CFD aspects of ADSS target design

International Nuclear Information System (INIS)

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

2004-03-01

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

76 FR 12942 - Proposed Information Collection; Comment Request; Defining Target Levels for Ecosystem Components...

Science.gov (United States)

2011-03-09

... Collection; Comment Request; Defining Target Levels for Ecosystem Components: A Socio-Ecological Approach... inception, the Puget Sound ecosystem has become a national example of ecosystem-based management (EBM) implementation. The Partnership Action Agenda indentified 80 near-term actions that are required for ecosystem...

Optical and mechanical design of beam-target coupling sensor

International Nuclear Information System (INIS)

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

2012-01-01

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

Design of the target area for the National Ignition Facility

International Nuclear Information System (INIS)

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

1997-01-01

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

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.

Conceptual design studies for the liquid metal target META:LIC

International Nuclear Information System (INIS)

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

2014-01-01

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

The Landscape of microRNA Targeting in Prostate Cancer Defined by AGO-PAR-CLIP

Directory of Open Access Journals (Sweden)

Mark P. Hamilton

2016-06-01

Full Text Available MicroRNA (miRNA deregulation in prostate cancer (PCa contributes to PCa initiation and metastatic progression. To comprehensively define the cancer-associated changes in miRNA targeting and function in commonly studied models of PCa, we performed photoactivatable ribonucleoside-enhanced cross-linking immunoprecipitation of the Argonaute protein in a panel of PCa cell lines modeling different stages of PCa progression. Using this comprehensive catalogue of miRNA targets, we analyzed miRNA targeting on known drivers of PCa and examined tissue-specific and stage-specific pathway targeting by miRNAs. We found that androgen receptor is the most frequently targeted PCa oncogene and that miR-148a targets the largest number of known PCa drivers. Globally, tissue-specific and stage-specific changes in miRNA targeting are driven by homeostatic response to active oncogenic pathways. Our findings indicate that, even in advanced PCa, the miRNA pool adapts to regulate continuing alterations in the cancer genome to balance oncogenic molecular changes. These findings are important because they are the first to globally characterize miRNA changes in PCa and demonstrate how the miRNA target spectrum responds to staged tumorigenesis.

Safety and environmental requirements and design targets for TIBER-II

International Nuclear Information System (INIS)

Piet, S.J.

1987-09-01

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

Imaging Voltage in Genetically Defined Neuronal Subpopulations with a Cre Recombinase-Targeted Hybrid Voltage Sensor.

Science.gov (United States)

Bayguinov, Peter O; Ma, Yihe; Gao, Yu; Zhao, Xinyu; Jackson, Meyer B

2017-09-20

Genetically encoded voltage indicators create an opportunity to monitor electrical activity in defined sets of neurons as they participate in the complex patterns of coordinated electrical activity that underlie nervous system function. Taking full advantage of genetically encoded voltage indicators requires a generalized strategy for targeting the probe to genetically defined populations of cells. To this end, we have generated a mouse line with an optimized hybrid voltage sensor (hVOS) probe within a locus designed for efficient Cre recombinase-dependent expression. Crossing this mouse with Cre drivers generated double transgenics expressing hVOS probe in GABAergic, parvalbumin, and calretinin interneurons, as well as hilar mossy cells, new adult-born neurons, and recently active neurons. In each case, imaging in brain slices from male or female animals revealed electrically evoked optical signals from multiple individual neurons in single trials. These imaging experiments revealed action potentials, dynamic aspects of dendritic integration, and trial-to-trial fluctuations in response latency. The rapid time response of hVOS imaging revealed action potentials with high temporal fidelity, and enabled accurate measurements of spike half-widths characteristic of each cell type. Simultaneous recording of rapid voltage changes in multiple neurons with a common genetic signature offers a powerful approach to the study of neural circuit function and the investigation of how neural networks encode, process, and store information. SIGNIFICANCE STATEMENT Genetically encoded voltage indicators hold great promise in the study of neural circuitry, but realizing their full potential depends on targeting the sensor to distinct cell types. Here we present a new mouse line that expresses a hybrid optical voltage sensor under the control of Cre recombinase. Crossing this line with Cre drivers generated double-transgenic mice, which express this sensor in targeted cell types. In

Target based drug design - a reality in virtual sphere.

Science.gov (United States)

Verma, Saroj; Prabhakar, Yenamandra S

2015-01-01

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

Spallation neutron source target station design, development, and commissioning

Energy Technology Data Exchange (ETDEWEB)

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

2014-11-11

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

Technical Design Report, Second Target Station

International Nuclear Information System (INIS)

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

2015-01-01

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

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

OpenAIRE

MESKENS, Jan; LUYTEN, Kris; CONINX, Karin

2009-01-01

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

A consensus-based guideline defining the clinical target volume for pelvic lymph nodes in external beam radiotherapy for uterine cervical cancer

International Nuclear Information System (INIS)

Toita, Takafumi; Ohno, Tatsuya; Kaneyasu, Yuko

2010-01-01

The objective of this study was to develop a consensus-based guideline as well as an atlas defining pelvic nodal clinical target volumes in external beam radiotherapy for uterine cervical cancer. A working subgroup to establish the consensus-based guideline on clinical target volumes for uterine cervical cancer was formulated by the Radiation Therapy Study Group of the Japan Clinical Oncology Group in July 2008. The working subgroup consisted of seven radiation oncologists. The process resulting in the consensus included a comparison of contouring on CT images among the members, reviewing of published textbooks and the relevant literature and a distribution analysis of metastatic nodes on computed tomography/magnetic resonance imaging of actual patients. The working subgroup defined the pelvic nodal clinical target volumes for cervical cancer and developed an associated atlas. As a basic criterion, the lymph node clinical target volume was defined as the area encompassed by a 7 mm margin around the applicable pelvic vessels. Modifications were made in each nodal area to cover adjacent adipose tissues at risk of microscopic nodal metastases. Although the bones and muscles were excluded, the bowel was not routinely excluded in the definition. Each of the following pelvic node regions was defined: common iliac, external iliac, internal iliac, obturator and presacral. Anatomical structures bordering each lymph node region were defined for six directions; anterior, posterior, lateral, medial, cranial and caudal. Drafts of the definition and the atlas were reviewed by members of the JCOG Gynecologic Cancer Study Group (GCSG). We developed a consensus-based guideline defining the pelvic node clinical target volumes that included an atlas. The guideline will be continuously updated to reflect the ongoing changes in the field. (author)

Designing high power targets with computational fluid dynamics (CFD)

International Nuclear Information System (INIS)

Covrig, S. D.

2013-01-01

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

Designing high power targets with computational fluid dynamics (CFD)

Energy Technology Data Exchange (ETDEWEB)

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

2013-11-07

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

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

Science.gov (United States)

Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

2018-03-15

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

Adaptive Waveform Design for Cognitive Radar in Multiple Targets Situations

Directory of Open Access Journals (Sweden)

Xiaowen Zhang

2018-02-01

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

Digitally-assisted analog and RF CMOS circuit design for software-defined radio

CERN Document Server

Okada, Kenichi

2011-01-01

This book describes the state-of-the-art in RF, analog, and mixed-signal circuit design for Software Defined Radio (SDR). It synthesizes for analog/RF circuit designers the most important general design approaches to take advantage of the most recent CMOS technology, which can integrate millions of transistors, as well as several real examples from the most recent research results.

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.

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Defining internal target volume (ITV) for hepatocellular carcinoma using four-dimensional CT

International Nuclear Information System (INIS)

X, Mian; Liu Mengzhong; Deng Xiaowu; Zhang Li; Huang Xiaoyan; Liu Hui; Li Qiaoqiao; Hu Yonghong; Cai Ling; Cui Nianji

2007-01-01

Background and purpose: To define individualized internal target volume (ITV) for hepatocellular carcinoma using four-dimensional computed tomography (4DCT). Materials and methods: Gross tumor volumes (GTVs) and clinical target volumes (CTVs) were contoured on all 10 respiratory phases of 4DCT scans in 10 patients with hepatocellular carcinoma. The 3D and 4D treatment plans were performed for each patient using two different planning target volumes (PTVs): (1) PTV 3D was derived from a single CTV plus conventional margins; (2) PTV 4D was derived from ITV 4D , which encompassed all 10 CTVs plus setup margins (SMs). The volumes of PTVs and dose distribution were compared between the two plans. Results: The average PTV volume of the 4D plans (328.4 ± 152.2 cm 3 ) was less than 3D plans (407.0 ± 165.6 cm 3 ). The 4D plans spared more surrounding normal tissues than 3D plans, especially normal liver. Compared with 3D plans, the mean dose to normal liver (MDTNL) decreased from 22.7 to 20.3 Gy. Without increasing the normal tissue complication probability (NTCP), the 4D plans allowed for increasing the calculated dose from 50.4 ± 1.3 to 54.2 ± 2.6 Gy, an average increase of 7.5% (range 4.0-16.0%). Conclusions: The conventional 3D plans can result in geometric miss and include excess normal tissues. The 4DCT-based plans can reduce the target volumes to spare more normal tissues and allow dose escalation compared with 3D plans

Water-cooled target-box design at LAMPF

International Nuclear Information System (INIS)

Grisham, D.; Lambert, J.

1983-01-01

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

Review of laser mega joule target area: Design and processes

International Nuclear Information System (INIS)

Geitzholz, M.; Lanternier, C.

2006-01-01

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

Quantifying design trade-offs of beryllium targets on NIF

Science.gov (United States)

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

2017-10-01

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

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

Directory of Open Access Journals (Sweden)

J.H. You

2016-12-01

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

Optimum design of exploding pusher target to produce maximum neutrons

International Nuclear Information System (INIS)

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

1985-03-01

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

Benchmarking CRISPR on-target sgRNA design.

Science.gov (United States)

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

2017-02-15

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

Targeting and design of chilled water network

International Nuclear Information System (INIS)

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

2014-01-01

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

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...

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 ...

Design of ignition targets for the National Ignition Facility

International Nuclear Information System (INIS)

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

1999-01-01

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

A consensus-based guideline defining clinical target volume for primary disease in external beam radiotherapy for intact uterine cervical cancer

International Nuclear Information System (INIS)

Toita, Takafumi; Ohno, Tatsuya; Kaneyasu, Yuko

2011-01-01

The objective of this study was to develop a consensus-based guideline to define clinical target volume for primary disease (clinical target volume primary) in external beam radiotherapy for intact uterine cervical cancer. The working subgroup of the Japan Clinical Oncology Group (JCOG) Radiation Therapy Study Group began developing a guideline for primary clinical target volume in November 2009. The group consisted of 10 radiation oncologists and 2 gynecologic oncologists. The process started with comparing the contouring on computed tomographic images of actual cervical cancer cases among the members. This was followed by a comprehensive literature review that included primary research articles and textbooks as well as information on surgical procedures. Extensive discussion occurred in face-to-face meetings (three occasions) and frequent e-mail communications until a consensus was reached. The working subgroup reached a consensus on the definition for the clinical target volume primary. The clinical target volume primary consists of the gross tumor volume, uterine cervix, uterine corpus, parametrium, vagina and ovaries. Definitions for these component structures were determined. Anatomical boundaries in all directions were defined for the parametrium. Examples delineating these boundaries were prepared for the posterior border of the parametrium for various clinical situations (id est (i.e.) central tumor bulk, degree of parametrial involvement). A consensus-based guideline defining the clinical target volume primary was developed for external beam radiotherapy for intact uterine cervical cancer. This guideline will serve as a template for radiotherapy protocols in future clinical trials. It may also be used in actual clinical practice in the setting of highly precise external beam radiotherapy, including intensity-modulated radiotherapy. (author)

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 ...

Customizable de novo design strategies for DOCK: Application to HIVgp41 and other therapeutic targets.

Science.gov (United States)

Allen, William J; Fochtman, Brian C; Balius, Trent E; Rizzo, Robert C

2017-11-15

De novo design can be used to explore vast areas of chemical space in computational lead discovery. As a complement to virtual screening, from-scratch construction of molecules is not limited to compounds in pre-existing vendor catalogs. Here, we present an iterative fragment growth method, integrated into the program DOCK, in which new molecules are built using rules for allowable connections based on known molecules. The method leverages DOCK's advanced scoring and pruning approaches and users can define very specific criteria in terms of properties or features to customize growth toward a particular region of chemical space. The code was validated using three increasingly difficult classes of calculations: (1) Rebuilding known X-ray ligands taken from 663 complexes using only their component parts (focused libraries), (2) construction of new ligands in 57 drug target sites using a library derived from ∼13M drug-like compounds (generic libraries), and (3) application to a challenging protein-protein interface on the viral drug target HIVgp41. The computational testing confirms that the de novo DOCK routines are robust and working as envisioned, and the compelling results highlight the potential utility for designing new molecules against a wide variety of important protein targets. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Present status of the conceptual design of IFMIF target facility

International Nuclear Information System (INIS)

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

1998-01-01

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

Super liquid density target designs

International Nuclear Information System (INIS)

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

1976-01-01

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

Design and Implementation of a Mobile Phone Locator Using Software Defined Radio

National Research Council Canada - National Science Library

Larsen, Ian P

2007-01-01

...) signal using software defined radio and commodity computer hardware. Using software designed by the GNU free software project as a base, standard GSM packets were transmitted and received over the air, and their arrival times detected...

IFMIF target and test cell - design and integration

International Nuclear Information System (INIS)

Heinzel, V.

2007-01-01

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

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

Science.gov (United States)

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

2017-08-18

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

Catalysis by Design: Well-Defined Single-Site Heterogeneous Catalysts

KAUST Repository

Pelletier, Jeremie

2016-03-09

ConspectusHeterogeneous catalysis, a field important industrially and scientifically, is increasingly seeking and refining strategies to render itself more predictable. The main issue is due to the nature and the population of catalytically active sites. Their number is generally low to very low, their "acid strengths" or " redox properties" are not homogeneous, and the material may display related yet inactive sites on the same material. In many heterogeneous catalysts, the discovery of a structure-activity reationship is at best challenging. One possible solution is to generate single-site catalysts in which most, if not all, of the sites are structurally identical. Within this context and using the right tools, the catalyst structure can be designed and well-defined, to reach a molecular understanding. It is then feasible to understand the structure-activity relationship and to develop predictable heterogeneous catalysis. Single-site well-defined heterogeneous catalysts can be prepared using concepts and tools of surface organometallic chemistry (SOMC). This approach operates by reacting organometallic compounds with surfaces of highly divided oxides (or of metal nanoparticles). This strategy has a solid track record to reveal structure-activity relationship to the extent that it is becoming now quite predictable. Almost all elements of the periodical table have been grafted on surfaces of oxides (from simple oxides such as silica or alumina to more sophisticated materials regarding composition or porosity).Considering catalytic hydrocarbon transformations, heterogeneous catalysis outcome may now be predicted based on existing mechanistic proposals and the rules of molecular chemistry (organometallic, organic) associated with some concepts of surface sciences. A thorough characterization of the grafted metal centers must be carried out using tools spanning from molecular organometallic or surface chemistry. By selection of the metal, its ligand set, and the

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

International Nuclear Information System (INIS)

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

1982-03-01

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

Massively parallel de novo protein design for targeted therapeutics

KAUST Repository

Chevalier, Aaron

2017-09-26

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

Massively parallel de novo protein design for targeted therapeutics

KAUST Repository

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

2017-01-01

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

Massively parallel de novo protein design for targeted therapeutics

Science.gov (United States)

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

2018-01-01

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

From Game Design Elements to Gamefulness: Defining “Gamification”

DEFF Research Database (Denmark)

Deterding, Sebastian; Dixon, Dan; Khaled, Rilla

2011-01-01

Recent years have seen a rapid proliferation of mass-market consumer software that takes inspiration from video games. Usually summarized as “gamification”, this trend connects to a sizeable body of existing concepts and research in human- computer interaction and game studies, such as serious...... games, pervasive games, alternate reality games, or playful design. However, it is not clear how “gamification” relates to these, whether it denotes a novel phenomenon, and how to define it. Thus, in this paper we investigate “gamification” and the historical origins of the term in relation...... to precursors and similar concepts. It is suggested that “gamified” applications provide insight into novel, gameful phenomena complementary to playful phenomena. Based on our research, we propose a definition of “gamification” as the use of game design elements in non-game contexts....

Design considerations for foil windows for PET radioisotope targets

International Nuclear Information System (INIS)

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

1992-01-01

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

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

Science.gov (United States)

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

2018-01-01

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

Target/blanket conceptual design for the Los Alamos ATW concept

International Nuclear Information System (INIS)

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

1992-01-01

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

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

Flat cladding and pellets in the design of an irradiation target

International Nuclear Information System (INIS)

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

2003-01-01

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

Rare isotope accelerator—conceptual design of target areas

Science.gov (United States)

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

2006-06-01

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

Rare isotope accelerator - conceptual design of target areas

International Nuclear Information System (INIS)

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

2006-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1997-07-01

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

Conceptual design considerations and neutronics of lithium fall laser target chambers

International Nuclear Information System (INIS)

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

1978-01-01

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

Target station design for a 1 MW pulsed spallation neutron source

International Nuclear Information System (INIS)

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

1993-01-01

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

Risk based seismic design criteria

International Nuclear Information System (INIS)

Kennedy, R.P.

1999-01-01

In order to develop a risk based seismic design criteria the following four issues must be addressed: (1) What target annual probability of seismic induced unacceptable performance is acceptable? (2) What minimum seismic margin is acceptable? (3) Given the decisions made under Issues 1 and 2, at what annual frequency of exceedance should the safe-shutdown-earthquake (SSE) ground motion be defined? (4) What seismic design criteria should be established to reasonably achieve the seismic margin defined under Issue 2? The first issue is purely a policy decision and is not addressed in this paper. Each of the other three issues are addressed. Issues 2 and 3 are integrally tied together so that a very large number of possible combinations of responses to these two issues can be used to achieve the target goal defined under Issue 1. Section 2 lays out a combined approach to these two issues and presents three potentially attractive combined resolutions of these two issues which reasonably achieves the target goal. The remainder of the paper discusses an approach which can be used to develop seismic design criteria aimed at achieving the desired seismic margin defined in resolution of Issue 2. Suggestions for revising existing seismic design criteria to more consistently achieve the desired seismic margin are presented. (orig.)

The design, construction and performance of the MICE target

International Nuclear Information System (INIS)

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

2013-01-01

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

Rare Isotope Accelerator - Conceptual Design of Target Areas

Energy Technology Data Exchange (ETDEWEB)

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

2006-01-01

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

Rare isotope accelerator-conceptual design of target areas

Energy Technology Data Exchange (ETDEWEB)

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

2006-06-23

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2001-03-01

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

Autonomous Rover Traverse and Precise Arm Placement on Remotely Designated Targets

Science.gov (United States)

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

2011-01-01

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

Verification of the hydraulic design of the FMIT liquid lithium target

International Nuclear Information System (INIS)

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

1983-01-01

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

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

International Nuclear Information System (INIS)

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

2006-01-01

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

Chitosan encapsulation of essential oil "cocktails" with well-defined binary Zn(II)-Schiff base species targeting antibacterial medicinal nanotechnology.

Science.gov (United States)

Halevas, Eleftherios; Nday, Christiane M; Chatzigeorgiou, Evanthia; Varsamis, Vasileios; Eleftheriadou, Despoina; Jackson, Graham E; Litsardakis, Georgios; Lazari, Diamanto; Ypsilantis, Konstantinos; Salifoglou, Athanasios

2017-11-01

The advent of biodegradable nanomaterials with enhanced antibacterial activity stands as a challenge to the global research community. In an attempt to pursue the development of novel antibacterial medicinal nanotechnology, we herein a) synthesized ionic-gelated chitosan nanoparticles, b) compared and evaluated the antibacterial activity of essential oils extracted from nine different herbs (Greek origin) and their combinations with a well-defined antibacterial Zn(II)-Schiff base compound, and c) encapsulated the most effective hybrid combination of Zn(II)-essential oils inside the chitosan matrix, thereby targeting well-formulated nanoparticles of distinct biological impact. The empty and loaded chitosan nanoparticles were physicochemically characterized by FT-IR, Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), with the entrapment and drug release studies being conducted through UV-Visible and atomic absorption techniques. The antimicrobial properties of the novel hybrid materials were demonstrated against Gram positive (S. aureus, B. subtilis, and B. cereus) and Gram negative (E. coli and X. campestris) bacteria using modified agar diffusion methods. The collective physicochemical profile of the hybrid Zn(II)-essential oil cocktails, formulated so as to achieve optimal activity when loaded to chitosan nanoparticles, signifies the importance of design in the development of efficient nanomedicinal pharmaceuticals a) based on both natural products and biogenic metal ionic cofactors, and b) targeting bacterial infections and drug resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

George W. Howe

2016-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

Conceptual design study of IFMIF target system

International Nuclear Information System (INIS)

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

1997-01-01

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

Computer-aided approach for design of tailor-made blended products

DEFF Research Database (Denmark)

Yunus, Nor Alafiza; Gernaey, Krist; Woodley, John

2012-01-01

A computer-aided methodology has been developed for the design of blended (mixture) products. Through this methodology, it is possible to identify the most suitable chemicals for blending, and “tailor” the blend according to specified product needs (usually product attributes, e.g. performance...... as well as regulatory). The product design methodology has four tasks. First, the design problem is defined: the product needs are identified, translated into target properties and the constraints for each target property are defined. Secondly, target property models are retrieved from a property model...

Investigation of IFMIF target assembly structure design

International Nuclear Information System (INIS)

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

2006-10-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

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

Science.gov (United States)

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

2014-02-21

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

Test Information Targeting Strategies for Adaptive Multistage Testing Designs.

Science.gov (United States)

Luecht, Richard M.; Burgin, William

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

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

Science.gov (United States)

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

2015-01-01

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

Design of a cryogenic deuterium gas target for neutron therapy

International Nuclear Information System (INIS)

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

1976-01-01

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

Introduction to spallation physics and spallation-target design

Energy Technology Data Exchange (ETDEWEB)

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

1995-10-01

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

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

Science.gov (United States)

Lim, Brian Y.

1991-01-01

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

Spallation neutron source target design for radioactive waste transmutation

International Nuclear Information System (INIS)

Beard, C.A.

1992-01-01

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

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

Science.gov (United States)

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

2017-11-01

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

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

International Nuclear Information System (INIS)

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

1978-01-01

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

National Ignition Facility subsystem design requirements target positioning subsystem SSDR 1.8.2

International Nuclear Information System (INIS)

Pittenger, L.

1996-01-01

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

Design choices and issues in fixed-target B experiments

International Nuclear Information System (INIS)

Camilleri, L.

1993-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-06-12

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

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

International Nuclear Information System (INIS)

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

1993-05-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1993-05-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1993-05-01

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

Defining Potential Vaccine Targets of Haemophilus ducreyi Trimeric Autotransporter Adhesin DsrA.

