient satisfaction, physical activity, eating behaviour, smoking status, depression and determinants of behaviour change. Differences between changes in the two groups will be analysed according to the intention-to-treat principle, with 95% confidence intervals. The power calculation is based on the risk for cardiovascular disease and we calculated that 97 patients

  20. Design Targets for Wind Turbine Blade Optimization%风力机叶片优化设计目标

    Institute of Scientific and Technical Information of China (English)

    吴江海; 王同光; 赵新华

    2011-01-01

    Blade aerodynamic performance calculation, blade design load evaluation, blade structure de-sign, system cost evaluation and wind farm operation model for variable-pitch wind turbines are investi-gated and then integrated. As a result, the analysis method for the cost of energy (COE) is derived, and a new target of wind farm profit (WFP) for wind turbine blade design is developed. Based on the shape parameterization, a 1. 5 MW blade for pitch regulated wind turbine is designed with different objectives using the adaptive simulated annealing algorithm (ASAA). The difference between the COE and WFP is analyzed. Results show that with grid rate, blade design with the target of the maximum WFP it is more reasonable than that with COE.%研究了变桨型风力机叶片的气动性能计算、叶片设计载荷评估、叶片结构设计、风力机组成本评估及风电场运营模型,并将这些模块进行了整合,得到了度电成本的计算方法,同时提出了风场运营收益最大这一叶片设计目标.基于有针对性的叶片参数化描述,采用自适应模拟退火算法,分别以不同的目标优化设计了1.5MW变桨型的叶片.分析比较了度电成本及风场收益两个指标在平衡发电量和成本上的区别,认为在可以确定上网电价的情况下,以风场收益最大为目标设计叶片能为风电运营商带来更多的收益.