Conceptual design of the 7 megawatt Mod-5B wind turbine generator

NASA Technical Reports Server (NTRS)

Douglas, R. R.

1982-01-01

Similar to MOD-2, the MOD-5B wind turbine generator system is designed for the sole purpose of providing electrical power for distribution by a major utility network. The objectives of the MOD-2 and MOD-5B programs are essentially identical with one important exception; the cost-of-electricity (COE) target is reduced from 4 cent/Kwhr on MOD-2 to 3 cent/Kwhr on MOD-5B, based on mid 1977 dollars and large quantity production. The MOD-5B concept studies and eventual concept selection confirmed that the program COE targets could not only be achieved but substantially bettered. Starting from the established MOD-2 technology as a base, this achievement resulted from a combination of concept changes, size changes, and design refinements. The result of this effort is a wind turbine system that can compete with conventional power generation over significant geographical areas, increasing commercial market potential by an order of magnitude.

Advances in target design for heavy ion fusion

NASA Astrophysics Data System (ADS)

Callahan, D. A.; Tabak, M.; Bennett, G. R.; Cuneo, M. E.; Vesey, R. A.; Nikroo, A.; Czechowicz, D.; Steinman, D.

2005-12-01

Over the past few years, the emphasis in heavy ion target design has moved from the distributed radiator target to the 'hybrid' target because the hybrid target allows a larger beam focal spot than the distributed radiator (~5 mm radius rather than ~2 mm radius). The larger spot relaxes some of the requirements on the driver, but introduces some new target physics issues. Most notable is the use of shine shields and shims in the hohlraum to achieve symmetry rather than achieving symmetry by beam placement. The shim is a thin layer of material placed on or near the capsule surface to block a small amount of excess radiation. While we have been developing this technique for the heavy ion hybrid target, the technique can also be used in any indirect drive target. We have begun testing the concept of a shim to improve symmetry using a double-ended z-pinch hohlraum on the Sandia Z-machine. Experiments using shimmed thin wall capsules have shown that we can reverse the sign of a P2 asymmetry and significantly reduce the size of a P4 asymmetry. These initial experiments demonstrate the concept of a shim as another method for controlling early time asymmetries in ICF capsules.

The ADVANCE project : formal evaluation of the targeted deployment. Volume 2

DOT National Transportation Integrated Search

1997-01-01

This document reports on the formal evaluation of the targeted (limited but highly focused) deployment of the Advanced Driver and Vehicle Advisory Navigation ConcEpt (ADVANCE), an in-vehicle advanced traveler information system designed to provide sh...

Cultural Influence on Pupils' Understanding of Conception, Birth of Twins and Sex Determination in Kenya

ERIC Educational Resources Information Center

Keraro, Fred N.; Okere, Mark I. O.; Anditi, Zephania O.

2013-01-01

This study investigated the extent to which primary and secondary school pupils believe in cultural interpretations of the biological concepts of conception, birth of twins and sex determination and the influence of education level and gender. Cross-sectional survey research design was used. The target population was Standard Seven (7th grade in…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwan, T.J.T.; Moir, D.C.; Snell, C.M.

In high resolution flash x-ray imaging technology the electric field developed between the electron beam and the converter target is large enough to draw ions from the target surface. The ions provide fractional neutralization and cause the electron beam to focus radially inward, and the focal point subsequently moves upstream due to the expansion of the ion column. A self-bias target concept is proposed and verified via computer simulation that the electron charge deposited on the target can generate an electric potential, which can effectively limit the ion motion and thereby stabilize the growth of the spot size. A targetmore » chamber using the self bias target concept was designed and tested in the Integrated Test Stand (ITS). The authors have obtained good agreement between computer simulation and experiment.« less

DESTINY+ Trajectory Design to (3200) Phaethon

NASA Astrophysics Data System (ADS)

Sarli, Bruno Victorino; Horikawa, Makoto; Yam, Chit Hong; Kawakatsu, Yasuhiro; Yamamoto, Takayuki

2018-03-01

This work explores the target selection and trajectory design of the mission candidate for ISAS/JAXA's small science satellite series, DESTINY PLUS or DESTINY+. This mission combines unique aspects of the latest satellite technology and exploration of transition bodies to fill a technical and scientific gap in the Japanese space science program. The spacecraft is targeted to study the comet-asteroid transition body (3200) Phaethon through a combination of low-thrust propulsion and Earth Gravity Assist. The trajectory design concept is presented in details together with the launch window and flyby date analysis. Alternative targets for a possible mission extension scenario are also explored.

Novel Composites for Wing and Fuselage Applications. Task 1; Novel Wing Design Concepts

NASA Technical Reports Server (NTRS)

Suarez, J. A.; Buttitta, C.; Flanagan, G.; DeSilva, T.; Egensteiner, W.; Bruno, J.; Mahon, J.; Rutkowski, C.; Collins, R.; Fidnarick, R.;

Development of the ASTRI heliostat

NASA Astrophysics Data System (ADS)

Coventry, Joe; Arjomandi, Maziar; Barry, John; Blanco, Manuel; Burgess, Greg; Campbell, Jonathan; Connor, Phil; Emes, Matthew; Fairman, Philip; Farrant, David; Ghanadi, Farzin; Grigoriev, Victor; Hall, Colin; Koltun, Paul; Lewis, David; Martin, Scott; Nathan, Graham; Pye, John; Qiu, Ang; Stuart, Wayne; Tang, Youhong; Venn, Felix; Yu, Jeremy

2016-05-01

The Australian Solar Thermal Research Initiative (ASTRI) aims to develop a high optical quality heliostat with target cost - manufactured, installed and operational - of 90 AUD/m2. Three different heliostat design concepts are described, each with features identified during a prior scoping study as having the potential to contribute to cost reduction compared to the current state-of-the-art. The three concepts which are being developed will be down-selected to a single concept for testing in late 2016. The heliostat concept development work is supported by technology development streams, developing novel sandwich panel mirror facet structures, analysing and testing wind loads on heliostats in both stow and operation positions, and developing new heliostat field layouts and software tools for optical analysis of heliostats design concepts.

Deployment Analysis of a Simple Tape-Spring Hinge Using Probabilistic Methods

NASA Technical Reports Server (NTRS)

Lyle, Karen H.; Horta, Lucas G.

2012-01-01

Acceptance of new deployable structures architectures and concepts requires validated design methods to minimize the expense involved with technology validation flight testing. Deployable concepts for large lightweight spacecraft include booms, antennae, and masts. This paper explores the implementation of probabilistic methods in the design process for the deployment of a strain-energy mechanism, specifically a simple tape-spring hinge. Strain-energy mechanisms are attractive for deployment in very lightweight systems because they do not require the added mass and complexity associated with motors and controllers. However, designers are hesitant to include free deployment, strain-energy mechanisms because of the potential for uncontrolled behavior. In the example presented here, the tapespring cross-sectional dimensions have been varied and a target displacement during deployment has been selected as the design metric. Specifically, the tape-spring should reach the final position in the shortest time with the minimal amount of overshoot and oscillations. Surrogate models have been used to reduce computational expense. Parameter values to achieve the target response have been computed and used to demonstrate the approach. Based on these results, the application of probabilistic methods for design of a tape-spring hinge has shown promise as a means of designing strain-energy components for more complex space concepts.

Exoplanet Yield Estimation for Decadal Study Concepts using EXOSIMS

NASA Astrophysics Data System (ADS)

Morgan, Rhonda; Lowrance, Patrick; Savransky, Dmitry; Garrett, Daniel

2016-01-01

The anticipated upcoming large mission study concepts for the direct imaging of exo-earths present an exciting opportunity for exoplanet discovery and characterization. While these telescope concepts would also be capable of conducting a broad range of astrophysical investigations, the most difficult technology challenges are driven by the requirements for imaging exo-earths. The exoplanet science yield for these mission concepts will drive design trades and mission concept comparisons.To assist in these trade studies, the Exoplanet Exploration Program Office (ExEP) is developing a yield estimation tool that emphasizes transparency and consistent comparison of various design concepts. The tool will provide a parametric estimate of science yield of various mission concepts using contrast curves from physics-based model codes and Monte Carlo simulations of design reference missions using realistic constraints, such as solar avoidance angles, the observatory orbit, propulsion limitations of star shades, the accessibility of candidate targets, local and background zodiacal light levels, and background confusion by stars and galaxies. The python tool utilizes Dmitry Savransky's EXOSIMS (Exoplanet Open-Source Imaging Mission Simulator) design reference mission simulator that is being developed for the WFIRST Preliminary Science program. ExEP is extending and validating the tool for future mission concepts under consideration for the upcoming 2020 decadal review. We present a validation plan and preliminary yield results for a point design.

The Impact of a Summer Institute on Inservice Early Childhood Teachers' Knowledge of Earth and Space Science Concepts

ERIC Educational Resources Information Center

Sackes, Mesut; Trundle, Kathy Cabe; Krissek, Lawrence A.

2011-01-01

This study investigated inservice PreK to Grade two teachers' knowledge of some earth and space science concepts before and after a short-term teacher institute. A one-group pre-test-post-test design was used in the current study. Earth science concepts targeted during the professional development included properties of rocks and soils, and the…

Approach range and velocity determination using laser sensors and retroreflector targets

NASA Technical Reports Server (NTRS)

Donovan, William J.

1991-01-01

A laser docking sensor study is currently in the third year of development. The design concept is considered to be validated. The concept is based on using standard radar techniques to provide range, velocity, and bearing information. Multiple targets are utilized to provide relative attitude data. The design requirements were to utilize existing space-qualifiable technology and require low system power, weight, and size yet, operate from 0.3 to 150 meters with a range accuracy greater than 3 millimeters and a range rate accuracy greater than 3 mm per second. The field of regard for the system is +/- 20 deg. The transmitter and receiver design features a diode laser, microlens beam steering, and power control as a function of range. The target design consists of five target sets, each having seven 3-inch retroreflectors, arranged around the docking port. The target map is stored in the sensor memory. Phase detection is used for ranging, with the frequency range-optimized. Coarse bearing measurement is provided by the scanning system (one set of binary optics) angle. Fine bearing measurement is provided by a quad detector. A MIL-STD-1750 A/B computer is used for processing. Initial test results indicate a probability of detection greater than 99 percent and a probability of false alarm less than 0.0001. The functional system is currently at the MIT/Lincoln Lab for demonstration.

Flexible weapons architecture design

NASA Astrophysics Data System (ADS)

Pyant, William C., III

Present day air-delivered weapons are of a closed architecture, with little to no ability to tailor the weapon for the individual engagement. The closed architectures require weaponeers to make the target fit the weapon instead of fitting the individual weapons to a target. The concept of a flexible weapons aims to modularize weapons design using an open architecture shell into which different modules are inserted to achieve the desired target fractional damage while reducing cost and civilian casualties. This thesis shows that the architecture design factors of damage mechanism, fusing, weapons weight, guidance, and propulsion are significant in enhancing weapon performance objectives, and would benefit from modularization. Additionally, this thesis constructs an algorithm that can be used to design a weapon set for a particular target class based on these modular components.

Definition of a 5MW/61.5m wind turbine blade reference model.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Resor, Brian Ray

2013-04-01

A basic structural concept of the blade design that is associated with the frequently utilized %E2%80%9CNREL offshore 5-MW baseline wind turbine%E2%80%9D is needed for studies involving blade structural design and blade structural design tools. The blade structural design documented in this report represents a concept that meets basic design criteria set forth by IEC standards for the onshore turbine. The design documented in this report is not a fully vetted blade design which is ready for manufacture. The intent of the structural concept described by this report is to provide a good starting point for more detailed and targeted investigationsmore » such as blade design optimization, blade design tool verification, blade materials and structures investigations, and blade design standards evaluation. This report documents the information used to create the current model as well as the analyses used to verify that the blade structural performance meets reasonable blade design criteria.« less

Conceptual Design and Dynamics Testing and Modeling of a Mars Tumbleweed Rover

NASA Technical Reports Server (NTRS)

Calhoun Philip C.; Harris, Steven B.; Raiszadeh, Behzad; Zaleski, Kristina D.

2005-01-01

The NASA Langley Research Center has been developing a novel concept for a Mars planetary rover called the Mars Tumbleweed. This concept utilizes the wind to propel the rover along the Mars surface, bringing it the potential to cover vast distances not possible with current Mars rover technology. This vehicle, in its deployed configuration, must be large and lightweight to provide the ratio of drag force to rolling resistance necessary to initiate motion from rest on the Mars surface. One Tumbleweed design concept that satisfies these considerations is called the Eggbeater-Dandelion. This paper describes the basic design considerations and a proposed dynamics model of the concept for use in simulation studies. It includes a summary of rolling/bouncing dynamics tests that used videogrammetry to better understand, characterize, and validate the dynamics model assumptions, especially the effective rolling resistance in bouncing/rolling dynamic conditions. The dynamics test used cameras to capture the motion of 32 targets affixed to a test article s outer structure. Proper placement of the cameras and alignment of their respective fields of view provided adequate image resolution of multiple targets along the trajectory as the test article proceeded down the ramp. Image processing of the frames from multiple cameras was used to determine the target positions. Position data from a set of these test runs was compared with results of a three dimensional, flexible dynamics model. Model input parameters were adjusted to match the test data for runs conducted. This process presented herein provided the means to characterize the dynamics and validate the simulation of the Eggbeater-Dandelion concept. The simulation model was used to demonstrate full scale Tumbleweed motion from a stationary condition on a flat-sloped terrain using representative Mars environment parameters.

Designing divertor targets for uniform power load

NASA Astrophysics Data System (ADS)

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

2015-08-01

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

Orion Entry, Descent, and Landing Performance and Mission Design

NASA Technical Reports Server (NTRS)

Broome, Joel M.; Johnson, Wyatt

2007-01-01

The Orion Vehicle is the next spacecraft to take humans into space and will include missions to ISS as well as missions to the Moon. As part of that challenge, the vehicle will have to accommodate multiple mission design concepts, since return from Low Earth Orbit and return from the Moon can be quite different. Commonality between the different missions as it relates to vehicle systems, guidance capability, and operations concepts is the goal. Several unique mission design concepts include the specification of multiple land-based landing sites for a vehicle with closed-loop direct and skip entry guidance, followed by a parachute descent and landing attenuation system. This includes the ability of the vehicle to accurately target and land at a designated landing site, including site location aspects, landing site size, and landing opportunities assessments. Analyses associated with these mission design and flight performance challenges and constraints will be discussed as well as potential operational concepts to provide feasibility and/or mission commonality.

Differentiating Instruction for Students with Learning Disabilities: Best Teaching Practices for General and Special Educators.

ERIC Educational Resources Information Center

Bender, William N.

This book provides classroom-proven strategies designed to empower the teacher to target instructional modifications to the content, process, and products for students with learning disabilities in the general and special education classrooms. Chapter 1 presents the concept of differentiated instruction and how that concept translates into…

Canadian Forces in Joint Fires Support - Human Factors Analysis: Coalition Operations

DTIC Science & Technology

2010-08-01

mesure/l’estimation des dommages collatéraux (EDC). Outil pour comprendre l’EDC de certains pays comparativement à celle des membres de l’OTAN et...Program (TDP). The TDP is aimed at concept development, evaluation for force design , and the demonstration of technologies fostered by Defence Research...logistics and the designation of targets on the joint targeting list. • Tactical capability / response time / training. The tactical capability of a fire

Key features for ATA / ATR database design in missile systems

NASA Astrophysics Data System (ADS)

Özertem, Kemal Arda

2017-05-01

Automatic target acquisition (ATA) and automatic target recognition (ATR) are two vital tasks for missile systems, and having a robust detection and recognition algorithm is crucial for overall system performance. In order to have a robust target detection and recognition algorithm, an extensive image database is required. Automatic target recognition algorithms use the database of images in training and testing steps of algorithm. This directly affects the recognition performance, since the training accuracy is driven by the quality of the image database. In addition, the performance of an automatic target detection algorithm can be measured effectively by using an image database. There are two main ways for designing an ATA / ATR database. The first and easy way is by using a scene generator. A scene generator can model the objects by considering its material information, the atmospheric conditions, detector type and the territory. Designing image database by using a scene generator is inexpensive and it allows creating many different scenarios quickly and easily. However the major drawback of using a scene generator is its low fidelity, since the images are created virtually. The second and difficult way is designing it using real-world images. Designing image database with real-world images is a lot more costly and time consuming; however it offers high fidelity, which is critical for missile algorithms. In this paper, critical concepts in ATA / ATR database design with real-world images are discussed. Each concept is discussed in the perspective of ATA and ATR separately. For the implementation stage, some possible solutions and trade-offs for creating the database are proposed, and all proposed approaches are compared to each other with regards to their pros and cons.

RF Systems in Space. Volume I. Space Antennas Frequency (SARF) Simulation.

DTIC Science & Technology

1983-04-01

lens SBR designs were investigated. The survivability of an SBR system was analyzed. The design of ground based SBR validation experiments for large...aperture SBR concepts were investigated. SBR designs were investigated for ground target detection. N1’IS GRAMI DTIC TAB E Unannounced E Justificat... designs :~~.~...: .-..:. ->.. - . *.* . ..- . . .. . -. . ..- . .4. To analyze the survivability of space radar 5. To design ground-based validation

30MM GAU-8/A Plastic Frangible Projectile

DTIC Science & Technology

1977-03-01

20. ABSTRACT fContlnuo on rmvert» tld» 11 nacaaaary and Idontlly by block numbmr) ■feA 30mm target practice (TP) projectile, designed to break...contract to solve these problems. As a result, the Air Force has decided to delay further development of this projectile design concept...Section Title I INTRODUCTION II TECHNICAL DISCUSSION Design Parameters Final Projectile Design Design Evolution Acceptance Testing III

Conventional Prompt Global Strike and Long-Range Ballistic Missiles: Background and Issues

DTIC Science & Technology

2011-04-21

winglets , rather than on the winged design of the HTV-2. Upon nearing a target, the weapon would be able to maneuver to avoid flying over third party...concept from PGS, Congress, initially at least, blended both into the request for a new report. The Air Force submitted its report on the CAV concept of

Microwave blackbodies for spaceborne receivers

NASA Technical Reports Server (NTRS)

Stacey, J. M.

1985-01-01

The properties of microwave blackbody targets are explained as they apply to the calibration of spaceborne receivers. Also described are several practicable, blackbody targets used to test and calibrate receivers in the laboratory and in the thermal vacuum chamber. Problems with the precision and the accuracy of blackbody targets, and blackbody target design concepts that overcome some of the accuracy limitations present in existing target designs, are presented. The principle of the Brewster angle blackbody target is described where the blackbody is applied as a fixed-temperature test target in the laboratory and as a variable-temperature target in the thermal vacuum chamber. The reflectivity of a Brewster angle target is measured in the laboratory. From this measurement, the emissivity of the target is calculated. Radiatively cooled thermal suspensions are discussed as the coolants of blackbody targets and waveguide terminations that function as calibration devices in spaceborne receivers. Examples are given for the design of radiatively cooled thermal suspensions. Corrugated-horn antennas used to observe the cosmic background and to provide a cold-calibration source for spaceborne receivers are described.

Mercury target R&D for the Oak Ridge spallation neutron source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haines, J.R.; DiStefano, J.; Farrell, K.

1996-06-01

The conceptual design for the Oak Ridge Spallation Neutron Source (ORSNS) incorporates liquid mercury as its reference target material. A flowing liquid target was selected mainly because of the increased power handling capability possible with the convective transport process. The major reasons for choosing mercury as the liquid target material are because it: (1) is a liquid at room temperature, (2) has good heat transport properties, and (3) has a high atomic number and mass density resulting in high neutron yield and source brightness. Since liquid targets are not widely utilized in presently operating accelerator targets and because of themore » challenges posed by the intense, pulsed thermal energy deposition ({approximately}20-100 kJ deposited during each 1-10 {mu}s pulse), considerable R&D is planned for the mercury target concept. The key feasibility issue that will be addressed in early R&D efforts are the effects of the thermal shock environment, which will include development and testing of approaches to mitigate these effects. Materials compatiblity and ES&H issues associated with the use of liquid mercury are also of major importance in early R&D efforts. A brief description of the mercury target design concept, results of initial evaluations of its performance characteristics, identification of its critical issues, and an outline of the R&D program aimed at addressing these issues will be presented.« less

Carbon Rod Radiant Source for Blast/Fire Interaction Experiments: Proof of Concept and Design.

DTIC Science & Technology

1980-08-30

Contracting Officer’s Technical Representative was David W. Bensen ISt. KEY IFORCS (C~rnuen orm rwv.,,, took of otarfam d *Oent.-y by block fmtr.) Blast/F...42 13b Irradiance at Target Surface Elliptical Reflectors .. ..... 43 13c Irradiance at Target Surface Parabolic and Elliptical Reflectors...44 14 Flux Distribution at Target Surface for One Rod, Parabolic and Elliptical Reflectors ...................... 15

Optimal Path to a Laser Fusion Energy Power Plant

NASA Astrophysics Data System (ADS)

Bodner, Stephen

2013-10-01

There was a decision in the mid 1990s to attempt ignition using indirect-drive targets. It is now obvious that this decision was unjustified. The target design was too geometrically complex, too inefficient, and too far above plasma instability thresholds. By that same time, the mid 1990s, there had also been major advances in the direct-drive target concept. It also was not yet ready for a major test. Now, finally, because of significant advances in target designs, laser-target experiments, and laser development, the direct-drive fusion concept is ready for significant enhancements in funding, on the path to commercial fusion energy. There are two laser contenders. A KrF laser is attractive because of its shortest wavelength, broad bandwidth, and superb beam uniformity. A frequency-converted DPSSL has the disadvantage of inherently narrow bandwidth and longer wavelength, but by combining many beams in parallel one might be able to produce at the target the equivalent of an ultra-broad bandwidth. One or both of these lasers may also meet all of the engineering and economic requirements for a reactor. It is time to further develop and evaluate these two lasers as rep-rate systems, in preparation for a future high-gain fusion test.