Science.gov (United States)

Fusco, William G; Choudhary, Neelima R; Stewart, Shelley M; Alam, S Munir; Sempowski, Gregory D; Elkins, Christopher; Leduc, Isabelle

2015-04-01

Haemophilus ducreyi is the causative agent of the sexually transmitted genital ulcer disease chancroid. Strains of H. ducreyi are grouped in two classes (I and II) based on genotypic and phenotypic differences, including those found in DsrA, an outer membrane protein belonging to the family of multifunctional trimeric autotransporter adhesins. DsrA is a key serum resistance factor of H. ducreyi that prevents binding of natural IgM at the bacterial surface and functions as an adhesin to fibronectin, fibrinogen, vitronectin, and human keratinocytes. Monoclonal antibodies (MAbs) were developed to recombinant DsrA (DsrA(I)) from prototypical class I strain 35000HP to define targets for vaccine and/or therapeutics. Two anti-DsrAI MAbs bound monomers and multimers of DsrA from genital and non-genital/cutaneous H. ducreyi strains in a Western blot and reacted to the surface of the genital strains; however, these MAbs did not recognize denatured or native DsrA from class II strains. In a modified extracellular matrix protein binding assay using viable H. ducreyi, one of the MAbs partially inhibited binding of fibronectin, fibrinogen, and vitronectin to class I H. ducreyi strain 35000HP, suggesting a role for anti-DsrA antibodies in preventing binding of H. ducreyi to extracellular matrix proteins. Standard ELISA and surface plasmon resonance using a peptide library representing full-length, mature DsrAI revealed the smallest nominal epitope bound by one of the MAbs to be MEQNTHNINKLS. Taken together, our findings suggest that this epitope is a potential target for an H. ducreyi vaccine.

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

Science.gov (United States)

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

2009-04-22

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

Straight-Line Target Tracking for Unmanned Surface Vehicles

Directory of Open Access Journals (Sweden)

Morten Breivik

2008-10-01

Full Text Available This paper considers the subject of straight-line target tracking for unmanned surface vehicles (USVs. Target-tracking represents motion control scenarios where no information about the target behavior is known in advance, i.e., the path that the target traverses is not defined apriori. Specifically, this work presents the design of a motion control system which enables an underactuated USV to track a target that moves in a straight line at high speed. The motion control system employs a guidance principle originally developed for interceptor missiles, as well as a novel velocity controller inspired by maneuverability and agility concepts found in fighter aircraft literature. The performance of the suggested design is illustrated through full-scale USV experiments in the Trondheimsfjord.

Validation of a new design of tellurium dioide-irradiated target

Energy Technology Data Exchange (ETDEWEB)

Fllaoui, Aziz; Ghamad, Younes; Zoubir, Brahim; Ayaz, Zinel Abidine; El Morabiti, Aissam; Amayoud, Hafid [Centre National de l' Energie des Sciences et des Techniques Nucleaires, Rabat (Morocco); Chakir, El Mahjoub [Nuclear Physics Department, University Ibn Toufail, Kenitra (Morocco)

2016-10-15

Production of iodine-131 by neutron activation of tellurium in tellurium dioxide (TeO{sub 2}) material requires a target that meets the safety requirements. In a radiopharmaceutical production unit, a new lid for a can was designed, which permits tight sealing of the target by using tungsten inert gas welding. The leakage rate of all prepared targets was assessed using a helium mass spectrometer. The accepted leakage rate is ≤ 10 - 4 mbr.L/s, according to the approved safety report related to iodine-131 production in the TRIGA Mark II research reactor (TRIGA: Training, Research, Isotopes, General Atomics). To confirm the resistance of the new design to the irradiation conditions in the TRIGA Mark II research reactor's central thimble, a study of heat effect on the sealed targets for 7 hours in an oven was conducted and the leakage rates were evaluated. The results show that the tightness of the targets is ensured up to 600 .deg. C with the appearance of deformations on lids beyond 450 .deg. C. The study of heat transfer through the target was conducted by adopting a one-dimensional approximation, under consideration of the three transfer modes-convection, conduction, and radiation. The quantities of heat generated by gamma and neutron heating were calculated by a validated computational model for the neutronic simulation of the TRIGA Mark II research reactor using the Monte Carlo N-Particle transport code. Using the heat transfer equations according to the three modes of heat transfer, the thermal study of I-131 production by irradiation of the target in the central thimble showed that the temperatures of materials do not exceed the corresponding melting points. To validate this new design, several targets have been irradiated in the central thimble according to a preplanned irradiation program, going from 4 hours of irradiation at a power level of 0.5 MW up to 35 hours (7 h/d for 5 days a week) at 1.5 MW. The results show that the irradiated targets are

Validation of a New Design of Tellurium Dioxide-Irradiated Target

Directory of Open Access Journals (Sweden)

Aziz Fllaoui

2016-10-01

Full Text Available Production of iodine-131 by neutron activation of tellurium in tellurium dioxide (TeO2 material requires a target that meets the safety requirements. In a radiopharmaceutical production unit, a new lid for a can was designed, which permits tight sealing of the target by using tungsten inert gas welding. The leakage rate of all prepared targets was assessed using a helium mass spectrometer. The accepted leakage rate is ≤ 10−4 mbr.L/s, according to the approved safety report related to iodine-131 production in the TRIGA Mark II research reactor (TRIGA: Training, Research, Isotopes, General Atomics. To confirm the resistance of the new design to the irradiation conditions in the TRIGA Mark II research reactor's central thimble, a study of heat effect on the sealed targets for 7 hours in an oven was conducted and the leakage rates were evaluated. The results show that the tightness of the targets is ensured up to 600°C with the appearance of deformations on lids beyond 450°C. The study of heat transfer through the target was conducted by adopting a one-dimensional approximation, under consideration of the three transfer modes—convection, conduction, and radiation. The quantities of heat generated by gamma and neutron heating were calculated by a validated computational model for the neutronic simulation of the TRIGA Mark II research reactor using the Monte Carlo N-Particle transport code. Using the heat transfer equations according to the three modes of heat transfer, the thermal study of I-131 production by irradiation of the target in the central thimble showed that the temperatures of materials do not exceed the corresponding melting points. To validate this new design, several targets have been irradiated in the central thimble according to a preplanned irradiation program, going from 4 hours of irradiation at a power level of 0.5 MW up to 35 hours (7 h/d for 5 days a week at 1.5 MW. The results show that the irradiated targets are

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

International Nuclear Information System (INIS)

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

2005-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-11-15

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

High-Level Design for Ultra-Fast Software Defined Radio Prototyping on Multi-Processors Heterogeneous Platforms

OpenAIRE

Moy , Christophe; Raulet , Mickaël

2010-01-01

International audience; The design of Software Defined Radio (SDR) equipments (terminals, base stations, etc.) is still very challenging. We propose here a design methodology for ultra-fast prototyping on heterogeneous platforms made of GPPs (General Purpose Processors), DSPs (Digital Signal Processors) and FPGAs (Field Programmable Gate Array). Lying on a component-based approach, the methodology mainly aims at automating as much as possible the design from an algorithmic validation to a mul...

Target validation: linking target and chemical properties to desired product profile.

Science.gov (United States)

Wyatt, Paul G; Gilbert, Ian H; Read, Kevin D; Fairlamb, Alan H

2011-01-01

The discovery of drugs is a lengthy, high-risk and expensive business taking at least 12 years and is estimated to cost upwards of US$800 million for each drug to be successfully approved for clinical use. Much of this cost is driven by the late phase clinical trials and therefore the ability to terminate early those projects destined to fail is paramount to prevent unwanted costs and wasted effort. Although neglected diseases drug discovery is driven more by unmet medical need rather than financial considerations, the need to minimise wasted money and resources is even more vital in this under-funded area. To ensure any drug discovery project is addressing the requirements of the patients and health care providers and delivering a benefit over existing therapies, the ideal attributes of a novel drug needs to be pre-defined by a set of criteria called a target product profile. Using a target product profile the drug discovery process, clinical study design, and compound characteristics can be defined all the way back through to the suitability or druggability of the intended biochemical target. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success.

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...

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

Directory of Open Access Journals (Sweden)

Clare Selden

2018-04-01

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

High gain direct drive target designs and supporting experiments with KrF

International Nuclear Information System (INIS)

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

2013-01-01

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

Design of a tripartite network for the prediction of drug targets

Science.gov (United States)

Kunimoto, Ryo; Bajorath, Jürgen

2018-02-01

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

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

International Nuclear Information System (INIS)

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

1996-01-01

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

Toward 5G software defined radio receiver front-ends

CERN Document Server

Spiridon, Silvian

2016-01-01

This book introduces a new intuitive design methodology for the optimal design path for next-generation software defined radio front-ends (SDRXs). The methodology described empowers designers to "attack" the multi-standard environment in a parallel way rather than serially, providing a critical tool for any design methodology targeting 5G circuits and systems. Throughout the book the SDRX design follows the key wireless standards of the moment (i.e., GSM, WCDMA, LTE, Bluetooth, WLAN), since a receiver compatible with these standards is the most likely candidate for the first design iteration in a 5G deployment. The author explains the fundamental choice the designer has to make regarding the optimal channel selection: how much of the blockers/interferers will be filtered in the analog domain and how much will remain to be filtered in the digital domain. The system-level analysis the author describes entails the direct sampling architecture is treated as a particular case of mixer-based direct conversion archi...

Target designs for energetics experiments on the National Ignition Facility

International Nuclear Information System (INIS)

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

2008-01-01

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

New designs of LMJ targets for early ignition experiments

International Nuclear Information System (INIS)

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

2008-01-01

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

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.

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

Directory of Open Access Journals (Sweden)

Desheng Cheng

2016-04-01

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

Summary of the target-blanket breakout group

Energy Technology Data Exchange (ETDEWEB)

Capiello, M.; Bell, C. [Los Alamos National Laboratory, NM (United States); Barthold, W.

1995-10-01

This breakout group discussed a number of topics and issues pertaining to target and blanket concepts for accelerator-driven systems. This major component area is one marked by a broad spectrum of technical approaches. It is therefore less defined than other major component areas such as the accelerator and is at an earlier stage of technical needs and task specification. The working group did reach a number of general conclusions and recommendations that are summarized. The Conference and the Target/Blanket Breakout Group provided a first opportunity for people working on a variety of missions and concepts to get together and exchange information. A number of subcritical systems applicable for a spectrum of missions were proposed at the Conference and discussed in the Breakout Group. Missions included plutonium disposition, energy production, waste destruction, isotope production, and neutron scattering. The Target/Blanket Breakout Group also defined areas where parameters and data should be addressed as target/blanket design activities become more detailed and sophisticated.

Some Aspects on Filter Design for Target Tracking

Directory of Open Access Journals (Sweden)

Bertil Ekstrand

2012-01-01

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

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

International Nuclear Information System (INIS)

Reitz, T.

1996-01-01

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

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.

Targeted proteins for diabetes drug design

International Nuclear Information System (INIS)

Trang Nguyen, Ngoc Doan; Le, Ly Thi

2012-01-01

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

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

Directory of Open Access Journals (Sweden)

WANG Jian

2017-10-01

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

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.

Design and Implementation of the Automated Rendezvous Targeting Algorithms for Orion

Science.gov (United States)

DSouza, Christopher; Weeks, Michael

2010-01-01

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

Conceptual design of a high current ISOL target area at TRIUMF

International Nuclear Information System (INIS)

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

1993-05-01

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

Modern design of far-field target motion simulators

Science.gov (United States)

Hauser, Robin; Swamp, Michael; Havlicsek, Howard

2006-05-01

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

Design and Characterization of High Power Targets for RIB Generation

International Nuclear Information System (INIS)

Zhang, Y.

2001-01-01

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

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.

Design and Fabrication of Titanium Target for Portable Neutron Generator

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Science.gov (United States)

Rekand, Illimar Hugo; Brenk, Ruth

2017-09-01

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

Design Research as Conceptual Designing

DEFF Research Database (Denmark)

Ylirisku, Salu; Jacucci, Giulio; Sellen, Abigail

2015-01-01

define conceptual designing as a constructive framing and re-framing activity, which is mediated by and targeted at the creation of new design concepts. Conceptual designing as an approach is valuable for addressing the fuzziness and ambiguity typical of research that explores novel areas with new...... partners, methods and resources. It is by no means a new phenomenon, and the main contribution of the article is the clarification of conceptual designing as a particular approach to designing and researching. The approach embraces openness, resource-construction and collaboration. We conclude...... that conceptual designing can be especially useful in research and design projects that bring different kinds of people, organizations, technologies and domains together into the forming of new well-founded proposals for development. The presentation of conceptual designing in this paper is written...

Preliminary design implications of SSC fixed-target operation

International Nuclear Information System (INIS)

Zisman, M.S.

1984-06-01

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

National Ignition Facility subsystem design requirements target diagnostics subsystem SSDR 1.8.3

International Nuclear Information System (INIS)

Lee, D.

1996-01-01

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

Mock Target Window OTR and IR Design and Testing

Energy Technology Data Exchange (ETDEWEB)

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

2017-09-19

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

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

International Nuclear Information System (INIS)

Shamloo, Amir; Selahi, AmirAli; Madadelahi, Masoud

2016-01-01

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

An adaptive software defined radio design based on a standard space telecommunication radio system API

Science.gov (United States)

Xiong, Wenhao; Tian, Xin; Chen, Genshe; Pham, Khanh; Blasch, Erik

2017-05-01

Software defined radio (SDR) has become a popular tool for the implementation and testing for communications performance. The advantage of the SDR approach includes: a re-configurable design, adaptive response to changing conditions, efficient development, and highly versatile implementation. In order to understand the benefits of SDR, the space telecommunication radio system (STRS) was proposed by NASA Glenn research center (GRC) along with the standard application program interface (API) structure. Each component of the system uses a well-defined API to communicate with other components. The benefit of standard API is to relax the platform limitation of each component for addition options. For example, the waveform generating process can support a field programmable gate array (FPGA), personal computer (PC), or an embedded system. As long as the API defines the requirements, the generated waveform selection will work with the complete system. In this paper, we demonstrate the design and development of adaptive SDR following the STRS and standard API protocol. We introduce step by step the SDR testbed system including the controlling graphic user interface (GUI), database, GNU radio hardware control, and universal software radio peripheral (USRP) tranceiving front end. In addition, a performance evaluation in shown on the effectiveness of the SDR approach for space telecommunication.

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

International Nuclear Information System (INIS)

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

2006-01-01

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

Generic study on the design and operation of high power targets

Directory of Open Access Journals (Sweden)

A. Ahmad

2014-02-01

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

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

Science.gov (United States)

Laffite, S.; Loiseau, P.

2010-10-01

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

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

International Nuclear Information System (INIS)

Laffite, S.; Loiseau, P.

2010-01-01

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

Establishing seismic design criteria to achieve an acceptable seismic margin

International Nuclear Information System (INIS)

Kennedy, R.P.

1997-01-01

In order to develop a risk based seismic design criteria the following four issues must be addressed: (1) What target annual probability of seismic induced unacceptable performance is acceptable? (2). What minimum seismic margin is acceptable? (3) Given the decisions made under Issues 1 and 2, at what annual frequency of exceedance should the Safe Shutdown Earthquake ground motion be defined? (4) What seismic design criteria should be established to reasonably achieve the seismic margin defined under Issue 2? The first issue is purely a policy decision and is not addressed in this paper. Each of the other three issues are addressed. Issues 2 and 3 are integrally tied together so that a very large number of possible combinations of responses to these two issues can be used to achieve the target goal defined under Issue 1. Section 2 lays out a combined approach to these two issues and presents three potentially attractive combined resolutions of these two issues which reasonably achieves the target goal. The remainder of the paper discusses an approach which can be used to develop seismic design criteria aimed at achieving the desired seismic margin defined in resolution of Issue 2. Suggestions for revising existing seismic design criteria to more consistently achieve the desired seismic margin are presented

Design specification for the European Spallation Source neutron generating target element

International Nuclear Information System (INIS)

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

2017-01-01

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

Design specification for the European Spallation Source neutron generating target element

Energy Technology Data Exchange (ETDEWEB)

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

2017-06-01

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

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

Science.gov (United States)

Lund, Glenn

1993-01-01

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

Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems

Science.gov (United States)

Mullen, Douglas Gurnett

Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution. Motivated by the problems experienced with the modular design, the actual composition of nanoparticle-ligand distributions were examined using a model dendrimer-ligand system. High Pressure Liquid Chromatography (HPLC) resolved the distribution of components in samples with mean ligand/dendrimer ratios ranging from 0.4 to 13. A peak fitting analysis enabled the quantification of the component distribution. Quantified distributions were found to be significantly more heterogeneous than commonly expected and standard analytical parameters, namely the mean ligand/nanoparticle ratio, failed to adequately represent the component heterogeneity. The distribution of components was also found to be sensitive to particle modifications that preceded the ligand conjugation. With the knowledge gained from this detailed distribution analysis, a new platform design was developed to provide a system with dramatically improved control over the number of components and with improved batch reproducibility. Using semi-preparative HPLC, individual dendrimer-ligand components were isolated. The isolated dendrimer with precise numbers of ligands were characterized by NMR and analytical HPLC. In total, nine different dendrimer-ligand components were obtained with degrees of purity ≥80%. This system has the potential to serve as a platform to which a precise number of functional molecules

A unified modeling approach for physical experiment design and optimization in laser driven inertial confinement fusion

Energy Technology Data Exchange (ETDEWEB)

Li, Haiyan [Mechatronics Engineering School of Guangdong University of Technology, Guangzhou 510006 (China); Huang, Yunbao, E-mail: Huangyblhy@gmail.com [Mechatronics Engineering School of Guangdong University of Technology, Guangzhou 510006 (China); Jiang, Shaoen, E-mail: Jiangshn@vip.sina.com [Laser Fusion Research Center, China Academy of Engineering Physics, Mianyang 621900 (China); Jing, Longfei, E-mail: scmyking_2008@163.com [Laser Fusion Research Center, China Academy of Engineering Physics, Mianyang 621900 (China); Tianxuan, Huang; Ding, Yongkun [Laser Fusion Research Center, China Academy of Engineering Physics, Mianyang 621900 (China)

2015-11-15

Highlights: • A unified modeling approach for physical experiment design is presented. • Any laser facility can be flexibly defined and included with two scripts. • Complex targets and laser beams can be parametrically modeled for optimization. • Automatically mapping of laser beam energy facilitates targets shape optimization. - Abstract: Physical experiment design and optimization is very essential for laser driven inertial confinement fusion due to the high cost of each shot. However, only limited experiments with simple structure or shape on several laser facilities can be designed and evaluated in available codes, and targets are usually defined by programming, which may lead to it difficult for complex shape target design and optimization on arbitrary laser facilities. A unified modeling approach for physical experiment design and optimization on any laser facilities is presented in this paper. Its core idea includes: (1) any laser facility can be flexibly defined and included with two scripts, (2) complex shape targets and laser beams can be parametrically modeled based on features, (3) an automatically mapping scheme of laser beam energy onto discrete mesh elements of targets enable targets or laser beams be optimized without any additional interactive modeling or programming, and (4) significant computation algorithms are additionally presented to efficiently evaluate radiation symmetry on the target. Finally, examples are demonstrated to validate the significance of such unified modeling approach for physical experiments design and optimization in laser driven inertial confinement fusion.

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

Science.gov (United States)

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

2015-09-01

A cancer-targeted conjugate of the selenadiazole derivative BSeC (benzo[1,2,5] selenadiazole-5-carboxylic acid) with RGD peptide as targeting molecule and PEI (polyethylenimine) as a linker is rationally designed and synthesized in the present study. The results show that RGD-PEI-BSeC forms nanoparticles in aqueous solution with a core-shell nanostructure and high stability under physiological conditions. This rational design effectively enhances the selective cellular uptake and cellular retention of BSeC in human glioma cells, and increases its selectivity between cancer and normal cells. The nanoparticles enter the cells through receptor-mediated endocytosis via clathrin-mediated and nystatin-dependent lipid raft-mediated pathways. Internalized nanoparticles trigger glioma cell apoptosis by activation of ROS-mediated p53 phosphorylation. Therefore, this study provides a strategy for the rational design of selenium-containing cancer-targeted theranostics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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)

New "Risk-Targeted" Seismic Maps Introduced into Building Codes

Science.gov (United States)

Luco, Nicholas; Garrett, B.; Hayes, J.

2012-01-01

Throughout most municipalities of the United States, structural engineers design new buildings using the U.S.-focused International Building Code (IBC). Updated editions of the IBC are published every 3 years. The latest edition (2012) contains new "risk-targeted maximum considered earthquake" (MCER) ground motion maps, which are enabling engineers to incorporate a more consistent and better defined level of seismic safety into their building designs.

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Defining the RNA Internal Loops Preferred by Benzimidazole Derivatives via Two-Dimensional Combinatorial Screening and Computational Analysis

Science.gov (United States)

Velagapudi, Sai Pradeep; Seedhouse, Steven J.; French, Jonathan

2011-01-01

RNA is an important therapeutic target, however, RNA targets are generally underexploited due to a lack of understanding of the small molecules that bind RNA and the RNA motifs that bind small molecules. Herein, we describe the identification of the RNA internal loops derived from a 4096-member 3×3 nucleotide loop library that are the most specific and highest affinity binders to a series of four designer, drug-like benzimidazoles. These studies establish a potentially general protocol to define the highest affinity and most specific RNA motif targets for heterocyclic small molecules. Such information could be used to target functionally important RNAs in genomic sequence. PMID:21604752

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

International Nuclear Information System (INIS)

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

2002-01-01

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

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.

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

Science.gov (United States)

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

2015-01-01

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

RNAblueprint: flexible multiple target nucleic acid sequence design.

Science.gov (United States)

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

2017-09-15

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

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

NARCIS (Netherlands)

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

2009-01-01

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

Miniature EVA Software Defined Radio

Science.gov (United States)

Pozhidaev, Aleksey

2012-01-01

As NASA embarks upon developing the Next-Generation Extra Vehicular Activity (EVA) Radio for deep space exploration, the demands on EVA battery life will substantially increase. The number of modes and frequency bands required will continue to grow in order to enable efficient and complex multi-mode operations including communications, navigation, and tracking applications. Whether conducting astronaut excursions, communicating to soldiers, or first responders responding to emergency hazards, NASA has developed an innovative, affordable, miniaturized, power-efficient software defined radio that offers unprecedented power-efficient flexibility. This lightweight, programmable, S-band, multi-service, frequency- agile EVA software defined radio (SDR) supports data, telemetry, voice, and both standard and high-definition video. Features include a modular design, an easily scalable architecture, and the EVA SDR allows for both stationary and mobile battery powered handheld operations. Currently, the radio is equipped with an S-band RF section. However, its scalable architecture can accommodate multiple RF sections simultaneously to cover multiple frequency bands. The EVA SDR also supports multiple network protocols. It currently implements a Hybrid Mesh Network based on the 802.11s open standard protocol. The radio targets RF channel data rates up to 20 Mbps and can be equipped with a real-time operating system (RTOS) that can be switched off for power-aware applications. The EVA SDR's modular design permits implementation of the same hardware at all Network Nodes concept. This approach assures the portability of the same software into any radio in the system. It also brings several benefits to the entire system including reducing system maintenance, system complexity, and development cost.

MOOC Design Workshop

DEFF Research Database (Denmark)

Nørgård, Rikke Toft; Mor, Yishay; Warburton, Steven

2016-01-01

For the last two years we have been running a series of successful MOOC design workshops. These workshops build on previous work in learning design and MOOC design patterns. The aim of these workshops is to aid practitioners in defining and conceptualising educational innovations (predominantly......, but not exclusively MOOCs) which are based on an empathic user-centered view of the target learners and teachers. In this paper, we share the main principles, patterns and resources of our workshops and present some initial results for their effectiveness...

The target effect: visual memory for unnamed search targets.

Science.gov (United States)

Thomas, Mark D; Williams, Carrick C

2014-01-01

Search targets are typically remembered much better than other objects even when they are viewed for less time. However, targets have two advantages that other objects in search displays do not have: They are identified categorically before the search, and finding them represents the goal of the search task. The current research investigated the contributions of both of these types of information to the long-term visual memory representations of search targets. Participants completed either a predefined search or a unique-object search in which targets were not defined with specific categorical labels before searching. Subsequent memory results indicated that search target memory was better than distractor memory even following ambiguously defined searches and when the distractors were viewed significantly longer. Superior target memory appears to result from a qualitatively different representation from those of distractor objects, indicating that decision processes influence visual memory.

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

International Nuclear Information System (INIS)

Tabak, M.; Callahan-Miller, D.

1997-01-01

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

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

International Nuclear Information System (INIS)

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

2001-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-10-15

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

Primary design of Si cooling arm structure in ICF cryogenic target

International Nuclear Information System (INIS)

Zhang Yong; Yi Yong; Tang Changhuan; Zhang Jicheng

2013-01-01

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

Inflation targeting and core inflation

OpenAIRE

Julie Smith

2005-01-01

This paper examines the interaction of core inflation and inflation targeting as a monetary policy regime. Interest in core inflation has grown because of inflation targeting. Core inflation is defined in numerous ways giving rise to many potential measures; this paper defines core inflation as the best forecaster of inflation. A cross-country study finds before the start of inflation targeting, but not after, core inflation differs between non-inflation targeters and inflation targeters. Thr...

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-06-15

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

Recycling issues facing target and RTL materials of inertial fusion designs

International Nuclear Information System (INIS)

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

2005-01-01

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

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

International Nuclear Information System (INIS)

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

1991-12-01

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

Design and implementation of typical target image database system

International Nuclear Information System (INIS)

Qin Kai; Zhao Yingjun

2010-01-01

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

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

International Nuclear Information System (INIS)

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

2004-01-01

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

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

International Nuclear Information System (INIS)

Atzeni, S; Marocchino, A; Schiavi, A

2015-01-01

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

Multiple Target Laser Designator (MTLD)

Science.gov (United States)

2007-03-01

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

An FPGA Scalable Software Defined Radio Platform Design for Educational and Research Purposes

Directory of Open Access Journals (Sweden)

Marcos Hervás

2016-06-01

Full Text Available In a digital modem design, the integration of the Analog to Digital Converters (ADC and Digital to Analog Converters (DAC with the core processor is usually a major issue for the designer. In this paper an FPGA scalable Software Defined Radio platform based on a Spartan-6 as a control unit is presented, developed for both educational and research purposes, which can fit the different application requirements in terms of analog front-end performance, processing unit and cost. The resolution and sampling frequency of the analog front-end are its main adjustable parameters. The processing core requirements involve the FPGA and the communication ports. A multidisciplinary working group was required to design a high performance system for both analog front-end and digital processing core in terms of signal integrity and electromagnetic compatibility. The platform has 5 different peripheral ports ranging from 16 kbps to 2.5 Gbps. The communication ports allow our students to develop a high range of applications for both on-site and online courses applying teaching methodology based on learning by doing using a real system to help them to reach other transversal skills.

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

Science.gov (United States)

Macfarlane, Joseph; Golovkin, Igor; Sebald, James

2017-10-01

The 3-D view factor code VISRAD is widely used in designing HEDP experiments at major laser and pulsed-power facilities, including NIF, OMEGA, OMEGA-EP, ORION, Z, and LMJ. It simulates target designs by generating a 3-D grid of surface elements, utilizing a variety of 3-D primitives and surface removal algorithms, and can be used to compute the radiation flux throughout the surface element grid by computing element-to-element view factors and solving power balance equations. Target set-up and beam pointing are facilitated by allowing users to specify positions and angular orientations using a variety of coordinates systems (e.g., that of any laser beam, target component, or diagnostic port). Analytic modeling for laser beam spatial profiles for OMEGA DPPs and NIF CPPs is used to compute laser intensity profiles throughout the grid of surface elements. VISRAD includes a variety of user-friendly graphics for setting up targets and displaying results, can readily display views from any point in space, and can be used to generate image sequences for animations. We will discuss recent improvements to conveniently assess beam capture on target and beam clearance of diagnostic components, as well as plans for future developments.

Toward defining deep brain stimulation targets in MNI space: A subcortical atlas based on multimodal MRI, histology and structural connectivity.

Science.gov (United States)

Ewert, Siobhan; Plettig, Philip; Li, Ningfei; Chakravarty, M Mallar; Collins, D Louis; Herrington, Todd M; Kühn, Andrea A; Horn, Andreas

2018-04-15

Three-dimensional atlases of subcortical brain structures are valuable tools to reference anatomy in neuroscience and neurology. For instance, they can be used to study the position and shape of the three most common deep brain stimulation (DBS) targets, the subthalamic nucleus (STN), internal part of the pallidum (GPi) and ventral intermediate nucleus of the thalamus (VIM) in spatial relationship to DBS electrodes. Here, we present a composite atlas based on manual segmentations of a multimodal high resolution brain template, histology and structural connectivity. In a first step, four key structures were defined on the template itself using a combination of multispectral image analysis and manual segmentation. Second, these structures were used as anchor points to coregister a detailed histological atlas into standard space. Results show that this approach significantly improved coregistration accuracy over previously published methods. Finally, a sub-segmentation of STN and GPi into functional zones was achieved based on structural connectivity. The result is a composite atlas that defines key nuclei on the template itself, fills the gaps between them using histology and further subdivides them using structural connectivity. We show that the atlas can be used to segment DBS targets in single subjects, yielding more accurate results compared to priorly published atlases. The atlas will be made publicly available and constitutes a resource to study DBS electrode localizations in combination with modern neuroimaging methods. Copyright © 2017 Elsevier Inc. All rights reserved.

EXPERIMENTAL TARGET INJECTION AND TRACKING SYSTEM CONSTRUCTION AND SINGLE SHOT TESTING

International Nuclear Information System (INIS)

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

2003-01-01

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

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

International Nuclear Information System (INIS)

Chon-Sen, N.

2009-01-01

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

Neutronics for the SNS long wavelength target station

International Nuclear Information System (INIS)

Iverson, E.B.; Micklich, B.J.; Carpenter, J.M.

2001-01-01

One of the most significant and adventurous aspects of the LWTS (Long Wavelength Target Station) design concept is the use of slab moderators, historically considered to be awkward due to the high contamination of the neutron beams with fast and high- energy neutrons. Concern over this contamination is the reason behind our proposition that none of the beam on a slab moderator should be viewed directly, that is, without a curved guide, compact bender, or other fast and high-energy neutron filter. We made a large number of calculations concerning fast neutron source term of the solid target-slab moderator configuration with monolithic solid methane, which includes a curved guide or compact beam bender. We also made optimization on target position, beam void open angle, target gap and target division of the split target configuration. All fast and high-energy neutron spectra will be reported as lethargy spectra, normalized to 1 eV. In this way, we will attempt to define the 'cost' of using slab moderators as a function of the payoff gained from their use. We report these data for general information and discussion, and further draw the conclusions. Numerous issues have arisen in the course of the LWTS concept development, which require more information than is now in hand to provide the basis for detailed design and for potential design innovations. Some of the R and D issues are listed, along with proposed efforts to fill design needs. We have devised a highly effective 'base case' conceptual design for LWTS, which we are still evaluating and optimizing. LWTS will provide distinctly unique capabilities complimentary to SNS (Spallation Neutron Source) HPTS (High Power Target Station). The configuration of LWTS is strongly coupled to instrument requirements through close interaction with scientists formulating the science case and instrument suite. (Tanaka, Y.)

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

NARCIS (Netherlands)

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

2016-01-01

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

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

NARCIS (Netherlands)

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

2016-01-01

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

Target design for materials processing very far from equilibrium

Science.gov (United States)

Barnard, John J.; Schenkel, Thomas

2016-10-01

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

The ISIS target

International Nuclear Information System (INIS)

Carne, A.; Broome, T.A.; Hogston, J.R.; Holding, M.

1989-01-01

This presentation discusses the two target failures that have occurred, gives the understanding of the causes and indicates the steps being taken to alleviate the problems. At the outset of the design it was understood that the target would have a finite lifetime, due to radiation damage effects, exacerbated by mechanical damage due to thermal cycling and fatigue. Estimates of target lifetime at full intensity are about 2 years for radiation damage swelling and about 10E4 gross thermal excursions. The latter number is the one which gives uncertainty in defining the life of the target, since it is dependent on the reliability of the accelerator and quality of the proton beam. The commissioning of an accelerator system and bringing it up to high beam intensities have their own special problems. There must be protection of components against uncontrolled beam loss, which produces thermal damage, prompt radiation and induced activity. Fast beam trips for beam loss protection, or equipment failures, result in quenches from high temperature in the target which get bigger with increasing beam intensity. But the target itself is a difficult device to make, taking about 12 months to manufacture. Further, changing one is a complex and time consuming task, not without its hazards. There is thus something of a balancing act to bring the accelerator towards specification before the target fails due to thermal cycling fatigue. In the early days of ISIS beam loss protection was the dominant consideration and the target was regarded somewhat as a sacrificial lamb to the goddess of machine reliability. 2 refs., 6 figs

Comparison of internal target volumes defined on 3-dimensional, 4-dimensonal, and cone-beam CT images of non-small-cell lung cancer

Directory of Open Access Journals (Sweden)

Li F

2016-11-01

Full Text Available Fengxiang Li,1 Jianbin Li,1 Zhifang Ma,1 Yingjie Zhang,1 Jun Xing,1 Huanpeng Qi,1 Dongping Shang21Department of Radiation Oncology, 2Department of Big Bore CT Room, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of ChinaPurpose: The purpose of this study was to compare the positional and volumetric differences of internal target volumes defined on three-dimensional computed tomography (3DCT, four-dimensional CT (4DCT, and cone-beam CT (CBCT images of non-small-cell lung cancer (NSCLC. Materials and methods: Thirty-one patients with NSCLC sequentially underwent 3DCT and 4DCT simulation scans of the thorax during free breathing. The first CBCT was performed and registered to the planning CT using the bony anatomy registration during radiotherapy. The gross tumor volumes were contoured on the basis of 3DCT, maximum intensity projection (MIP of 4DCT, and CBCT. CTV3D (clinical target volume, internal target volumes, ITVMIP and ITVCBCT, were defined with a 7 mm margin accounting for microscopic disease. ITV10 mm and ITV5 mm were defined on the basis of CTV3D: ITV10 mm with a 5 mm margin in left–right (LR, anterior–posterior (AP directions and 10 mm in cranial–caudal (CC direction; ITV5 mm with an isotropic internal margin (IM of 5 mm. The differences in the position, size, Dice’s similarity coefficient (DSC and inclusion relation of different volumes were evaluated.Results: The median size ratios of ITV10 mm, ITV5 mm, and ITVMIP to ITVCBCT were 2.33, 1.88, and 1.03, respectively, for tumors in the upper lobe and 2.13, 1.76, and 1.1, respectively, for tumors in the middle-lower lobe. The median DSCs of ITV10 mm, ITV5 mm, ITVMIP, and ITVCBCT were 0.6, 0.66, and 0.83 for all patients. The median percentages of ITVCBCT not included in ITV10 mm, ITV5 mm, and ITVMIP were 0.1%, 1.63%, and 15.21%, respectively, while the median percentages of ITV10 mm, ITV5 mm

Soft computing model for optimized siRNA design by identifying off target possibilities using artificial neural network model.

Science.gov (United States)

Murali, Reena; John, Philips George; Peter S, David

2015-05-15

The ability of small interfering RNA (siRNA) to do posttranscriptional gene regulation by knocking down targeted genes is an important research topic in functional genomics, biomedical research and in cancer therapeutics. Many tools had been developed to design exogenous siRNA with high experimental inhibition. Even though considerable amount of work has been done in designing exogenous siRNA, design of effective siRNA sequences is still a challenging work because the target mRNAs must be selected such that their corresponding siRNAs are likely to be efficient against that target and unlikely to accidentally silence other transcripts due to sequence similarity. In some cases, siRNAs may tolerate mismatches with the target mRNA, but knockdown of genes other than the intended target could make serious consequences. Hence to design siRNAs, two important concepts must be considered: the ability in knocking down target genes and the off target possibility on any nontarget genes. So before doing gene silencing by siRNAs, it is essential to analyze their off target effects in addition to their inhibition efficacy against a particular target. Only a few methods have been developed by considering both efficacy and off target possibility of siRNA against a gene. In this paper we present a new design of neural network model with whole stacking energy (ΔG) that enables to identify the efficacy and off target effect of siRNAs against target genes. The tool lists all siRNAs against a particular target with their inhibition efficacy and number of matches or sequence similarity with other genes in the database. We could achieve an excellent performance of Pearson Correlation Coefficient (R=0. 74) and Area Under Curve (AUC=0.906) when the threshold of whole stacking energy is ≥-34.6 kcal/mol. To the best of the author's knowledge, this is one of the best score while considering the "combined efficacy and off target possibility" of siRNA for silencing a gene. The proposed model

A real-time brain-machine interface combining motor target and trajectory intent using an optimal feedback control design.

Directory of Open Access Journals (Sweden)

Maryam M Shanechi

Full Text Available Real-time brain-machine interfaces (BMI have focused on either estimating the continuous movement trajectory or target intent. However, natural movement often incorporates both. Additionally, BMIs can be modeled as a feedback control system in which the subject modulates the neural activity to move the prosthetic device towards a desired target while receiving real-time sensory feedback of the state of the movement. We develop a novel real-time BMI using an optimal feedback control design that jointly estimates the movement target and trajectory of monkeys in two stages. First, the target is decoded from neural spiking activity before movement initiation. Second, the trajectory is decoded by combining the decoded target with the peri-movement spiking activity using an optimal feedback control design. This design exploits a recursive Bayesian decoder that uses an optimal feedback control model of the sensorimotor system to take into account the intended target location and the sensory feedback in its trajectory estimation from spiking activity. The real-time BMI processes the spiking activity directly using point process modeling. We implement the BMI in experiments consisting of an instructed-delay center-out task in which monkeys are presented with a target location on the screen during a delay period and then have to move a cursor to it without touching the incorrect targets. We show that the two-stage BMI performs more accurately than either stage alone. Correct target prediction can compensate for inaccurate trajectory estimation and vice versa. The optimal feedback control design also results in trajectories that are smoother and have lower estimation error. The two-stage decoder also performs better than linear regression approaches in offline cross-validation analyses. Our results demonstrate the advantage of a BMI design that jointly estimates the target and trajectory of movement and more closely mimics the sensorimotor control system.

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

DEFF Research Database (Denmark)

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

2017-01-01

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

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

International Nuclear Information System (INIS)

Steiner, E.W.

1992-01-01

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

Maximizing in vivo target clearance by design of pH-dependent target binding antibodies with altered affinity to FcRn.

Science.gov (United States)

Yang, Danlin; Giragossian, Craig; Castellano, Steven; Lasaro, Marcio; Xiao, Haiguang; Saraf, Himanshu; Hess Kenny, Cynthia; Rybina, Irina; Huang, Zhong-Fu; Ahlberg, Jennifer; Bigwarfe, Tammy; Myzithras, Maria; Waltz, Erica; Roberts, Simon; Kroe-Barrett, Rachel; Singh, Sanjaya

2017-10-01

Antibodies with pH-dependent binding to both target antigens and neonatal Fc receptor (FcRn) provide an alternative tool to conventional neutralizing antibodies, particularly for therapies where reduction in antigen level is challenging due to high target burden. However, the requirements for optimal binding kinetic framework and extent of pH dependence for these antibodies to maximize target clearance from circulation are not well understood. We have identified a series of naturally-occurring high affinity antibodies with pH-dependent target binding properties. By in vivo studies in cynomolgus monkeys, we show that pH-dependent binding to the target alone is not sufficient for effective target removal from circulation, but requires Fc mutations that increase antibody binding to FcRn. Affinity-enhanced pH-dependent FcRn binding that is double-digit nM at pH 7.4 and single-digit nM at pH 6 achieved maximal target reduction when combined with similar target binding affinities in reverse pH directions. Sustained target clearance below the baseline level was achieved 3 weeks after single-dose administration at 1.5 mg/kg. Using the experimentally derived mechanistic model, we demonstrate the essential kinetic interplay between target turnover and antibody pH-dependent binding during the FcRn recycling, and identify the key components for achieving maximal target clearance. These results bridge the demand for improved patient dosing convenience with the "know-how" of therapeutic modality by design.

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

International Nuclear Information System (INIS)

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

2001-01-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Defining Requirements and Related Methods for Designing Sensorized Garments

Directory of Open Access Journals (Sweden)

Giuseppe Andreoni

2016-05-01

Full Text Available Designing smart garments has strong interdisciplinary implications, specifically related to user and technical requirements, but also because of the very different applications they have: medicine, sport and fitness, lifestyle monitoring, workplace and job conditions analysis, etc. This paper aims to discuss some user, textile, and technical issues to be faced in sensorized clothes development. In relation to the user, the main requirements are anthropometric, gender-related, and aesthetical. In terms of these requirements, the user’s age, the target application, and fashion trends cannot be ignored, because they determine the compliance with the wearable system. Regarding textile requirements, functional factors—also influencing user comfort—are elasticity and washability, while more technical properties are the stability of the chemical agents’ effects for preserving the sensors’ efficacy and reliability, and assuring the proper duration of the product for the complete life cycle. From the technical side, the physiological issues are the most important: skin conductance, tolerance, irritation, and the effect of sweat and perspiration are key factors for reliable sensing. Other technical features such as battery size and duration, and the form factor of the sensor collector, should be considered, as they affect aesthetical requirements, which have proven to be crucial, as well as comfort and wearability.

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

International Nuclear Information System (INIS)

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

1997-09-01

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

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

Directory of Open Access Journals (Sweden)

Mahmoud ElHefnawi

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

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

International Nuclear Information System (INIS)

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

2002-01-01

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

Heterogeneity in head and neck IMRT target design and clinical practice

International Nuclear Information System (INIS)

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

2012-01-01

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

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

Science.gov (United States)

Hoyer, Annemarie

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2006-06-15

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

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

Science.gov (United States)

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

2006-06-01

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

How to Tackle the Challenge of siRNA Delivery with Sequence-Defined Oligoamino Amides.

Science.gov (United States)

Reinhard, Sören; Wagner, Ernst

2017-01-01

RNA interference (RNAi) as a mechanism of gene regulation provides exciting opportunities for medical applications. Synthetic small interfering RNA (siRNA) triggers the knockdown of complementary mRNA sequences in a catalytic fashion and has to be delivered into the cytosol of the targeted cells. The design of adequate carrier systems to overcome multiple extracellular and intracellular roadblocks within the delivery process has utmost importance. Cationic polymers form polyplexes through electrostatic interaction with negatively charged nucleic acids and present a promising class of carriers. Issues of polycations regarding toxicity, heterogeneity, and polydispersity can be overcome by solid-phase-assisted synthesis of sequence-defined cationic oligomers. These medium-sized highly versatile nucleic acid carriers display low cytotoxicity and can be modified and tailored in multiple ways to meet specific requirements of nucleic acid binding, polyplex size, shielding, targeting, and intracellular release of the cargo. In this way, sequence-defined cationic oligomers can mimic the dynamic and bioresponsive behavior of viruses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

International Nuclear Information System (INIS)

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

2000-01-01

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

Lujan Center Mark-IV Target Neutronics Design Internal Review Report

Energy Technology Data Exchange (ETDEWEB)

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

2018-02-26

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

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

International Nuclear Information System (INIS)

Gadalla, Mamdouh A.

2015-01-01

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

Accelerator-driven subcritical facility:Conceptual design development

Science.gov (United States)

Gohar, Yousry; Bolshinsky, Igor; Naberezhnev, Dmitry; Duo, Jose; Belch, Henry; Bailey, James

2006-06-01

A conceptual design development of an accelerator-driven subcritical facility has been carried out in the preparation of a joint activity with Kharkov Institute of Physics and Technology of Ukraine. The main functions of the facility are the medical isotope production and the support of the Ukraine nuclear industry. An electron accelerator is considered to drive the subcritical assembly. The neutron source intensity and spectrum have been studied. The energy deposition, spatial neutron generation, neutron utilization fraction, and target dimensions have been quantified to define the main target performance parameters, and to select the target material and beam parameters. Different target conceptual designs have been developed based the engineering requirements including heat transfer, thermal hydraulics, structure, and material issues. The subcritical assembly is designed to obtain the highest possible neutron flux level with a Keff of 0.98. Different fuel materials, uranium enrichments, and reflector materials are considered in the design process. The possibility of using low enrichment uranium without penalizing the facility performance is carefully evaluated. The mechanical design of the facility has been developed to maximize its utility and minimize the time for replacing the target and the fuel assemblies. Safety, reliability, and environmental considerations are included in the facility conceptual design. The facility is configured to accommodate future design improvements, upgrades, and new missions. In addition, it has large design margins to accommodate different operating conditions and parameters. In this paper, the conceptual design and the design analyses of the facility will be presented.

Computer-aided Molecular Design of Compounds Targeting Histone Modifying Enzymes

Science.gov (United States)

Andreoli, Federico; Del Rio, Alberto

2015-01-01

Growing evidences show that epigenetic mechanisms play crucial roles in the genesis and progression of many physiopathological processes. As a result, research in epigenetic grew at a fast pace in the last decade. In particular, the study of histone post-translational modifications encountered an extraordinary progression and many modifications have been characterized and associated to fundamental biological processes and pathological conditions. Histone modifications are the catalytic result of a large set of enzyme families that operate covalent modifications on specific residues at the histone tails. Taken together, these modifications elicit a complex and concerted processing that greatly contribute to the chromatin remodeling and may drive different pathological conditions, especially cancer. For this reason, several epigenetic targets are currently under validation for drug discovery purposes and different academic and industrial programs have been already launched to produce the first pre-clinical and clinical outcomes. In this scenario, computer-aided molecular design techniques are offering important tools, mainly as a consequence of the increasing structural information available for these targets. In this mini-review we will briefly discuss the most common types of known histone modifications and the corresponding operating enzymes by emphasizing the computer-aided molecular design approaches that can be of use to speed-up the efforts to generate new pharmaceutically relevant compounds. PMID:26082827

Defining cyber warfare

Directory of Open Access Journals (Sweden)

Dragan D. Mladenović

2012-04-01

Full Text Available Cyber conflicts represent a new kind of warfare that is technologically developing very rapidly. Such development results in more frequent and more intensive cyber attacks undertaken by states against adversary targets, with a wide range of diverse operations, from information operations to physical destruction of targets. Nevertheless, cyber warfare is waged through the application of the same means, techniques and methods as those used in cyber criminal, terrorism and intelligence activities. Moreover, it has a very specific nature that enables states to covertly initiate attacks against their adversaries. The starting point in defining doctrines, procedures and standards in the area of cyber warfare is determining its true nature. In this paper, a contribution to this effort was made through the analysis of the existing state doctrines and international practice in the area of cyber warfare towards the determination of its nationally acceptable definition.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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

International Nuclear Information System (INIS)

Mensink, D.L.