Peptide-Drug Conjugate: A Novel Drug Design Approach.

PubMed

Ma, Liang; Wang, Chao; He, Zihao; Cheng, Biao; Zheng, Ling; Huang, Kun

2017-01-01

More than 100 years ago, German physician Paul Ehrlich first proposed the concept of selectively delivering "magic bullets" to tumors through targeting agents. The targeting therapy with antibody-drug conjugates (ADCs) and peptide-drug conjugate (PDCs), which are usually composed of monoclonal antibodies or peptides, toxic payloads and cleavage/ noncleavage linkers, has been extensively studied for decades. The conjugates enable selective delivery of cytotoxic payloads to target cells, which results in improved efficacy, reduced systemic toxicity and improved pharmacokinetics (PK)/pharmacodynamics (PD) compared with traditional chemotherapy. PDC and ADC share similar concept, but with vastly different structures and properties. Humanized antibodies introduce high specificity and prolonged half-life, while small molecule weight peptides exhibit higher drug loading and enhanced tissue penetration capacity, and the flexible linear or cyclic peptides are also modified more easily. In this review, the principles of design, synthesis approaches and the latest advances of PDCs are summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Parental Socio-Economic Status, Self-Concept and Gender Differences on Students' Academic Performance in Borno State Colleges of Education: Implications for Counselling

ERIC Educational Resources Information Center

Goni, Umar; Bello, S.

2016-01-01

This is a survey study, designed to determine gender differences and socio-economic status, self-concept on students' academic performance in Colleges of Education, Borno State: Implications for counselling. The study set two research objectives, answered two research questions and tested two research hypotheses. The target population of this…

Interventions and assessment tools addressing key concepts people need to know to appraise claims about treatment effects: a systematic mapping review.

PubMed

Austvoll-Dahlgren, Astrid; Nsangi, Allen; Semakula, Daniel

2016-12-29

People's ability to appraise claims about treatment effects is crucial for informed decision-making. Our objective was to systematically map this area of research in order to (a) provide an overview of interventions targeting key concepts that people need to understand to assess treatment claims and (b) to identify assessment tools used to evaluate people's understanding of these concepts. The findings of this review provide a starting point for decisions about which key concepts to address when developing new interventions, and which assessment tools should be considered. We conducted a systematic mapping review of interventions and assessment tools addressing key concepts important for people to be able to assess treatment claims. A systematic literature search was done by a reserach librarian in relevant databases. Judgement about inclusion of studies and data collection was done by at least two researchers. We included all quantitative study designs targeting one or more of the key concepts, and targeting patients, healthy members of the public, and health professionals. The studies were divided into four categories: risk communication and decision aids, evidence-based medicine and critical appraisal, understanding of controlled trials, and science education. Findings were summarised descriptively. We included 415 studies, of which the interventions and assessment tools we identified included only a handful of the key concepts. The most common key concepts in interventions were "Treatments usually have beneficial and harmful effects," "Treatment comparisons should be fair," "Compare like with like," and "Single studies can be misleading." A variety of assessment tools were identified, but only four assessment tools included 10 or more key concepts. There is great potential for developing learning and assessment tools targeting key concepts that people need to understand to assess claims about treatment effects. There is currently no instrument covering assessment of all these key concepts.

Small SWAP 3D imaging flash ladar for small tactical unmanned air systems

NASA Astrophysics Data System (ADS)

Bird, Alan; Anderson, Scott A.; Wojcik, Michael; Budge, Scott E.

2015-05-01

The Space Dynamics Laboratory (SDL), working with Naval Research Laboratory (NRL) and industry leaders Advanced Scientific Concepts (ASC) and Hood Technology Corporation, has developed a small SWAP (size, weight, and power) 3D imaging flash ladar (LAser Detection And Ranging) sensor system concept design for small tactical unmanned air systems (STUAS). The design utilizes an ASC 3D flash ladar camera and laser in a Hood Technology gyro-stabilized gimbal system. The design is an autonomous, intelligent, geo-aware sensor system that supplies real-time 3D terrain and target images. Flash ladar and visible camera data are processed at the sensor using a custom digitizer/frame grabber with compression. Mounted in the aft housing are power, controls, processing computers, and GPS/INS. The onboard processor controls pointing and handles image data, detection algorithms and queuing. The small SWAP 3D imaging flash ladar sensor system generates georeferenced terrain and target images with a low probability of false return and <10 cm range accuracy through foliage in real-time. The 3D imaging flash ladar is designed for a STUAS with a complete system SWAP estimate of <9 kg, <0.2 m3 and <350 W power. The system is modeled using LadarSIM, a MATLAB® and Simulink®- based ladar system simulator designed and developed by the Center for Advanced Imaging Ladar (CAIL) at Utah State University. We will present the concept design and modeled performance predictions.

Inverse Design of Low-Boom Supersonic Concepts Using Reversed Equivalent-Area Targets

NASA Technical Reports Server (NTRS)

Li, Wu; Rallabhand, Sriam

2011-01-01

A promising path for developing a low-boom configuration is a multifidelity approach that (1) starts from a low-fidelity low-boom design, (2) refines the low-fidelity design with computational fluid dynamics (CFD) equivalent-area (Ae) analysis, and (3) improves the design with sonic-boom analysis by using CFD off-body pressure distributions. The focus of this paper is on the third step of this approach, in which the design is improved with sonic-boom analysis through the use of CFD calculations. A new inverse design process for off-body pressure tailoring is formulated and demonstrated with a low-boom supersonic configuration that was developed by using the mixed-fidelity design method with CFD Ae analysis. The new inverse design process uses the reverse propagation of the pressure distribution (dp/p) from a mid-field location to a near-field location, converts the near-field dp/p into an equivalent-area distribution, generates a low-boom target for the reversed equivalent area (Ae,r) of the configuration, and modifies the configuration to minimize the differences between the configuration s Ae,r and the low-boom target. The new inverse design process is used to modify a supersonic demonstrator concept for a cruise Mach number of 1.6 and a cruise weight of 30,000 lb. The modified configuration has a fully shaped ground signature that has a perceived loudness (PLdB) value of 78.5, while the original configuration has a partially shaped aft signature with a PLdB of 82.3.

Elderly’s Family Life Supplies - Innovative Chinese Checkers Game Board

NASA Astrophysics Data System (ADS)

CHAO, Fanglin

2017-09-01

The product design course for industrial design students was implemented in our university which spans 9 weeks. Throughout the creativity rules and field study, students achieve high standard on problem identification and concept generation. The prototype test with elderly in design projects is helpful to make students with deeper understand user demand, which in turn enhance the concept further. Traditional Chinese checkers are redesigned using special checkers with different height or shape and specific rules to increase user interest and game diversity. Game is more challenging due to location weighting on score calculation to planning its strategies. Redesign Chinese checkers game board include reconfigurable board and several shape checkers. Checkers has 3 parts: standing ring body, the base body, both support the side holding structure. The body shows slightly concave to facilitate the fingers hold. The upper portion of the body is provided with different shapes extension section which can be engaged with base body. Player move the checker to the opposite target area. When one of player moved all the checkers to the opposite target area; they shift to the scoring calculation stage. The participant may develop specific strategy to gain higher score by maximized weighted checkers into its target block regions.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

McManamy, T.; Booth, R.; Cleaves, J.

1996-06-01

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

Molecular beacon-based photodynamic therapy

NASA Astrophysics Data System (ADS)

Chen, Juan; Stefflova, Klara; Kim, Soungkyoo; Li, Hui; Marotta, Diane; Chance, Britton; Glickson, Jerry D.; Zheng, Gang

2005-01-01

A new concept for photodynamic therapy (PDT) has been developed based on incorporating a photosensitizer (PS) and a singlet oxygen (1O2) quenching/scavenging molecule (Q) onto a disease-targeting carrier, such that the PS becomes activatable by light only when targeting has occurred. This has the potential to give very high disease specificity in PDT treatment. The first model compound designed using this concept was synthesized containing a pyropheophorbide as the PS and a carotenoid as the 1O2 quencher. These were kept in close proximity by the self-folding of a caspase-3 specific peptide sequence. Upon caspase-3-induced cleavage, the 1O2 production increase has been validated by direct 1O2 luminescence and lifetime measurements, providing proof-of-concept of this 'PDT beacon.'

Conventional Prompt Global Strike and Long-Range Ballistic Missiles: Background and Issues

DTIC Science & Technology

2011-03-01

deployed. It also would be based on a conical design, with winglets , rather than on the winged design of the HTV-2. Upon nearing a target, the weapon...nuclear and conventional strike forces as a separate mission and separate concept from PGS, Congress, initially at least, blended both into the

Applying Theory of Mind Concepts When Designing Interventions Targeting Social Cognition among Youth Offenders

ERIC Educational Resources Information Center

Noel, Kristine K.; Westby, Carol

2014-01-01

This study employed a multiple baseline, across-participants, single-subject design to investigate the feasibility of an individual, narrative-based, social problem-solving intervention on the social problem-solving, narrative, and theory of mind (ToM) abilities of 3 incarcerated adolescent youth offenders identified as having emotional…

Experimental clean combustor program, phase 1

NASA Technical Reports Server (NTRS)

Bahr, D. W.; Gleason, C. C.

1975-01-01

Full annular versions of advanced combustor designs, sized to fit within the CF6-50 engine, were defined, manufactured, and tested at high pressure conditions. Configurations were screened, and significant reductions in CO, HC, and NOx emissions levels were achieved with two of these advanced combustor design concepts. Emissions and performance data at a typical AST cruise condition were also obtained along with combustor noise data as a part of an addendum to the basic program. The two promising combustor design approaches evolved in these efforts were the Double Annular Combustor and the Radial/Axial Combustor. With versions of these two basic combustor designs, CO and HC emissions levels at or near the target levels were obtained. Although the low target NOx emissions level was not obtained with these two advanced combustor designs, significant reductions were relative to the NOx levels of current technology combustors. Smoke emission levels below the target value were obtained.

Description of the dynamic infrared background/target simulator (DIBS)

NASA Astrophysics Data System (ADS)

Lujan, Ignacio

1988-01-01

The purpose of the Dynamic Infrared Background/Target Simulator (DIBS) is to project dynamic infrared scenes to a test sensor; e.g., a missile seeker that is sensitive to infrared energy. The projected scene will include target(s) and background. This system was designed to present flicker-free infrared scenes in the 8 micron to 12 micron wavelength region. The major subassemblies of the DIBS are the laser write system (LWS), vanadium dioxide modulator assembly, scene data buffer (SDB), and the optical image translator (OIT). This paper describes the overall concept and design of the infrared scene projector followed by some details of the LWS and VO2 modulator. Also presented are brief descriptions of the SDB and OIT.

Label-free optical biosensors based on aptamer-functionalized porous silicon scaffolds.

PubMed

Urmann, Katharina; Walter, Johanna-Gabriela; Scheper, Thomas; Segal, Ester

2015-02-03

A proof-of-concept for a label-free and reagentless optical biosensing platform based on nanostructured porous silicon (PSi) and aptamers is presented in this work. Aptamers are oligonucleotides (single-stranded DNA or RNA) that can bind their targets with high affinity and specificity, making them excellent recognition elements for biosensor design. Here we describe the fabrication and characterization of aptamer-conjugated PSi biosensors, where a previously characterized his-tag binding aptamer (6H7) is used as model system. Exposure of the aptamer-functionalized PSi to the target proteins as well as to complex fluids (i.e., bacteria lysates containing target proteins) results in robust and well-defined changes in the PSi optical interference spectrum, ascribed to specific aptamer-protein binding events occurring within the nanoscale pores, monitored in real time. The biosensors show exceptional stability and can be easily regenerated by a short rinsing step for multiple biosensing analyses. This proof-of-concept study demonstrates the possibility of designing highly stable and specific label-free optical PSi biosensors, employing aptamers as capture probes, holding immense potential for application in detection of a broad range of targets, in a simple yet reliable manner.

Feasibility Study for a Combined Radiation Environment in the ACRR-FRECII Cavity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parma, Edward J.

The objective of this report is to determine the feasibility of a combined pulsed - power accelerator machine, similar to HERMES - III, with the Annular Core Research Reactor (ACRR) Fueled - Ring External Cavity (FREC - II) in a new facility. The document is conceptual in nature, and includes some neutronic analysis that i llustrates that that the physics of such a concept would be feasible. There would still be many engineering design considerations and issues that would need to be investigated in order to determine the true viability of such a concept. This report does n ot addressmore » engineering design details, the cost of such a facility, or what would be required to develop the safety authorization of the concept. The radiation requirements for the "on - target" gamma - ray dose and dose rate are not addressed in this report . It is assumed that if the same general on - target specifications for a HERMES - III type machine could be met with the proposed concept, that the machine would b e considered highly useful as a radiation effects sciences platform. In general, the combined accelerator/ACRR reactor concept can be shown to be feasible with no major issues that would preclude the usefulness of such a facility. The new facility would provide a capability that currently does not exist in the radiation testing complex.« less

Planning Coverage Campaigns for Mission Design and Analysis: CLASP for DESDynl

NASA Technical Reports Server (NTRS)

Knight, Russell L.; McLaren, David A.; Hu, Steven

2013-01-01

Mission design and analysis presents challenges in that almost all variables are in constant flux, yet the goal is to achieve an acceptable level of performance against a concept of operations, which might also be in flux. To increase responsiveness, automated planning tools are used that allow for the continual modification of spacecraft, ground system, staffing, and concept of operations, while returning metrics that are important to mission evaluation, such as area covered, peak memory usage, and peak data throughput. This approach was applied to the DESDynl mission design using the CLASP planning system, but since this adaptation, many techniques have changed under the hood for CLASP, and the DESDynl mission concept has undergone drastic changes. The software produces mission evaluation products, such as memory highwater marks, coverage percentages, given a mission design in the form of coverage targets, concept of operations, spacecraft parameters, and orbital parameters. It tries to overcome the lack of fidelity and timeliness of mission requirements coverage analysis during mission design. Previous techniques primarily use Excel in ad hoc fashion to approximate key factors in mission performance, often falling victim to overgeneralizations necessary in such an adaptation. The new program allows designers to faithfully represent their mission designs quickly, and get more accurate results just as quickly.

The Evolution of Air-Sea Battle: How Army Attack/Reconnaissance Aviation Fits into the Joint Concept for Access and Maneuver in the Global Commons

DTIC Science & Technology

2016-05-13

System (MTADS) has a day TV capability to laser designate and auto track tank-sized targets at 6,000 meters and a Forward Looking Infrared (FLIR...capability to laser designate and auto track tank-sized targets at 3,500 meters. The AH-64 D/E also possesses a Fire Control Radar (FCR) that allows it...a broad spectrum of size, capacity, duration, and security. At the low end are Forward Area Refueling Equipment ( FARE ) systems. These allow CH-47

Direct-drive inertial confinement fusion: A review

NASA Astrophysics Data System (ADS)

Craxton, R. S.; Anderson, K. S.; Boehly, T. R.; Goncharov, V. N.; Harding, D. R.; Knauer, J. P.; McCrory, R. L.; McKenty, P. W.; Meyerhofer, D. D.; Myatt, J. F.; Schmitt, A. J.; Sethian, J. D.; Short, R. W.; Skupsky, S.; Theobald, W.; Kruer, W. L.; Tanaka, K.; Betti, R.; Collins, T. J. B.; Delettrez, J. A.; Hu, S. X.; Marozas, J. A.; Maximov, A. V.; Michel, D. T.; Radha, P. B.; Regan, S. P.; Sangster, T. C.; Seka, W.; Solodov, A. A.; Soures, J. M.; Stoeckl, C.; Zuegel, J. D.

2015-11-01

The direct-drive, laser-based approach to inertial confinement fusion (ICF) is reviewed from its inception following the demonstration of the first laser to its implementation on the present generation of high-power lasers. The review focuses on the evolution of scientific understanding gained from target-physics experiments in many areas, identifying problems that were demonstrated and the solutions implemented. The review starts with the basic understanding of laser-plasma interactions that was obtained before the declassification of laser-induced compression in the early 1970s and continues with the compression experiments using infrared lasers in the late 1970s that produced thermonuclear neutrons. The problem of suprathermal electrons and the target preheat that they caused, associated with the infrared laser wavelength, led to lasers being built after 1980 to operate at shorter wavelengths, especially 0.35 μm—the third harmonic of the Nd:glass laser—and 0.248 μm (the KrF gas laser). The main physics areas relevant to direct drive are reviewed. The primary absorption mechanism at short wavelengths is classical inverse bremsstrahlung. Nonuniformities imprinted on the target by laser irradiation have been addressed by the development of a number of beam-smoothing techniques and imprint-mitigation strategies. The effects of hydrodynamic instabilities are mitigated by a combination of imprint reduction and target designs that minimize the instability growth rates. Several coronal plasma physics processes are reviewed. The two-plasmon-decay instability, stimulated Brillouin scattering (together with cross-beam energy transfer), and (possibly) stimulated Raman scattering are identified as potential concerns, placing constraints on the laser intensities used in target designs, while other processes (self-focusing and filamentation, the parametric decay instability, and magnetic fields), once considered important, are now of lesser concern for mainline direct-drive target concepts. Filamentation is largely suppressed by beam smoothing. Thermal transport modeling, important to the interpretation of experiments and to target design, has been found to be nonlocal in nature. Advances in shock timing and equation-of-state measurements relevant to direct-drive ICF are reported. Room-temperature implosions have provided an increased understanding of the importance of stability and uniformity. The evolution of cryogenic implosion capabilities, leading to an extensive series carried out on the 60-beam OMEGA laser [Boehly et al., Opt. Commun. 133, 495 (1997)], is reviewed together with major advances in cryogenic target formation. A polar-drive concept has been developed that will enable direct-drive-ignition experiments to be performed on the National Ignition Facility [Haynam et al., Appl. Opt. 46(16), 3276 (2007)]. The advantages offered by the alternative approaches of fast ignition and shock ignition and the issues associated with these concepts are described. The lessons learned from target-physics and implosion experiments are taken into account in ignition and high-gain target designs for laser wavelengths of 1/3 μm and 1/4 μm. Substantial advances in direct-drive inertial fusion reactor concepts are reviewed. Overall, the progress in scientific understanding over the past five decades has been enormous, to the point that inertial fusion energy using direct drive shows significant promise as a future environmentally attractive energy source.

Target selection for a hypervelocity asteroid intercept vehicle flight validation mission

NASA Astrophysics Data System (ADS)

Wagner, Sam; Wie, Bong; Barbee, Brent W.

2015-02-01

Asteroids and comets have collided with the Earth in the past and will do so again in the future. Throughout Earth's history these collisions have played a significant role in shaping Earth's biological and geological histories. The planetary defense community has been examining a variety of options for mitigating the impact threat of asteroids and comets that approach or cross Earth's orbit, known as near-Earth objects (NEOs). This paper discusses the preliminary study results of selecting small (100-m class) NEO targets and mission analysis and design trade-offs for validating the effectiveness of a Hypervelocity Asteroid Intercept Vehicle (HAIV) concept, currently being investigated for a NIAC (NASA Advanced Innovative Concepts) Phase 2 study. In particular this paper will focus on the mission analysis and design for single spacecraft direct impact trajectories, as well as several mission types that enable a secondary rendezvous spacecraft to observe the HAIV impact and evaluate it's effectiveness.

Deleterious effects of nonthermal electrons in shock ignition concept.

PubMed

Nicolaï, Ph; Feugeas, J-L; Touati, M; Ribeyre, X; Gus'kov, S; Tikhonchuk, V

2014-03-01

Shock ignition concept is a promising approach to inertial confinement fusion that may allow obtaining high fusion energy gains with the existing laser technology. However, the spike driving laser intensities in the range of 1-10 PW/cm2 produces the energetic electrons that may have a significant effect on the target performance. The hybrid numerical simulations including a radiation hydrodynamic code coupled to a rapid Fokker-Planck module are used to asses the role of hot electrons in the shock generation and the target preheat in the time scale of 100 ps and spatial scale of 100 μm. It is shown that depending on the electron energy distribution and the target density profile the hot electrons can either increase the shock amplitude or preheat the imploding shell. In particular, the exponential electron energy spectrum corresponding to the temperature of 30 keV in the present HiPER target design preheats the deuterium-tritium shell and jeopardizes its compression. Ways of improving the target performance are suggested.

Analysis and Test of Repair Concepts for a Carbon-Rod Reinforced Laminate

NASA Technical Reports Server (NTRS)

Baker, Donald J.; Rousseau, Carl Q.

2000-01-01

The use of pultruded carbon-epoxy rods for the reinforcement of composite laminates in some structures results in an efficient structural concept. The results of an analytical and experimental investigation of repair concepts of completely severed carbon-epoxy rods is presented. Three repair concepts are considered: (a) bonded repair with outside moldline and inside moldline doublers; (b) bonded repair with fasteners, and (c) bonded repair with outside moldline doubler only. The stiffness of the repairs was matched with the stiffness of the baseline specimen. The failure strains for the bonded repair with fasteners and the bonded repair with an outside moldline doubler exceeded a target design strain set for the repair concepts.

Comparison of a Stimulus Equivalence Protocol and Traditional Lecture for Teaching Single-Subject Designs

ERIC Educational Resources Information Center

Lovett, Sadie; Rehfeldt, Ruth Anne; Garcia, Yors; Dunning, Johnna

2011-01-01

This study compared the effects of a computer-based stimulus equivalence protocol to a traditional lecture format in teaching single-subject experimental design concepts to undergraduate students. Participants were assigned to either an equivalence or a lecture group, and performance on a paper-and-pencil test that targeted relations among the…

Putative and unique gene sequence utilization for the design of species specific probes as modeled by Lactobacillus plantarum

USDA-ARS?s Scientific Manuscript database

The concept of utilizing putative and unique gene sequences for the design of species specific probes was tested. The abundance profile of assigned functions within the Lactobacillus plantarum genome was used for the identification of the putative and unique gene sequence, csh. The targeted gene (cs...

Chemistry Science Investigation: Dognapping Workshop, an Outreach Program Designed to Introduce Students to Science through a Hands-On Mystery

ERIC Educational Resources Information Center

Boyle, Timothy J.; Sears, Jeremiah M.; Hernandez-Sanchez, Bernadette A.; Casillas, Maddison R.; Nguyen, Thao H.

2017-01-01

The Chemistry Science Investigation: Dognapping Workshop was designed to (i) target and inspire fourth grade students to view themselves as "Junior Scientists" before their career decisions are solidified; (ii) enable hands-on experience in fundamental scientific concepts; (iii) increase public interaction with science, technology,…

Endoradiotherapy in cancer treatment--basic concepts and future trends.

PubMed

Zoller, Frederic; Eisenhut, Michael; Haberkorn, Uwe; Mier, Walter

2009-12-25

Endoradiotherapy represents an alternative therapeutic method in cancer treatment with advantageous features compared to chemotherapy and radiation therapy. Intelligent dose delivery concepts using small drugs, peptides or antibodies as radionuclide carriers enable the verification of a selective accumulation in the tumour lesion and to reduce radiation toxicity for the peripheral organs. The development of endoradiotherapeutic agents, especially chelator-conjugated biomolecules, for example ibritumomab tiuxetan or DOTATOC, gains importance due to the stable complexation of versatile radiometals, such as (90)Y or (177)Lu. The rational design of novel target binding sides and their grafting into a drug scaffold is a highly promising strategy, which may promote further implication in endoradiotherapy. This review highlights the basic concepts of endoradiotherapy and discusses the potential of targeted therapy and the properties of energy-rich particles emitted by radionuclides for tumour therapy.

Spanwise morphing trailing edge on a finite wing

NASA Astrophysics Data System (ADS)

Pankonien, Alexander M.; Inman, Daniel J.

2015-04-01

Unmanned Aerial Vehicles are prime targets for morphing implementation as they must adapt to large changes in flight conditions associated with locally varying wind or large changes in mass associated with payload delivery. The Spanwise Morphing Trailing Edge concept locally varies the trailing edge camber of a wing or control surface, functioning as a modular replacement for conventional ailerons without altering the spar box. Utilizing alternating active sections of Macro Fiber Composites (MFCs) driving internal compliant mechanisms and inactive sections of elastomeric honeycombs, the SMTE concept eliminates geometric discontinuities associated with shape change, increasing aerodynamic performance. Previous work investigated a representative section of the SMTE concept and investigated the effect of various skin designs on actuation authority. The current work experimentally evaluates the aerodynamic gains for the SMTE concept for a representative finite wing as compared with a conventional, articulated wing. The comparative performance for both wings is evaluated by measuring the drag penalty associated with achieving a design lift coefficient from an off-design angle of attack. To reduce experimental complexity, optimal control configurations are predicted with lifting line theory and experimentally measured control derivatives. Evaluated over a range of off-design flight conditions, this metric captures the comparative capability of both concepts to adapt or "morph" to changes in flight conditions. Even with this simplistic model, the SMTE concept is shown to reduce the drag penalty due to adaptation up to 20% at off-design conditions, justifying the increase in mass and complexity and motivating concepts capable of larger displacement ranges, higher fidelity modelling, and condition-sensing control.

The 'retro-design' concept for novel kinase inhibitors.

PubMed

Müller, Gerhard; Sennhenn, Peter C; Woodcock, Timothy; Neumann, Lars

2010-07-01

Protein kinases are among the most attractive therapeutic targets for a broad range of diseases. This feature review highlights and classifies the main design principles employed to generate active and selective kinase inhibitors. In particular, emphasis is focused on a fragment-based lead-generation approach, which constitutes a novel design method for developing type II kinase inhibitors with distinct binding kinetic attributes. This 'retro-design' strategy relies on a customized fragment library, and contrasts the traditional approach used in the design of type II inhibitors.

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

PubMed

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.

Planning Coverage Campaigns for Mission Design and Analysis: Clasp for the Proposed DESDynI Mission

NASA Technical Reports Server (NTRS)

Knight, Russell; McLaren, David; Hu, Steven

2012-01-01

Mission design and analysis present challenges in that almost all variables are in constant flux, yet the goal is to achieve an acceptable level of performance against a concept of operations, which might also be in flux. To increase responsiveness, our approach is to use automated planning tools that allow for the continual modification of spacecraft, ground system, staffing, and concept of operations while returning metrics that are important to mission evaluation, such as area covered, peak memory usage, and peak data throughput. We have applied this approach to DESDynI (Deformation, Ecosystem Structure, and Dynamics of Ice) mission design concept using the CLASP (Compressed Large-scale Activity Scheduler/Planner) planning system [7], but since this adaptation many techniques have changed under the hood for CLASP and the DESDynI mission concept has undergone drastic changes, including that it has been renamed the Earth Radar Mission. Over the past two years, we have run more than fifty simulations with the CLASP-DESDynI adaptation, simulating different mission scenarios with changing parameters including targets, swaths, instrument modes, and data and downlink rates. We describe the evolution of simulations through the DESDynI MCR (Mission Concept Review) and afterwards.

Fluorescence in vivo imaging of live tumor cells with pH-activatable targeted probes via receptor-mediated endocytosis

NASA Astrophysics Data System (ADS)

Asanuma, Daisuke; Urano, Yasuteru; Nagano, Tetsuo; Hama, Yukihiro; Koyama, Yoshinori; Kobayashi, Hisataka

2009-02-01

One goal of molecular imaging is to establish a widely applicable technique for specific detection of tumors with minimal background. Here, we achieve specific in vivo tumor visualization with a newly-designed "activatable" targeted fluorescence probe. This agent is activated after cellular internalization by sensing the pH change in the lysosome. Novel acidic pH-activatable probes based on the BODIPY fluorophore were synthesized, and then conjugated to a cancer-targeting monoclonal antibody, Trastuzumab, or galactosyl serum albumin (GSA). As proof of concept, ex and in vivo imaging of two different tumor mouse models was performed: HER2-overexpressed lung metastasis tumor with Trastuzumab-pH probe conjugates and lectin-overexpressed i.p. disseminated tumor with GSA-pH probe conjugates. These pH-activatable targeted probes were highly specific for tumors with minimal background signal. Because the acidic pH in lysosomes is maintained by the energy-consuming proton pump, only viable cancer cells were successfully visualized. Furthermore, this strategy was also applied to fluorescence endoscopy in tumor mouse models, resulting in specific visualization of tumors as small as submillimeter in size that could hardly detected by naked eyes because of their poor contrast against normal tissues. The design concept can be widely adapted to cancer-specific cell-surface-targeting molecules that result in cellular internalization.

The ADVANCE project : formal evaluation of the targeted deployment. Volume 1

DOT National Transportation Integrated Search

1997-01-01

The Advanced Driver and Vehicle Advisory Navigation ConcEpt (ADVANCE) was an in-vehicle advanced traveler information system (ATIS) that operated in the northwest suburbs of Chicago, Illinois. It was designed to provide origin-destination shortest-ti...

Advantages of Structure-Based Drug Design Approaches in Neurological Disorders

PubMed Central

Aarthy, Murali; Panwar, Umesh; Selvaraj, Chandrabose; Singh, Sanjeev Kumar

2017-01-01

Objective: The purpose of the review is to portray the theoretical concept on neurological disorders from research data. Background: The freak changes in chemical response of nerve impulse causes neurological disorders. The research evidence of the effort done in the older history suggests that the biological drug targets and their effective feature with responsive drugs could be valuable in promoting the future development of health statistics structure for improved treatment for curing the nervous disorders. Methods: In this review, we summarized the most iterative theoretical concept of structure based drug design approaches in various neurological disorders to unfathomable understanding of reported information for future drug design and development. Results: On the premise of reported information we analyzed the model of theoretical drug designing process for understanding the mechanism and pathology of the neurological diseases which covers the development of potentially effective inhibitors against the biological drug targets. Finally, it also suggests the management and implementation of the current treatment in improving the human health system behaviors. Conclusion: With the survey of reported information we concluded the development strategies of diagnosis and treatment against neurological diseases which leads to supportive progress in the drug discovery. PMID:28042767

Biomass Feedstock and Conversion Supply System Design and Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobson, Jacob J.; Roni, Mohammad S.; Lamers, Patrick

Idaho National Laboratory (INL) supports the U.S. Department of Energy’s bioenergy research program. As part of the research program INL investigates the feedstock logistics economics and sustainability of these fuels. A series of reports were published between 2000 and 2013 to demonstrate the feedstock logistics cost. Those reports were tailored to specific feedstock and conversion process. Although those reports are different in terms of conversion, some of the process in the feedstock logistic are same for each conversion process. As a result, each report has similar information. A single report can be designed that could bring all commonality occurred inmore » the feedstock logistics process while discussing the feedstock logistics cost for different conversion process. Therefore, this report is designed in such a way that it can capture different feedstock logistics cost while eliminating the need of writing a conversion specific design report. Previous work established the current costs based on conventional equipment and processes. The 2012 programmatic target was to demonstrate a delivered biomass logistics cost of $55/dry ton for woody biomass delivered to fast pyrolysis conversion facility. The goal was achieved by applying field and process demonstration unit-scale data from harvest, collection, storage, preprocessing, handling, and transportation operations into INL’s biomass logistics model. The goal of the 2017 Design Case is to enable expansion of biofuels production beyond highly productive resource areas by breaking the reliance of cost-competitive biofuel production on a single, low-cost feedstock. The 2017 programmatic target is to supply feedstock to the conversion facility that meets the in-feed conversion process quality specifications at a total logistics cost of $80/dry T. The $80/dry T. target encompasses total delivered feedstock cost, including both grower payment and logistics costs, while meeting all conversion in-feed quality targets. The 2012 $55/dry T. programmatic target included only logistics costs with a limited focus on biomass quantity, quality and did not include a grower payment. The 2017 Design Case explores two approaches to addressing the logistics challenge: one is an agronomic solution based on blending and integrated landscape management and the second is a logistics solution based on distributed biomass preprocessing depots. The concept behind blended feedstocks and integrated landscape management is to gain access to more regional feedstock at lower access fees (i.e., grower payment) and to reduce preprocessing costs by blending high quality feedstocks with marginal quality feedstocks. Blending has been used in the grain industry for a long time; however, the concept of blended feedstocks in the biofuel industry is a relatively new concept. The blended feedstock strategy relies on the availability of multiple feedstock sources that are blended using a least-cost formulation within an economical supply radius, which, in turn, decreases the grower payment by reducing the amount of any single biomass. This report will introduce the concepts of blending and integrated landscape management and justify their importance in meeting the 2017 programmatic goals.« less

Next Gen NEAR: Near Earth Asteroid Human Robotic Precursor Mission Concept

NASA Technical Reports Server (NTRS)

Rivkin, Andrew S.; Kirby, Karen; Cheng, Andrew F.; Gold, Robert; Kelly, Daniel; Reed, Cheryl; Abell, Paul; Garvin, James; Landis, Rob

2012-01-01

Asteroids have long held the attention of the planetary science community. In particular, asteroids that evolve into orbits near that of Earth, called near-Earth objects (NEO), are of high interest as potential targets for exploration due to the relative ease (in terms of delta V) to reach them. NASA's Flexible Path calls for missions and experiments to be conducted as intermediate steps towards the eventual goal of human exploration of Mars; piloted missions to NEOs are such example. A human NEO mission is a valuable exploratory step beyond the Earth-Moon system enhancing capabilities that surpass our current experience, while also developing infrastructure for future mars exploration capabilities. To prepare for a human rendezvous with an NEO, NASA is interested in pursuing a responsible program of robotic NEO precursor missions. Next Gen NEAR is such a mission, building on the NEAR Shoemaker mission experience at the JHU/APL Space Department, to provide an affordable, low risk solution with quick data return. Next Gen NEAR proposes to make measurements needed for human exploration to asteroids: to demonstrate proximity operations, to quantify hazards for human exploration and to characterize an environment at a near-Earth asteroid representative of those that may be future human destinations. The Johns Hopkins University Applied Physics Laboratory has demonstrated exploration-driven mission feasibility by developing a versatile spacecraft design concept using conventional technologies that satisfies a set of science, exploration and mission objectives defined by a concept development team in the summer of 2010. We will describe the mission concept and spacecraft architecture in detail. Configuration options were compared with the mission goals and objectives in order to select the spacecraft design concept that provides the lowest cost, lowest implementation risk, simplest operation and the most benefit for the mission implementation. The Next Gen NEAR spacecraft was designed to support rendezvous with a range of candidate asteroid targets and could easily be launched with one of several NASA launch vehicles. The Falcon 9 launch vehicle supports a Next Gen NEAR launch to target many near-Earth asteroids under consideration that could be reached with a C3 of 18 km2/sec2 or less, and the Atlas V-401 provides added capability supporting launch to NEAs that require more lift capacity while at the same time providing such excess lift capability that another payload of opportunity could be launch in conjunction with Next Gen NEAR. Next Gen NEAR will measure and interact with the target surface in ways never undertaken at an asteroid, and will prepare for first human precursor mission by demonstrating exploration science operations at an accessible NEO. This flexible mission and spacecraft design concept supports target selection based on upcoming Earth-based observations and also provides opportunities for co-manifest & international partnerships. JHU/APL has demonstrated low cost, low risk, high impact missions and this mission will help to prepare NASA for human NEO exploration by combining the best of NASA s human and robotic exploration capabilities.

Theory of mind in dogs?: examining method and concept.

PubMed

Horowitz, Alexandra

2011-12-01

In line with other research, Udell, Dorey, and Wynne's (in press) finding that dogs and wolves pass on some trials of a putative theory-of-mind test and fail on others is as informative about the methods and concepts of the research as about the subjects. This commentary expands on these points. The intertrial differences in the target article demonstrate how critical the choice of cues is in experimental design; the intersubject-group differences demonstrate how life histories can interact with experimental design. Even the best-designed theory-of-mind tests have intractable logical problems. Finally, these and previous research results call for the introduction of an intermediate stage of ability, a rudimentary theory of mind, to describe subjects' performance.

Human supervision and microprocessor control of an optical tracking system

NASA Technical Reports Server (NTRS)

Bigley, W. J.; Vandenberg, J. D.

1981-01-01

Gunners using small calibre anti-aircraft systems have not been able to track high-speed air targets effectively. Substantial improvement in the accuracy of surface fire against attacking aircraft has been realized through the design of a director-type weapon control system. This system concept frees the gunner to exercise a supervisory/monitoring role while the computer takes over continuous target tracking. This change capitalizes on a key consideration of human factors engineering while increasing system accuracy. The advanced system design, which uses distributed microprocessor control, is discussed at the block diagram level and is contrasted with the previous implementation.

Lunar Nautics: Designing a Mission to Live and Work on the Moon. An Educator's Guide for Grades 6-8. EG-2008-09-129-MSFC

ERIC Educational Resources Information Center

National Aeronautics and Space Administration (NASA), 2007

2007-01-01

Lunar Nautics is a hands-on curriculum targeted to youth in grades 6 to 8, that allows the students to design, test, analyze and manage a space mission from initial concept to project funding. Lunar Nautics provides opportunities for development of problem solving skills and critical thinking skills that are needed to design, organize and manage a…

Rethinking the architectural design concept in the digital culture (in architecture's practice perspective)

NASA Astrophysics Data System (ADS)

Prawata, Albertus Galih

2017-11-01

The architectural design stages in architectural practices or in architectural design studio consist of many aspects. One of them is during the early phases of the design process, where the architects or designers try to interpret the project brief into the design concept. This paper is a report of the procedure of digital tools in the early design process in an architectural practice in Jakarta. It targets principally the use of BIM and digital modeling to generate information and transform them into conceptual forms, which is not very common in Indonesian architectural practices. Traditionally, the project brief is transformed into conceptual forms by using sketches, drawings, and physical model. The new method using digital tools shows that it is possible to do the same thing during the initial stage of the design process to create early architectural design forms. Architect's traditional tools and methods begin to be replaced effectively by digital tools, which would drive bigger opportunities for innovation.

Design trade-off and proof of concept for LOUPE, the Lunar Observatory for Unresolved Polarimetry of Earth.

PubMed

Hoeijmakers, H J; Arts, M L J; Snik, F; Keller, C U; Kuiper, J M

2016-09-19

We provide a proof of the technical feasibility of LOUPE, the first integral-field snapshot spectropolarimeter, designed to monitor the reflected flux and polarization spectrum of Earth. These are to be used as benchmark data for the retrieval of biomarkers and atmospheric and surface characteristics from future direct observations of exoplanets. We perform a design trade-off for an implementation in which LOUPE performs snapshot integral-field spectropolarimetry at visible wavelengths. We used off-the-shelf optics to construct a polarization modulator, in which polarization information is encoded into the spectrum as a wavelength-dependent modulation, while spatial resolution is maintained using a micro-lens array. The performance of this design concept is validated in a laboratory setup. Our proof-of-concept is capable of measuring a grid of 50 × 50 polarization spectra between 610 and 780 nm of a mock target planet - proving the merit of this design. The measurements are affected by systematic noise on the percent level, and we discuss how to mitigate this in future iterations. We conclude that LOUPE can be small and robust while meeting the science goals of this particular space application, and note the many potential applications that may benefit from our concept for doing snapshot integral-field spectropolarimetry.

Direct-drive inertial confinement fusion: A review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craxton, R. S.; Anderson, K. S.; Boehly, T. R.

The direct-drive, laser-based approach to inertial confinement fusion (ICF) is reviewed from its inception following the demonstration of the first laser to its implementation on the present generation of high-power lasers. The review focuses on the evolution of scientific understanding gained from target-physics experiments in many areas, identifying problems that were demonstrated and the solutions implemented. The review starts with the basic understanding of laser–plasma interactions that was obtained before the declassification of laser-induced compression in the early 1970s and continues with the compression experiments using infrared lasers in the late 1970s that produced thermonuclear neutrons. The problem of suprathermalmore » electrons and the target preheat that they caused, associated with the infrared laser wavelength, led to lasers being built after 1980 to operate at shorter wavelengths, especially 0.35 μm—the third harmonic of the Nd:glass laser—and 0.248 μm (the KrF gas laser). The main physics areas relevant to direct drive are reviewed. The primary absorption mechanism at short wavelengths is classical inverse bremsstrahlung. Nonuniformities imprinted on the target by laser irradiation have been addressed by the development of a number of beam-smoothing techniques and imprint-mitigation strategies. The effects of hydrodynamic instabilities are mitigated by a combination of imprint reduction and target designs that minimize the instability growth rates. Several coronal plasma physics processes are reviewed. The two-plasmon–decay instability, stimulated Brillouin scattering (together with cross-beam energy transfer), and (possibly) stimulated Raman scattering are identified as potential concerns, placing constraints on the laser intensities used in target designs, while other processes (self-focusing and filamentation, the parametric decay instability, and magnetic fields), once considered important, are now of lesser concern for mainline direct-drive target concepts. Filamentation is largely suppressed by beam smoothing. Thermal transport modeling, important to the interpretation of experiments and to target design, has been found to be nonlocal in nature. Advances in shock timing and equation-of-state measurements relevant to direct-drive ICF are reported. Room-temperature implosions have provided an increased understanding of the importance of stability and uniformity. The evolution of cryogenic implosion capabilities, leading to an extensive series carried out on the 60-beam OMEGA laser [Boehly et al., Opt. Commun. 133, 495 (1997)], is reviewed together with major advances in cryogenic target formation. A polar-drive concept has been developed that will enable direct-drive–ignition experiments to be performed on the National Ignition Facility [Haynam et al., Appl. Opt. 46(16), 3276 (2007)]. The advantages offered by the alternative approaches of fast ignition and shock ignition and the issues associated with these concepts are described. The lessons learned from target-physics and implosion experiments are taken into account in ignition and high-gain target designs for laser wavelengths of 1/3 μm and 1/4 μm. Substantial advances in direct-drive inertial fusion reactor concepts are reviewed. Overall, the progress in scientific understanding over the past five decades has been enormous, to the point that inertial fusion energy using direct drive shows significant promise as a future environmentally attractive energy source.« less

Direct-drive inertial confinement fusion: A review

DOE PAGES

Craxton, R. S.; Anderson, K. S.; Boehly, T. R.; ...