1994-01-01

A preconceptual engineering design has been developed for the 3 He Target/Blanket (T/B) System for the Accelerator Production of Tritium Project. This concept uses an array of pressure tubes containing tungsten rods for the neutron spallation source and 3 He gas contained in a metal tank and blanket tubes as the tritium production material. The engineering design is based on a physics model optimized for efficient tritium production. Principle engineering consideration were: provisions for cooling all materials including the 3 He gas; containment of the gas and radionuclides; remote handling; material compatibility; minimization of 3 He, D 2 O, and activated waste; modularity; and manufacturability. The design provides a basis for estimating the cost to implement the system

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

Science.gov (United States)

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

2018-04-01

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

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

International Nuclear Information System (INIS)

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

2003-01-01

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

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

International Nuclear Information System (INIS)

Ludwig, S.B.

2003-01-01

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

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

International Nuclear Information System (INIS)

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

1997-03-01

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

Modern Prodrug Design for Targeted Oral Drug Delivery

Directory of Open Access Journals (Sweden)

Arik Dahan

2014-10-01

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

Automated design of degenerate codon libraries.

Science.gov (United States)

Mena, Marco A; Daugherty, Patrick S

2005-12-01

Degenerate codon libraries are frequently used in protein engineering and evolution studies but are often limited to targeting a small number of positions to adequately limit the search space. To mitigate this, codon degeneracy can be limited using heuristics or previous knowledge of the targeted positions. To automate design of libraries given a set of amino acid sequences, an algorithm (LibDesign) was developed that generates a set of possible degenerate codon libraries, their resulting size, and their score relative to a user-defined scoring function. A gene library of a specified size can then be constructed that is representative of the given amino acid distribution or that includes specific sequences or combinations thereof. LibDesign provides a new tool for automated design of high-quality protein libraries that more effectively harness existing sequence-structure information derived from multiple sequence alignment or computational protein design data.

Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-γ and IL-17 production in blood from TB + patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras.

Science.gov (United States)

Alvarez-Corrales, Nancy; Ahmed, Raija K; Rodriguez, Carol A; Balaji, Kithiganahalli N; Rivera, Rebeca; Sompallae, Ramakrishna; Vudattu, Nalini K; Hoffner, Sven E; Zumla, Alimuddin; Pineda-Garcia, Lelany; Maeurer, Markus

2013-03-06

A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-γ and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-γ production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. The pattern of immune target recognition is different in regard to IFN-γ and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras.

Topical report on a preconceptual design for the Spallation-Induced Lithium Conversion (SILC) target for the accelerator production of tritium (APT)

International Nuclear Information System (INIS)

Van Tuyle, G.J.; Cokinos, D.M.; Czajkowski, C.; Franz, E.M.; Kroeger, P.; Todosow, M.; Youngblood, R.; Zucker, M.

1993-01-01

The preconceptual design of the APT Li-Al target system, also referred to as the Spallation-Induced Lithium Conversion (SILC), target system, is summarized in this report. The system has been designed to produce a ''3/8 Goal'' quantity of tritium using the 200-mA, 1.0 GeV proton beam emerging from the LANL-designed LINAC. The SILC target system consists of a beam expander, a heavy-water-cooled lead spallation neutron source assembly surrounded by light-water-cooled Li-Al blankets, a target window, heat removal systems, and related safety systems. The preconceptual design of each of these major components is described. Descriptions are also provided for the target fabrication, tritium extraction, and waste-steam processes. Performance characteristics are presented and discussed

Topical report on a preconceptual design for the Spallation-Induced Lithium Conversion (SILC) target for the accelerator production of tritium (APT)

Energy Technology Data Exchange (ETDEWEB)

Van Tuyle, G.J.; Cokinos, D.M.; Czajkowski, C.; Franz, E.M.; Kroeger, P.; Todosow, M.; Youngblood, R.; Zucker, M.

1993-09-30

The preconceptual design of the APT Li-Al target system, also referred to as the Spallation-Induced Lithium Conversion (SILC), target system, is summarized in this report. The system has been designed to produce a ``3/8 Goal`` quantity of tritium using the 200-mA, 1.0 GeV proton beam emerging from the LANL-designed LINAC. The SILC target system consists of a beam expander, a heavy-water-cooled lead spallation neutron source assembly surrounded by light-water-cooled Li-Al blankets, a target window, heat removal systems, and related safety systems. The preconceptual design of each of these major components is described. Descriptions are also provided for the target fabrication, tritium extraction, and waste-steam processes. Performance characteristics are presented and discussed.

Designer interface peptide grafts target estrogen receptor alpha dimerization

International Nuclear Information System (INIS)

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

2016-01-01

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

Designer interface peptide grafts target estrogen receptor alpha dimerization

Energy Technology Data Exchange (ETDEWEB)

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

2016-09-09

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

Target scattering characteristics for OAM-based radar

Directory of Open Access Journals (Sweden)

Kang Liu

2018-02-01

Full Text Available The target scattering characteristics are crucial for radar systems. However, there is very little study conducted for the recently developed orbital angular momentum (OAM based radar system. To illustrate the role of OAM-based radar cross section (ORCS, conventional radar equation is modified by taking characteristics of the OAM waves into account. Subsequently, the ORCS is defined in analogy to classical radar cross section (RCS. The unique features of the incident OAM-carrying field are analyzed. The scattered field is derived, and the analytical expressions of ORCSs for metal plate and cylinder targets are obtained. Furthermore, the ORCS and RCS are compared to illustrate the influences of OAM mode number, target size and signal frequency on the ORCS. Analytical studies demonstrate that the mirror-reflection phenomenon disappears and peak values of ORCS are in the non-specular direction. Finally, the ORCS features are summarized to show its advantages in radar target detection. This work can provide theoretical guidance to the design of OAM-based radar as well as the target detection and identification applications.

Target scattering characteristics for OAM-based radar

Science.gov (United States)

Liu, Kang; Gao, Yue; Li, Xiang; Cheng, Yongqiang

2018-02-01

The target scattering characteristics are crucial for radar systems. However, there is very little study conducted for the recently developed orbital angular momentum (OAM) based radar system. To illustrate the role of OAM-based radar cross section (ORCS), conventional radar equation is modified by taking characteristics of the OAM waves into account. Subsequently, the ORCS is defined in analogy to classical radar cross section (RCS). The unique features of the incident OAM-carrying field are analyzed. The scattered field is derived, and the analytical expressions of ORCSs for metal plate and cylinder targets are obtained. Furthermore, the ORCS and RCS are compared to illustrate the influences of OAM mode number, target size and signal frequency on the ORCS. Analytical studies demonstrate that the mirror-reflection phenomenon disappears and peak values of ORCS are in the non-specular direction. Finally, the ORCS features are summarized to show its advantages in radar target detection. This work can provide theoretical guidance to the design of OAM-based radar as well as the target detection and identification applications.

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-02-15

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

Beams configuration design in target area with successive quadratic programming method

International Nuclear Information System (INIS)

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

1998-01-01

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

Geolocating thermal binoculars based on a software defined camera core incorporating HOT MCT grown by MOVPE

Science.gov (United States)

Pillans, Luke; Harmer, Jack; Edwards, Tim; Richardson, Lee

2016-05-01

Geolocation is the process of calculating a target position based on bearing and range relative to the known location of the observer. A high performance thermal imager with integrated geolocation functions is a powerful long range targeting device. Firefly is a software defined camera core incorporating a system-on-a-chip processor running the AndroidTM operating system. The processor has a range of industry standard serial interfaces which were used to interface to peripheral devices including a laser rangefinder and a digital magnetic compass. The core has built in Global Positioning System (GPS) which provides the third variable required for geolocation. The graphical capability of Firefly allowed flexibility in the design of the man-machine interface (MMI), so the finished system can give access to extensive functionality without appearing cumbersome or over-complicated to the user. This paper covers both the hardware and software design of the system, including how the camera core influenced the selection of peripheral hardware, and the MMI design process which incorporated user feedback at various stages.

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

International Nuclear Information System (INIS)

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

2006-01-01

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

High-resolution imaging and target designation through clouds or smoke

Science.gov (United States)

Perry, Michael D.

2003-01-01

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

Nuclease Target Site Selection for Maximizing On-target Activity and Minimizing Off-target Effects in Genome Editing

Science.gov (United States)

Lee, Ciaran M; Cradick, Thomas J; Fine, Eli J; Bao, Gang

2016-01-01

The rapid advancement in targeted genome editing using engineered nucleases such as ZFNs, TALENs, and CRISPR/Cas9 systems has resulted in a suite of powerful methods that allows researchers to target any genomic locus of interest. A complementary set of design tools has been developed to aid researchers with nuclease design, target site selection, and experimental validation. Here, we review the various tools available for target selection in designing engineered nucleases, and for quantifying nuclease activity and specificity, including web-based search tools and experimental methods. We also elucidate challenges in target selection, especially in predicting off-target effects, and discuss future directions in precision genome editing and its applications. PMID:26750397

Mechanical design of experimental apparatus for FIREX cryo-target cooling

Science.gov (United States)

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

2016-05-01

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

Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-γ and IL-17 production in blood from TB + patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras

Science.gov (United States)

2013-01-01

Background A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Methods Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-γ and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). Results M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-γ production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. Conclusions The pattern of immune target recognition is different in regard to IFN-γ and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras. PMID:23497342

Treating rheumatoid arthritis to target

DEFF Research Database (Denmark)

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

2010-01-01

BACKGROUND: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). OBJECTIVE: /st> To develop recommendations for achieving optimal therapeutic outcomes in RA. METHODS....... Levels of evidence, strength of recommendations and levels of agreement were derived. RESULTS: The treat-to-target activity resulted in 10 recommendations. The treatment aim was defined as remission with low disease activity being an alternative goal in patients with long-standing disease. Regular follow...

Defining Patient Centric Pharmaceutical Drug Product Design.

Science.gov (United States)

Stegemann, Sven; Ternik, Robert L; Onder, Graziano; Khan, Mansoor A; van Riet-Nales, Diana A

2016-09-01

The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved.

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

Science.gov (United States)

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

2015-08-01

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

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

Science.gov (United States)

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

2015-11-01

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

Targeting of Mesenchymal Stromal Cells by Cre-Recombinase Transgenes Commonly Used to Target Osteoblast Lineage Cells.

Science.gov (United States)

Zhang, Jingzhu; Link, Daniel C

2016-11-01

The targeting specificity of tissue-specific Cre-recombinase transgenes is a key to interpreting phenotypes associated with their use. The Ocn-Cre and Dmp1-Cre transgenes are widely used to target osteoblasts and osteocytes, respectively. Here, we used high-resolution microscopy of bone sections and flow cytometry to carefully define the targeting specificity of these transgenes. These transgenes were crossed with Cxcl12 gfp mice to identify Cxcl12-abundant reticular (CAR) cells, which are a perivascular mesenchymal stromal population implicated in hematopoietic stem/progenitor cell maintenance. We show that in addition to osteoblasts, Ocn-Cre targets a majority of CAR cells and arteriolar pericytes. Surprisingly, Dmp1-Cre also targets a subset of CAR cells, in which expression of osteoblast-lineage genes is enriched. Finally, we introduce a new tissue-specific Cre-recombinase, Tagln-Cre, which efficiently targets osteoblasts, a majority of CAR cells, and both venous sinusoidal and arteriolar pericytes. These data show that Ocn-Cre and Dmp1-Cre target broader stromal cell populations than previously appreciated and may aid in the design of future studies. Moreover, these data highlight the heterogeneity of mesenchymal stromal cells in the bone marrow and provide tools to interrogate this heterogeneity. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Prediction methodologies for target scene generation in the aerothermal targets analysis program (ATAP)

Science.gov (United States)

Hudson, Douglas J.; Torres, Manuel; Dougherty, Catherine; Rajendran, Natesan; Thompson, Rhoe A.

2003-09-01

The Air Force Research Laboratory (AFRL) Aerothermal Targets Analysis Program (ATAP) is a user-friendly, engineering-level computational tool that features integrated aerodynamics, six-degree-of-freedom (6-DoF) trajectory/motion, convective and radiative heat transfer, and thermal/material response to provide an optimal blend of accuracy and speed for design and analysis applications. ATAP is sponsored by the Kinetic Kill Vehicle Hardware-in-the-Loop Simulator (KHILS) facility at Eglin AFB, where it is used with the CHAMP (Composite Hardbody and Missile Plume) technique for rapid infrared (IR) signature and imagery predictions. ATAP capabilities include an integrated 1-D conduction model for up to 5 in-depth material layers (with options for gaps/voids with radiative heat transfer), fin modeling, several surface ablation modeling options, a materials library with over 250 materials, options for user-defined materials, selectable/definable atmosphere and earth models, multiple trajectory options, and an array of aerodynamic prediction methods. All major code modeling features have been validated with ground-test data from wind tunnels, shock tubes, and ballistics ranges, and flight-test data for both U.S. and foreign strategic and theater systems. Numerous applications include the design and analysis of interceptors, booster and shroud configurations, window environments, tactical missiles, and reentry vehicles.

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

Science.gov (United States)

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

2013-01-01

For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures. Copyright © 2013 John Wiley & Sons, Ltd.

HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies

DEFF Research Database (Denmark)

Monforte, Antonella d'Arminio; Abrams, Donald; Pradier, Christian

2008-01-01

OBJECTIVE: To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM) in the D:A:D Study and to investigate the relationship between these deaths and immunodeficiency. DESIGN: Observational cohort study. METHODS: Patients (23 437) were followed prospectively......-fold higher latest CD4 cell count was associated with a halving of the risk of ADM mortality. Other predictors of an increased risk of ADM mortality were homosexual risk group, older age, a previous (non-malignancy) AIDS diagnosis and earlier calendar years. Predictors of an increased risk of nADM mortality...

Exploration of the medical periodic table: towards new targets.

Science.gov (United States)

Barry, Nicolas P E; Sadler, Peter J

2013-06-07

Metallodrugs offer potential for unique mechanisms of drug action based on the choice of the metal, its oxidation state, the types and number of coordinated ligands and the coordination geometry. We discuss recent progress in identifying new target sites and elucidating the mechanisms of action of anti-cancer, anti-bacterial, anti-viral, anti-parasitic, anti-inflammatory, and anti-neurodegenerative agents, as well as in the design of metal-based diagnostic agents. Progress in identifying and defining target sites has been accelerated recently by advances in proteomics, genomics and metal speciation analysis. Examples of metal compounds and chelating agents (enzyme inhibitors) currently in clinical use, clinical trials or preclinical development are highlighted.

High-energy, twelve-channel laser facility (DEFIN) for spherical irradiation of thermonuclear targets

International Nuclear Information System (INIS)

Basov, N.G.; Danilov, A.E.; Krokhin, O.N.; Kruglov, B.V.; Mikhailov, Yu.A.; Sklizkov, G.V.; Fedotov, S.I.; Fedorov, A.N.

This paper describes a high-energy, twelve-channel laser facility (DELFIN) intended for high-temperature heating of thermonuclear targets with spherical symmetry. The facility includes a neodymium-glass laser with the ultimate radiation energy of 10 kJ, a pulse length of approximately 10 -10 to 10 -9 s, beam divergence of 5 x 10 -4 radians, a vacuum chamber in which laser radiation interacts with the plasma, and a system of diagnostic instrumentation for the observation of laser beam and plasma parameters. Described are the optical scheme and construction details of the laser facility. Presented is an analysis of focusing schemes for target irradiation and described is the focusing scheme of the DELFIN facility, which is capable of attaining a high degree of spherical symmetry in irradiating targets with maximum beam intensity at the target surface of approximately 10 15 W/cm 2 . This paper examines the most important problems connected with the physical investigations of thermonuclear laser plasma and the basic diagnostic problems involved in their solution

Cultural sensitivity in public health: defined and demystified.

Science.gov (United States)

Resnicow, K; Baranowski, T; Ahluwalia, J S; Braithwaite, R L

1999-01-01

There is consensus that health promotion programs should be culturally sensitive (CS). Yet, despite the ubiquitous nature of CS within public health research and practice, there has been surprisingly little attention given to defining CS or delineating a framework for developing culturally sensitive programs and practitioners. This paper describes a model for understanding CS from a public health perspective; describes a process for applying this model in the development of health promotion and disease prevention interventions; and highlights research priorities. Cultural sensitivity is defined by two dimensions: surface and deep structures. Surface structure involves matching intervention materials and messages to observable, "superficial" characteristics of a target population. This may involve using people, places, language, music, food, locations, and clothing familiar to, and preferred by, the target audience. Surface structure refers to how well interventions fit within a specific culture. Deep structure involves incorporating the cultural, social, historical, environmental and psychological forces that influence the target health behavior in the proposed target population. Whereas surface structure generally increases the "receptivity" or "acceptance" of messages, deep structure conveys salience. Techniques, borrowed from social marketing and health communication theory, for developing culturally sensitive interventions are described. Research is needed to determine the effectiveness of culturally sensitive programs.

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

Science.gov (United States)

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

2010-04-01

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

Using Web-Based Instruction to Teach Music Theory in the Piano Studio: Defining, Designing, and Implementing an Integrative Approach

Science.gov (United States)

Carney, Robert D.

2010-01-01

This dissertation rationalizes the best use of Web-based instruction (WBI) for teaching music theory to private piano students in the later primary grades. It uses an integrative research methodology for defining, designing, and implementing a curriculum that includes WBI. Research from the fields of music education, educational technology,…

Mapping the course of the EU "Power Target Model"... on its own terms

OpenAIRE

GLACHANT, Jean-Michel

2016-01-01

The European Union took more than 20 years to start defining a common market design for its internal electricity market: a European Power Target Model. And, a further 10 years to fully implement it. Meanwhile, the reference generation set of that model has shifted from CCGT burning gas to RES units transforming intermittent natural resources. Could the existing EU target model continue to work well for the short- term operation and long-term investment? If not, can the existing EU institution...

Effects of Age, Gender and Target Location on Seated Reach Capacity and Posture

OpenAIRE

CHATEAUROUX, E; WANG, X

2008-01-01

The aim of this study was to investigate the effects of age, gender, and target location upon arm reach capacity and posture. Background: The older adult population is growing in number. Their specific needs must be better understood to improve the design of work and life spaces. Method: Thirty-eight adults, divided into four groups according to their gender and age, participated in the experiment. They were asked to reach 84 targets located in a large space defined according to their anthrop...

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

International Nuclear Information System (INIS)

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

1978-03-01

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

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

Science.gov (United States)

Giménez, Ana; Saldamando, Luis de; Curutchet, María Rosa; Ares, Gastón

2017-06-12

Marketing of unhealthy products has been identified as one of the main characteristics of the food environment that negatively affects children's eating patterns. Restrictions on advertising of unhealthy foods to children have already been imposed in different countries. However, marketing strategies are not limited to broadcast and digital advertising, but also include package design. In this context, the current study aimed to describe the food products targeted at children and sold in supermarkets in Montevideo, Uruguay, in terms of package design and nutrient profile. Two supermarkets in Montevideo were selected for data collection. In each supermarket, all products targeted at children were identified. Products were analyzed in terms of package design and nutritional profile, considering the Pan American Health Organization Nutrient Profile Model. A total of 180 unique products were identified, which included a wide range of product categories. The great majority of the products corresponded to ultra-processed products with excessive amounts of sodium, free sugars, total fat, saturated fat, and/or trans fat, which are not recommended for frequent consumption. Several marketing strategies were identified in the design of packages to attract children's attention and drive their preferences. The most common strategies were the inclusion of cartoon characters, bright colors, childish lettering, and a wide range of claims related to health and nutrition, as well as the products' sensory and hedonic characteristics. The study's findings provide additional evidence on the need to regulate packaging of products targeted at children.

Nephrologists’ Perspectives on Defining and Applying Patient-Centered Outcomes in Hemodialysis

Science.gov (United States)

Winkelmayer, Wolfgang C.; Wheeler, David C.; van Biesen, Wim; Tugwell, Peter; Manns, Braden; Hemmelgarn, Brenda; Harris, Tess; Crowe, Sally; Ju, Angela; O’Lone, Emma; Evangelidis, Nicole; Craig, Jonathan C.

2017-01-01

Background and objectives Patient centeredness is widely advocated as a cornerstone of health care, but it is yet to be fully realized, including in nephrology. Our study aims to describe nephrologists’ perspectives on defining and implementing patient-centered outcomes in hemodialysis. Design, setting, participants, & measurements Face-to-face, semistructured interviews were conducted with 58 nephrologists from 27 dialysis units across nine countries, including the United States, the United Kingdom, Australia, Austria, Belgium, Canada, Germany, Singapore, and New Zealand. Transcripts were thematically analyzed. Results We identified five themes on defining and implementing patient-centered outcomes in hemodialysis: explicitly prioritized by patients (articulated preferences and goals, ascertaining treatment burden, defining hemodialysis success, distinguishing a physician-patient dichotomy, and supporting shared decision making), optimizing wellbeing (respecting patient choice, focusing on symptomology, perceptible and tangible, and judging relevance and consequence), comprehending extensive heterogeneity of clinical and quality of life outcomes (distilling diverse priorities, highly individualized, attempting to specify outcomes, and broadening context), clinically hamstrung (professional deficiency, uncertainty and complexity in measurement, beyond medical purview, specificity of care, mechanistic mindset [focused on biochemical targets and comorbidities], avoiding alarm, and paradoxical dilemma), and undermined by system pressures (adhering to overarching policies, misalignment with mandates, and resource constraints). Conclusions Improving patient-centered outcomes is regarded by nephrologists to encompass strategies that address patient goals and improve wellbeing and treatment burden in patients on hemodialysis. However, efforts are hampered by ambiguities about how to prioritize, measure, and manage the plethora of critical comorbidities and broader

Impact of metabolic, hemodynamic and inflammatory factors on target organ damage in healthy subjects

DEFF Research Database (Denmark)

Blicher, M.; Kruger, R.; Olesen, Thomas Bastholm

2015-01-01

Objective: We wanted to test the impact of metabolic, hemodynamic and inflammatory factors on target organ damage (TOD) defined as cardiac hypertrophy, atherosclerosis, arterioclerosis and microvascular damage. Design and method: In a population based cohort study of 2115 healthy subjects (1049...... associated to hypertrophy, arteriosclerosis and microvascular damage in healthy subjects....

Targeted electroporation of defined lateral ventricular walls: a novel and rapid method to study fate specification during postnatal forebrain neurogenesis

Directory of Open Access Journals (Sweden)

Cremer Harold

2011-04-01

Full Text Available Abstract Background Postnatal olfactory bulb (OB neurogenesis involves the generation of granule and periglomerular cells by neural stem cells (NSCs located in the walls of the lateral ventricle (LV. Recent studies show that NSCs located in different regions of the LV give rise to different types of OB neurons. However, the molecular mechanisms governing neuronal specification remain largely unknown and new methods to approach these questions are needed. Results In this study, we refine electroporation of the postnatal forebrain as a technique to perform precise and accurate delivery of transgenes to NSCs located in distinct walls of the LV in the mouse. Using this method, we confirm and expand previous studies showing that NSCs in distinct walls of the LV produce neurons that invade different layers of the OB. Fate mapping of the progeny of radial glial cells located in these distinct LV walls reveals their specification into defined subtypes of granule and periglomerular neurons. Conclusions Our results provide a baseline with which future studies aiming at investigating the role of factors in postnatal forebrain neuronal specification can be compared. Targeted electroporation of defined LV NSC populations will prove valuable to study the genetic factors involved in forebrain neuronal specification.

Productively infected murine Kaposi's sarcoma-like tumors define new animal models for studying and targeting KSHV oncogenesis and replication.

Directory of Open Access Journals (Sweden)

Brittany M Ashlock

Full Text Available Kaposi's sarcoma (KS is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV. KS tumors are composed of KSHV-infected spindle cells of vascular origin with aberrant neovascularization and erythrocyte extravasation. KSHV genes expressed during both latent and lytic replicative cycles play important roles in viral oncogenesis. Animal models able to recapitulate both viral and host biological characteristics of KS are needed to elucidate oncogenic mechanisms, for developing targeted therapies, and to trace cellular components of KS ontogeny. Herein, we describe two new murine models of Kaposi's sarcoma. We found that murine bone marrow-derived cells, whether established in culture or isolated from fresh murine bone marrow, were infectable with rKSHV.219, formed KS-like tumors in immunocompromised mice and produced mature herpesvirus-like virions in vivo. Further, we show in vivo that the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat enhanced viral lytic reactivation. We propose that these novel models are ideal for studying both viral and host contributions to KSHV-induced oncogenesis as well as for testing virally-targeted antitumor strategies for the treatment of Kaposi's sarcoma. Furthermore, our isolation of bone marrow-derived cell populations containing a cell type that, when infected with KSHV, renders a tumorigenic KS-like spindle cell, should facilitate systematic identification of KS progenitor cells.

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

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

Science.gov (United States)

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

2015-06-01

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

Targeted repression of AXIN2 and MYC gene expression using designer TALEs

International Nuclear Information System (INIS)

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

2014-01-01

Highlights: • We designed TALE–SID fusion proteins to target AXIN2 and MYC. • TALE–SIDs bound the chromosomal AXIN2 and MYC genes and repressed their expression. • TALE–SIDs repress β-catenin S45F -dependent AXIN2 and MYC transcription. - Abstract: Designer TALEs (dTALEs) are chimeric transcription factors that can be engineered to regulate gene expression in mammalian cells. Whether dTALEs can block gene transcription downstream of signal transduction cascades, however, has yet to be fully explored. Here we tested whether dTALEs can be used to target genes whose expression is controlled by Wnt/β-catenin signaling. TALE DNA binding domains were engineered to recognize sequences adjacent to Wnt responsive enhancer elements (WREs) that control expression of axis inhibition protein 2 (AXIN2) and c-MYC (MYC). These custom DNA binding domains were linked to the mSin3A interaction domain (SID) to generate TALE–SID chimeric repressors. The TALE–SIDs repressed luciferase reporter activity, bound their genomic target sites, and repressed AXIN2 and MYC expression in HEK293 cells. We generated a novel HEK293 cell line to determine whether the TALE–SIDs could function downstream of oncogenic Wnt/β-catenin signaling. Treating these cells with doxycycline and tamoxifen stimulates nuclear accumulation of a stabilized form of β-catenin found in a subset of colorectal cancers. The TALE–SIDs repressed AXIN2 and MYC expression in these cells, which suggests that dTALEs could offer an effective therapeutic strategy for the treatment of colorectal cancer

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.

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

International Nuclear Information System (INIS)

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

2001-01-01

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

Defining DSL design principles for enhancing the requirements elicitation process

Directory of Open Access Journals (Sweden)

Gustavo Arroyo

2012-03-01

Full Text Available La Elicitación de Requisitos propicia el entendimiento de las necesidades de los usuarios con respecto a un desarrollo de software. Los métodos que se emplean provienen de las ciencias sociales por lo que se carece de una retroalimentación ejecutable. Consecuentemente, la primera versión del software podría no cumplir con las expectativas. El uso de DSLs como herramientas para el descubrimiento de requisitos es una idea aceptada, desafortunadamente, muy pocos trabajos en la literatura se enfocan en la definición de principios de diseño de DSLs. En este trabajo planteamos principios de diseño de DSLs orientados a la elicitación de requisitos, enseguida, generamos casos de prueba en ANTLR, Ruby y Curry. También, enunciamos el perfil que debe tener el nuevo analista de software. Con ello, se incrementa la retroalimentación entre los involucrados en el desarrollo de software y se mejora el producto.Requirements elicitation is concerned with learning and understanding the needs of users w.r.t. a new software development. Frequently the methods employed for requirements elicitation are adapted from areas like social sciences that do not include executable (prototype based on feedback. As a consequence, it is relatively common to discover that the first release does not fit the requirements defined at the beginning of the project. Using domain-specific languages (DSLs as an auxiliary tool for requirements elicitation is a commonly well accepted idea. Unfortunately, there are few works in the literature devoted to the definition of design principles for DSLs to be experienced in the frameworks for DSL developing such as ANTLR, Ruby, and Curry. We propose design principles for the DSL development (regardless of paradigm which are sufficient to model the domain in a requirements phase. Further more we enunciate a new profile for the requirements analyst and a set of elicitation steps. The use of DSLs not only giveus an immediate feedback with

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

Science.gov (United States)

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

2016-07-01

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

Modular Software-Defined Radio

Directory of Open Access Journals (Sweden)

Rhiemeier Arnd-Ragnar

2005-01-01

Full Text Available In view of the technical and commercial boundary conditions for software-defined radio (SDR, it is suggestive to reconsider the concept anew from an unconventional point of view. The organizational principles of signal processing (rather than the signal processing algorithms themselves are the main focus of this work on modular software-defined radio. Modularity and flexibility are just two key characteristics of the SDR environment which extend smoothly into the modeling of hardware and software. In particular, the proposed model of signal processing software includes irregular, connected, directed, acyclic graphs with random node weights and random edges. Several approaches for mapping such software to a given hardware are discussed. Taking into account previous findings as well as new results from system simulations presented here, the paper finally concludes with the utility of pipelining as a general design guideline for modular software-defined radio.

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

Science.gov (United States)

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

2018-04-05

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

Application-Defined Decentralized Access Control

Science.gov (United States)

Xu, Yuanzhong; Dunn, Alan M.; Hofmann, Owen S.; Lee, Michael Z.; Mehdi, Syed Akbar; Witchel, Emmett

2014-01-01

DCAC is a practical OS-level access control system that supports application-defined principals. It allows normal users to perform administrative operations within their privilege, enabling isolation and privilege separation for applications. It does not require centralized policy specification or management, giving applications freedom to manage their principals while the policies are still enforced by the OS. DCAC uses hierarchically-named attributes as a generic framework for user-defined policies such as groups defined by normal users. For both local and networked file systems, its execution time overhead is between 0%–9% on file system microbenchmarks, and under 1% on applications. This paper shows the design and implementation of DCAC, as well as several real-world use cases, including sandboxing applications, enforcing server applications’ security policies, supporting NFS, and authenticating user-defined sub-principals in SSH, all with minimal code changes. PMID:25426493

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

Directory of Open Access Journals (Sweden)

Ana Giménez

Full Text Available Abstract: Marketing of unhealthy products has been identified as one of the main characteristics of the food environment that negatively affects children’s eating patterns. Restrictions on advertising of unhealthy foods to children have already been imposed in different countries. However, marketing strategies are not limited to broadcast and digital advertising, but also include package design. In this context, the current study aimed to describe the food products targeted at children and sold in supermarkets in Montevideo, Uruguay, in terms of package design and nutrient profile. Two supermarkets in Montevideo were selected for data collection. In each supermarket, all products targeted at children were identified. Products were analyzed in terms of package design and nutritional profile, considering the Pan American Health Organization Nutrient Profile Model. A total of 180 unique products were identified, which included a wide range of product categories. The great majority of the products corresponded to ultra-processed products with excessive amounts of sodium, free sugars, total fat, saturated fat, and/or trans fat, which are not recommended for frequent consumption. Several marketing strategies were identified in the design of packages to attract children’s attention and drive their preferences. The most common strategies were the inclusion of cartoon characters, bright colors, childish lettering, and a wide range of claims related to health and nutrition, as well as the products’ sensory and hedonic characteristics. The study’s findings provide additional evidence on the need to regulate packaging of products targeted at children.

The modelling and design of radio tomography antennas

CSIR Research Space (South Africa)

Vogt, DR

2000-09-01

Full Text Available , as are the in- terfaces between layers of different materials. By contrast, RT is a transmission technique. It can produce images of targets where there is no clearly defined boundary between the target and the host rock. Disseminated sulphide mineralization... stream_source_info Vogt_2000.pdf.txt stream_content_type text/plain stream_size 311829 Content-Encoding UTF-8 stream_name Vogt_2000.pdf.txt Content-Type text/plain; charset=UTF-8 The Modelling and Design of Radio...

Evolution of sequence-defined highly functionalized nucleic acid polymers

Science.gov (United States)

Chen, Zhen; Lichtor, Phillip A.; Berliner, Adrian P.; Chen, Jonathan C.; Liu, David R.

2018-03-01

The evolution of sequence-defined synthetic polymers made of building blocks beyond those compatible with polymerase enzymes or the ribosome has the potential to generate new classes of receptors, catalysts and materials. Here we describe a ligase-mediated DNA-templated polymerization and in vitro selection system to evolve highly functionalized nucleic acid polymers (HFNAPs) made from 32 building blocks that contain eight chemically diverse side chains on a DNA backbone. Through iterated cycles of polymer translation, selection and reverse translation, we discovered HFNAPs that bind proprotein convertase subtilisin/kexin type 9 (PCSK9) and interleukin-6, two protein targets implicated in human diseases. Mutation and reselection of an active PCSK9-binding polymer yielded evolved polymers with high affinity (KD = 3 nM). This evolved polymer potently inhibited the binding between PCSK9 and the low-density lipoprotein receptor. Structure-activity relationship studies revealed that specific side chains at defined positions in the polymers are required for binding to their respective targets. Our findings expand the chemical space of evolvable polymers to include densely functionalized nucleic acids with diverse, researcher-defined chemical repertoires.

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

Science.gov (United States)

Garland, Anthony

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

Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs.

Science.gov (United States)

Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

2010-09-01

We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.

Fabrication and testing of W7-X pre-series target elements

International Nuclear Information System (INIS)

Boscary, J; Boeswirth, B; Greuner, H; Grigull, P; Missirlian, M; Plankensteiner, A; Schedler, B; Friedrich, T; Schlosser, J; Streibl, B; Traxler, H

2007-01-01

The assembly of the highly-loaded target plates of the WENDELSTEIN 7-X (W7-X) divertor requires the fabrication of 890 target elements (TEs). The plasma facing material is made of CFC NB31 flat tiles bonded to a CuCrZr copper alloy water-cooled heat sink. The elements are designed to remove a stationary heat flux and power up to 10 MW m -2 and 100 kW, respectively. Before launching the serial fabrication, pre-series activities aimed at qualifying the design, the manufacturing route and the non-destructive examinations (NDEs). High heat flux (HHF) tests performed on full-scale pre-series TEs resulted in an improvement of the design of the bond between tiles and heat sink to reduce the stresses during operation. The consequence is the fabrication of additional pre-series TEs to be tested in the HHF facility GLADIS. NDEs of this bond based on thermography methods are developed to define the acceptance criteria suitable for serial fabrication

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

Energy Technology Data Exchange (ETDEWEB)

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

1995-10-01

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

Preconceptual design of a Long-Pulse Spallation Source (LPSS) at the LANSCE Facility: Target system, facility, and material handling considerations

International Nuclear Information System (INIS)

Sommer, W.F.

1995-12-01

This report provides a summary of a preconceptual design study for the proposed Long-Pulse Spallation. Source (LPSS) at the Los Alamos Neutron Science Center (LANSCE). The LPSS will use a 0.8-MW proton beam to produce neutrons from a tungsten target. This study focuses on the design of the target station and changes to the existing building that would be made to accommodate the LPSS. The LPSS will provide fifteen flight paths to neutron scattering instruments. In addition, options for generating ultracold neutrons, pions, and muons will be available. Flight-energy, forward-scattered neutrons on the downstream side of the target will also be available for autoradiography studies. A Target Test Bed (TTB) is also proposed for full-beam tests of component materials and advanced spallation neutron sources. The design allows for separation of the experiment hall from the beam line, target, and flight paths. The target and moderator systems and the systems/components to be tested in the TTB will be emplaced and removed separately by remotely operated, shielded equipment. Irradiated materials will be transported to a hot cell adjacent to the target chamber for testing by remotely operated instruments. These tests will provide information about how materials properties are affected by proton and neutron beams

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

Directory of Open Access Journals (Sweden)

Lin Xinwei

2015-01-01

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

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

Science.gov (United States)

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

2016-01-13

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

Geographic miss of lung tumours due to respiratory motion: a comparison of 3D vs 4D PET/CT defined target volumes

International Nuclear Information System (INIS)

Callahan, Jason; Kron, Tomas; Siva, Shankar; Simoens, Nathalie; Edgar, Amanda; Everitt, Sarah; Schneider, Michal E; Hicks, Rodney J

2014-01-01

PET/CT scans acquired in the radiotherapy treatment position are typically performed without compensating for respiratory motion. The purpose of this study was to investigate geographic miss of lung tumours due to respiratory motion for target volumes defined on a standard 3D-PET/CT. 29 patients staged for pulmonary malignancy who completed both a 3D-PET/CT and 4D-PET/CT were included. A 3D-Gross Tumour Volume (GTV) was defined on the standard whole body PET/CT scan. Subsequently a 4D-GTV was defined on a 4D-PET/CT MIP. A 5 mm, 10 mm, 15 mm symmetrical and 15×10 mm asymmetrical Planning Target Volume (PTV) was created by expanding the 3D-GTV and 4D-GTV’s. A 3D conformal plan was generated and calculated to cover the 3D-PTV. The 3D plan was transferred to the 4D-PTV and analysed for geographic miss. Three types of miss were measured. Type 1: any part of the 4D-GTV outside the 3D-PTV. Type 2: any part of the 4D-PTV outside the 3D-PTV. Type 3: any part of the 4D-PTV receiving less than 95% of the prescribed dose. The lesion motion was measured to look at the association between lesion motion and geographic miss. When a standard 15 mm or asymmetrical PTV margin was used there were 1/29 (3%) Type 1 misses. This increased 7/29 (24%) for the 10 mm margin and 23/29 (79%) for a 5 mm margin. All patients for all margins had a Type 2 geographic miss. There was a Type 3 miss in 25 out of 29 cases in the 5, 10, and 15 mm PTV margin groups. The asymmetrical margin had one additional Type 3 miss. Pearson analysis showed a correlation (p < 0.01) between lesion motion and the severity of the different types of geographic miss. Without any form of motion suppression, the current standard of a 3D- PET/CT and 15 mm PTV margin employed for lung lesions has an increasing risk of significant geographic miss when tumour motion increases. Use of smaller asymmetric margins in the cranio-caudal direction does not comprise tumour coverage. Reducing PTV margins for volumes defined on 3D

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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

Science.gov (United States)

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

2018-06-01

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

A computer-aided approach for achieving sustainable process design by process intensification

DEFF Research Database (Denmark)

Anantasarn, Nateetorn; Suriyapraphadilok, Uthaiporn; Babi, Deenesh Kavi

2017-01-01

to generate flowsheet alternatives that satisfy the design targets thereby, minimizing and/or eliminating the process hot-spots. The application of the framework is highlighted through the production of para-xylene via toluene methylation where more sustainable flowsheet alternatives that consist of hybrid......Process intensification can be applied to achieve sustainable process design. In this paper, a systematic, 3-stage synthesis-intensification framework is applied to achieve more sustainable design. In stage 1, the synthesis stage, an objective function and design constraints are defined and a base...... case is synthesized. In stage 2, the design and analysis stage, the base case is analyzed using economic and environmental analyses to identify process hot-spots that are translated into design targets. In stage 3, the innovation design stage, phenomena-based process intensification is performed...

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.

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.

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-02-01

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

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

International Nuclear Information System (INIS)

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

2004-01-01

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

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

Science.gov (United States)

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

2012-01-31

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

International Nuclear Information System (INIS)

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

1996-01-01

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

Conceptual design study of the hylife lithium waterfall laser fusion chamber. FY 1978 annual report to Lawrence Livermore Laboratory

International Nuclear Information System (INIS)

1978-01-01

Conceptual design studies of the target chamber defined the general configuration and dimensions of the chamber and the inlet plenum, orifice plate, and nozzle plate concepts required to generate the desired lithium jet fall. Preliminary studies were performed of the target chamber interfaces with the liquid lithium supply system, the laser system, the pellet injection system, and the target chamber mounting and support system. Target chamber environmental effects resulting from typical thermonuclear burns were evaluated. The outlet region of the target chamber was outlined conceptually, and preliminary design considerations were given to the annular graphite reflector regions of the target chamber and the associated liquid lithium coolant passages

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

International Nuclear Information System (INIS)

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

1999-11-01

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

Indirect-drive noncryogenic double-shell ignition targets for the National Ignition Facility: Design and analysis

International Nuclear Information System (INIS)

Amendt, Peter; Colvin, J.D.; Tipton, R.E.; Hinkel, D.E.; Edwards, M.J.; Landen, O.L.; Ramshaw, J.D.; Suter, L.J.; Varnum, W.S.; Watt, R.G.

2002-01-01

Analysis and design of indirect-drive National Ignition Facility double-shell targets with hohlraum temperatures of 200 eV and 250 eV are presented. The analysis of these targets includes the assessment of two-dimensional radiation asymmetry and nonlinear mix. Two-dimensional integrated hohlraum simulations indicate that the x-ray illumination can be adjusted to provide adequate symmetry control in hohlraums specially designed to have high laser-coupling efficiency [Suter et al., Phys. Plasmas 7, 2092 (2000)]. These simulations also reveal the need to diagnose and control localized 10-15 keV x-ray emission from the high-Z hohlraum wall because of strong absorption by the high-Z inner shell. Preliminary estimates of the degree of laser backscatter from an assortment of laser-plasma interactions suggest comparatively benign hohlraum conditions. The application of a variety of nonlinear mix models and phenomenological tools, including buoyancy-drag models, multimode simulations and fall-line optimization, indicates a possibility of achieving ignition, i.e., fusion yields greater than 1 MJ. Planned experiments on the Omega laser will test current understanding of high-energy radiation flux asymmetry and mix-induced yield degradation in double-shell targets

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

International Nuclear Information System (INIS)

Brown, M.L.

1986-06-01

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

Some safety studies of the MEGAPIE spallation source target performed using computational fluid dynamics

International Nuclear Information System (INIS)

Smith, B.L.

2011-01-01

Such a target forms part of the evolutionary Accelerator-Driven System (ADS) concept in which neutrons are generated in an otherwise sub-critical core by spallation reactions resulting from bombardment by a proton beam. The international project MEGAPIE had the objective of demonstrating the feasibility of the spallation process for a particular target design under strict test conditions. The test was carried over a period of four months at the end of 2006 at the SINQ facility of the Paul Scherrer Institute in Switzerland. The design studies carried out for the MEGAPIE target prior to irradiation using Computational Fluid Dynamics (CFD) resulted in an optimum flow configuration being defined for the coolant circulation. Simultaneously, stresses in the structural components were examined using Finite Element Method (FEM) techniques. To this purpose, an interface program was written which enabled different specialist groups to carry out the thermal hydraulics and structural mechanics analyses within the project with fully consistent model data. Results for steady-state operation of the target show that the critical lower target components are adequately cooled, and that stresses and displacements are well within tolerances. Transient analyses were also performed to demonstrate the robustness of the design in the event of abnormal operation, including pump failure and burn-through of the target casing by the proton beam. In the latter case, the CFD analyses complemented and extended full-scale tests. (author)

Some safety studies of the MEGAPIE spallation source target performed using computational fluid dynamics

Energy Technology Data Exchange (ETDEWEB)

Smith, B.L., E-mail: brian.smith@psi.ch [Paul Scherrer Institute, OHSA/C08, 5232 Villigen PSI (Switzerland)

2011-07-01

Such a target forms part of the evolutionary Accelerator-Driven System (ADS) concept in which neutrons are generated in an otherwise sub-critical core by spallation reactions resulting from bombardment by a proton beam. The international project MEGAPIE had the objective of demonstrating the feasibility of the spallation process for a particular target design under strict test conditions. The test was carried over a period of four months at the end of 2006 at the SINQ facility of the Paul Scherrer Institute in Switzerland. The design studies carried out for the MEGAPIE target prior to irradiation using Computational Fluid Dynamics (CFD) resulted in an optimum flow configuration being defined for the coolant circulation. Simultaneously, stresses in the structural components were examined using Finite Element Method (FEM) techniques. To this purpose, an interface program was written which enabled different specialist groups to carry out the thermal hydraulics and structural mechanics analyses within the project with fully consistent model data. Results for steady-state operation of the target show that the critical lower target components are adequately cooled, and that stresses and displacements are well within tolerances. Transient analyses were also performed to demonstrate the robustness of the design in the event of abnormal operation, including pump failure and burn-through of the target casing by the proton beam. In the latter case, the CFD analyses complemented and extended full-scale tests. (author)

Design study of ITER-like divertor target for DEMO

International Nuclear Information System (INIS)

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

2015-01-01

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

Design study of ITER-like divertor target for DEMO

Energy Technology Data Exchange (ETDEWEB)

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

2015-10-15

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

Studying time to pregnancy by use of a retrospective design

DEFF Research Database (Denmark)

Joffe, Michael; Key, Jane; Best, Nicky

2005-01-01

Biologic fertility can be measured using time to pregnancy (TTP). Retrospective designs, although lacking detailed timed information about behavior and exposure, are useful since they have a well-defined target population, often have good response rates, and are simpler and less expensive...... at the beginning of unprotected intercourse. More complete inference is possible if the study design covers the whole population, not just those who achieve a pregnancy....

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

Science.gov (United States)

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

2017-09-01

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

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

International Nuclear Information System (INIS)

Lin, J.C.; Elson, J.

1997-01-01

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

An investigation of the ability to produce a defined 'target pressure' using the PressCise compression bandage.