2015-11-25

In this study, the direct-drive, laser-based approach to inertial confinement fusion (ICF) is reviewed from its inception following the demonstration of the first laser to its implementation on the present generation of high-power lasers. The review focuses on the evolution of scientific understanding gained from target-physics experiments in many areas, identifying problems that were demonstrated and the solutions implemented. The review starts with the basic understanding of laser–plasma interactions that was obtained before the declassification of laser-induced compression in the early 1970s and continues with the compression experiments using infrared lasers in the late 1970s that produced thermonuclear neutrons. Themore » problem of suprathermal electrons and the target preheat that they caused, associated with the infrared laser wavelength, led to lasers being built after 1980 to operate at shorter wavelengths, especially 0.35 um—the third harmonic of the Nd:glass laser—and 0.248 um (the KrF gas laser). The main physics areas relevant to direct drive are reviewed. The primary absorption mechanism at short wavelengths is classical inverse bremsstrahlung. Nonuniformities imprinted on the target by laser irradiation have been addressed by the development of a number of beam-smoothing techniques and imprint-mitigation strategies. The effects of hydrodynamic instabilities are mitigated by a combination of imprint reduction and target designs that minimize the instability growth rates. Several coronal plasma physics processes are reviewed. The two-plasmon–decay instability, stimulated Brillouin scattering (together with cross-beam energy transfer), and (possibly) stimulated Raman scattering are identified as potential concerns, placing constraints on the laser intensities used in target designs, while other processes (self-focusing and filamentation, the parametric decay instability, and magnetic fields), once considered important, are now of lesser concern for mainline direct-drive target concepts. Filamentation is largely suppressed by beam smoothing. Thermal transport modeling, important to the interpretation of experiments and to target design, has been found to be non-local in nature. Advances in shock timing and equation-of-state measurements relevant to direct-drive ICF are reported. Room-temperature implosions have provided an increased understanding of the importance of stability and uniformity. The evolution of cryogenic implosion capabilities, leading to an extensive series carried out on the 60-beam OMEGA laser [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)], is reviewed together with major advances in cryogenic target formation. A polar-drive concept has been developed that will enable direct-drive–ignition experiments to be performed on the National Ignition Facility [C. A. Haynam et al., Appl. Opt. 46 (16), 3276 (2007)]. The advantages offered by the alternative approaches of fast ignition and shock ignition and the issues associated with these concepts are described. The lessons learned from target-physics and implosion experiments are taken into account in ignition and high-gain target designs for laser wavelengths of 1/3 μm and 1/4 μm. Substantial advances in direct-drive inertial fusion reactor concepts are reviewed. Overall, the progress in scientific understanding over the past five decades has been enormous, to the point that inertial fusion energy using direct drive shows significant promise as a future environmentally attractive energy source.« less

Direct-drive inertial confinement fusion: A review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craxton, R. S.; Anderson, K. S.; Boehly, T. R.

In this study, the direct-drive, laser-based approach to inertial confinement fusion (ICF) is reviewed from its inception following the demonstration of the first laser to its implementation on the present generation of high-power lasers. The review focuses on the evolution of scientific understanding gained from target-physics experiments in many areas, identifying problems that were demonstrated and the solutions implemented. The review starts with the basic understanding of laser–plasma interactions that was obtained before the declassification of laser-induced compression in the early 1970s and continues with the compression experiments using infrared lasers in the late 1970s that produced thermonuclear neutrons. Themore » problem of suprathermal electrons and the target preheat that they caused, associated with the infrared laser wavelength, led to lasers being built after 1980 to operate at shorter wavelengths, especially 0.35 um—the third harmonic of the Nd:glass laser—and 0.248 um (the KrF gas laser). The main physics areas relevant to direct drive are reviewed. The primary absorption mechanism at short wavelengths is classical inverse bremsstrahlung. Nonuniformities imprinted on the target by laser irradiation have been addressed by the development of a number of beam-smoothing techniques and imprint-mitigation strategies. The effects of hydrodynamic instabilities are mitigated by a combination of imprint reduction and target designs that minimize the instability growth rates. Several coronal plasma physics processes are reviewed. The two-plasmon–decay instability, stimulated Brillouin scattering (together with cross-beam energy transfer), and (possibly) stimulated Raman scattering are identified as potential concerns, placing constraints on the laser intensities used in target designs, while other processes (self-focusing and filamentation, the parametric decay instability, and magnetic fields), once considered important, are now of lesser concern for mainline direct-drive target concepts. Filamentation is largely suppressed by beam smoothing. Thermal transport modeling, important to the interpretation of experiments and to target design, has been found to be non-local in nature. Advances in shock timing and equation-of-state measurements relevant to direct-drive ICF are reported. Room-temperature implosions have provided an increased understanding of the importance of stability and uniformity. The evolution of cryogenic implosion capabilities, leading to an extensive series carried out on the 60-beam OMEGA laser [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)], is reviewed together with major advances in cryogenic target formation. A polar-drive concept has been developed that will enable direct-drive–ignition experiments to be performed on the National Ignition Facility [C. A. Haynam et al., Appl. Opt. 46 (16), 3276 (2007)]. The advantages offered by the alternative approaches of fast ignition and shock ignition and the issues associated with these concepts are described. The lessons learned from target-physics and implosion experiments are taken into account in ignition and high-gain target designs for laser wavelengths of 1/3 μm and 1/4 μm. Substantial advances in direct-drive inertial fusion reactor concepts are reviewed. Overall, the progress in scientific understanding over the past five decades has been enormous, to the point that inertial fusion energy using direct drive shows significant promise as a future environmentally attractive energy source.« less

Design of a remotely piloted vehicle for a low Reynolds number station keeping mission

NASA Technical Reports Server (NTRS)

1990-01-01

Six teams of senior level Aerospace Engineering undergraduates were given a request for proposal, asking for a design concept for a remotely piloted vehicle (RPV). This RPV was to be designed to fly at a target Reynolds number of 1 times 10(exp 5). The craft was to maximize loiter time and perform an indoor, closed course flight. As part of the proposal, each team was required to construct a prototype and validate their design with a flight demonstration.

Interactive Multimedia-Based Animation: A Study of Effectiveness on Fashion Design Technology Learning

NASA Astrophysics Data System (ADS)

Wiana, W.

2018-01-01

The learning process is believed will reach optimal results if facilitated by diversity of learning’s device from aspects of the approach, method, media or it’s evaluation system, in individually, groups, or as well as classical. One of the learning’s Device can be developed in an attempt to improve the results of the study is Computer Based Learning (CBL). CBL was developed aim to help students to understand the concepts of the learning material which presented interactively by the system and able to provide information and learning process better. This research is closely related to efforts to improve the quality of Fashion design in digital format learning, with specific targets to generate interactive multimedia-based animation as effective media and learning resources for fashion design learning. Applications that are generated may be an option for delivering learning material as well as to engender interest in learning as well as understanding with students against the subject matter so that it can improve the learning achievements of students. The instruments used to collect data is a test sheet of mastering the concept which developed on the basis of indicators understanding the concept of fashion design, the material elements and principles of fashion design as well as application on making fashion design. As for the skills test is done through test performance to making fashion design in digital format. The results of testing against the mastery of concepts and skills of fashion designing in digital formatted shows that experimental group obtained significantly higher qualifications compared to the control group. That means that the use of interactive multimedia-based animation, effective to increased mastery of concepts and skills on making fashion design in digital format.

E-TALEN: a web tool to design TALENs for genome engineering.

PubMed

Heigwer, Florian; Kerr, Grainne; Walther, Nike; Glaeser, Kathrin; Pelz, Oliver; Breinig, Marco; Boutros, Michael

2013-11-01

Use of transcription activator-like effector nucleases (TALENs) is a promising new technique in the field of targeted genome engineering, editing and reverse genetics. Its applications span from introducing knockout mutations to endogenous tagging of proteins and targeted excision repair. Owing to this wide range of possible applications, there is a need for fast and user-friendly TALEN design tools. We developed E-TALEN (http://www.e-talen.org), a web-based tool to design TALENs for experiments of varying scale. E-TALEN enables the design of TALENs against a single target or a large number of target genes. We significantly extended previously published design concepts to consider genomic context and different applications. E-TALEN guides the user through an end-to-end design process of de novo TALEN pairs, which are specific to a certain sequence or genomic locus. Furthermore, E-TALEN offers a functionality to predict targeting and specificity for existing TALENs. Owing to the computational complexity of many of the steps in the design of TALENs, particular emphasis has been put on the implementation of fast yet accurate algorithms. We implemented a user-friendly interface, from the input parameters to the presentation of results. An additional feature of E-TALEN is the in-built sequence and annotation database available for many organisms, including human, mouse, zebrafish, Drosophila and Arabidopsis, which can be extended in the future.

An advanced wide area chemical sensor testbed

NASA Astrophysics Data System (ADS)

Seeley, Juliette A.; Kelly, Michael; Wack, Edward; Ryan-Howard, Danette; Weidler, Darryl; O'Brien, Peter; Colonero, Curtis; Lakness, John; Patel, Paras

2005-11-01

In order to meet current and emerging needs for remote passive standoff detection of chemical agent threats, MIT Lincoln Laboratory has developed a Wide Area Chemical Sensor (WACS) testbed. A design study helped define the initial concept, guided by current standoff sensor mission requirements. Several variants of this initial design have since been proposed to target other applications within the defense community. The design relies on several enabling technologies required for successful implementation. The primary spectral component is a Wedged Interferometric Spectrometer (WIS) capable of imaging in the LWIR with spectral resolutions as narrow as 4 cm-1. A novel scanning optic will enhance the ability of this sensor to scan over large areas of concern with a compact, rugged design. In this paper, we shall discuss our design, development, and calibration process for this system as well as recent testbed measurements that validate the sensor concept.

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

PubMed

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.

FTIR Analyses of Hypervelocity Impact Deposits: DebriSat Tests

DTIC Science & Technology

2015-03-27

Aerospace Concept Design Center advised on selection of materials for various subsystems. • Test chamber lined with “soft catch” foam panels to trap...C-0001 Authorized by: Space Systems Group Distribution Statement A: Approved for public release; distribution unlimited Report...Pre Preshot target was a multi-shock shield supplied by NASA designed to catch the projectile. It consisted of seven bumper panels consisting of

Acoustic metamaterials with synergetic coupling

NASA Astrophysics Data System (ADS)

Ma, Fuyin; Huang, Meng; Wu, Jiu Hui

2017-12-01

In this paper, we propose a general design concept for acoustic metamaterials that introduces a ubiquitous synergetic behavior into the design procedure, in which the structure of the design is driven by its functional requirements. Since the physical properties of the widely used, resonant-type metamaterials are mainly determined by the eigenmodes of the structure, we first introduce the design concept through the modal displacement distributions on two typical plate-type structures. Next, by employing broadband sound attenuations that involve both the insulation and absorption as the typical targets, two synergetic coupling behaviors are systematically revealed among the dense resonant modes and multi-cell. Furthermore, through plate-type multiple-cell structures assembled from nine oscillators, the design is shown to realize strong broadband attenuations with either the average sound transmission loss (STL) below 2000 Hz higher than 40 dB or the absorption approximately 0.99 in the range of 400-700 Hz wherein the average absorption below 800 Hz remains higher than 0.8. Finally, two multi-cell plate-type samples are fabricated and then used experimentally to measure the STLs in support of the proposed synergetic coupling design method. Both the computational and experimental results demonstrate that the proposed synergetic design concept could effectively initiate a design for metamaterials that offer a new degree of freedom for broadband sound attenuations.

Los Angeles congestion reduction demonstration (Metro ExpressLanes) program. National evaluation : traffic system data test plan.

DOT National Transportation Integrated Search

1997-01-01

This document reports on the formal evaluation of the targeted (limited but highly focused) deployment of the Advanced Driver and Vehicle Advisory Navigation ConcEpt (ADVANCE), an in-vehicle advanced traveler information system designed to provide sh...

Examining key design decisions involved in developing a serious game for child sexual abuse prevention.

PubMed

Stieler-Hunt, Colleen; Jones, Christian M; Rolfe, Ben; Pozzebon, Kay

2014-01-01

This paper presents a case study of the key decisions made in the design of Orbit, a child sexual abuse prevention computer game targeted at school students between 8 and 10 years of age. Key decisions include providing supported delivery for the target age group, featuring adults in the program, not over-sanitizing game content, having a focus on building healthy self-concept of players, making the game engaging and relatable for all players and evaluating the program. This case study has implications for the design of Serious Games more generally, including that research should underpin game design decisions, game designers should consider ways of bridging the game to real life, the learning that arises from the game should go beyond rote-learning, designers should consider how the player can make the game-world their own and comprehensive evaluations of Serious Games should be undertaken.

Examining key design decisions involved in developing a serious game for child sexual abuse prevention

PubMed Central

Stieler-Hunt, Colleen; Jones, Christian M.; Rolfe, Ben; Pozzebon, Kay

2014-01-01

This paper presents a case study of the key decisions made in the design of Orbit, a child sexual abuse prevention computer game targeted at school students between 8 and 10 years of age. Key decisions include providing supported delivery for the target age group, featuring adults in the program, not over-sanitizing game content, having a focus on building healthy self-concept of players, making the game engaging and relatable for all players and evaluating the program. This case study has implications for the design of Serious Games more generally, including that research should underpin game design decisions, game designers should consider ways of bridging the game to real life, the learning that arises from the game should go beyond rote-learning, designers should consider how the player can make the game-world their own and comprehensive evaluations of Serious Games should be undertaken. PMID:24550880

Development of the Biological Experimental Design Concept Inventory (BEDCI)

PubMed Central

Deane, Thomas; Jeffery, Erica; Pollock, Carol; Birol, Gülnur

2014-01-01

Interest in student conception of experimentation inspired the development of a fully validated 14-question inventory on experimental design in biology (BEDCI) by following established best practices in concept inventory (CI) design. This CI can be used to diagnose specific examples of non–expert-like thinking in students and to evaluate the success of teaching strategies that target conceptual changes. We used BEDCI to diagnose non–expert-like student thinking in experimental design at the pre- and posttest stage in five courses (total n = 580 students) at a large research university in western Canada. Calculated difficulty and discrimination metrics indicated that BEDCI questions are able to effectively capture learning changes at the undergraduate level. A high correlation (r = 0.84) between responses by students in similar courses and at the same stage of their academic career, also suggests that the test is reliable. Students showed significant positive learning changes by the posttest stage, but some non–expert-like responses were widespread and persistent. BEDCI is a reliable and valid diagnostic tool that can be used in a variety of life sciences disciplines. PMID:25185236

Advanced Radioisotope Power System Enabled Titan Rover Concept with Inflatable Wheels

NASA Astrophysics Data System (ADS)

Balint, Tibor S.; Schriener, Timothy M.; Shirley, James H.

2006-01-01

The Decadal Survey identified Titan as one of the top priority science destinations in the large moons category, while NASA's proposed Design Reference Mission Set ranked a Titan in-situ explorer second, after a recommended Europa Geophysical Explorer mission. This paper discusses a Titan rover concept, enabled by a single advanced Radioisotope Power System that could provide about 110 We (BOL). The concept targets the smaller Flagship or potentially the New Frontiers mission class. This MSL class rover would traverse on four 1.5 m diameter inflatable wheels during its 3 years mission duration and would use as much design and flight heritage as possible to reduce mission cost. Direct to Earth communication would remove the need for a relay orbiter. Details on the strawman instrument payload, and rover subsystems are given for this science driven mission concept. In addition, power system trades between Advanced RTG, TPV, and Advanced-Stirling and Brayton RPSs are outlined. While many possible approaches exist for Titan in-situ exploration, the Titan rover concept presented here could provide a scientifically interesting and programmatically affordable solution.

ARPS Enabled Titan Rover Concept with Inflatable Wheels

NASA Technical Reports Server (NTRS)

Balint, Tibor S.; Schriener, Timothy M.; Shirley, James H.

2006-01-01

The Decadal Survey identified Titan as one of the top priority science destinations in the large moons category, while NASA's proposed Design Reference Mission Set ranked a Titan in-situ explorer second, after a recommended Europa Geophysical Observer mission. This paper discusses a Titan rover concept, enabled by a single advanced Radioisotope Power System that could provide about 110We (BOL). The concept targets the smaller Flagship or potentially the New Frontiers mission class. This MSL class rover would traverse on four 1.5 m diameter inflatable wheels during its 3 years mission duration and would use as much design and flight heritage as possible to reduce mission cost. Direct to Earth communication would remove the need for a relay orbiter. Details on the strawman instrument payload, and rover subsystems are given for this science driven mission concept. In addition, power system trades between Advanced RTG, TPV, and Advanced Stirling and Brayton Radioisotope Power Systems (RPS) are outlined. While many possible approaches exist for Titan in-situ exploration, the Titan rover concept presented here could provide a scientifically interesting and programmatically affordable solution.

Strategies and Challenges in Clinical Trials Targeting Human Aging

PubMed Central

Newman, John C.; Milman, Sofiya; Hashmi, Shahrukh K.; Austad, Steve N.; Kirkland, James L.; Halter, Jeffrey B.

2016-01-01

Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use. We review the evidence that some drugs already in clinical use may target fundamental aging processes. We discuss the design principles of clinical trials to test such interventions in humans, including study populations, interventions, and outcomes. As examples, we offer several scenarios for potential clinical trials centered on the concepts of health span (delayed multimorbidity and functional decline) and resilience (response to or recovery from an acute health stress). Finally, we describe how this discussion helped inform the design of the proposed Targeting Aging with Metformin study. PMID:27535968

Gastrointestinal cancers in the era of theranostics: Updates and future perspectives

PubMed Central

Ghosn, Marwan; Kourie, Hampig Raphael; Tabchi, Samer

2015-01-01

Theranostics are one of the practical aspects of personalized medicine. This concept was designed to describe a material combining diagnosis, treatment and follow up of a disease. It evolved and included molecular targeting and nanotechnologies that incorporate both diagnosis and therapeutics. In this editorial, we are presenting briefly the concept and evolution of theranostics, highlighting many applications of theranostics in daily practice and discussing future perspectives and aspects of this model in gastro-intestincal cancers. PMID:26229391

Are Financial Incentives for Lifestyle Behavior Change Informed or Inspired by Behavioral Economics? A Mapping Review.

PubMed

McGill, Bronwyn; O'Hara, Blythe J; Bauman, Adrian; Grunseit, Anne C; Phongsavan, Philayrath

2018-01-01

To identify the behavioral economics (BE) conceptual underpinnings of lifestyle financial incentive (FI) interventions. A mapping review of peer-reviewed literature was conducted by searching electronic databases. Inclusion criteria were real-world FI interventions explicitly mentioning BE, targeting individuals, or populations with lifestyle-related behavioral outcomes. Exclusion criteria were hypothetical studies, health professional focus, clinically oriented interventions. Study characteristics were tabulated according to purpose, categorization of BE concepts and FI types, design, outcome measures, study quality, and findings. Data Synthesis and Analysis: Financial incentives were categorized according to type and payment structure. Behavioral economics concepts explicitly used in the intervention design were grouped based on common patterns of thinking. The interplay between FI types, BE concepts, and outcome was assessed. Seventeen studies were identified from 1452 unique records. Analysis showed 76.5% (n = 13) of studies explicitly incorporated BE concepts. Six studies provided clear theoretical justification for the inclusion of BE. No pattern in the type of FI and BE concepts used was apparent. Not all FI interventions claiming BE inclusion did so. For interventions that explicitly included BE, the degree to which this was portrayed and woven into the design varied. This review identified BE concepts common to FI interventions, a first step in providing emergent and pragmatic information to public health and health promotion program planners.

Capacity-Building in Open Education: An Australian Approach

ERIC Educational Resources Information Center

Bossu, Carina; Fountain, Wendy

2015-01-01

Addressing the gap between global open educational resource (OER) proliferation and the slow adoption of OER and open educational practices (OEP) in Australian higher education, this paper focuses on a capacity-building project targeting academics, academic support staff and educational developers. The conception, design, development, piloting and…

Studies for the electro-magnetic calorimeter SplitCal for the SHiP experiment at CERN with shower direction reconstruction capability

NASA Astrophysics Data System (ADS)

Bonivento, Walter M.

2018-02-01

This paper describes the basic ideas and the first simulation results of a new electro-magnetic calorimeter concept, named SplitCal, aimed at optimising the measurement of photon direction in fixed-target experiment configuration, with high photon detection efficiency. This calorimeter was designed for the invariant mass reconstruction of axion-like particles decaying into two photons in the mass range 200 MeV to 1 GeV for the proposed proton beam dump experiment SHiP at CERN. Preliminary results indicate that angular resolutions better than obtained by past experiments can be achieved with this design. An implementation of this concept with real technologies is under study.

RS-84 Engine Completes Design Review

NASA Technical Reports Server (NTRS)

2003-01-01

This is an artist's concept of the kerosene-fueled RS-84 engine, one of several technologies competing to power NASA's next generation of launch vehicles. The RS-84 has successfully completed its preliminary design review as a reusable, liquid kerosene booster engine that will deliver a thrust level of 1 million pounds of force. The preliminary design review is a lengthy technical analysis that evaluates engine design according to stringent system requirements. The review ensures development is on target to meet Next Generation Launch Technology goals: Improved safety, reliability, and cost.