Science.gov (United States)

Wiklander, Kerstin; Andersson, Annette Erichsen; Källman, Ulrika

2016-12-01

Compression therapy is the cornerstone in the prevention and treatment of leg ulcers related to chronic venous insufficiency. The application of optimal high pressure is essential for a successful outcome, but the literature has reported difficulty applying the intended pressure, even among highly skilled nurses. The PressCise bandage has a novel design, with both longitudinal and horizontal reference points for correct application. In the current experimental study, the results for the general linear model, where the data set is treated optimally, showed that all 95% confidence intervals of the expected values for pressure were, at most, 5 mmHg from the target value of 50 mmHg, independent of the position on the leg and the state of activity. Moreover, even nurses with limited experience were consistently able to reach the targeted pressure goal. Future studies are needed to determine how well the bandage works on legs of different shapes, the optimal way of using the bandage (day only or both day and night) and whether the bandage should be combined with an outer bandage layer. In addition, special attention should be paid to subjective patient experiences in relation to the treatment as pain, discomfort and bulk are factors that can compromise patients' willingness to adhere to the treatment protocol and thereby prolong the healing process. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

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

Human Systems Interface Design Methods Using Ecological Interface Design Principles

International Nuclear Information System (INIS)

Hong, Seung Kweon; Park, Jung Chul; Kim, Sun Su; Sim, Kwang Pyo; Yuk, Seung Yul; Choi, Jae Hyeon; Yoon, Seung Hyun

2009-12-01

The results of this study categorized into two parts. The first part is the guidelines for EID designs. The procedure to observe for EID design is composed of 6 steps; 1) to define a target system, 2) to make an abstraction hierarchy model, 3) to check the link structure among each components included in the layers of abstraction hierarchy model, 4) to transform information requirements to variables, 5) to make the graphs related to each variables, 6) to check the graphs by visual display design principles and heuristic rules. The second part is an EID design alternative for nuclear power plant. The EID for high level function represents the energy balance and energy flow in each loop of nuclear power plant. The EID for middle level function represents the performance indicators of each equipment involved in the all processes of changing from coolants to steam. The EID for low level function represents the values measured in each equipment such as temperature, pressure, water level and so on

Re-Defining Traditional Bazaar Areas and Shade Structures Via Parametric Design Methods

Directory of Open Access Journals (Sweden)

Ahmet Emre Dinçer

2017-12-01

Full Text Available For the continuation of life, people created various equipment and goods. To create mutual benefits, they’ve exchanged the overpruduced items with different products. This has begun the shopping act. By the increased amount of transactions, a need of defined area for shopping have arisen.  For a temporary time, trading areas have been developed at different locations at a certain period. In the course of time, beside trading, these areas served as socio-cultural spaces where the human relations were established. Moreover, demand of being able to immediately access to needed goods have emerged. This situation made having a permanent trading area essential. Therefore, enclosed and permanent trade areas from bazaar, inn, bedesten, arasta to shopping malls have emerged. Next to all these trading areas, traditional bazaar areas keep being established. Nowadays, there is a need of providing some determined comfort conditions to the users for these street alley bazaars. Decreasing the effect of unfavorable weather conditions and providing supportive certain services and units (like WCs, security, cleanliness, etc. are some of them. As a fundamental solution, without disengaging the user relations with the outside, shade structures are generally provided. Shade structures can support cleaning and similar jobs by gathering and using rainwater besides its purpose of protecting the user from bad weather conditions. Application examples of these systems are gradually increasing. However, it is necessary to develop new approaches, in order to stop these proposed shade structures, become prototypes and to adapt the proposal to its environment and to increase diversity. In this study, a convenient shade structure and its alternatives, which are adapted to environmental conditions, were designed to create a sample model for other bazaar areas. In models, basically, folding design approaches were pursued. For production of these shade structure models

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

Brand market positions estimation and defining the strategic targets of its development

OpenAIRE

S.M. Makhnusha

2010-01-01

In this article the author generalizes the concept of brand characteristics which influenceits profitability and market positions. An approach to brand market positions estimation anddefining the strategic targets of its development is proposed.Keywords: brand, brand expansion, brand extension, brand value, brand power, brandrelevance, brand awareness.

A Method for Co-Designing Theory-Based Behaviour Change Systems for Health Promotion.

Science.gov (United States)

Janols, Rebecka; Lindgren, Helena

2017-01-01

A methodology was defined and developed for designing theory-based behaviour change systems for health promotion that can be tailored to the individual. Theories from two research fields were combined with a participatory action research methodology. Two case studies applying the methodology were conducted. During and between group sessions the participants created material and designs following the behaviour change strategy themes, which were discussed, analysed and transformed into a design of a behaviour change system. Theories in behavioural change and persuasive technology guided the data collection, data analyses, and the design of a behaviour change system. The methodology has strong emphasis on the target group's participation in the design process. The different aspects brought forward related to behaviour change strategies defined in literature on persuasive technology, and the dynamics of these are associated to needs and motivation defined in literature on behaviour change. It was concluded that the methodology aids the integration of theories into a participatory action research design process, and aids the analyses and motivations of design choices.

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...

Defining process design space for monoclonal antibody cell culture.

Science.gov (United States)

Abu-Absi, Susan Fugett; Yang, LiYing; Thompson, Patrick; Jiang, Canping; Kandula, Sunitha; Schilling, Bernhard; Shukla, Abhinav A

2010-08-15

The concept of design space has been taking root as a foundation of in-process control strategies for biopharmaceutical manufacturing processes. During mapping of the process design space, the multidimensional combination of operational variables is studied to quantify the impact on process performance in terms of productivity and product quality. An efficient methodology to map the design space for a monoclonal antibody cell culture process is described. A failure modes and effects analysis (FMEA) was used as the basis for the process characterization exercise. This was followed by an integrated study of the inoculum stage of the process which includes progressive shake flask and seed bioreactor steps. The operating conditions for the seed bioreactor were studied in an integrated fashion with the production bioreactor using a two stage design of experiments (DOE) methodology to enable optimization of operating conditions. A two level Resolution IV design was followed by a central composite design (CCD). These experiments enabled identification of the edge of failure and classification of the operational parameters as non-key, key or critical. In addition, the models generated from the data provide further insight into balancing productivity of the cell culture process with product quality considerations. Finally, process and product-related impurity clearance was evaluated by studies linking the upstream process with downstream purification. Production bioreactor parameters that directly influence antibody charge variants and glycosylation in CHO systems were identified.

Target Control in Logical Models Using the Domain of Influence of Nodes.

Science.gov (United States)

Yang, Gang; Gómez Tejeda Zañudo, Jorge; Albert, Réka

2018-01-01

Dynamical models of biomolecular networks are successfully used to understand the mechanisms underlying complex diseases and to design therapeutic strategies. Network control and its special case of target control, is a promising avenue toward developing disease therapies. In target control it is assumed that a small subset of nodes is most relevant to the system's state and the goal is to drive the target nodes into their desired states. An example of target control would be driving a cell to commit to apoptosis (programmed cell death). From the experimental perspective, gene knockout, pharmacological inhibition of proteins, and providing sustained external signals are among practical intervention techniques. We identify methodologies to use the stabilizing effect of sustained interventions for target control in Boolean network models of biomolecular networks. Specifically, we define the domain of influence (DOI) of a node (in a certain state) to be the nodes (and their corresponding states) that will be ultimately stabilized by the sustained state of this node regardless of the initial state of the system. We also define the related concept of the logical domain of influence (LDOI) of a node, and develop an algorithm for its identification using an auxiliary network that incorporates the regulatory logic. This way a solution to the target control problem is a set of nodes whose DOI can cover the desired target node states. We perform greedy randomized adaptive search in node state space to find such solutions. We apply our strategy to in silico biological network models of real systems to demonstrate its effectiveness.

Summary abstract: microspot target development with seeded and patterned plasma polymers

International Nuclear Information System (INIS)

Letts, S.A.; Miller, D.E.; Corley, R.A.; Tillotson, T.M.; Witt, L.A.

1985-01-01

In inertial confinement fusion (ICF) energy is transferred from the laser to the target through the interaction of extremely high intensity laser light with the target plasma. To better understand laser-plasma interactions, a new class of targets was designed to study long scale-length plasmas (many hundred times the laser wavelength) by measurement of the temperature and density of the plasma as a function of time. The specifications for the target called for a freestanding hydrocarbon polymer (CH) film with a sharply defined spot (microspot) in the center seeded with either silicon or sulfur. The target film was fabricated using a three-step procedure which consisted of deposition of the hydrocarbon film, definition of the microspot, and then deposition of a seeded spot through a mask. In the final assembly step, the film containing the microspot was mounted over a 1.5 mm diam hole in a support. The support was either a plastic ring or a copper foil electroplated with 3 μm of gold. The fabrication of this type of target is described

Design of Thymidine Analogues Targeting Thymidilate Kinase of Mycobacterium tuberculosis

Directory of Open Access Journals (Sweden)

Luc Calvin Owono Owono

2013-01-01

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

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.

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Science.gov (United States)

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

2015-07-01

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

Target discovery focused approaches to overcome bottlenecks in the exploitation of antimycobacterial natural products.

Science.gov (United States)

Baptista, Rafael; Bhowmick, Sumana; Nash, Robert J; Baillie, Les; Mur, Luis Aj

2018-04-01

Tuberculosis is a major global health hazard. The search for new antimycobacterials has focused on such as screening combinational chemistry libraries or designing chemicals to target predefined pockets of essential bacterial proteins. The relative ineffectiveness of these has led to a reappraisal of natural products for new antimycobacterial drug leads. However, progress has been limited, we suggest through a failure in many cases to define the drug target and optimize the hits using this information. We highlight methods of target discovery needed to develop a drug into a candidate for clinical trials. We incorporate these into suggested analysis pipelines which could inform the research strategies to accelerate the development of new drug leads from natural products.

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

Science.gov (United States)

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

2015-01-01

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

Target reactor development problems

International Nuclear Information System (INIS)

Lathrop, K.D.; Vigil, J.C.

1977-01-01

Target-blanket design studies are discussed for an accelerator-breeder concept employing a linear accelerator in conjunction with a modified conventional power reactor to produce both fissile fuel and power. The following problems in target and blanket system design are discussed: radiation damage, heat removal, neutronic design, and economics

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.

Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice.

Directory of Open Access Journals (Sweden)

Trevor D Lawley

Full Text Available Relapsing C. difficile disease in humans is linked to a pathological imbalance within the intestinal microbiota, termed dysbiosis, which remains poorly understood. We show that mice infected with epidemic C. difficile (genotype 027/BI develop highly contagious, chronic intestinal disease and persistent dysbiosis characterized by a distinct, simplified microbiota containing opportunistic pathogens and altered metabolite production. Chronic C. difficile 027/BI infection was refractory to vancomycin treatment leading to relapsing disease. In contrast, treatment of C. difficile 027/BI infected mice with feces from healthy mice rapidly restored a diverse, healthy microbiota and resolved C. difficile disease and contagiousness. We used this model to identify a simple mixture of six phylogenetically diverse intestinal bacteria, including novel species, which can re-establish a health-associated microbiota and clear C. difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. Further, we demonstrate a rational approach to harness the therapeutic potential of health-associated microbial communities to treat C. difficile disease and potentially other forms of intestinal dysbiosis.

Designers and Stakeholders Defining Design Opportunities "In-Situ" through Co-reflection

NARCIS (Netherlands)

Tomico, O.; Garcia, I.; Buur, J.

2011-01-01

this article proposes co-reflection as a workshop to situate design practice in its context of application and presents a case study done at the eLearn Center of the Open University of Catalonia. Co-reflection is a re!ective practice. In the half-aday workshop developed, co-reflection was

Targets development at Sandia National Laboratories

International Nuclear Information System (INIS)

Smith, M.L.; Hebron, D.; Derzon, M.; Olson, R.; Alberts, T.

1997-01-01

For many years, Sandia National Laboratories under contract to the Department of Energy has produced targets designed to understand complex ion beam and z-pinch plasma physics. This poster focuses on the features of target designs that make them suitable for Z-pinch plasma physics applications. Precision diagnostic targets will prove critical in understanding the plasma physics model needed for future ion beam and z-pinch design. Targets are designed to meet specific physics needs; in this case the authors have fabricated targets to maximize information about the end-on versus side-on x-ray emission and z-pinch hohlraum development. In this poster, they describe the fabrication and characterization techniques. They include discussion of current targets under development as well as target fabrication capabilities. Advanced target designs are fabricated by Sandia National Laboratories in cooperation with General Atomics of San Diego, CA and W.J. Schafer Associates, Inc. of Livermore, CA

Definably compact groups definable in real closed fields. I

OpenAIRE

Barriga, Eliana

2017-01-01

We study definably compact definably connected groups definable in a sufficiently saturated real closed field $R$. We introduce the notion of group-generic point for $\\bigvee$-definable groups and show the existence of group-generic points for definably compact groups definable in a sufficiently saturated o-minimal expansion of a real closed field. We use this notion along with some properties of generic sets to prove that for every definably compact definably connected group $G$ definable in...

Design of tailor-made chemical blend using a decomposition-based computer-aided approach

DEFF Research Database (Denmark)

Yunus, Nor Alafiza; Gernaey, Krist; Manan, Z.A.

2011-01-01

Computer aided techniques form an efficient approach to solve chemical product design problems such as the design of blended liquid products (chemical blending). In chemical blending, one tries to find the best candidate, which satisfies the product targets defined in terms of desired product...... methodology for blended liquid products that identifies a set of feasible chemical blends. The blend design problem is formulated as a Mixed Integer Nonlinear Programming (MINLP) model where the objective is to find the optimal blended gasoline or diesel product subject to types of chemicals...... and their compositions and a set of desired target properties of the blended product as design constraints. This blend design problem is solved using a decomposition approach, which eliminates infeasible and/or redundant candidates gradually through a hierarchy of (property) model based constraints. This decomposition...

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

Energy Technology Data Exchange (ETDEWEB)

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

2001-07-01

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

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

International Nuclear Information System (INIS)

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

2001-07-01

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

Spallation source neutron target systems

International Nuclear Information System (INIS)

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

1996-01-01

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

Target support for inertial confinement fusion

International Nuclear Information System (INIS)

Schultz, K.R.

1995-08-01

General Atomics (GA) plays an important industrial support role for the US Inertial Confinement Fusion (ICF) program in the area of target technology. This includes three major activities: target fabrication support, target handling systems development, and target chamber design. The work includes target fabrication for existing ICF experiments, target and target system development for future experiments, and target research and target chamber design for experiments on future machines, such as the National Ignition Facility (NIF)

CHAOS: An SDN-Based Moving Target Defense System

Directory of Open Access Journals (Sweden)

Yuan Shi

2017-01-01

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

Urban Growth Areas, Priority Funding Area (PFA) - Vector Database. PFAs are geographic growth areas defined under State law and designated by local jurisdictions to provide a map for targeting State investment in infrastructure., Published in 1998, 1:24000 (1in=2000ft) scale, Maryland Department of Planning.

Data.gov (United States)

NSGIC State | GIS Inventory — Urban Growth Areas dataset current as of 1998. Priority Funding Area (PFA) - Vector Database. PFAs are geographic growth areas defined under State law and designated...

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

International Nuclear Information System (INIS)

Watanabe, N.

1991-01-01

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

Design Process for Integrated Concepts with Responsive Building Elements

DEFF Research Database (Denmark)

Aa, Van der A.; Heiselberg, Per

2008-01-01

An integrated building concept is a prerequisite to come to an energy efficient building with a good and healthy IAQ indoor comfort. A design process that defines the targets and boundary conditions in the very first stage of the design and guarantees them until the building is finished and used...... is needed. The hard question is however: how to make the right choice of the combination of individual measures from building components and building services elements. Within the framework of IEA-ECBCS Annex 44 research has been conducted about the design process for integrated building concepts...

Analysis of Individuals from a Dengue-Endemic Region Helps Define the Footprint and Repertoire of Antibodies Targeting Dengue Virus 3 Type-Specific Epitopes.

Science.gov (United States)

Andrade, Daniela V; Katzelnick, Leah C; Widman, Doug G; Balmaseda, Angel; de Silva, Aravinda M; Baric, Ralph S; Harris, Eva

2017-09-19

The four dengue virus serotypes (DENV1 to 4) cause dengue, a major public health problem worldwide. Individuals exposed to primary DENV infections develop serotype-specific neutralizing antibodies, including strongly neutralizing antibodies targeting quaternary epitopes. To date, no studies have measured the levels and kinetics of serum antibodies directed to such epitopes among populations in regions where dengue is endemic. Here, we use a recombinant DENV4 (rDENV4/3-M14) displaying a major DENV3 type-specific quaternary epitope recognized by human monoclonal antibody 5J7 to measure the proportion, magnitude, and kinetics of DENV3 type-specific neutralizing antibody responses targeting this epitope. Primary DENV3 sera from 30 individuals in a dengue hospital-based study in Nicaragua were studied 3, 6, 12, and 18 months post-infection, alongside samples collected annually 1 to 4 years post-primary DENV3 infection from 10 individuals in a cohort study in Nicaragua. We found substantial individual variation in the proportion of DENV3 type-specific neutralizing antibody titers attributed to the 5J7 epitope (range, 0 to 100%), with the mean significantly increasing from 22.6% to 41.4% from 3 to 18 months. We extended the transplanted DENV3 5J7 epitope on the virion (rDENV4/3-M16), resulting in increased recognition in several individuals, helping define the footprint of the epitope. However, 37% and 13% of the subjects still showed little to no recognition of the 5J7 epitope at 3 and 18 months, respectively, indicating that one or more additional DENV3 type-specific epitopes exist. Overall, this study demonstrates how DENV-immune plasma from populations from areas of endemicity, when coupled with structurally guided recombinant viruses, can help characterize the epitope-specific neutralizing antibody response in natural DENV infections, with direct implications for design and evaluation of dengue vaccines. IMPORTANCE The four serotypes of dengue virus cause dengue

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

International Nuclear Information System (INIS)

Green, M.C.

1984-01-01

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

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

International Nuclear Information System (INIS)

Green, M.C.

1984-05-01

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

The HERMES polarized hydrogen and deuterium gas target in the HERA electron storage ring

International Nuclear Information System (INIS)

Airapetian, A.; Akopov, N.; Akopov, Z.

2005-01-01

The HERMES hydrogen and deuterium nuclear-polarized gas targets have been in use since 1996 with the polarized electron beam of HERA at DESY to study the spin structure of the nucleon. Polarized atoms from a Stern-Gerlach Atomic Beam Source are injected into a storage cell internal to the HERA electron ring. Atoms diffusing from the center of the storage cell into a side tube are analyzed to determine the atomic fraction and the atomic polarizations. The atoms have a nuclear polarization, the axis of which is defined by an external magnetic holding field. The holding field was longitudinal during 1996-2000, and was changed to transverse in 2001. The design of the target is described, the method for analyzing the target polarization is outlined, and the performance of the target in the various running periods is presented

The HERMES polarized hydrogen and deuterium gas target in the HERA electron storage ring

International Nuclear Information System (INIS)

Airapetian, A.; Akopov, N.; Akopov, Z.; Peking University, Beijing

2004-08-01

The HERMES hydrogen and deuterium nuclear-polarized gas targets have been in use since 1996 with the polarized electron beam of HERA at DESY to study the spin structure of the nucleon. Polarized atoms from a Stern-Gerlach Atomic Beam Source are injected into a storage cell internal to the HERA electron ring. Atoms diffusing from the center of the storage cell into a side tube are analyzed to determine the atomic fraction and the atomic polarizations. The atoms have a nuclear polarization, the axis of which is defined by an external magnetic holding field. The holding field was longitudinal during 1996-2000, and was changed to transverse in 2001. The design of the target is described, the method for analyzing the target polarization is outlined, and the performance of the target in the various running periods is presented. (orig.)

[siRNAs with high specificity to the target: a systematic design by CRM algorithm].

Science.gov (United States)

Alsheddi, T; Vasin, L; Meduri, R; Randhawa, M; Glazko, G; Baranova, A

2008-01-01

'Off-target' silencing effect hinders the development of siRNA-based therapeutic and research applications. Common solution to this problem is an employment of the BLAST that may miss significant alignments or an exhaustive Smith-Waterman algorithm that is very time-consuming. We have developed a Comprehensive Redundancy Minimizer (CRM) approach for mapping all unique sequences ("targets") 9-to-15 nt in size within large sets of sequences (e.g. transcriptomes). CRM outputs a list of potential siRNA candidates for every transcript of the particular species. These candidates could be further analyzed by traditional "set-of-rules" types of siRNA designing tools. For human, 91% of transcripts are covered by candidate siRNAs with kernel targets of N = 15. We tested our approach on the collection of previously described experimentally assessed siRNAs and found that the correlation between efficacy and presence in CRM-approved set is significant (r = 0.215, p-value = 0.0001). An interactive database that contains a precompiled set of all human siRNA candidates with minimized redundancy is available at http://129.174.194.243. Application of the CRM-based filtering minimizes potential "off-target" silencing effects and could improve routine siRNA applications.

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

Science.gov (United States)

Sun, Lihui; Wang, Yongzhong; He, Yongqiang

2007-01-01

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

Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery.

Science.gov (United States)

Habibi, Neda; Kamaly, Nazila; Memic, Adnan; Shafiee, Hadi

2016-02-01

Self-assembly of peptides can yield an array of well-defined nanostructures that are highly attractive nanomaterials for many biomedical applications such as drug delivery. Some of the advantages of self-assembled peptide nanostructures over other delivery platforms include their chemical diversity, biocompatibility, high loading capacity for both hydrophobic and hydrophilic drugs, and their ability to target molecular recognition sites. Furthermore, these self-assembled nanostructures could be designed with novel peptide motifs, making them stimuli-responsive and achieving triggered drug delivery at disease sites. The goal of this work is to present a comprehensive review of the most recent studies on self-assembled peptides with a focus on their "smart" activity for formation of targeted and responsive drug-delivery carriers.

A screen to identify drug resistant variants to target-directed anti-cancer agents

Directory of Open Access Journals (Sweden)

Azam Mohammad

2003-01-01

Full Text Available The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib (Gleevec, a specific inhibitor of the Chronic Myeloid Leukemia (CML-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR/ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair.

The History of Target-Controlled Infusion

NARCIS (Netherlands)

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

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

Remote maintenance systems requirements are being developed to provide design guidelines for machine components, to define maintenance interfaces, and to quantify maintenance equipment and procedures needed

International Nuclear Information System (INIS)

Spampinato, P.T.; Tabor, M.A.

1988-01-01

Remote maintenance systems requirements are being developed to provide design guidelines for machine components, to define maintenance interfaces, and to quantify maintenance equipment and procedures needed

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

Science.gov (United States)

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

2004-12-01

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

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

Science.gov (United States)

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

2018-03-01

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

Defining Hepatocellular Carcinoma Subtypes and Treatment Responses in Patient-Derived Tumorgrafts

Science.gov (United States)

2017-10-01

Specific AIM 2: Determine the efficacy of small RNA therapeutics against the LIN28B/LET-7 pathway in PDXs activating this oncogenic pathway Major...Task 1: Identify and deliver small RNAs to target PDX populations (ongoing). Major Task 2: Define response to small RNAs in target PDX populations...Allow time to receive the regulatory approval for animal use (IACUC and DoD ACURO). This task was performed by Drs. Yopp, Singal, and Zhu. We

Metallochaperone UreG serves as a new target for design of urease inhibitor: A novel strategy for development of antimicrobials.

Directory of Open Access Journals (Sweden)

Xinming Yang

2018-01-01

Full Text Available Urease as a potential target of antimicrobial drugs has received considerable attention given its versatile roles in microbial infection. Development of effective urease inhibitors, however, is a significant challenge due to the deeply buried active site and highly specific substrate of a bacterial urease. Conventionally, urease inhibitors are designed by either targeting the active site or mimicking substrate of urease, which is not efficient. Up to now, only one effective inhibitor-acetohydroxamic acid (AHA-is clinically available, but it has adverse side effects. Herein, we demonstrate that a clinically used drug, colloidal bismuth subcitrate, utilizes an unusual way to inhibit urease activity, i.e., disruption of urease maturation process via functional perturbation of a metallochaperone, UreG. Similar phenomena were also observed in various pathogenic bacteria, suggesting that UreG may serve as a general target for design of new types of urease inhibitors. Using Helicobacter pylori UreG as a showcase, by virtual screening combined with experimental validation, we show that two compounds targeting UreG also efficiently inhibited urease activity with inhibitory concentration (IC50 values of micromolar level, resulting in attenuated virulence of the pathogen. We further demonstrate the efficacy of the compounds in a mammalian cell infection model. This study opens up a new opportunity for the design of more effective urease inhibitors and clearly indicates that metallochaperones involved in the maturation of important microbial metalloenzymes serve as new targets for devising a new type of antimicrobial drugs.

Metallochaperone UreG serves as a new target for design of urease inhibitor: A novel strategy for development of antimicrobials.

Science.gov (United States)

Yang, Xinming; Koohi-Moghadam, Mohamad; Wang, Runming; Chang, Yuen-Yan; Woo, Patrick C Y; Wang, Junwen; Li, Hongyan; Sun, Hongzhe

2018-01-01

Urease as a potential target of antimicrobial drugs has received considerable attention given its versatile roles in microbial infection. Development of effective urease inhibitors, however, is a significant challenge due to the deeply buried active site and highly specific substrate of a bacterial urease. Conventionally, urease inhibitors are designed by either targeting the active site or mimicking substrate of urease, which is not efficient. Up to now, only one effective inhibitor-acetohydroxamic acid (AHA)-is clinically available, but it has adverse side effects. Herein, we demonstrate that a clinically used drug, colloidal bismuth subcitrate, utilizes an unusual way to inhibit urease activity, i.e., disruption of urease maturation process via functional perturbation of a metallochaperone, UreG. Similar phenomena were also observed in various pathogenic bacteria, suggesting that UreG may serve as a general target for design of new types of urease inhibitors. Using Helicobacter pylori UreG as a showcase, by virtual screening combined with experimental validation, we show that two compounds targeting UreG also efficiently inhibited urease activity with inhibitory concentration (IC)50 values of micromolar level, resulting in attenuated virulence of the pathogen. We further demonstrate the efficacy of the compounds in a mammalian cell infection model. This study opens up a new opportunity for the design of more effective urease inhibitors and clearly indicates that metallochaperones involved in the maturation of important microbial metalloenzymes serve as new targets for devising a new type of antimicrobial drugs.

Power and the objectification of social targets.

Science.gov (United States)

Gruenfeld, Deborah H; Inesi, M Ena; Magee, Joe C; Galinsky, Adam D

2008-07-01

Objectification has been defined historically as a process of subjugation whereby people, like objects, are treated as means to an end. The authors hypothesized that objectification is a response to social power that involves approaching useful social targets regardless of the value of their other human qualities. Six studies found that under conditions of power, approach toward a social target was driven more by the target's usefulness, defined in terms of the perceiver's goals, than in low-power and baseline conditions. This instrumental response to power, which was linked to the presence of an active goal, was observed using multiple instantiations of power, different measures of approach, a variety of goals, and several types of instrumental and noninstrumental target attributes. Implications for research on the psychology of power, automatic goal pursuit, and self-objectification theory are discussed.

Evolved Control of Natural Plants: Crossing the Reality Gap for User-Defined Steering of Growth and Motion

DEFF Research Database (Denmark)

Hofstadler, Daniel Nicolas; Wahby, Mostafa; Heinrich, Mary Katherine

2017-01-01

Mixing societies of natural and artificial systems can provide interesting and potentially fruitful research targets. Here we mix robotic setups and natural plants in order to steer the motion behavior of plants while growing. The robotic setup uses a camera to observe the plant and uses a pair...... of light sources to trigger phototropic response, steering the plant to user-defined targets. An evolutionary robotic approach is used to design a controller for the setup. Initially, preliminary experiments are performed with a simple predetermined controller and a growing bean plant. The plant behavior......-evolved controller in the real setup controlling a natural bean plant. The results demonstrate a successful crossing of the reality gap in the setup. The success of the approach allows for future extensions to more complex tasks including control of the shape of plants and pattern formation in multiple plant setups....

Integration of computational modeling and experimental techniques to design fuel surrogates

DEFF Research Database (Denmark)

Choudhury, H.A.; Intikhab, S.; Kalakul, Sawitree

2017-01-01

performance. A simplified alternative is to develop surrogate fuels that have fewer compounds and emulate certain important desired physical properties of the target fuels. Six gasoline blends were formulated through a computer aided model based technique “Mixed Integer Non-Linear Programming” (MINLP...... Virtual Process-Product Design Laboratory (VPPD-Lab) are applied onto the defined compositions of the surrogate gasoline. The aim is to primarily verify the defined composition of gasoline by means of VPPD-Lab. ρ, η and RVP are calculated with more accuracy and constraints such as distillation curve...... and flash point on the blend design are also considered. A post-design experiment-based verification step is proposed to further improve and fine-tune the “best” selected gasoline blends following the computation work. Here, advanced experimental techniques are used to measure the RVP, ρ, η, RON...

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

Science.gov (United States)

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

2014-03-01

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

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.

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

Definably compact groups definable in real closed fields.II

OpenAIRE

Barriga, Eliana

2017-01-01

We continue the analysis of definably compact groups definable in a real closed field $\\mathcal{R}$. In [3], we proved that for every definably compact definably connected semialgebraic group $G$ over $\\mathcal{R}$ there are a connected $R$-algebraic group $H$, a definable injective map $\\phi$ from a generic definable neighborhood of the identity of $G$ into the group $H\\left(R\\right)$ of $R$-points of $H$ such that $\\phi$ acts as a group homomorphism inside its domain. The above result and o...

Design of multiplier-less sharp non-uniform cosine modulated filter banks for efficient channelizers in software defined radio

Directory of Open Access Journals (Sweden)

Shaeen Kalathil

2016-03-01

Full Text Available Forthcoming software defined radios require filter banks which satisfy stringent specifications efficiently with low implementation complexity. Cosine modulated filter banks (CMFB have simple and efficient design procedure. The different wireless standards have different channel spacing or bandwidths and hence demand non-uniform decomposition of subbands. The non-uniform CMFB can be obtained from a uniform CMFB in a simple and efficient approach by merging the adjacent channels of the uniform CMFB. Very narrow transition width filters with low complexity can be achieved using frequency response masking (FRM filter as prototype filter. The complexity is further reduced by the multiplier-less realization of filter banks in which the least number of signed power of two (SPT terms is achieved by representing the filter coefficients using canonic signed digit (CSD representation and then optimizing using suitable modified meta-heuristic algorithms. Hybrid meta-heuristic algorithms are used in this paper. A hybrid algorithm combines the qualities of two meta-heuristic algorithms and results in improved performances with low implementation complexity. Highly frequency selective filter banks characterized by small passband ripple, narrow transition width and high stopband attenuation with non-uniform decomposition of subbands can be designed with least the implementation complexity, using this approach. A digital channelizer can be designed for SDR implementations, using the proposed approach. In this paper, the non-uniform CMFB is designed for various existing wireless standards.

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

International Nuclear Information System (INIS)

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

2005-01-01

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

Novel targeted therapies for cancer cachexia.

Science.gov (United States)

Argilés, Josep M; López-Soriano, Francisco Javier; Stemmler, Britta; Busquets, Sílvia

2017-07-27

Anorexia and metabolic alterations are the main components of the cachectic syndrome. Glucose intolerance, fat depletion, muscle protein catabolism and other alterations are involved in the development of cancer cachexia, a multi-organ syndrome. Nutritional approach strategies are not satisfactory in reversing the cachectic syndrome. The aim of the present review is to deal with the recent therapeutic targeted approaches that have been designed to fight and counteract wasting in cancer patients. Indeed, some promising targeted therapeutic approaches include ghrelin agonists, selective androgen receptor agonists, β-blockers and antimyostatin peptides. However, a multi-targeted approach seems absolutely essential to treat patients affected by cancer cachexia. This approach should not only involve combinations of drugs but also nutrition and an adequate program of physical exercise, factors that may lead to a synergy, essential to overcome the syndrome. This may efficiently reverse the metabolic changes described above and, at the same time, ameliorate the anorexia. Defining this therapeutic combination of drugs/nutrients/exercise is an exciting project that will stimulate many scientific efforts. Other aspects that will, no doubt, be very important for successful treatment of cancer wasting will be an optimized design of future clinical trials, together with a protocol for staging cancer patients in relation to their degree of cachexia. This will permit that nutritional/metabolic/pharmacological support can be started early in the course of the disease, before severe weight loss occurs. Indeed, timing is crucial and has to be taken very seriously when applying the therapeutic approach. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

In search of new lead compounds for trypanosomiasis drug design: A protein structure-based linked-fragment approach

Science.gov (United States)

Verlinde, Christophe L. M. J.; Rudenko, Gabrielle; Hol, Wim G. J.

1992-04-01

A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness.

IMPACT OF ENERGY GROUP STRUCTURE ON NUCLEAR DATA TARGET ACCURACY REQUIREMENTS FOR ADVANCED REACTOR SYSTEMS

Energy Technology Data Exchange (ETDEWEB)

G. Palmiotti; M. Salvatores; H. Hiruta

2011-06-01

A target accuracy assessment study using both a fine and a broad energy structure has shown that less stringent nuclear data accuracy requirements are needed for the latter energy structure. However, even though a reduction is observed, still the requirements will be very difficult to be met unless integral experiments are also used to reduce nuclear data uncertainties. Target accuracy assessment is the inverse problem of the uncertainty evaluation. To establish priorities and target accuracies on data uncertainty reduction, a formal approach can be adopted by defining target accuracy on design parameters and finding out required accuracy on data in order to meet them. In fact, the unknown uncertainty data requirements can be obtained by solving a minimization problem where the sensitivity coefficients in conjunction with the constraints on the integral parameters provide the needed quantities for finding the solutions.

Defining New Parameters for Green Engineering Design of Treatment Reactors

Directory of Open Access Journals (Sweden)

Susana Boeykens

2016-06-01

Full Text Available This study proposes a green way to design Plug Flow Reactors (PFR that use biodegradable polymer solutions, capable of contaminant retaining, for industrial wastewater treatment. Usually, to the design of a PFR, the reaction rate is determined by tests on a Continuous Stirred-Tank Reactor (CSTR, these generate toxic effluents and also increase the cost of the design. In this work, empirical expressions (called “slip functions”, in terms of the average concentration of the contaminant, were developed through the study of the transport behaviour of CrVI into solutions of xanthan gum. “In situ” XRµF was selected as a no-invasive micro-technique to determine local concentrations. Slip functions were used with laboratory PFR experiments planned in similar conditions, to obtain useful dimensionless parameters for the industrial design. 

Statistical Inference for Data Adaptive Target Parameters.

Science.gov (United States)

Hubbard, Alan E; Kherad-Pajouh, Sara; van der Laan, Mark J

2016-05-01

Consider one observes n i.i.d. copies of a random variable with a probability distribution that is known to be an element of a particular statistical model. In order to define our statistical target we partition the sample in V equal size sub-samples, and use this partitioning to define V splits in an estimation sample (one of the V subsamples) and corresponding complementary parameter-generating sample. For each of the V parameter-generating samples, we apply an algorithm that maps the sample to a statistical target parameter. We define our sample-split data adaptive statistical target parameter as the average of these V-sample specific target parameters. We present an estimator (and corresponding central limit theorem) of this type of data adaptive target parameter. This general methodology for generating data adaptive target parameters is demonstrated with a number of practical examples that highlight new opportunities for statistical learning from data. This new framework provides a rigorous statistical methodology for both exploratory and confirmatory analysis within the same data. Given that more research is becoming "data-driven", the theory developed within this paper provides a new impetus for a greater involvement of statistical inference into problems that are being increasingly addressed by clever, yet ad hoc pattern finding methods. To suggest such potential, and to verify the predictions of the theory, extensive simulation studies, along with a data analysis based on adaptively determined intervention rules are shown and give insight into how to structure such an approach. The results show that the data adaptive target parameter approach provides a general framework and resulting methodology for data-driven science.

Targeted Nanotechnology for Cancer Imaging

Science.gov (United States)

Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

2014-01-01

Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

Design and Implementation of Adaptive Turbo Encoder for Quantized Software Defined Low-Power DVB-RCS Radios

Directory of Open Access Journals (Sweden)

S. H. Elramly

2010-11-01

Full Text Available Turbo codes are employed in every robust wireless digital communications system. Those codes have been adopted for the satellite return channel in DVB-RCS (Return Channel via Satellite standard. In Software Defined Radios (SDRs, Field Programmable Gate Array technology (FPGA is considered a highly configurable option for implementing many sophisticated signal processing tasks. The implementation for such codes is complex and dissipates a large amount of power. This paper studies the efficient implementation of quantized DVB-RCS turbo coding. Also, a low-power, turbo encoder for DVB-RCS is described using a VHDL code. The proposed encoder design is implemented on Xilinx Virtex-II Pro, XC2vpx30 FPGA chip. FPGA Advantage Pro package provided by Mentor Graphics is used for VHDL description and ISE 10.1 by Xilinx is used for synthetization.

Computation-based virtual screening for designing novel antimalarial drugs by targeting falcipain-III: a structure-based drug designing approach.

Science.gov (United States)

Kesharwani, Rajesh Kumar; Singh, Durg Vijay; Misra, Krishna

2013-01-01

Cysteine proteases (falcipains), a papain-family of enzymes of Plasmodium falciparum, are responsible for haemoglobin degradation and thus necessary for its survival during asexual life cycle phase inside the human red blood cells while remaining non-functional for the human body. Therefore, these can act as potential targets for designing antimalarial drugs. The P. falciparum cysteine proteases, falcipain-II and falcipain- III are the enzymes which initiate the haemoglobin degradation, therefore, have been selected as targets. In the present study, we have designed new leupeptin analogues and subjected to virtual screening using Glide at the active site cavity of falcipain-II and falcipain-III to select the best docked analogues on the basis of Glide score and also compare with the result of AutoDock. The proposed analogues can be synthesized and tested in vivo as future potent antimalarial drugs. Protein falcipain-II and falcipain-III together with bounds inhibitors epoxysuccinate E64 (E64) and leupeptin respectively were retrieved from protein data bank (PDB) and latter leupeptin was used as lead molecule to design new analogues by using Ligbuilder software and refined the molecules on the basis of Lipinski rule of five and fitness score parameters. All the designed leupeptin analogues were screened via docking simulation at the active site cavity of falcipain-II and falcipain-III by using Glide software and AutoDock. The 104 new leupeptin-based antimalarial ligands were designed using structure-based drug designing approach with the help of Ligbuilder and subjected for virtual screening via docking simulation method against falcipain-II and falcipain-III receptor proteins. The Glide docking results suggest that the ligands namely result_037 shows good binding and other two, result_044 and result_042 show nearly similar binding than naturally occurring PDB bound ligand E64 against falcipain-II and in case of falcipain-III, 15 designed leupeptin analogues having

Environmental release targets for fusion power plants

International Nuclear Information System (INIS)

Gulden, W.; Raskob, W.

2005-01-01

Within the European fission community, so called European Utility Requirements were developed to define common targets, criteria and evaluation methods for, amongst others, safety, environmental protection and public health with respect to future nuclear fission power plant development. In the case of severe accidents, the objective is to restrict the radiological consequences to the vicinity of the plant, i.e., to avoid early and late countermeasures such as evacuation or relocation of the population, and to restrict food banning to small areas and the first year after the accident. Within the European Fusion Technology Programme, a methodology is being developed in compliance with these European Utility Requirements, to define design requirements for future fusion reactors. First results are presented. Concerning food banning, calculations revealed extremely conservative values for tritium in EU regulations and recommendations. This does not affect assessments for fission reactors, but is an overestimation of the tritium dose impact from ingestion. Therefore, in compliance with scientific justification, considerably higher maximum permissible activity levels for tritium should be considered

Defining Quality in Undergraduate Education

Directory of Open Access Journals (Sweden)

Alison W. Bowers

2018-01-01

Full Text Available Objectives: This research brief explores the literature addressing quality in undergraduate education to identify what previous research has said about quality and to offer future directions for research on quality in undergraduate education. Method: We conducted a scoping review to provide a broad overview of existing research. Using targeted search terms in academic databases, we identified and reviewed relevant academic literature to develop emergent themes and implications for future research. Results: The exploratory review of the literature revealed a range of thoughtful discussions and empirical studies attempting to define quality in undergraduate education. Many publications highlighted the importance of including different stakeholder perspectives and presented some of the varying perceptions of quality among different stakeholders. Conclusions: While a number of researchers have explored and written about how to define quality in undergraduate education, there is not a general consensus regarding a definition of quality in undergraduate education. Past research offers a range of insights, models, and data to inform future research. Implication for Theory and/or Practice: We provide four recommendations for future research to contribute to a high quality undergraduate educational experience. We suggest more comprehensive systematic reviews of the literature as a next step.

Human Exploration Using Real-Time Robotic Operations (HERRO)- Crew Telerobotic Control Vehicle (CTCV) Design

Science.gov (United States)

Oleson, Steven R.; McGuire, Melissa L.; Burke, Laura; Chato, David; Fincannon, James; Landis, Geoff; Sandifer, Carl; Warner, Joe; Williams, Glenn; Colozza, Tony;

Where can pixel counting area estimates meet user-defined accuracy requirements?

Science.gov (United States)

Waldner, François; Defourny, Pierre

2017-08-01

Pixel counting is probably the most popular way to estimate class areas from satellite-derived maps. It involves determining the number of pixels allocated to a specific thematic class and multiplying it by the pixel area. In the presence of asymmetric classification errors, the pixel counting estimator is biased. The overarching objective of this article is to define the applicability conditions of pixel counting so that the estimates are below a user-defined accuracy target. By reasoning in terms of landscape fragmentation and spatial resolution, the proposed framework decouples the resolution bias and the classifier bias from the overall classification bias. The consequence is that prior to any classification, part of the tolerated bias is already committed due to the choice of the spatial resolution of the imagery. How much classification bias is affordable depends on the joint interaction of spatial resolution and fragmentation. The method was implemented over South Africa for cropland mapping, demonstrating its operational applicability. Particular attention was paid to modeling a realistic sensor's spatial response by explicitly accounting for the effect of its point spread function. The diagnostic capabilities offered by this framework have multiple potential domains of application such as guiding users in their choice of imagery and providing guidelines for space agencies to elaborate the design specifications of future instruments.

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

Science.gov (United States)

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

2012-01-01

Nanostructured lipid carriers (NLC) are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol), lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of -25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

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...

Software defined networking applications in distributed datacenters

CERN Document Server

Qi, Heng

2016-01-01

This SpringerBrief provides essential insights on the SDN application designing and deployment in distributed datacenters. In this book, three key problems are discussed: SDN application designing, SDN deployment and SDN management. This book demonstrates how to design the SDN-based request allocation application in distributed datacenters. It also presents solutions for SDN controller placement to deploy SDN in distributed datacenters. Finally, an SDN management system is proposed to guarantee the performance of datacenter networks which are covered and controlled by many heterogeneous controllers. Researchers and practitioners alike will find this book a valuable resource for further study on Software Defined Networking. .

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

Science.gov (United States)

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

2016-09-30

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

Defining Interactions and Interfaces in Engineering Design

DEFF Research Database (Denmark)

Parslov, Jakob Filippson

documents of legal matter and must therefore be unambiguously and completely described. Following this observation, a comprehensive and systematic literature review has been performed in order to investigate the definition and perception of an interface. The review resulted in a classification revealing 13......This PhD thesis focuses on the understanding and definition of interactions and interfaces during the architectural decomposition of complex, multi-technological products. The Interaction and Interface Framework developed in this PhD project contribute to the field of engineering design research...... the framework, it has been possible to arrive at a classification of interaction mechanism, which is mutually exclusive (no overlap) and collectively exhaustive (no gaps). This contribution changes the existing paradigm of reasoning about interactions and allows for an unambiguous architectural decomposition...

JAERI/KEK target material program overview

International Nuclear Information System (INIS)

Kikuchi, Kenji; Kogawa, Hiroyuki; Sasa, Toshinobu

2001-01-01

Mercury target was designed for megawatt neutron scattering facility in JAERI/KEK spallation neutron source. The incident proton energy and current are 3 GeV and 333 μA, respectively: the total proton energy is 1 MW in short pulses at a frequency of 25 Hz. Under the guide rule the mercury target was designed: the maximum temperature of target window is 170degC and induced stresses for the type 316 stainless steel are within limits of design guide. In order to demonstrate ADS (Accelerator Driven Systems) transmutation critical and engineering facilities have been designed conceptually. In engineering facility lead-bismuth spallation target station is to be planned. Objective to build the facility is to demonstrate material irradiation. According to neutronics calculation irradiation damage of the target vessel window will be 5 dpa per year. (author)

Process of system design and analysis

International Nuclear Information System (INIS)

Gardner, B.

1995-01-01

The design of an effective physical protection system includes the determination of the physical protection system objectives, the initial design of a physical protection system, the evaluation of the design, and, probably, a redesign or refinement of the system. To develop the objectives, the designer must begin by gathering information about facility operations and conditions, such as a comprehensive description of the facility, operating states, and the physical protection requirements. The designer then needs to define the threat. This involves considering factors about potential adversaries: Class of adversary, adversary's capabilities, and range of adversary's tactics. Next, the designer should identify targets. Determination of whether or not nuclear materials are attractive targets is based mainly on the ease or difficulty of acquisition and desirability of the materiaL The designer now knows the objectives of the physical protection system, that is, ''What to protect against whom.'' The next step is to design the system by determining how best to combine such elements as fences, vaults, sensors, procedures, communication devices, and protective force personnel to meet the objectives of the system. Once a physical protection system is designed, it must be analyzed and evaluated to ensure it meets the physical protection objectives. Evaluation must allow for features working together to assure protection rather than regarding each feature separately. Due to the complexity of protection systems, an evaluation usually requires modeling techniques. If any vulnerabilities are found, the initial system must be redesigned to correct the vulnerabilities and a reevaluation conducted

Premium quality for a mechanical design department

OpenAIRE

Rofín Serrà, Guillem

2009-01-01

This Thesis has been carried out in a market which is expected to grow rapidly in the next decade. Because of this, actors in the market like Alpha want to strengthen their business position through refining the quality of their products and processes. One of the internal targets of MD, a mechanical design department within Alpha, referred to “premium product quality parameters” although these were not defined. Hence, this Thesis intends to contribute in the definition and understanding that ...

Defining the end-point of mastication: A conceptual model.