The Material Plasma Exposure eXperiment (MPEX)

NASA Astrophysics Data System (ADS)

Rapp, J.; Biewer, T. M.; Bigelow, T. S.; Canik, J.; Caughman, J. B. O.; Duckworth, R. C.; Goulding, R. H.; Hillis, D. L.; Lore, J. D.; Lumsdaine, A.; McGinnis, W. D.; Meitner, S. J.; Owen, L. W.; Shaw, G. C.; Luo, G.-N.

2014-10-01

Next generation plasma generators have to be able to access the plasma conditions expected on the divertor targets in ITER and future devices. The Material Plasma Exposure eXperiment (MPEX) will address this regime with electron temperatures of 1--10 eV and electron densities of 1021--1020 m-3. The resulting heat fluxes are about 10 MW/m2. MPEX is designed to deliver those plasma conditions with a novel Radio Frequency plasma source able to produce high density plasmas and heat electron and ions separately with Electron Bernstein Wave (EBW) heating and Ion Cyclotron Resonance Heating (ICRH). Preliminary modeling has been used for pre-design studies of MPEX. MPEX will be capable to expose neutron irradiated samples. In this concept targets will be irradiated in ORNL's High Flux Isotope Reactor (HFIR) or possibly at the Spallation Neutron Source (SNS) and then subsequently (after a sufficient long cool-down period) exposed to fusion reactor relevant plasmas in MPEX. The current state of the pre-design of MPEX including the concept of handling irradiated samples will be presented. ORNL is managed by UT-Battelle, LLC, for the U.S. DOE under Contract DE-AC-05-00OR22725.

Free-form Fresnel RXI Köhler design with spectrum-splitting for photovoltaics

NASA Astrophysics Data System (ADS)

Buljan, M.; Benítez, P.; Mohedano, R.; Miñano, J. C.; Sun, Y.; Falicoff, W.; Vilaplana, J.; Chaves, J.; Biot, G.; López, J.

2011-10-01

Here we present a novel optical design of the high concentration photovoltaics (HPCV) nonimaging concentrator (>500x) with built-in spectrum splitting concept. The primary optical element (POE) is a flat Fresnel lens and the secondary optical element (SOE) is a free-form RXI-type concentrator with a band-pass filter embedded in it, both POE and SOE performing Köhler integration to produce light homogenization on the target. It uses the combination of a commercial concentration GaInP/GaInAs/Ge 3J cell and a concentration Back-Point-Contact (BPC) silicon cell for efficient spectral utilization, and external confinement techniques for recovering the 3J cell's reflection. Design targets equivalent cell efficiency ~46% using commercial 39% 3J and 26% Si cells, and CPV module efficiency greater than 38%, achieved at a concentration level larger than 500X and wide acceptance angle (+/-1°). A first proof-of concept receiver prototype has been manufactured using a simpler optical architecture (with a lower concentration, ~100x and lower simulated added efficiency), and experimental measurements have shown up to 39.8% 4J receiver efficiency using a 3J with peak efficiency of 36.9%.

Quality By Design: Concept To Applications.

PubMed

Swain, Suryakanta; Padhy, Rabinarayan; Jena, Bikash Ranjan; Babu, Sitty Manohar

2018-03-08

Quality by Design is associated to the modern, systematic, scientific and novel approach which is concerned with pre-distinct objectives that not only focus on product, process understanding but also leads to process control. It predominantly signifies the design and product improvement and the manufacturing process in order to fulfill the predefined manufactured goods or final products quality characteristics. It is quite essential to identify desire and required product performance report such as Target Product Profile, typical Quality Target Product Profile (QTPP) and Critical Quality attributes (CQA). This review highlighted about the concepts of QbD design space, for critical material attributes (CMAs) as well as the critical process parameters that can totally affect the CQAs within which the process shall be unaffected and consistently manufacture the required product. Risk assessment tools and design of experiments are its prime components. This paper outlines the basic knowledge of QbD, the key elements; steps as well as various tools for QbD implementation in pharmaceutics field are presented briefly. In addition to this, quite a lot of applications of QbD in numerous pharmaceutical related unit operations are discussed and summarized. This article provides a complete data as well as the road map for universal implementation and application of QbD for pharmaceutical products. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Design and Analysis of Efficient Learning Algorithms

DTIC Science & Technology

1991-01-01

will be c-close to the target concept with high probability. (Technically, their approach needs some minor modifications to handle, for instance, a...test in the sense that if cii = cik = cik then nothing can be concluded about the relative depth of 17, and Fk . However, our next lemnas give

RAD hard PROM design study

NASA Technical Reports Server (NTRS)

1981-01-01

The results of a preliminary study on the design of a radiation hardened fusible link programmable read-only memory (PROM) are presented. Various fuse technologies and the effects of radiation on MOS integrated circuits are surveyed. A set of design rules allowing the fabrication of a radiation hardened PROM using a Si-gate CMOS process is defined. A preliminary cell layout was completed and the programming concept defined. A block diagram is used to describe the circuit components required for a 4 K design. A design goal data sheet giving target values for the AC, DC, and radiation parameters of the circuit is presented.

Conceptual studies for a mercury target circuit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sigg, B.

1996-06-01

For the now favored target design of the European Spallation Source project, i.e. the version using mercury as target material, a basic concept of the primary system has been worked out. It does not include a detailed design of the various components of the target circuit, but tries to outline a feasible solution for the system. Besides the removal of the thermal power of about 3MW produced in the target by the proton beam, the primary system has to satisfy a number of other requirements related to processing, safety, and operation. The basic proposal uses an electromagnetic pump and amore » mercury-water intermediate heat excanger, but other alternatives are also being discussed. Basic safety requirements, i.e. protection against radiation and toxic mercury vapours, are satisfied by a design using an air-tight primary system containment, double-walled tubes in the intermediate heat exchanger, a fail-safe system for decay heat removal, and a remote handling facility for the active part of the system. Much engineering work has still to be done, because many details of the design of the mercury and gas processing systems remain to be clarified, the thermal-hydraulic components need further optimisation, the system for control and instrumentation is only known in outline and a through safety analysis will be required.« less

Simulation study on dynamics model of two kinds of on-orbit soft-contact mechanism

NASA Astrophysics Data System (ADS)

Ye, X.; Dong, Z. H.; Yang, F.

2018-05-01

Aiming at the problem that the operating conditions of the space manipulator is harsh and the space manipulator could not bear the large collision momentum, this paper presents a new concept and technical method, namely soft contact technology. Based on ADAMS dynamics software, this paper compares and simulates the mechanism model of on-orbit soft-contact mechanism based on the bionic model and the integrated double joint model. The main purpose is to verify the path planning ability and the momentum buffering ability based on the different design concept mechanism. The simulation results show that both the two mechanism models have the path planning function before the space target contact, and also has the momentum buffer and controllability during the space target contact process.

Targeted prodrugs in oral drug delivery: the modern molecular biopharmaceutical approach.

PubMed

Dahan, Arik; Khamis, Mustafa; Agbaria, Riad; Karaman, Rafik

2012-08-01

The molecular revolution greatly impacted the field of drug design and delivery in general, and the utilization of the prodrug approach in particular. The increasing understanding of membrane transporters has promoted a novel 'targeted-prodrug' approach utilizing carrier-mediated transport to increase intestinal permeability, as well as specific enzymes to promote activation to the parent drug. This article provides the reader with a concise overview of this modern approach to prodrug design. Targeting the oligopeptide transporter PEPT1 for absorption and the serine hydrolase valacyclovirase for activation will be presented as examples for the successful utilization of this approach. Additionally, the use of computational approaches, such as DFT and ab initio molecular orbital methods, in modern prodrugs design will be discussed. Overall, in the coming years, more and more information will undoubtedly become available regarding intestinal transporters and potential enzymes that may be exploited for the targeted modern prodrug approach. Hence, the concept of prodrug design can no longer be viewed as merely a chemical modification to solve problems associated with parent compounds. Rather, it opens promising opportunities for precise and efficient drug delivery, as well as enhancement of treatment options and therapeutic efficacy.

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

PubMed Central

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.

2016-01-01

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. PMID:26758806

Reflector Technology Development and System Design for Concentrating Solar Power Technologies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adam Schaut

2011-12-30

Alcoa began this program in March of 2008 with the goal of developing and validating an advanced CSP trough design to lower the levelized cost of energy (LCOE) as compared to existing glass based, space-frame trough technology. In addition to showing a pathway to a significant LCOE reduction, Alcoa also desired to create US jobs to support the emerging CSP industry. Alcoa's objective during Phase I: Concept Feasibility was to provide the DOE with a design approach that demonstrates significant overall system cost savings without sacrificing performance. Phase I consisted of two major tasks; reflector surface development and system conceptmore » development. Two specific reflective surface technologies were investigated, silver metallized lamination, and thin film deposition both applied on an aluminum substrate. Alcoa prepared samples; performed test validation internally; and provided samples to the NREL for full-spectrum reflectivity measurements. The final objective was to report reflectivity at t = 0 and the latest durability results as of the completion of Phase 1. The target criteria for reflectance and durability were as follows: (1) initial (t = 0), hemispherical reflectance >93%, (2) initial spectral reflectance >90% for 25-mrad reading and >87% for 7-mrad reading, and (3) predicted 20 year durability of less than 5% optical performance drop. While the results of the reflective development activities were promising, Alcoa was unable to down-select on a reflective technology that met the target criteria. Given the progress and potential of both silver film and thin film technologies, Alcoa continued reflector surface development activities in Phase II. The Phase I concept development activities began with acquiring baseline CSP system information from both CSP Services and the DOE. This information was used as the basis to develop conceptual designs through ideation sessions. The concepts were evaluated based on estimated cost and high-level structural performance. The target criteria for the concept development was to achieve a solar field cost savings of 25%-50% thereby meeting or exceeding the DOE solar field cost savings target of $350/m2. After evaluating various structural design approaches, Alcoa down-selected to a monocoque, dubbed Wing Box, design that utilizes the reflective surface as a structural, load carrying member. The cost and performance potential of the Wing Box concept was developed via initial finite element analysis (FEA) and cost modeling. The structural members were sized through material utilization modeling when subjected to representative loading conditions including wind loading. Cost modeling was utilized to refine potential manufacturing techniques that could be employed to manufacture the structural members. Alcoa concluded that an aluminum intensive collector design can achieve significant cost savings without sacrificing performance. Based on the cost saving potential of this Concept Feasibility study, Alcoa recommended further validation of this CSP approach through the execution of Phase II: Design and Prototype Development. Alcoa Phase II objective was to provide the DOE with a validated CSP trough design that demonstrates significant overall system cost savings without sacrificing performance. Phase II consisted of three major tasks; Detail System Design, Prototype Build, and System Validation. Additionally, the reflector surface development that began in Phase I was continued in Phase II. After further development work, Alcoa was unable to develop a reflective technology that demonstrated significant performance or cost benefits compared to commercially available CSP reflective products. After considering other commercially available reflective surfaces, Alcoa selected Alano's MIRO-SUN product for use on the full scale prototype. Although MIRO-SUN has a lower specular reflectivity compared to other options, its durability in terms of handling, cleaning, and long-term reflectivity was deemed the most important attribute to successfully validate Alcoa's advanced trough architecture. To validate the performance of the Wing Box trough, a 6 meter aperture by 14 meter long prototype trough was built. For ease of shipping to and assembly at NREL's test facility, the prototype was fabricated in two half modules and joined along the centerline to create the Wing Box trough. The trough components were designed to achieve high precision of the reflective surface while leveraging high volume manufacturing and assembly techniques.« less

THE MASTER PROTOCOL CONCEPT

PubMed Central

Allegra, Carmen J.

2015-01-01

During the past decade, biomedical technologies have undergone an explosive evolution---from the publication of the first complete human genome in 2003, after more than a decade of effort and at a cost of hundreds of millions of dollars---to the present time, where a complete genomic sequence can be available in less than a day and at a small fraction of the cost of the original sequence. The widespread availability of next generation genomic sequencing has opened the door to the development of precision oncology. The need to test multiple new targeted agents both alone and in combination with other targeted therapies, as well as classic cytotoxic agents, demand the development of novel therapeutic platforms (particularly Master Protocols) capable of efficiently and effectively testing multiple targeted agents or targeted therapeutic strategies in relatively small patient subpopulations. Here, we describe the Master Protocol concept, with a focus on the expected gains and complexities of the use of this design. An overview of Master Protocols currently active or in development is provided along with a more extensive discussion of the Lung Master Protocol (Lung-MAP study). PMID:26433553

Conceptual design of laser fusion reactor KOYO-fast Concepts of reactor system and laser driver

NASA Astrophysics Data System (ADS)

Kozaki, Y.; Miyanaga, N.; Norimatsu, T.; Soman, Y.; Hayashi, T.; Furukawa, H.; Nakatsuka, M.; Yoshida, K.; Nakano, H.; Kubomura, H.; Kawashima, T.; Nishimae, J.; Suzuki, Y.; Tsuchiya, N.; Kanabe, T.; Jitsuno, T.; Fujita, H.; Kawanaka, J.; Tsubakimoto, K.; Fujimoto, Y.; Lu, J.; Matsuoka, S.; Ikegawa, T.; Owadano, Y.; Ueda, K.; Tomabechi, K.; Reactor Design Committee in Ife Forum, Members Of

2006-06-01

We have carried out the design studies of KOYO-Fast laser fusion power plant, using fast ignition cone targets, DPSSL lasers, and LiPb liquid wall chambers. Using fast ignition targets, we could design a middle sized 300 MWe reactor module, with 200 MJ fusion pulse energy and 4 Hz rep-rates, and 1200MWe modular power plants with 4 reactor modules and a 16 Hz laser driver. The liquid wall chambers with free surface cascade flows are proposed for cooling surface quickly enough to a 4 Hz pulse operation. We examined the potential of Yb-YAG ceramic lasers operated at 150˜ 225 K for both implosion and heating laser systems required for a 16-Hz repetition and 8 % total efficiency.

Assessment of the Performance Potential of Advanced Subsonic Transport Concepts for NASA's Environmentally Responsible Aviation Project

NASA Technical Reports Server (NTRS)

Nickol, Craig L.; Haller, William J.

2016-01-01

NASA's Environmentally Responsible Aviation (ERA) project has matured technologies to enable simultaneous reductions in fuel burn, noise, and nitrogen oxide (NOx) emissions for future subsonic commercial transport aircraft. The fuel burn reduction target was a 50% reduction in block fuel burn (relative to a 2005 best-in-class baseline aircraft), utilizing technologies with an estimated Technology Readiness Level (TRL) of 4-6 by 2020. Progress towards this fuel burn reduction target was measured through the conceptual design and analysis of advanced subsonic commercial transport concepts spanning vehicle size classes from regional jet (98 passengers) to very large twin aisle size (400 passengers). Both conventional tube-and-wing (T+W) concepts and unconventional (over-wing-nacelle (OWN), hybrid wing body (HWB), mid-fuselage nacelle (MFN)) concepts were developed. A set of propulsion and airframe technologies were defined and integrated onto these advanced concepts which were then sized to meet the baseline mission requirements. Block fuel burn performance was then estimated, resulting in reductions relative to the 2005 best-in-class baseline performance ranging from 39% to 49%. The advanced single-aisle and large twin aisle T+W concepts had reductions of 43% and 41%, respectively, relative to the 737-800 and 777-200LR aircraft. The single-aisle OWN concept and the large twin aisle class HWB concept had reductions of 45% and 47%, respectively. In addition to their estimated fuel burn reduction performance, these unconventional concepts have the potential to provide significant noise reductions due, in part, to engine shielding provided by the airframe. Finally, all of the advanced concepts also have the potential for significant NOx emissions reductions due to the use of advanced combustor technology. Noise and NOx emissions reduction estimates were also generated for these concepts as part of the ERA project.

Epithermal neutron formation for boron neutron capture therapy by adiabatic resonance crossing concept

NASA Astrophysics Data System (ADS)

Khorshidi, A.; Ghafoori-Fard, H.; Sadeghi, M.

2014-05-01

Low-energy protons from the cyclotron in the range of 15-30 MeV and low current have been simulated on beryllium (Be) target with a lead moderator around the target. This research was accomplished to design an epithermal neutron beam for Boron Neutron Capture Therapy (BNCT) using the moderated neutron on the average produced from 9Be target via (p, xn) reaction in Adiabatic Resonance Crossing (ARC) concept. Generation of neutron to proton ratio, energy distribution, flux and dose components in head phantom have been simulated by MCNP5 code. The reflector and collimator were designed in prevention and collimation of derivation neutrons from proton bombarding. The scalp-skull-brain phantom consisting of bone and brain equivalent material has been simulated in order to evaluate the dosimetric effect on the brain. Results of this analysis demonstrated while the proton energy decreased, the dose factor altered according to filters thickness. The maximum epithermal flux revealed using fluental, Fe and bismuth (Bi) filters with thicknesses of 9.4, 3 and 2 cm, respectively and also the epithermal to thermal neutron flux ratio was 103.85. The potential of the ARC method to replace or complement the current reactor-based supply sources of BNCT purposes.

Rexin-G, a targeted genetic medicine for cancer.

PubMed

Gordon, Erlinda M; Hall, Frederick L

2010-05-01

Rexin-G, a tumor-targeted retrovector bearing a cytocidal cyclin G1 construct, is the first targeted gene therapy vector to gain fast track designation and orphan drug priorities for multiple cancer indications in the US. This review describes the major milestones in the clinical development of Rexin-G: from the molecular cloning and characterization of the human cyclin G1 proto-oncogene in 1994, to the design of the first knockout constructs and genetic engineering of the targeted delivery system from 1995 to 1997, through the initial proofs-of-concept, molecular pharmacology and toxicology studies of Rexin-G in preclinical cancer models from 1997 to 2001, to the pioneering clinical studies in humans from 2002 to 2004, which--together with the advancements in bioprocess development of high-potency clinical grade vectors circa 2005 - 2006--led to the accelerated approval of Rexin-G for all solid tumors by the Philippine FDA in 2007 and the rapid progression of clinical studies from 2007 to 2009 to the cusp of pivotal Phase III trials in the US. In recording the development of Rexin-G as a novel form of targeted biological therapy, this review also highlights important aspects of vector design engineering which served to overcome the physiological barriers to gene delivery as it addresses the key regulatory issues involved in the development of a targeted gene therapy product. Progressive clinical development of Rexin-G demonstrates the potential safety and efficacy of targeted genetic medicine, while validating the design engineering of the molecular biotechnology platform.

Characterization studies of prototype ISOL targets for the RIA

NASA Astrophysics Data System (ADS)

Greene, John P.; Burtseva, Tatiana; Neubauer, Janelle; Nolen, Jerry A.; Villari, Antonio C. C.; Gomes, Itacil C.

2005-12-01

Targets employing refractory compounds are being developed for the rare isotope accelerator (RIA) facility to produce ion species far from stability. With the 100 kW beams proposed for the production targets, dissipation of heat becomes a challenging issue. In our two-step target design, neutrons are generated in a refractory primary target, inducing fission in the surrounding uranium carbide. The interplay of density, grain size, thermal conductivity and diffusion properties of the UC2 needs to be well understood before fabrication. Thin samples of uranium carbide were prepared for thermal conductivity measurements using an electron beam to heat the sample and an optical pyrometer to observe the thermal radiation. Release efficiencies and independent thermal analysis on these samples are being undertaken at Oak Ridge National Laboratory (ORNL). An alternate target concept for RIA, the tilted slab approach promises to be simple with fast ion release and capable of withstanding high beam intensities while providing considerable yields via spallation. A proposed small business innovative research (SBIR) project will design a prototype tilted target, exploring the materials needed for fabrication and testing at an irradiation facility to address issues of heat transfer and stresses within the target.

The European scene regarding spallation neutron sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bauer, G.S.

1996-06-01

In Europe, a short pulse spallation neutron source, ISIS, has been operating for over 10 years, working its way up to a beam power level of 200 kW. A continuous source, SINQ, designed for a beam power of up to 1 MW, is scheduled to start operating at the end of 1996, and a detailed feasibility study has been completed for a 410 kW short pulse source, AUSTRON. Each of these sources seems to have settled for a target concept which is at or near the limits of its feasibility: The ISIS depleted uranium plate targets, heavy water cooled andmore » Zircaloy clad, have so far not shown satisfactory service time and operation is likely to continue with a Ta-plate target, which, in the past has been used successfully for the equivalent of one full-beam-year before it was taken out of service due to degrading thermal properties. SINQ will initially use a rod target, made of Zircaloy only, but plans exist to move on to clad lead rods as quickly as possible. Apart from the not yet explored effect of hydrogen and helium production, there are also concerns about the generation of 7-Be in the cooling water from the spallation of oxygen, which might result in undesirably high radioactivity in the cooling plant room. A Liquid metal target, also under investigation for SINQ, would not only reduce this problem to a level of about 10 %, but would also minimize the risk of radiolytic corrosion in the beam interaction zone. Base on similar arguments, AUSTRON has been designed for edge cooled targets, but thermal and stress analyses show, that this concept is not feasible at higher power levels.« less

The development and testing of the thermal break divertor monoblock target design delivering 20 MW m-2 heat load capability

NASA Astrophysics Data System (ADS)

Fursdon, M.; Barrett, T.; Domptail, F.; Evans, Ll M.; Luzginova, N.; Greuner, N. H.; You, J.-H.; Li, M.; Richou, M.; Gallay, F.; Visca, E.

2017-12-01

The design and development of a novel plasma facing component (for fusion power plants) is described. The component uses the existing ‘monoblock’ construction which consists of a tungsten ‘block’ joined via a copper interlayer to a through CuCrZr cooling pipe. In the new concept the interlayer stiffness and conductivity properties are tuned so that stress in the principal structural element of the component (the cooling pipe) is reduced. Following initial trials with off-the-shelf materials, the concept was realized by machined features in an otherwise solid copper interlayer. The shape and distribution of the features were tuned by finite element analyses subject to ITER structural design criterion in-vessel components (SDC-IC) design rules. Proof of concept mock-ups were manufactured using a two stage brazing process verified by tomography and micrographic inspection. Full assemblies were inspected using ultrasound and thermographic (SATIR) test methods at ENEA and CEA respectively. High heat flux tests using IPP’s GLADIS facility showed that 200 cycles at 20 MW m-2 and five cycles at 25 MW m-2 could be sustained without apparent component damage. Further testing and component development is planned.

Harnessing RNA interference to develop neonatal therapies: from Nobel Prize winning discovery to proof of concept clinical trials.

PubMed

DeVincenzo, John P

2009-10-01

A revolution in the understanding of RNA biological processing and control is leading to revolutionary new concepts in human therapeutics. It has become increasingly clear that the so called "non-coding RNA" exerts specific and profound functional control on regulation of protein production and indeed controls the expression of all genes. Harnessing this naturally-occurring RNA-mediated regulation of protein production has immense human therapeutic potential. These processes are collectively known as RNA interference (RNAi). RNAi is a recently discovered, naturally-occurring intracellular process that regulates gene expression through the silencing of specific mRNAs. Methods of harnessing this natural pathway are being developed that allow the catalytic degradation of targeted mRNAs using specifically designed complementary small inhibitory RNAs (siRNA). siRNAs are being chemically modified to acquire drug-like properties. Numerous recent high profile publications have provided proofs of concept that RNA interference may be useful therapeutically. Much of the design of these siRNAs can be accomplished bioinformatically, thus potentially expediting drug discovery and opening new avenues of therapy for many uncommon, orphan, or emerging diseases. This makes this approach very attractive for developing therapies targeting orphan diseases including neonatal diseases. Theoretically, any disease that can be ameliorated through knockdown of any endogenous or exogenous protein is a potential therapeutic target for RNAi-based therapeutics. Lung diseases are particularly attractive targets for RNAi therapeutics since the affected cells' location increases their accessibility to topical administration of siRNA, for example by aerosol. Respiratory viral infections and chronic lung disease are examples of such diseases. RNAi therapeutics have been shown to be active against RSV, parainfluenza and human metapneumoviruses in vitro and in vivo resulting in profound antiviral effects. The first proof of concept test of efficacy of an RNAi-based therapeutic in man has been initiated. A discussion of the science behind RNA interference is followed by a presentation of the potential practical issues in applying this technology to neonatal respiratory viral diseases. RNAi may offer new strategies for the treatment of a variety of orphan diseases including neonatal diseases, RSV infections, and other respiratory viruses.

The ISIS Mission Concept: An Impactor for Surface and Interior Science

NASA Technical Reports Server (NTRS)

Chesley, Steven R.; Elliot, John O.; Abell, Paul A.; Asphaug, Erik; Bhaskaran, Shyam; Lam, Try; Lauretta, Dante S.

2013-01-01

The Impactor for Surface and Interior Science (ISIS) mission concept is a kinetic asteroid impactor mission to the target of NASA's OSIRIS-REx (Origins-Spectral Interpretation-Resource Identification-Security-Regolith Explorer) asteroid sample return mission. The ISIS mission concept calls for the ISIS spacecraft, an independent and autonomous smart impactor, to guide itself to a hyper-velocity impact with 1999 RQ36 while the OSIRIS-REx spacecraft observes the collision. Later the OSIRIS-REx spacecraft descends to reconnoiter the impact site and measure the momentum imparted to the asteroid through the impact before departing on its journey back to Earth. In this paper we discuss the planetary science, human exploration and impact mitigation drivers for mission, and we describe the current mission concept and flight system design.

Active Debris Removal mission design in Low Earth Orbit

NASA Astrophysics Data System (ADS)

Martin, Th.; Pérot, E.; Desjean, M.-Ch.; Bitetti, L.

2013-03-01

Active Debris Removal (ADR) aims at removing large sized intact objects ― defunct satellites, rocket upper-stages ― from space crowded regions. Why? Because they constitute the main source of the long-term debris environment deterioration caused by possible future collisions with fragments and worse still with other intact but uncontrolled objects. In order to limit the growth of the orbital debris population in the future (referred to as the Kessler syndrome), it is now highly recommended to carry out such ADR missions, together with the mitigation measures already adopted by national agencies (such as postmission disposal). At the French Space Agency, CNES, and in the frame of advanced studies, the design of such an ADR mission in Low Earth Orbit (LEO) is under evaluation. A two-step preliminary approach has been envisaged. First, a reconnaissance mission based on a small demonstrator (˜500 kg) rendezvousing with several targets (observation and in-flight qualification testing). Secondly, an ADR mission based on a larger vehicle (inherited from the Orbital Transfer Vehicle (OTV) concept) being able to capture and deorbit several preselected targets by attaching a propulsive kit to these targets. This paper presents a flight dynamics level tradeoff analysis between different vehicle and mission concepts as well as target disposal options. The delta-velocity, times, and masses required to transfer, rendezvous with targets and deorbit are assessed for some propelled systems and propellant less options. Total mass budgets are then derived for two end-to-end study cases corresponding to the reconnaissance and ADR missions mentioned above.

A strategy for actualization of active targeting nanomedicine practically functioning in a living body.

PubMed

Lee, Kyoung Jin; Shin, Seol Hwa; Lee, Jae Hee; Ju, Eun Jin; Park, Yun-Yong; Hwang, Jung Jin; Suh, Young-Ah; Hong, Seung-Mo; Jang, Se Jin; Lee, Jung Shin; Song, Si Yeol; Jeong, Seong-Yun; Choi, Eun Kyung

2017-10-01

Designing nanocarriers with active targeting has been increasingly emphasized as for an ideal delivery mechanism of anti-cancer therapeutic agents, but the actualization has been constrained by lack of reliable strategy ultimately applicable. Here, we designed and verified a strategy to achieve active targeting nanomedicine that works in a living body, utilizing animal models bearing a patient's tumor tissue and subjected to the same treatments that would be used in the clinic. The concept for this strategy was that a novel peptide probe and its counterpart protein, which responded to a therapy, were identified, and then the inherent ability of the peptide to target the designated tumor protein was used for active targeting in vivo. An initial dose of ionizing radiation was locally delivered to the gastric cancer (GC) tumor of a patient-derived xenograft mouse model, and phage-displayed peptide library was intravenously injected. The peptides tightly bound to the tumor were recovered, and the counterpart protein was subsequently identified. Peptide-conjugated liposomal drug showed dramatically improved therapeutic efficacy and possibility of diagnostic imaging with radiation. These results strongly suggested the potential of our strategy to achieve in vivo functional active targeting and to be applied clinically for human cancer treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamics of human protein kinase Aurora A linked to drug selectivity

DOE PAGES

Pitsawong, Warintra; Buosi, Vanessa; Otten, Renee; ...

2018-06-14

Protein kinases are major drug targets, but the development of highly-selective inhibitors has been challenging due to the similarity of their active sites. The observation of distinct structural states of the fully-conserved Asp-Phe-Gly (DFG) loop has put the concept of conformational selection for the DFG-state at the center of kinase drug discovery. Recently, it was shown that Gleevec selectivity for the Tyr-kinases Abl was instead rooted in conformational changes after drug binding. Here, we investigate whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase Auroramore » A. Using a combination of biophysical techniques, we propose a universal drug-binding mechanism, that rationalizes selectivity, affinity and long on-target residence time for kinase inhibitors. These new concepts, where protein dynamics in the drug-bound state plays the crucial role, can be applied to inhibitor design of targets outside the kinome.« less

Dynamics of human protein kinase Aurora A linked to drug selectivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pitsawong, Warintra; Buosi, Vanessa; Otten, Renee

Protein kinases are major drug targets, but the development of highly-selective inhibitors has been challenging due to the similarity of their active sites. The observation of distinct structural states of the fully-conserved Asp-Phe-Gly (DFG) loop has put the concept of conformational selection for the DFG-state at the center of kinase drug discovery. Recently, it was shown that Gleevec selectivity for the Tyr-kinases Abl was instead rooted in conformational changes after drug binding. Here, we investigate whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase Auroramore » A. Using a combination of biophysical techniques, we propose a universal drug-binding mechanism, that rationalizes selectivity, affinity and long on-target residence time for kinase inhibitors. These new concepts, where protein dynamics in the drug-bound state plays the crucial role, can be applied to inhibitor design of targets outside the kinome.« less

The Data Gap in the EHR for Clinical Research Eligibility Screening.

PubMed

Butler, Alex; Wei, Wei; Yuan, Chi; Kang, Tian; Si, Yuqi; Weng, Chunhua

2018-01-01

Much effort has been devoted to leverage EHR data for matching patients into clinical trials. However, EHRs may not contain all important data elements for clinical research eligibility screening. To better design research-friendly EHRs, an important step is to identify data elements frequently used for eligibility screening but not yet available in EHRs. This study fills this knowledge gap. Using the Alzheimer's disease domain as an example, we performed text mining on the eligibility criteria text in Clinicaltrials.gov to identify frequently used eligibility criteria concepts. We compared them to the EHR data elements of a cohort of Alzheimer's Disease patients to assess the data gap by usingthe OMOP Common Data Model to standardize the representations for both criteria concepts and EHR data elements. We identified the most common SNOMED CT concepts used in Alzheimer 's Disease trials, andfound 40% of common eligibility criteria concepts were not even defined in the concept space in the EHR dataset for a cohort of Alzheimer 'sDisease patients, indicating a significant data gap may impede EHR-based eligibility screening. The results of this study can be useful for designing targeted research data collection forms to help fill the data gap in the EHR.

Conceptual astronomy: A novel model for teaching postsecondary science courses

NASA Astrophysics Data System (ADS)

Zeilik, Michael; Schau, Candace; Mattern, Nancy; Hall, Shannon; Teague, Kathleen W.; Bisard, Walter

1997-10-01

An innovative, conceptually based instructional model for teaching large undergraduate astronomy courses was designed, implemented, and evaluated in the Fall 1995 semester. This model was based on cognitive and educational theories of knowledge and, we believe, is applicable to other large postsecondary science courses. Major components were: (a) identification of the basic important concepts and their interrelationships that are necessary for connected understanding of astronomy in novice students; (b) use of these concepts and their interrelationships throughout the design, implementation, and evaluation stages of the model; (c) identification of students' prior knowledge and misconceptions; and (d) implementation of varied instructional strategies targeted toward encouraging conceptual understanding in students (i.e., instructional concept maps, cooperative small group work, homework assignments stressing concept application, and a conceptually based student assessment system). Evaluation included the development and use of three measures of conceptual understanding and one of attitudes toward studying astronomy. Over the semester, students showed very large increases in their understanding as assessed by a conceptually based multiple-choice measure of misconceptions, a select-and-fill-in concept map measure, and a relatedness-ratings measure. Attitudes, which were slightly positive before the course, changed slightly in a less favorable direction.

A NOVEL SOLAR THERMAL COMBINED CYCLE WITH BIO-METHANE CARBON CAPTURE FOR DISTRIBUTED POWER GENERATION

EPA Science Inventory

During the course of our research, we expanded and evolved our initial concept to achieve design targets of minimized cost of electricity. Several biofuel pathways were examined, and each had drawbacks in terms of cost (2-3 times market rates for energy), land area required (5 to...

Developing a Multi-Dimensional Early Elementary Mathematics Screener and Diagnostic Tool: The Primary Mathematics Assessment

ERIC Educational Resources Information Center

Brendefur, Jonathan L.; Johnson, Evelyn S.; Thiede, Keith W.; Strother, Sam; Severson, Herb H.

2018-01-01

There is a critical need to identify primary level students experiencing difficulties in mathematics to provide immediate and targeted instruction that remediates their deficits. However, most early math screening instruments focus only on the concept of number, resulting in inadequate and incomplete information for teachers to design intervention…

Is Having More Prerequisite Knowledge Better for Learning from Productive Failure?

ERIC Educational Resources Information Center

Toh, Pee Li Leslie; Kapur, Manu

2017-01-01

A critical assumption made in Kapur's ("Instr Sci" 40:651-672, 2012) productive failure design is that students have the necessary prerequisite knowledge resources to generate and explore solutions to problems before learning the targeted concept. Through two quasi-experimental studies, we interrogated this assumption in the context of…

Parental Involvement Promotes Rural African American Youths Self-Pride and Sexual Self-Concepts

ERIC Educational Resources Information Center

McBride Murry, V.; Brody, Gene H.; McNair, Lily D.; Luo, Zupei; Gibbons, Frederick X.; Gerrard, Meg; Wills, Thomas Ashby

2005-01-01

This study, an evaluation of the Strong African American Families Program, was designed to determine whether intervention-induced changes in targeted parenting behaviors were associated with young adolescents development of racial pride, self-esteem, and sexual identity. Participants were 332 African American mothers and their 11-year-old children…

Accompanying Depression with FINE - A Smartphone-Based Approach.

PubMed

Dang, Marcel; Mielke, Corinna; Diehl, Alexander; Haux, Reinhold

2016-01-01

Major depression is the most prevalent mental disorder and one of the main reasons for disability. To be successful in treating depression, it is necessary to have early identification and intervention. Therefore, it is important to design more objective and more efficient depression screening techniques. Such interventions provided by mobile apps shows promise due to their capabilities to support people in their everyday lives. Until very recently, the design of mental health apps that works effectively in the context of diagnostics had not been widely explored. For this reason, we have investigated potentially significant depression-correlated parameters derived from self reports, smartphone usage pattern and sensor data to specify our concept. Following the results of the requirement analysis, we developed the Android app 'Fine'. A feasibility check with a specific target audience has shown that the app can record most of the selected parameters reliably. It has also shown that the overall concept has been accepted positively with the target audience. Further work is planned to improve the functionalities and to adapt specific needs for depression attendance.

An automated approach to magnetic divertor configuration design

NASA Astrophysics Data System (ADS)

Blommaert, M.; Dekeyser, W.; Baelmans, M.; Gauger, N. R.; Reiter, D.

2015-01-01

Automated methods based on optimization can greatly assist computational engineering design in many areas. In this paper an optimization approach to the magnetic design of a nuclear fusion reactor divertor is proposed and applied to a tokamak edge magnetic configuration in a first feasibility study. The approach is based on reduced models for magnetic field and plasma edge, which are integrated with a grid generator into one sensitivity code. The design objective chosen here for demonstrative purposes is to spread the divertor target heat load as much as possible over the entire target area. Constraints on the separatrix position are introduced to eliminate physically irrelevant magnetic field configurations during the optimization cycle. A gradient projection method is used to ensure stable cost function evaluations during optimization. The concept is applied to a configuration with typical Joint European Torus (JET) parameters and it automatically provides plausible configurations with reduced heat load.

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

PubMed

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 shall be useful for designing exogenous siRNA for therapeutic applications and gene silencing techniques in the area of bioinformatics. The software is developed as a desktop application and available at http://opsid.in/opsid/. Copyright © 2015 Elsevier B.V. All rights reserved.

The target plant concept-a history and brief overview

Treesearch

Thomas D. Landis

2011-01-01

The target plant concept originated with morphological classification of conifer nursery stock in the 1930s, and the concept was enhanced through physiological research and seedling testing towards the end of the century. Morphological grading standards such as shoot height, stem diameter, and root mass are the most common use of the target plant concept, and some...

How Have Cancer Clinical Trial Eligibility Criteria Evolved Over Time?

PubMed Central

Yaman, Anil; Chakrabarti, Shreya; Sen, Anando; Weng, Chunhua

2016-01-01

Knowledge reuse of cancer trial designs may benefit from a temporal understanding of the evolution of the target populations of cancer studies over time. Therefore, we conducted a retrospective analysis of the trends of cancer trial eligibility criteria between 1999 and 2014. The yearly distributions of eligibility concepts for chemicals and drugs, procedures, observations, and medical conditions extracted from free-text eligibility criteria of 32,000 clinical trials for 89 cancer types were analyzed. We identified the concepts that trend upwards or downwards in all or selected cancer types, and the concepts that show anomalous trends for some cancers. Later, concept trends were studied in a disease-specific manner and illustrated for breast cancer. Criteria trends observed in this study are also validated and interpreted using evidence from the existing medical literature. This study contributes a method for concept trend analysis and original knowledge of the trends in cancer clinical trial eligibility criteria. PMID:27570681

What's in a name? Young adolescents' implicit conceptions of invention

NASA Astrophysics Data System (ADS)

Plucker, Jonathan A.

2002-03-01

The past few years have seen an increase in the amount of attention focused on invention and design education at the college and K-12 levels. Given these efforts, the dearth of research on students' preexisting conceptions of invention is surprising. Knowledge of invention beliefs and attitudes will inform educational efforts by allowing educators to target the curriculum and accompanying activities more effectively than is possible without this knowledge. In this study, 55 sixth-grade students completed open-ended survey questions related to their conceptions of invention. Results suggest that students have few or simplistic conceptions of the invention and patent processes. Prior exposure to invention instruction or previous experience with inventing did not appear to have an impact on students' conceptions of invention. In order to dispel these superficial implicit theories, educators involved with invention programs should consider the use of active, situated teaching techniques such as project- and problem-based learning.

REBL: design progress toward 16 nm half-pitch maskless projection electron beam lithography

NASA Astrophysics Data System (ADS)

McCord, Mark A.; Petric, Paul; Ummethala, Upendra; Carroll, Allen; Kojima, Shinichi; Grella, Luca; Shriyan, Sameet; Rettner, Charles T.; Bevis, Chris F.

2012-03-01

REBL (Reflective Electron Beam Lithography) is a novel concept for high speed maskless projection electron beam lithography. Originally targeting 45 nm HP (half pitch) under a DARPA funded contract, we are now working on optimizing the optics and architecture for the commercial silicon integrated circuit fabrication market at the equivalent of 16 nm HP. The shift to smaller features requires innovation in most major subsystems of the tool, including optics, stage, and metrology. We also require better simulation and understanding of the exposure process. In order to meet blur requirements for 16 nm lithography, we are both shrinking the pixel size and reducing the beam current. Throughput will be maintained by increasing the number of columns as well as other design optimizations. In consequence, the maximum stage speed required to meet wafer throughput targets at 16 nm will be much less than originally planned for at 45 nm. As a result, we are changing the stage architecture from a rotary design to a linear design that can still meet the throughput requirements but with more conventional technology that entails less technical risk. The linear concept also allows for simplifications in the datapath, primarily from being able to reuse pattern data across dies and columns. Finally, we are now able to demonstrate working dynamic pattern generator (DPG) chips, CMOS chips with microfabricated lenslets on top to prevent crosstalk between pixels.

Human-in-the-Loop Assessment of Alternative Clearances in Interval Management Arrival Operations

NASA Technical Reports Server (NTRS)

Baxley, Brian T.; Wilson, Sara R.; Swieringa, Kurt A.; Johnson, William C.; Roper, Roy D.; Hubbs, Clay E.; Goess, Paul A.; Shay, Richard F.

2016-01-01

Interval Management Alternative Clearances (IMAC) was a human-in-the-loop simulation experiment conducted to explore the Air Traffic Management (ATM) Technology Demonstration (ATD-1) Concept of Operations (ConOps), which combines advanced arrival scheduling, controller decision support tools, and aircraft avionics to enable multiple time deconflicted, efficient arrival streams into a high-density terminal airspace. Interval Management (IM) is designed to support the ATD-1 concept by having an "Ownship" (IM-capable) aircraft achieve or maintain a specific time or distance behind a "Target" (preceding) aircraft. The IM software uses IM clearance information and the Ownship data (route of flight, current location, and wind) entered by the flight crew, and the Target aircraft's Automatic Dependent Surveillance-Broadcast state data, to calculate the airspeed necessary for the IM-equipped aircraft to achieve or maintain the assigned spacing goal.

Irreducible incoherence and intelligent design: a look into the conceptual toolbox of a pseudoscience.

PubMed

Boudry, Maarten; Blancke, Stefaan; Braeckman, Johan

2010-12-01

The concept of Irreducible Complexity (IC) has played a pivotal role in the resurgence of the creationist movement over the past two decades. Evolutionary biologists and philosophers have unambiguously rejected the purported demonstration of "intelligent design" in nature, but there have been several, apparently contradictory, lines of criticism. We argue that this is in fact due to Michael Behe's own incoherent definition and use of IC. This paper offers an analysis of several equivocations inherent in the concept of Irreducible Complexity and discusses the way in which advocates of the Intelligent Design Creationism (IDC) have conveniently turned IC into a moving target. An analysis of these rhetorical strategies helps us to understand why IC has gained such prominence in the IDC movement, and why, despite its complete lack of scientific merits, it has even convinced some knowledgeable persons of the impending demise of evolutionary theory.