Science.gov (United States)

Gray-Stuart, Eli M; Jones, Jim R; Bronlund, John E

2017-10-01

The great risks of swallowing are choking and aspiration of food into the lungs. Both are rare in normal functioning humans, which is remarkable given the diversity of foods and the estimated 10 million swallows performed in a lifetime. Nevertheless, it remains a major challenge to define the food properties that are necessary to ensure a safe swallow. Here, the mouth is viewed as a well-controlled processor where mechanical sensory assessment occurs throughout the occlusion-circulation cycle of mastication. Swallowing is a subsequent action. It is proposed here that, during mastication, temporal maps of interfacial property data are generated, which the central nervous system compares against a series of criteria in order to be sure that the bolus is safe to swallow. To determine these criteria, an engineering hazard analysis tool, alongside an understanding of fluid and particle mechanics, is used to deduce the mechanisms by which food may deposit or become stranded during swallowing. These mechanisms define the food properties that must be avoided. By inverting the thinking, from hazards to ensuring safety, six criteria arise which are necessary for a safe-to-swallow bolus. A new conceptual model is proposed to define when food is safe to swallow during mastication. This significantly advances earlier mouth models. The conceptual model proposed in this work provides a framework of decision-making to define when food is safe to swallow. This will be of interest to designers of dietary foods, foods for dysphagia sufferers and will aid the further development of mastication robots for preparation of artificial boluses for digestion research. It enables food designers to influence the swallow-point properties of their products. For example, a product may be designed to satisfy five of the criteria for a safe-to-swallow bolus, which means the sixth criterion and its attendant food properties define the swallow-point. Alongside other organoleptic factors, these

Prostate bed target interfractional motion using RTOG consensus definitions and daily CT on rails. Does target motion differ between superior and inferior portions of the clinical target volume

International Nuclear Information System (INIS)

Verma, Vivek; Zhou, Sumin; Enke, Charles A.; Wahl, Andrew O.; Chen, Shifeng

2017-01-01

Using high-quality CT-on-rails imaging, the daily motion of the prostate bed clinical target volume (PB-CTV) based on consensus Radiation Therapy Oncology Group (RTOG) definitions (instead of surgical clips/fiducials) was studied. It was assessed whether PB motion in the superior portion of PB-CTV (SUP-CTV) differed from the inferior PB-CTV (INF-CTV). Eight pT2-3bN0-1M0 patients underwent postprostatectomy intensity-modulated radiotherapy, totaling 300 fractions. INF-CTV and SUP-CTV were defined as PB-CTV located inferior and superior to the superior border of the pubic symphysis, respectively. Daily pretreatment CT-on-rails images were compared to the planning CT in the left-right (LR), superoinferior (SI), and anteroposterior (AP) directions. Two parameters were defined: ''total PB-CTV motion'' represented total shifts from skin tattoos to RTOG-defined anatomic areas; ''PB-CTV target motion'' (performed for both SUP-CTV and INF-CTV) represented shifts from bone to RTOG-defined anatomic areas (i. e., subtracting shifts from skin tattoos to bone). Mean (± standard deviation, SD) total PB-CTV motion was -1.5 (± 6.0), 1.3 (± 4.5), and 3.7 (± 5.7) mm in LR, SI, and AP directions, respectively. Mean (± SD) PB-CTV target motion was 0.2 (±1.4), 0.3 (±2.4), and 0 (±3.1) mm in the LR, SI, and AP directions, respectively. Mean (± SD) INF-CTV target motion was 0.1 (± 2.8), 0.5 (± 2.2), and 0.2 (± 2.5) mm, and SUP-CTV target motion was 0.3 (± 1.8), 0.5 (± 2.3), and 0 (± 5.0) mm in LR, SI, and AP directions, respectively. No statistically significant differences between INF-CTV and SUP-CTV motion were present in any direction. There are no statistically apparent motion differences between SUP-CTV and INF-CTV. Current uniform planning target volume (PTV) margins are adequate to cover both portions of the CTV. (orig.) [de

Navy Advertising: Targeting Generation Z

Science.gov (United States)

2015-12-01

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA MBA PROFESSIONAL REPORT NAVY ADVERTISING : TARGETING GENERATION Z December......study recommends improvements for Navy advertising efficiency by examining characteristics of recruits defined as Generation Z. Data gathered from five

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)

Defining RNA-Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA.

Science.gov (United States)

Velagapudi, Sai Pradeep; Luo, Yiling; Tran, Tuan; Haniff, Hafeez S; Nakai, Yoshio; Fallahi, Mohammad; Martinez, Gustavo J; Childs-Disney, Jessica L; Disney, Matthew D

2017-03-22

RNA drug targets are pervasive in cells, but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif-small molecule interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross-Linking and Isolation by Pull Down (Chem-CLIP), a covalent small molecule-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of noncoding RNAs.

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

Science.gov (United States)

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

2018-02-15

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

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.)

Target-Rich Environment

Science.gov (United States)

Perna, Mark C.

2005-01-01

Target marketing is defining school enrollment goals and then developing a strategic plan to accomplish those goals through the use of specific communication vehicles and community focus. It is critical to reach the right audience, with the right message, at the right time, for the right cost. In this brief article, the author describes several…

Impact of target reproducibility on tumor dose in stereotactic radiotherapy of targets in the lung and liver.

Science.gov (United States)

Wulf, Jörn; Hädinger, Ulrich; Oppitz, Ulrich; Thiele, Wibke; Flentje, Michael

2003-02-01

Previous analyses of target reproducibility in extracranial stereotactic radiotherapy have revealed standard security margins for planning target volume (PTV) definition of 5mm in axial and 5-10mm in longitudinal direction. In this study the reproducibility of the clinical target volume (CTV) of lung and liver tumors within the PTV over the complete course of hypofractionated treatment is evaluated. The impact of target mobility on dose to the CTV is assessed by dose-volume histograms (DVH). Twenty-two pulmonary and 21 hepatic targets were treated with three stereotactic fractions of 10 Gy to the PTV-enclosing 100%-isodose with normalization to 150% at the isocenter. A conformal dose distribution was related to the PTV, which was defined by margins of 5-10mm added to the CTV. Prior to each fraction a computed tomography (CT)-simulation over the complete target volume was performed resulting in a total of 60 CT-simulations for lung and 58 CT-simulations for hepatic targets. The CTV from each CT-simulation was segmented and matched with the CT-study used for treatment planning. A DVH of the simulated CTV was calculated for each fraction. The target coverage (TC) of dose to the simulated CTV was defined as the proportion of the CTV receiving at least the reference dose (100%). A decrease of TC to or=95% at each fraction of treatment. Pulmonary targets with increased breathing mobility and liver tumors >100 cm(3) are at risk for target deviation exceeding the standard security margins for PTV-definition at least for one fraction and require individual evaluation of sufficient margins.

Innovative design for a phase 1 trial with intra-patient dose escalation: The Crotoxin study

Directory of Open Access Journals (Sweden)

Jacques Medioni

2017-09-01

Full Text Available Introduction: Crotoxin has a broad antitumor activity but has shown frequent neurotoxic toxicity. To induce tolerance and limit this toxicity, we propose a new design with intra-patient dose escalation. Methods: A new Dose Limiting Toxicity definition was used. The concept of Target Ceiling Dose was introduced. Results: Dose Limiting Toxicity was the inability to dose escalate twice. Target Ceiling Dose was the highest planned dose to be administered to a patient and could change for patients along time. Recommended Dose was defined similarly as in a (3 + 3 conventional design. Conclusion: This innovant design was used and the clinical trial is now closed for inclusions. Results will be presented later. Keywords: Clinical trial, Phase 1, Intra-patient dose escalation, Cancer

SNS Target Test Facility for remote handling design and verification

International Nuclear Information System (INIS)

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

1998-01-01

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

Design principles, targets and criterions for a Multipurpose Advanced Reactor Inherently Safe (MARS). Evaluation of the total production cost of electric energy

International Nuclear Information System (INIS)

Cumo, M.

2001-01-01

To be accepted and to be, sooner or later, extensively utilized, a new technology must respect the nature and its equilibria. For a nuclear power plant, the full respect of nature and of its equilibria means: for normal operation of the plant, guaranteeing a radiological impact comparable to the standard deviation of the radioactive natural background; for worst design plant accidents, guaranteeing an external impact only with the same probability as that of ultra-catastrophic natural events, such as bolide impacts to the earth. In compliance with Prof. A. Weinberg's suggestions, the design of the MARS nuclear plant was conceived according to this philosophy. The main factors which have affected the design development process of the MARS nuclear plant are introduced in the following. They include design principles, design targets and design criteria. These factors will be presented in two groups: the first group refers to the most relevant ones, regarding project fundamentals, as design principles, targets and main criteria (paragraph 1). The second group refers to detailed design criteria adopted for systems, structures and components relevant to safety (paragraph 2). (author)

Ideal MHD stability analysis of KSTAR target AT mode

International Nuclear Information System (INIS)

Yi, S.M.; Kim, J.H.; You, K.I.; Kim, J.Y.

2009-01-01

Full text: A main research objective of KSTAR (Korea Superconducting Tokamak Advanced Research) device is to demonstrate the steady-state operation capability of high-performance AT (Advanced Tokamak) mode. To meet this goal, it is critical for KSTAR to have a good MHD stability boundary, particularly against the high-beta ideal instabilities such as the external kink and the ballooning modes. To support this MHD stability KSTAR has been designed to have a strong plasma shape and a close interval between plasma and passive- plate wall. During the conceptual design phase of KSTAR, a preliminary study was performed to estimate the high beta MHD stability limit of KSTAR target AT mode using PEST and VACUUM codes and it was shown that the target AT mode can be stable up to β N ∼ 5 with a well-defined plasma pressure and current profiles. Recently, a new calculation has been performed to estimate the ideal stability limit in various KSTAR operating conditions using DCON code, and it has been observed that there is some difference between the new and old calculation results, particularly in the dependence of the maximum β N value on the toroidal mode number. Here, we thus present a more detailed analysis of the ideal MHD stability limit of KSTAR target AT mode using various codes, which include GATO as well as PEST and DCON, in the comparison of calculation results among the three codes. (author)

The design and evaluation of a phantom for the audit of the treatment chain for prostate radiotherapy

International Nuclear Information System (INIS)

Perrin, Bruce A.; Jordan, Thomas J.; Hounsell, Alan R.

2001-01-01

Background and Purpose: A phantom has been designed and built for a multi-institutional technique audit of the planning and delivery for radiotherapy to the prostate. The phantom was designed to test both the geometric and dosimetric accuracy of each aspect of the process. Materials and Methods: The phantom consists of two curved water filled perspex tanks either side of a central block of solid water equivalent material. There are two options for the central section; a target defining block and a dose measurement block. The target defining block uses air holes to define a 3-D target volume for imaging via a CT scanner or a simulator. These holes can subsequently be filled with steel pins to allow megavoltage imaging. The dose measurement block allows thimble chamber measurements to be made at pre-selected points in a 5x5mm array. Five dose measurement points, typical for a prostate planning target volume (PTV) were selected. Initial evaluation of the phantom was performed by auditing the prostate radiotherapy planning and treatment chain at one institution. Results: Agreement between the phantom and planned geometry confirmed that the stages of image acquisition, transfer and manipulation were accurately performed. Agreement within 0.5% was found between phantom and water tank measurements for dose calibration at a reference point. The measured dose delivered was within 2% of the dose calculated by the planning computer for all of the selected measurement points. The target volume marked by the steel pins was visible using electronic portal imaging. Conclusions: The phantom is a useful tool for the technique audit of prostate radiotherapy

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.

A statistical approach designed for finding mathematically defined repeats in shotgun data and determining the length distribution of clone-inserts

DEFF Research Database (Denmark)

Zhong, Lan; Zhang, Kunlin; Huang, Xiangang

2003-01-01

that repeats of different copy number have different probabilities of appearance in shotgun data, so based on this principle, we constructed a statistical model and inferred criteria for mathematically defined repeats (MDRs) at different shotgun coverages. According to these criteria, we developed software...... MDRmasker to identify and mask MDRs in shotgun data. With repeats masked prior to assembly, the speed of assembly was increased with lower error probability. In addition, clone-insert size affect the accuracy of repeat assembly and scaffold construction, we also designed length distribution of clone...

No apparent influence of psychometrically-defined schizotypy on orientation-dependent contextual modulation of visual contrast detection

Directory of Open Access Journals (Sweden)

Damien J. Mannion

2017-01-01

Full Text Available We investigated the relationship between psychometrically-defined schizotypy and the ability to detect a visual target pattern. Target detection is typically impaired by a surrounding pattern (context with an orientation that is parallel to the target, relative to a surrounding pattern with an orientation that is orthogonal to the target (orientation-dependent contextual modulation. Based on reports that this effect is reduced in those with schizophrenia, we hypothesised that there would be a negative relationship between the relative score on psychometrically-defined schizotypy and the relative effect of orientation-dependent contextual modulation. We measured visual contrast detection thresholds and scores on the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE from a non-clinical sample (N = 100. Contrary to our hypothesis, we find an absence of a monotonic relationship between the relative magnitude of orientation-dependent contextual modulation of visual contrast detection and the relative score on any of the subscales of the O-LIFE. The apparent difference of this result with previous reports on those with schizophrenia suggests that orientation-dependent contextual modulation may be an informative condition in which schizophrenia and psychometrically-defined schizotypy are dissociated. However, further research is also required to clarify the strength of orientation-dependent contextual modulation in those with schizophrenia.

Impact of target reproducibility on tumor dose in stereotactic radiotherapy of targets in the lung and liver

International Nuclear Information System (INIS)

Wulf, Joern; Haedinger, Ulrich; Oppitz, Ulrich; Thiele, Wibke; Flentje, Michael

2003-01-01

Background and purpose: Previous analyses of target reproducibility in extracranial stereotactic radiotherapy have revealed standard security margins for planning target volume (PTV) definition of 5 mm in axial and 5-10 mm in longitudinal direction. In this study the reproducibility of the clinical target volume (CTV) of lung and liver tumors within the PTV over the complete course of hypofractionated treatment is evaluated. The impact of target mobility on dose to the CTV is assessed by dose-volume histograms (DVH). Materials and methods: Twenty-two pulmonary and 21 hepatic targets were treated with three stereotactic fractions of 10 Gy to the PTV-enclosing 100%-isodose with normalization to 150% at the isocenter. A conformal dose distribution was related to the PTV, which was defined by margins of 5-10 mm added to the CTV. Prior to each fraction a computed tomography (CT)-simulation over the complete target volume was performed resulting in a total of 60 CT-simulations for lung and 58 CT-simulations for hepatic targets. The CTV from each CT-simulation was segmented and matched with the CT-study used for treatment planning. A DVH of the simulated CTV was calculated for each fraction. The target coverage (TC) of dose to the simulated CTV was defined as the proportion of the CTV receiving at least the reference dose (100%). Results: A decrease of TC to 3 . Conclusions: Target reproducibility was precise within the reference isodose in 91% of lung and 81% of liver tumors with a TC of the complete CTV ≥95% at each fraction of treatment. Pulmonary targets with increased breathing mobility and liver tumors >100 cm 3 are at risk for target deviation exceeding the standard security margins for PTV-definition at least for one fraction and require individual evaluation of sufficient margins

Target-aimed versus wishful-thinking in designing efficient GHG reduction strategies for a metropolitan city: Taipei

International Nuclear Information System (INIS)

Liu, C.-M.; Liou, M.-L.; Yeh, S.-C.; Shang, N.-C.

2009-01-01

In recent years, many national and local governments claim for a specific GHG (greenhouse gas) reduction goal targeted for many years later. In 2005, the Taipei City government announced that Taipei's total GHG emission in 2015 will reach the same level as that in 2005 and then down to 75% of that level at year 2030. However, based on the estimated energy consumption and GHG emission and the proposed emission reduction plans from the local government, it is clear that these goals are not going to be accomplished. In Taipei, the residential and commercial sector contributes more than 78% of the total GHG emission. Thus, in a business as usual scenario, the total GHG emission in 2030 would be 79% more than that in 2005, far more than the target value proclaimed. As many key factors are uncontrollable by the local government, a target-aimed strategy designing process by looking into changes in Taipei and identifying major targets is proposed in this study. It is demonstrated that such a universally applicable approach will give more confidence to the public on working toward the expected GHG reduction goal

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.

Conceptual design studies for the European DEMO divertor: Rationale and first results

International Nuclear Information System (INIS)

You, J.H.; Mazzone, G.; Visca, E.; Bachmann, Ch.; Autissier, E.; Barrett, T.; Cocilovo, V.; Crescenzi, F.; Domalapally, P.K.; Dongiovanni, D.; Entler, S.; Federici, G.; Frosi, P.; Fursdon, M.; Greuner, H.; Hancock, D.; Marzullo, D.; McIntosh, S.; Müller, A.V.; Porfiri, M.T.

2016-01-01

Highlights: • A brief overview is given on the overall R&D activities of the work package Divertor which is a project of the EUROfusion Consortium. • The rationale of the hydraulic, thermal and structural design scheme is described. • The first results obtained for the preliminary DEMO divertor cassette model are presented. - Abstract: In the European fusion roadmap, reliable power handling has been defined as one of the most critical challenges for realizing a commercially viable fusion power. In this context, the divertor is the key in-vessel component, as it is responsible for power exhaust and impurity removal for which divertor target is subjected to very high heat flux loads. To this end, an integrated R&D project was launched in the EUROfusion Consortium in order to deliver a holistic conceptual design solution together with the core technologies for the entire divertor system of a DEMO reactor. The work package ‘Divertor’ consists of two project areas: ‘Cassette design and integration’ and ‘Target development’. The essential mission of the project is to develop and verify advanced design concepts and the required technologies for a divertor system being capable of meeting the physical and system requirements defined for the next-generation European DEMO reactor. In this contribution, a brief overview is presented of the works from the first project year (2014). Focus is put on the loads specification, design boundary conditions, materials requirements, design approaches, and R&D strategy. Initial ideas and first estimates are presented.

Conceptual design studies for the European DEMO divertor: Rationale and first results

Energy Technology Data Exchange (ETDEWEB)

You, J.H., E-mail: you@ipp.mpg.de [Max Planck Institute for Plasma Physics, Boltzmann Str. 2, 85748 Garching (Germany); Mazzone, G.; Visca, E. [ENEA, Unità Tecnica Fusione, ENEA C. R. Frascati, via E. Fermi 45, 00044 Frascati (Italy); Bachmann, Ch. [EUROfusion PMU, c/o IPP, Boltzmann Str. 2, 85748 Garching (Germany); Autissier, E. [CEA, IRFM, F-13108 Saint Paul Lez Durance (France); Barrett, T. [CCFE, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Cocilovo, V.; Crescenzi, F. [ENEA, Unità Tecnica Fusione, ENEA C. R. Frascati, via E. Fermi 45, 00044 Frascati (Italy); Domalapally, P.K. [Research Cnter Rez, Hlavní 130, 250 68 Husinec–Řež (Czech Republic); Dongiovanni, D. [ENEA, Unità Tecnica Fusione, ENEA C. R. Frascati, via E. Fermi 45, 00044 Frascati (Italy); Entler, S. [Institute of Plasma Physics CAS, Za Slovankou 3, 182 00 Praha 8 (Czech Republic); Federici, G. [EUROfusion PMU, c/o IPP, Boltzmann Str. 2, 85748 Garching (Germany); Frosi, P. [ENEA, Unità Tecnica Fusione, ENEA C. R. Frascati, via E. Fermi 45, 00044 Frascati (Italy); Fursdon, M. [CCFE, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Greuner, H. [Max Planck Institute for Plasma Physics, Boltzmann Str. 2, 85748 Garching (Germany); Hancock, D. [CCFE, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Marzullo, D. [CREATE, University of Naples Federico II, P.le Tecchio 80, 80125 Napoli (Italy); McIntosh, S. [CCFE, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Müller, A.V. [Max Planck Institute for Plasma Physics, Boltzmann Str. 2, 85748 Garching (Germany); Porfiri, M.T. [ENEA, Unità Tecnica Fusione, ENEA C. R. Frascati, via E. Fermi 45, 00044 Frascati (Italy); and others

2016-11-01

Highlights: • A brief overview is given on the overall R&D activities of the work package Divertor which is a project of the EUROfusion Consortium. • The rationale of the hydraulic, thermal and structural design scheme is described. • The first results obtained for the preliminary DEMO divertor cassette model are presented. - Abstract: In the European fusion roadmap, reliable power handling has been defined as one of the most critical challenges for realizing a commercially viable fusion power. In this context, the divertor is the key in-vessel component, as it is responsible for power exhaust and impurity removal for which divertor target is subjected to very high heat flux loads. To this end, an integrated R&D project was launched in the EUROfusion Consortium in order to deliver a holistic conceptual design solution together with the core technologies for the entire divertor system of a DEMO reactor. The work package ‘Divertor’ consists of two project areas: ‘Cassette design and integration’ and ‘Target development’. The essential mission of the project is to develop and verify advanced design concepts and the required technologies for a divertor system being capable of meeting the physical and system requirements defined for the next-generation European DEMO reactor. In this contribution, a brief overview is presented of the works from the first project year (2014). Focus is put on the loads specification, design boundary conditions, materials requirements, design approaches, and R&D strategy. Initial ideas and first estimates are presented.

Defining Marketing Strategies For Vihreä Tekno Finland

OpenAIRE

Manzari, Mohammad

2016-01-01

The main objective of this thesis is to define marketing strategies for Vihreä Tekno, a company in Vantaa, Finland. The company runs several businesses such as providing IT services, website designing, business/loyalty cards, professional logo design, PC repairs and installations, mobile application development, translation services, cleaning services, advertising and distribution services, billing/invoicing systems and so forth. In this thesis, the author analyzed the company’s current s...

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

Science.gov (United States)

Hoidn, Oliver; Seidler, Gerald T.

2018-01-01

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

Minor actinides transmutation scenario studies with PWRs, FRs and moderated targets

International Nuclear Information System (INIS)

Grouiller, J.P.; Pillon, S.; Saint Jean, C. de; Varaine, F.; Leyval, L.; Vambenepe, G.; Carlier, B.

2003-01-01

Using current technologies, we have demonstrated in this study that it is theoretically possible to obtain different minor actinide transmutation scenarios with a significant gain on the waste radiotoxicity inventory. The handling of objects with Am+Cm entails the significant increase of penetrating radiation sources (neutron and γ) whatever mixed scenario is envisioned; the PWR and FR scenario involving the recycling of Am + Cm in the form of targets results in the lowest flow. In the light of these outcomes, the detailed studies has allowed to design a target sub assembly with a high fission rate (90%) and define a drawing up of reprocessing diagram with the plant head, the minor actinide separation processes (PUREX, DIAMEX and SANEX). Some technological difficulties appear in manipulating curium, principally in manufacturing where the wet process ('sol-gel') is not acquired for (Am+Cm). (author)

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

Directory of Open Access Journals (Sweden)

Sare Andalib

2012-01-01

Full Text Available Background: Nanostructured lipid carriers (NLC are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. Materials and Methods: The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol, lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. Results: The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of −25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. Conclusions: The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

Adoption and Design of Emerging Dietary Policies to Improve Cardiometabolic Health in the US.

Science.gov (United States)

Huang, Yue; Pomeranz, Jennifer; Wilde, Parke; Capewell, Simon; Gaziano, Tom; O'Flaherty, Martin; Kersh, Rogan; Whitsel, Laurie; Mozaffarian, Dariush; Micha, Renata

2018-04-14

Suboptimal diet is a leading cause of cardiometabolic disease and economic burdens. Evidence-based dietary policies within 5 domains-food prices, reformulation, marketing, labeling, and government food assistance programs-appear promising at improving cardiometabolic health. Yet, the extent of new dietary policy adoption in the US and key elements crucial to define in designing such policies are not well established. We created an inventory of recent US dietary policy cases aiming to improve cardiometabolic health and assessed the extent of their proposal and adoption at federal, state, local, and tribal levels; and categorized and characterized the key elements in their policy design. Recent federal dietary policies adopted to improve cardiometabolic health include reformulation (trans-fat elimination), marketing (mass-media campaigns to increase fruits and vegetables), labeling (Nutrition Facts Panel updates, menu calorie labeling), and food assistance programs (financial incentives for fruits and vegetables in the Supplemental Nutrition Assistance Program (SNAP) and Women, Infant and Children (WIC) program). Federal voluntary guidelines have been proposed for sodium reformulation and food marketing to children. Recent state proposals included sugar-sweetened beverage (SSB) taxes, marketing restrictions, and SNAP restrictions, but few were enacted. Local efforts varied significantly, with certain localities consistently leading in the proposal or adoption of relevant policies. Across all jurisdictions, most commonly selected dietary targets included fruits and vegetables, SSBs, trans-fat, added sugar, sodium, and calories; other healthy (e.g., nuts) or unhealthy (e.g., processed meats) factors were largely not addressed. Key policy elements to define in designing these policies included those common across domains (e.g., level of government, target population, dietary target, dietary definition, implementation mechanism), and domain-specific (e.g., media channels