Understanding modern-day vaccines: what you need to know.

PubMed

Vetter, Volker; Denizer, Gülhan; Friedland, Leonard R; Krishnan, Jyothsna; Shapiro, Marla

2018-03-01

Vaccines are considered to be one of the greatest public health achievements of the last century. Depending on the biology of the infection, the disease to be prevented, and the targeted population, a vaccine may require the induction of different adaptive immune mechanisms to be effective. Understanding the basic concepts of different vaccines is therefore crucial to understand their mode of action, benefits, risks, and their potential real-life impact on protection. This review aims to provide healthcare professionals with background information about the main vaccine designs and concepts of protection in a simplified way to improve their knowledge and understanding, and increase their confidence in the science of vaccination ( Supplementary Material ). KEY MESSAGE Different vaccine designs, each with different advantages and limitations, can be applied for protection against a particular disease. Vaccines may contain live-attenuated pathogens, inactivated pathogens, or only parts of pathogens and may also contain adjuvants to stimulate the immune responses. This review explains the mode of action, benefits, risks and real-life impact of vaccines by highlighting key vaccine concepts. An improved knowledge and understanding of the main vaccine designs and concepts of protection will help support the appropriate use and expectations of vaccines, increase confidence in the science of vaccination, and help reduce vaccine hesitancy.

Three dimensional audio versus head down TCAS displays

NASA Technical Reports Server (NTRS)

Begault, Durand R.; Pittman, Marc T.

1994-01-01

The advantage of a head up auditory display was evaluated in an experiment designed to measure and compare the acquisition time for capturing visual targets under two conditions: Standard head down traffic collision avoidance system (TCAS) display, and three-dimensional (3-D) audio TCAS presentation. Ten commercial airline crews were tested under full mission simulation conditions at the NASA Ames Crew-Vehicle Systems Research Facility Advanced Concepts Flight Simulator. Scenario software generated targets corresponding to aircraft which activated a 3-D aural advisory or a TCAS advisory. Results showed a significant difference in target acquisition time between the two conditions, favoring the 3-D audio TCAS condition by 500 ms.

Aptamer-siRNA Chimeras: Discovery, Progress, and Future Prospects

PubMed Central

Kruspe, Sven; Giangrande, Paloma H.

2017-01-01

Synthetic nucleic acid ligands (aptamers) have emerged as effective delivery tools for many therapeutic oligonucleotide-based drugs, including small interfering RNAs (siRNAs). In this review, we summarize recent progress in the aptamer selection technology that has made possible the identification of cell-specific, cell-internalizing aptamers for the cell-targeted delivery of therapeutic oligonucleotides. In addition, we review the original, proof-of-concept aptamer-siRNA delivery studies and discuss recent advances in aptamer-siRNA conjugate designs for applications ranging from cancer therapy to the development of targeted antivirals. Challenges and prospects of aptamer-targeted siRNA drugs for clinical development are further highlighted. PMID:28792479

Intelligent tracking techniques

NASA Astrophysics Data System (ADS)

Willett, T. J.; Abruzzo, J.; Zagardo, V.; Shipley, J.; Kossa, L.

1980-10-01

This is the fifth quarterly report under a contract to investigate the design, test, and implementation of a set of algorithms to perform intelligent tracking and intelligent homing on FLIR and TV imagery. The system concept was described. The problem of target aspect determination in support of aimpoint selection was analyzed. Sequences of 875 line FLIR data were extracted from the data base and an example of aspect determination for a maneuvering target in the presence of obscurations was presented. An example was also presented for close in homing (less than 500 meters) and the emergence of interior features, target movement, and scale changes. Hardware implementation in terms of VLSI/VHSIC chips was analyzed.

Inertial Fusion Power Plant Concept of Operations and Maintenance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anklam, T.; Knutson, B.; Dunne, A. M.

2015-01-15

Parsons and LLNL scientists and engineers performed design and engineering work for power plant pre-conceptual designs based on the anticipated laser fusion demonstrations at the National Ignition Facility (NIF). Work included identifying concepts of operations and maintenance (O&M) and associated requirements relevant to fusion power plant systems analysis. A laser fusion power plant would incorporate a large process and power conversion facility with a laser system and fusion engine serving as the heat source, based in part on some of the systems and technologies advanced at NIF. Process operations would be similar in scope to those used in chemical, oilmore » refinery, and nuclear waste processing facilities, while power conversion operations would be similar to those used in commercial thermal power plants. While some aspects of the tritium fuel cycle can be based on existing technologies, many aspects of a laser fusion power plant presents several important and unique O&M requirements that demand new solutions. For example, onsite recovery of tritium; unique remote material handling systems for use in areas with high radiation, radioactive materials, or high temperatures; a five-year fusion engine target chamber replacement cycle with other annual and multi-year cycles anticipated for major maintenance of other systems, structures, and components (SSC); and unique SSC for fusion target waste recycling streams. This paper describes fusion power plant O&M concepts and requirements, how O&M requirements could be met in design, and how basic organizational and planning issues can be addressed for a safe, reliable, economic, and feasible fusion power plant.« less

Inertial fusion power plant concept of operations and maintenance

NASA Astrophysics Data System (ADS)

Knutson, Brad; Dunne, Mike; Kasper, Jack; Sheehan, Timothy; Lang, Dwight; Anklam, Tom; Roberts, Valerie; Mau, Derek

2015-02-01

Parsons and LLNL scientists and engineers performed design and engineering work for power plant pre-conceptual designs based on the anticipated laser fusion demonstrations at the National Ignition Facility (NIF). Work included identifying concepts of operations and maintenance (O&M) and associated requirements relevant to fusion power plant systems analysis. A laser fusion power plant would incorporate a large process and power conversion facility with a laser system and fusion engine serving as the heat source, based in part on some of the systems and technologies advanced at NIF. Process operations would be similar in scope to those used in chemical, oil refinery, and nuclear waste processing facilities, while power conversion operations would be similar to those used in commercial thermal power plants. While some aspects of the tritium fuel cycle can be based on existing technologies, many aspects of a laser fusion power plant presents several important and unique O&M requirements that demand new solutions. For example, onsite recovery of tritium; unique remote material handling systems for use in areas with high radiation, radioactive materials, or high temperatures; a five-year fusion engine target chamber replacement cycle with other annual and multi-year cycles anticipated for major maintenance of other systems, structures, and components (SSC); and unique SSC for fusion target waste recycling streams. This paper describes fusion power plant O&M concepts and requirements, how O&M requirements could be met in design, and how basic organizational and planning issues can be addressed for a safe, reliable, economic, and feasible fusion power plant.

ESS Cryogenic System Process Design

NASA Astrophysics Data System (ADS)

Arnold, P.; Hees, W.; Jurns, J.; Su, X. T.; Wang, X. L.; Weisend, J. G., II

2015-12-01

The European Spallation Source (ESS) is a neutron-scattering facility funded and supported in collaboration with 17 European countries in Lund, Sweden. Cryogenic cooling at ESS is vital particularly for the linear accelerator, the hydrogen target moderators, a test stand for cryomodules, the neutron instruments and their sample environments. The paper will focus on specific process design criteria, design decisions and their motivations for the helium cryoplants and auxiliary equipment. Key issues for all plants and their process concepts are energy efficiency, reliability, smooth turn-down behaviour and flexibility. The accelerator cryoplant (ACCP) and the target moderator cryoplant (TMCP) in particular need to be prepared for a range of refrigeration capacities due to the intrinsic uncertainties regarding heat load definitions. Furthermore the paper addresses questions regarding process arrangement, 2 K cooling methodology, LN2 precooling, helium storage, helium purification and heat recovery.

Soundscapes/Artabilitation - Evolution of a Hybrid Human Performance Concept, Method & Apparatus Where Digital Interactive Media, The Arts, & Entertainment are Combined

NASA Astrophysics Data System (ADS)

Brooks, A. L.

'SoundScapes' is a body of empirical research that for almost two decades has focused upon investigating noninvasive gesture control of multi-sensory stimuli and potential uses in therapy and the arts. In this context noninvasive gesture refers to motion in invisible activity zones of a system input device utilizing technology outside of human vision. Especially targeted are disabled people of all ages, and special focus has been on the profoundly impaired who especially have limited opportunities for creative self-articulation and playful interaction. The concept has been explored in various situations including: - live stage performances; interactive room installations for museums, workshops, and festivals; and in health-care sessions at hospitals, institutes and special schools. Multifaceted aspects continuously cross-inform in a systemic manner, and each situation where the motion-sensitive environment is applied is considered as a hybrid system. Whilst simplistic in concept, i.e. learning by playful and creative doings, inherent are complexities of optimizing the interactive system to user-experience and evaluation of same. This chapter presents the system in context to its conceived-for-target community; it also presents the parallel practice-led investigations in performance art. Reciprocal design and reflective cross-analysis of the activities has resulted such that performance informs design and strategies of intervention and evaluation with impaired users, and vice versa.

The 4MOST instrument concept overview

NASA Astrophysics Data System (ADS)

Haynes, Roger; Barden, Samuel; de Jong, Roelof; Schnurr, Olivier; Bellido, Olga; Walcher, Jakob; Haynes, Dionne; Winkler, Roland; Bauer, Svend-Marian; Dionies, Frank; Saviauk, Allar; Chiappini, Cristina; Schwope, Axel; Brynnel, Joar; Steinmetz, Matthias; McMahon, Richard; Feltzing, Sofia; Francois, Patrick; Trager, Scott; Parry, Ian; Irwin, Mike; Walton, Nicholas; King, David; Sun, David; Gonzalez-Solares, Eduaro; Tosh, Ian; Dalton, Gavin; Middleton, Kevin; Bonifacio, Piercarlo; Jagourel, Pascal; Mignot, Shan; Cohen, Mathieu; Amans, Jean-Philippe; Royer, Frederic; Sartoretti, Paola; Pragt, Johan; Gerlofsma, Gerrit; Roelfsema, Ronald; Navarro, Ramon; Thimm, Guido; Seifert, Walter; Christlieb, Norbert; Mandel, Holger; Trifonov, Trifon; Xu, Wenli; Lang-Bardl, Florian; Muschielok, Bernard; Schlichter, Jörg; Hess, Hans-Joachim; Grupp, Frank; Boehringer, Hans; Boller, Thomas; Dwelly, Tom; Bender, Ralf; Rosati, Piero; Iwert, Olaf; Finger, Gert; Lizon L'Allemand, Jean-Louis; Saunders, Will; Sheinis, Andrew; Frost, Gabriella; Farrell, Tony; Waller, Lewis; Depagne, Eric; Laurent, Florence; Caillier, Patrick; Kosmalski, Johan; Richard, Johan; Bacon, Roland; Ansorge, Wolfgang

2014-07-01

The 4MOST[1] instrument is a concept for a wide-field, fibre-fed high multiplex spectroscopic instrument facility on the ESO VISTA telescope designed to perform a massive (initially >25x106 spectra in 5 years) combined all-sky public survey. The main science drivers are: Gaia follow up of chemo-dynamical structure of the Milky Way, stellar radial velocities, parameters and abundances, chemical tagging; eROSITA follow up of cosmology with x-ray clusters of galaxies, X-ray AGN/galaxy evolution to z~5, Galactic X-ray sources and resolving the Galactic edge; Euclid/LSST/SKA and other survey follow up of Dark Energy, Galaxy evolution and transients. The surveys will be undertaken simultaneously requiring: highly advanced targeting and scheduling software, also comprehensive data reduction and analysis tools to produce high-level data products. The instrument will allow simultaneous observations of ~1600 targets at R~5,000 from 390-900nm and ~800 targets at R<18,000 in three channels between ~395-675nm (channel bandwidth: 45nm blue, 57nm green and 69nm red) over a hexagonal field of view of ~ 4.1 degrees. The initial 5-year 4MOST survey is currently expect to start in 2020. We provide and overview of the 4MOST systems: optomechanical, control, data management and operations concepts; and initial performance estimates.

Towards local implementation of Dutch health policy guidelines: a concept-mapping approach.

PubMed

Kuunders, Theo J M; van Bon-Martens, Marja J H; van de Goor, Ien A M; Paulussen, Theo G W M; van Oers, Hans A M

2017-02-22

To develop a targeted implementation strategy for a municipal health policy guideline, implementation targets of two guideline users [Regional Health Services (RHSs)] and guideline developers of leading national health institutes were made explicit. Therefore, characteristics of successful implementation of the guideline were identified. Differences and similarities in perceptions of these characteristics between RHSs and developers were explored. Separate concept mapping procedures were executed in two RHSs, one with representatives from partner local health organizations and municipalities, the second with RHS members only. A third map was conducted with the developers of the guideline. All mapping procedures followed the same design of generating statements up to interpretation of results with participants. Concept mapping, as a practical implementation tool, will be discussed in the context of international research literature on guideline implementation in public health. Guideline developers consider implementation successful when substantive components (health issues) of the guidelines, content are visible in local policy practice. RHSs, local organizations and municipalities view the implementation process itself within and between organizations as more relevant, and state that usability of the guideline for municipal policy and commitment by officials and municipal managers are critical targets for successful implementation. Between the RHSs, differences in implementation targets were smaller than between RHSs and guideline developers. For successful implementation, RHSs tend to focus on process targets while developers focus more on the thematic contents of the guideline. Implications of these different orientations for implementation strategies are dealt with in the discussion. © The Author 2017. Published by Oxford University Press.

Preliminary analysis of the benefits derived to US Air Force spacecraft from on-orbit refueling

NASA Astrophysics Data System (ADS)

Smith, Scott

1993-02-01

This analysis was undertaken during FY-91 as a preliminary step to identify potential benefits from refueling Air Force satellites on orbit. Both economic and operational benefits were included. Operational benefits were related in economic terms to allow evaluation. All economic comparisons were made using FY-91 costs. An additional purpose of the effort was to identify the preferred mission parameters, for an on-orbit refueling system. A companion study was being concurrently conducted by SSD/XRP and NASA/JPL to develop a hardware concept for an on-orbit refueling system. The mass estimates for refueling missions obtained from the companion study were used in conducting the economic analyses of this benefits study. For this study, on-orbit refueling was based on the concept developed in the companion JPL study. The concept involves launching an S/C carrying fuel that would be transferred to another 'target' S/C which is already in orbit. The two S/C would then rendezvous, dock, and transfer fuel. Another fluid, such as a cryogenic, might be included if needed by the target S/C. The hardware concept for refueling was intended to minimize costs. The re-fueler S/C was designated to be expendable and would contain only the minimal capabilities. It would be launched into the orbit plane and altitude of the target S/C(s). The re-fueler S/C would rendezvous and dock with the target S/C and the fluid transfer would occur. When the refueling mission was completed, the re-fueler S/C would be ejected from the orbit. In order to optimize launch costs, some missions involved launching two re-fueler S/C on the LV. In this case the second re-fueler S/C would be placed in a storage orbit until needed.

Preliminary analysis of the benefits derived to US Air Force spacecraft from on-orbit refueling

NASA Technical Reports Server (NTRS)

Smith, Scott

1993-01-01

This analysis was undertaken during FY-91 as a preliminary step to identify potential benefits from refueling Air Force satellites on orbit. Both economic and operational benefits were included. Operational benefits were related in economic terms to allow evaluation. All economic comparisons were made using FY-91 costs. An additional purpose of the effort was to identify the preferred mission parameters, for an on-orbit refueling system. A companion study was being concurrently conducted by SSD/XRP and NASA/JPL to develop a hardware concept for an on-orbit refueling system. The mass estimates for refueling missions obtained from the companion study were used in conducting the economic analyses of this benefits study. For this study, on-orbit refueling was based on the concept developed in the companion JPL study. The concept involves launching an S/C carrying fuel that would be transferred to another 'target' S/C which is already in orbit. The two S/C would then rendezvous, dock, and transfer fuel. Another fluid, such as a cryogenic, might be included if needed by the target S/C. The hardware concept for refueling was intended to minimize costs. The re-fueler S/C was designated to be expendable and would contain only the minimal capabilities. It would be launched into the orbit plane and altitude of the target S/C(s). The re-fueler S/C would rendezvous and dock with the target S/C and the fluid transfer would occur. When the refueling mission was completed, the re-fueler S/C would be ejected from the orbit. In order to optimize launch costs, some missions involved launching two re-fueler S/C on the LV. In this case the second re-fueler S/C would be placed in a storage orbit until needed.

Extension of quality-by-design concept to the early development phase of pharmaceutical R&D processes.

PubMed

Csóka, Ildikó; Pallagi, Edina; Paál, Tamás L

2018-03-27

Here, we propose the extension of the quality-by-design (QbD) concept to also fit the early development phases of pharmaceuticals by adding elements that are currently widely applied, but not yet included in the QbD model in a structured way. These are the introduction of a 'zero' preformulation phase (i.e., selection of drug substance, possible dosage forms and administration routes based on the evaluated therapeutic need); building in stakeholders' (industry, patient, and regulatory) requirements into the quality target product profile (QTTP); and the use of modern quality management tools during the composition and process design phase [collecting critical quality attributes (CQAs) and selection of CPPs) for (still laboratory-scale) design space (DS) development. Moreover, during industrial scale-up, CQAs (as well as critical process parameters; CPPs) can be changed; however, we recommend that the existing QbD elements are reconsidered and updated after this phase. Copyright © 2018 Elsevier Ltd. All rights reserved.

Thermal-hydraulic simulation of mercury target concepts for a pulsed spallation neutron source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siman-Tov, M.; Wendel, M.; Haines, J.

1996-06-01

The Oak Ridge Spallation Neutron Source (ORSNS) is a high-power, accelerator-based pulsed spallation neutron source being designed by a multi-laboratory team led by Oak Ridge National Laboratory to achieve very high fluxes of neutrons for scientific experiments. The ORSNS is projected to have a 1 MW proton beam upgradable to 5 MW. About 60% of the beam power (1-5 MW, 17-83 kJ/pulse in 0.5 microsec at 60 cps) is deposited in the liquid metal (mercury) target having the dimensions of 65x30x10 cm (about 19.5 liter). Peak steady state power density is about 150 and 785 MW/m{sup 3} for 1 MWmore » and 5 MW beam respectively, whereas peak pulsed power density is as high as 5.2 and 26.1 GW/m{sup 3}, respectively. The peak pulse temperature rise rate is 14 million C/s (for 5 MW beam) whereas the total pulse temperature rise is only 7 C. In addition to thermal shock and materials compatibility, key feasibility issues for the target are related to its thermal-hydraulic performance. This includes proper flow distribution, flow reversals, possible {open_quotes}hot spots{close_quotes} and the challenge of mitigating the effects of thermal shock through possible injection of helium bubbles throughout the mercury volume or other concepts. The general computational fluid dynamics (CFD) code CFDS-FLOW3D was used to simulate the thermal and flow distribution in three preliminary concepts of the mercury target. Very initial CFD simulation of He bubbles injection demonstrates some potential for simulating behavior of He bubbles in flowing mercury. Much study and development will be required to be able to `predict`, even in a crude way, such a complex phenomena. Future direction in both design and R&D is outlined.« less

Design and simulation of a sensor for heliostat field closed loop control

NASA Astrophysics Data System (ADS)

Collins, Mike; Potter, Daniel; Burton, Alex

2017-06-01

Significant research has been completed in pursuit of capital cost reductions for heliostats [1],[2]. The camera array closed loop control concept has potential to radically alter the way heliostats are controlled and installed by replacing high quality open loop targeting systems with low quality targeting devices that rely on measurement of image position to remove tracking errors during operation. Although the system could be used for any heliostat size, the system significantly benefits small heliostats by reducing actuation costs, enabling large numbers of heliostats to be calibrated simultaneously, and enabling calibration of heliostats that produce low irradiance (similar or less than ambient light images) on Lambertian calibration targets, such as small heliostats that are far from the tower. A simulation method for the camera array has been designed and verified experimentally. The simulation tool demonstrates that closed loop calibration or control is possible using this device.

DARPin-targeting of Measles Virus: Unique Bispecificity, Effective Oncolysis, and Enhanced Safety

PubMed Central

Friedrich, Katrin; Hanauer, Jan RH; Prüfer, Steffen; Münch, Robert C; Völker, Iris; Filippis, Christodoulos; Jost, Christian; Hanschmann, Kay-Martin; Cattaneo, Roberto; Peng, Kah-Whye; Plückthun, Andreas; Buchholz, Christian J; Cichutek, Klaus; Mühlebach, Michael D

2013-01-01

Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Many naturally occurring viruses have a preferential, although nonexclusive, tropism for tumors and tumor cells. In addition, specific targeting of cancer cells can be achieved at the virus entry level. We optimized retargeting of cell entry by elongating the measles virus attachment protein with designed ankyrin repeat proteins (DARPins), while simultaneously ablating entry through the natural receptors. DARPin-targeted viruses were strongly attenuated in off-target tissue, thereby enhancing safety, but completely eliminated tumor xenografts. Taking advantage of the unique properties of DARPins of being fused without generating folding problems, we generated a virus simultaneous targeting two different tumor markers. The bispecific virus retained the original oncolytic efficacy, while providing proof of concept for a strategy to counteract issues of resistance development. Thus, DARPin-targeting opens new prospects for the development of personalized, targeted therapeutics. PMID:23380817

Rotatable Aperture Coronagraph for Exoplanetary Studies (RACES)

NASA Astrophysics Data System (ADS)

Chakrabarti, Supriya; Mendillo, Christopher; Mukherjee, Sunip; Martel, Jason; Cook, Timothy; Polidan, Ronald S.; Rafanelli, Gerard L.; Spencer, Susan B.; Wolfe, Douglas w.

2018-01-01

We present the design and expected performance of RACES, a suborbital mission concept to directly image exo-Jupiters with a rotatable non-circular aperture telescope. By using a high-aspect ratio elliptical or rectangular primary mirror (2.3m x 0.6m), this mission achieves the same angular resolution and inner working angle as a 2.3m dia telescope. Such an elliptical or rectangular system would fill the volume of a cylindrical launch vehicle more efficiently and by choosing the aspect ratio one can appropriately tailor its light gathering power. RACES can therefore serve as a pathfinder for future larger missions for exoplanetary explorations. For example, the system described here approaches the collecting area of the well studied EXO-C concept and exceeds its angular resolution. The mission concept, design studies, observation strategy and expected target yield for RACES will be presented, as well as simulations of the high contrast vector vortex coronagraph operating with an un-obscured elliptical aperture.

GNC architecture for autonomous robotic capture of a non-cooperative target: Preliminary concept design

NASA Astrophysics Data System (ADS)

Jankovic, Marko; Paul, Jan; Kirchner, Frank

2016-04-01

Recent studies of the space debris population in low Earth orbit (LEO) have concluded that certain regions have already reached a critical density of objects. This will eventually lead to a cascading process called the Kessler syndrome. The time may have come to seriously consider active debris removal (ADR) missions as the only viable way of preserving the space environment for future generations. Among all objects in the current environment, the SL-8 (Kosmos 3M second stages) rocket bodies (R/Bs) are some of the most suitable targets for future robotic ADR missions. However, to date, an autonomous relative navigation to and capture of an non-cooperative target has never been performed. Therefore, there is a need for more advanced, autonomous and modular systems that can cope with uncontrolled, tumbling objects. The guidance, navigation and control (GNC) system is one of the most critical ones. The main objective of this paper is to present a preliminary concept of a modular GNC architecture that should enable a safe and fuel-efficient capture of a known but uncooperative target, such as Kosmos 3M R/B. In particular, the concept was developed having in mind the most critical part of an ADR mission, i.e. close range proximity operations, and state of the art algorithms in the field of autonomous rendezvous and docking. In the end, a brief description of the hardware in the loop (HIL) testing facility is made, foreseen for the practical evaluation of the developed architecture.

Fluorogenic reaction-based prodrug conjugates as targeted cancer theranostics.

PubMed

Lee, Min Hee; Sharma, Amit; Chang, Min Jung; Lee, Jinju; Son, Subin; Sessler, Jonathan L; Kang, Chulhun; Kim, Jong Seung

2018-01-02

Theranostic systems are receiving ever-increasing attention due to their potential therapeutic utility, imaging enhancement capability, and promise for advancing the field of personalized medicine, particularly as it relates to the diagnosis, staging, and treatment of cancer. In this Tutorial Review, we provide an introduction to the concepts of theranostic drug delivery effected via use of conjugates that are able to target cancer cells selectively, provide cytotoxic chemotherapeutics, and produce readily monitored imaging signals in vitro and in vivo. The underlying design concepts, requiring the synthesis of conjugates composed of imaging reporters, masked chemotherapeutic drugs, cleavable linkers, and cancer targeting ligands, are discussed. Particular emphasis is placed on highlighting the potential benefits of fluorogenic reaction-based targeted systems that are activated for both imaging and therapy by cellular entities, e.g., thiols, reactive oxygen species and enzymes, which are present at relatively elevated levels in tumour environments, physiological characteristics of cancer, e.g., hypoxia and acidic pH. Also discussed are systems activated by an external stimulus, such as light. The work summarized in this Tutorial Review will help define the role fluorogenic reaction-based, cancer-targeting theranostics may have in advancing drug discovery efforts, as well as improving our understanding of cellular uptake and drug release mechanisms.

Vision-based control for flight relative to dynamic environments

NASA Astrophysics Data System (ADS)

Causey, Ryan Scott

The concept of autonomous systems has been considered an enabling technology for a diverse group of military and civilian applications. The current direction for autonomous systems is increased capabilities through more advanced systems that are useful for missions that require autonomous avoidance, navigation, tracking, and docking. To facilitate this level of mission capability, passive sensors, such as cameras, and complex software are added to the vehicle. By incorporating an on-board camera, visual information can be processed to interpret the surroundings. This information allows decision making with increased situational awareness without the cost of a sensor signature, which is critical in military applications. The concepts presented in this dissertation facilitate the issues inherent to vision-based state estimation of moving objects for a monocular camera configuration. The process consists of several stages involving image processing such as detection, estimation, and modeling. The detection algorithm segments the motion field through a least-squares approach and classifies motions not obeying the dominant trend as independently moving objects. An approach to state estimation of moving targets is derived using a homography approach. The algorithm requires knowledge of the camera motion, a reference motion, and additional feature point geometry for both the target and reference objects. The target state estimates are then observed over time to model the dynamics using a probabilistic technique. The effects of uncertainty on state estimation due to camera calibration are considered through a bounded deterministic approach. The system framework focuses on an aircraft platform of which the system dynamics are derived to relate vehicle states to image plane quantities. Control designs using standard guidance and navigation schemes are then applied to the tracking and homing problems using the derived state estimation. Four simulations are implemented in MATLAB that build on the image concepts present in this dissertation. The first two simulations deal with feature point computations and the effects of uncertainty. The third simulation demonstrates the open-loop estimation of a target ground vehicle in pursuit whereas the four implements a homing control design for the Autonomous Aerial Refueling (AAR) using target estimates as feedback.

Pre-Conceptual Design for Northstar ⁹⁹Mo Process Tritium Removal System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nobile, Arthur; Reichert, Heidi; Hollis, William Kirk

2016-01-12

In this report we describe a preliminary concept for a Tritium Removal System (TRS) to remove tritium that is generated in the ⁹⁹Mo production process. Preliminary calculations have been performed to evaluate an approximate size for the system. The concept described utilizes well-established detritiation technology based on catalytic oxidation of tritium and tritiated hydrocarbons to water in a high temperature (400 °C) reactor and capture of water in a molecular sieve bed. The TRS concept involves use of a single system that would cycle through each of the seven online target systems and remove tritium that has been accumulated aftermore » one week’s run time. The TRS would perform cleanup operations on each target system for a period of approximately 24 hours. This would occur while the system is still online and just prior to target replacement, so tritium levels would at their minimum values for target replacement. In the concept, during normal operation a small fraction (1%) of the helium recirculating in the system would be diverted through the TRS and returned to the flow loop. With this approach sufficient levels of detritiation can be accomplished in a 24 hour period. In the study it was found that because of the need to maintain low oxygen levels in the system (<100 ppm) this increases the size of the catalytic reactor. As a result of this finding, consideration should be given to other methods for removing tritium from the system. Other methods such as catalytic exchange of tritium with an unsaturated organic compound and subsequent trapping on activated carbon or molecular sieve could offer advantages of reducing reactor size and operation at lower reactor temperature. However the most significant advantage of such an approach would be the ability to operate in very low oxygen environments, which would eliminate any concerns for oxidation of the target.« less

Targeting Key Transporters in Tumor Glycolysis as a Novel Anticancer Strategy.

PubMed

Shi, Yunli; Liu, Shengnan; Ahmad, Shabir; Gao, Qingzhi

2018-05-22

Increased glycolysis has been one of the metabolic characteristics known as the Warburg effect. The functional and therapeutic importance of the Warburg effect in targeted therapy is scientifically recognized and the glucose metabolic pathway has become a desirable target of anticancer strategies. Glucose transporters (GLUTs) play an important role in cancer glycolysis to sustain cancer cell proliferation, metastasis and survival. Utilizing the knowledge of differential expression and biological functions of GLUTs offers us the possibility of designing and delivering chemotherapeutics toward targeted tumor tissues for improved cancer selectivity. Inhibition of glucose uptake or glycolysis may effectively kill hypoxic cancer cells. Facilitative drug uptake via active transportation provides the potential opportunity to circumvent the drug resistance in chemotherapy. GLUTs as the hallmarks and biotargets of cancer metabolism enable the design and development of novel targeted theranostic agents. In this updated review, we examine the current scenario of the GLUTs as strategic targets in cancer and the unique concepts for discovery and development of GLUTs-targeted anticancer agents. We highlight the recent progresses on structural biology and underlying mechanism studies of GLUTs, with a brief introduction to the computational approaches in GLUT-mediated drug transport and tumor targeting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The geometry of periodic knots, polycatenanes and weaving from a chemical perspective: a library for reticular chemistry.

PubMed

Liu, Yuzhong; O'Keeffe, Michael; Treacy, Michael M J; Yaghi, Omar M

2018-05-04

The geometry of simple knots and catenanes is described using the concept of linear line segments (sticks) joined at corners. This is extended to include woven linear threads as members of the extended family of knots. The concept of transitivity that can be used as a measure of regularity is explained. Then a review is given of the simplest, most 'regular' 2- and 3-periodic patterns of polycatenanes and weavings. Occurrences in crystal structures are noted but most structures are believed to be new and ripe targets for designed synthesis.

Engineering liposomal nanoparticles for targeted gene therapy.

PubMed

Zylberberg, C; Gaskill, K; Pasley, S; Matosevic, S

2017-08-01

Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.

Environmental design implications for two deep space SmallSats

NASA Astrophysics Data System (ADS)

Kahn, Peter; Imken, Travis; Elliott, John; Sherwood, Brent; Frick, Andreas; Sheldon, Douglas; Lunine, Jonathan

2017-10-01

The extreme environmental challenges of deep space exploration force unique solutions to small satellite design in order to enable their use as scientifically viable spacecraft. The challenges of implementing small satellites within limited resources can be daunting when faced with radiation effects on delicate electronics that require shielding or unique adaptations for protection, or mass, power and volume limitations due to constraints placed by the carrier spacecraft, or even Planetary Protection compliant design techniques that drive assembly and testing. This paper will explore two concept studies where the environmental constraints and/or planetary protection mitigations drove the design of the Flight System. The paper will describe the key technical drivers on the Sylph mission concept to explore a plume at Europa as a secondary free-flyer as a part of the planned Europa Mission. Sylph is a radiation-hardened smallsat concept that would utilize terrain relative navigation to fly at low altitudes through a plume, if found, and relay the mass spectra data back through the flyby spacecraft during its 24-h mission. The second topic to be discussed will be the mission design constraints of the Near Earth Asteroid (NEA) Scout concept. NEAScout is a 6U cubesat that would utilize an 86 sq. m solar sail as propulsion to execute a flyby with a near-Earth asteroid and help retire Strategic Knowledge Gaps for future human exploration. NEAScout would cruise for 24 months to reach and characterize one Near-Earth asteroid that is representative of Human Exploration targets and telemeter that data directly back to Earth at the end of its roughly 2.5 year mission.

Concept of Operations Visualization in Support of Ares I Production

NASA Technical Reports Server (NTRS)

Chilton, James H.; Smith, Daid Alan

2008-01-01

Boeing was selected in 2007 to manufacture Ares I Upper Stage and Instrument Unit according to NASA's design which would require the use of the latest manufacturing and integration processes to meet NASA budget and schedule targets. Past production experience has established that the majority of the life cycle cost is established during the initial design process. Concept of Operations (CONOPs) visualizations/simulations help to reduce life cycle cost during the early design stage. Production and operation visualizations can reduce tooling, factory capacity, safety, and build process risks while spreading program support across government, academic, media and public constituencies. The NASA/Boeing production visualization (DELMIA; Digital Enterprise Lean Manufacturing Interactive Application) promotes timely, concurrent and collaborative producibility analysis (Boeing)while supporting Upper Stage Design Cycles (NASA). The DELMIA CONOPs visualization reduced overall Upper Stage production flow time at the manufacturing facility by over 100 man-days to 312.5 man-days and helped to identify technical access issues. The NASA/Boeing Interactive Concept of Operations (ICON) provides interactive access to Ares using real mission parameters, allows users to configure the mission which encourages ownership and identifies areas for improvement, allows mission operations or spacecraft detail to be added as needed, and provides an effective, low coast advocacy, outreach and education tool.

Micro unattended mobility system (MUMS)

NASA Astrophysics Data System (ADS)

Rudakevych, Pavlo; Greiner, Helen; Pletta, Bryan

1999-07-01

This report covers work under phase one of the Micro Unattended Mobility System project investigating the addition of a mobile sensor components to existing and future ground penetrator delivered unattended sensor systems. A typical unattended sensor strategy consists of air-dropping sensor packages into a target terrain for remote observation and intelligence gathering. Existing and planned unattended systems have no control over their location after the drop is complete. We propose to augment the capability of these sensing packages by giving them a degree of local mobility. From an assumed operational scenario, vehicle design specifications are identified that would be required for mission success. Three basic mobility concepts are presented and evaluated for their strengths and weaknesses in the proposed mission. The mobility concepts are grouped into wheeled, jumping, and crawling systems. Of the three mobility concepts discussed, the system that shows the most promise is presented in a more detailed design. This design consists of two side by side wheels which drag a reaction tail behind them. The control electronics, batteries, and drive motors are housed in a central body connected to the tail and two sensor payloads can be placed in the wheel hubs. This design is proposed for further development and testing in the second phase of this project.

Cost Modeling and Design of Field-Reversed Configuration Fusion Power Plants

NASA Astrophysics Data System (ADS)

Kirtley, David; Slough, John; Helion Team

2017-10-01

The Inductively Driven Liner (IDL) fusion concept uses the magnetically driven implosion of thin (0.5-1 mm) Aluminum hoops to magnetically compress a merged Field-Reversed Configuration (FRC) plasma to fusion conditions. Both the driver and the target have been studied experimentally and theoretically by researchers at Helion Energy, MSNW, and the University of Washington, demonstrating compression fields greater than 100 T and suitable fusion targets. In the presented study, a notional power plant facility using this approach will be described. In addition, a full cost study based on the LLNL Z-IFE and HYLIFE-II studies, the ARIES Tokamak concept, and RAND power plant studies will be described. Finally, the expected capital costs, development requirements, and LCOE for 50 and 500 MW power plants will be given. This analysis includes core FRC plant scaling, metallic liner recycling, radiation shielding, operations, and facilities capital requirements.

Optimization of Actuating Origami Networks

NASA Astrophysics Data System (ADS)

Buskohl, Philip; Fuchi, Kazuko; Bazzan, Giorgio; Joo, James; Gregory, Reich; Vaia, Richard

2015-03-01

Origami structures morph between 2D and 3D conformations along predetermined fold lines that efficiently program the form, function and mobility of the structure. By leveraging design concepts from action origami, a subset of origami art focused on kinematic mechanisms, reversible folding patterns for applications such as solar array packaging, tunable antennae, and deployable sensing platforms may be designed. However, the enormity of the design space and the need to identify the requisite actuation forces within the structure places a severe limitation on design strategies based on intuition and geometry alone. The present work proposes a topology optimization method, using truss and frame element analysis, to distribute foldline mechanical properties within a reference crease pattern. Known actuating patterns are placed within a reference grid and the optimizer adjusts the fold stiffness of the network to optimally connect them. Design objectives may include a target motion, stress level, or mechanical energy distribution. Results include the validation of known action origami structures and their optimal connectivity within a larger network. This design suite offers an important step toward systematic incorporation of origami design concepts into new, novel and reconfigurable engineering devices. This research is supported under the Air Force Office of Scientific Research (AFOSR) funding, LRIR 13RQ02COR.

Optimising adherence to childhood pneumonia treatment: the design and development of patient instructions and a job aid for amoxicillin dispersible tablets.

PubMed

Ebels, Kelly; Faulx, Dunia; Gerth-Guyette, Emily; Murunga, Peninah; Mahapatro, Samarendra; Das, Manoja Kumar; Ginsburg, Amy Sarah

2016-01-01

Pneumonia is the leading cause of death from infection in children worldwide. Despite global treatment recommendations that call for children with pneumonia to receive amoxicillin dispersible tablets, only one-third of children with pneumonia receive any antibiotics and many do not complete the full course of treatment. Poor adherence to antibiotics may be driven in part by a lack of user-friendly treatment instructions. In order to optimise childhood pneumonia treatment adherence at the community level, we developed a user-friendly product presentation for caregivers and a job aid for healthcare providers (HCPs). This paper aims to document the development process and offers a model for future health communication tools. We employed an iterative design process that included document review, key stakeholder interviews, engagement with a graphic designer and pre-testing design concepts among target users in India and Kenya. The consolidated criteria for reporting qualitative research were used in the description of results. Though resources for pneumonia treatment are available in some countries, their content is incomplete and inconsistent with global recommendations. Document review and stakeholder interviews provided the information necessary to convey to caregivers and recommendations for how to present this information. Target users in India and Kenya confirmed the need to support better treatment adherence, recommended specific modifications to design concepts and suggested the development of a companion job aid. There was a consensus among caregivers and HCPs that these tools would be helpful and improve adherence behaviours. The development of user-friendly instructions for medications for use in low-resource settings is a critically important but time-intensive and resource-intensive process that should involve engagement with target audiences. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Generation of Parametric Equivalent-Area Targets for Design of Low-Boom Supersonic Concepts

NASA Technical Reports Server (NTRS)

Li, Wu; Shields, Elwood

2011-01-01

A tool with an Excel visual interface is developed to generate equivalent-area (A(sub e)) targets that satisfy the volume constraints for a low-boom supersonic configuration. The new parametric Ae target explorer allows users to interactively study the tradeoffs between the aircraft volume constraints and the low-boom characteristics (e.g., loudness) of the ground signature. Moreover, numerical optimization can be used to generate the optimal A(sub e) target for given A(sub e) volume constraints. A case study is used to demonstrate how a generated low-boom Ae target can be matched by a supersonic configuration that includes a fuselage, wing, nacelle, pylon, aft pod, horizontal tail, and vertical tail. The low-boom configuration is verified by sonic-boom analysis with an off-body pressure distribution at three body lengths below the configuration

Mobile Aerial Tracking and Imaging System (MATRIS) for Aeronautical Research

NASA Technical Reports Server (NTRS)

Banks, Daniel W.; Blanchard, R. C.; Miller, G. M.

2004-01-01

A mobile, rapidly deployable ground-based system to track and image targets of aeronautical interest has been developed. Targets include reentering reusable launch vehicles (RLVs) as well as atmospheric and transatmospheric vehicles. The optics were designed to image targets in the visible and infrared wavelengths. To minimize acquisition cost and development time, the system uses commercially available hardware and software where possible. The conception and initial funding of this system originated with a study of ground-based imaging of global aerothermal characteristics of RLV configurations. During that study NASA teamed with the Missile Defense Agency/Innovative Science and Technology Experimentation Facility (MDA/ISTEF) to test techniques and analysis on two Space Shuttle flights.

Decentralized cooperative TOA/AOA target tracking for hierarchical wireless sensor networks.

PubMed

Chen, Ying-Chih; Wen, Chih-Yu

2012-11-08

This paper proposes a distributed method for cooperative target tracking in hierarchical wireless sensor networks. The concept of leader-based information processing is conducted to achieve object positioning, considering a cluster-based network topology. Random timers and local information are applied to adaptively select a sub-cluster for the localization task. The proposed energy-efficient tracking algorithm allows each sub-cluster member to locally estimate the target position with a Bayesian filtering framework and a neural networking model, and further performs estimation fusion in the leader node with the covariance intersection algorithm. This paper evaluates the merits and trade-offs of the protocol design towards developing more efficient and practical algorithms for object position estimation.

Generative Recurrent Networks for De Novo Drug Design.

PubMed

Gupta, Anvita; Müller, Alex T; Huisman, Berend J H; Fuchs, Jens A; Schneider, Petra; Schneider, Gisbert

2018-01-01

Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine-tuned the RNN's predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN-LSTM system for high-impact use cases, such as low-data drug discovery, fragment based molecular design, and hit-to-lead optimization for diverse drug targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Connecting Classroom Practice to Concepts of Culturally Responsive Teaching: Video Analysis in an Online Teacher Education Course

ERIC Educational Resources Information Center

Lopez, Leslie Ann

2013-01-01

Video has been shown to be an effective tool for synthesizing theory and connecting theory to practice in meaningful ways. This design-based research study examined how localized video of a practicing teacher impacted pre-service teachers' ability to learn culturally responsive teaching (CRT) methods and targeted strategies in an online…

Conceptual Design of Low-Boom Aircraft with Flight Trim Requirement

NASA Technical Reports Server (NTRS)

Ordaz, Irian; Geiselhart, Karl A.; Fenbert, James W.

2014-01-01

A new low-boom target generation approach is presented which allows the introduction of a trim requirement during the early conceptual design of supersonic aircraft. The formulation provides an approximation of the center of pressure for a presumed aircraft configuration with a reversed equivalent area matching a low-boom equivalent area target. The center of pressure is approximated from a surrogate lift distribution that is based on the lift component of the classical equivalent area. The assumptions of the formulation are verified to be sufficiently accurate for a supersonic aircraft of high fineness ratio through three case studies. The first two quantify and verify the accuracy and the sensitivity of the surrogate center of pressure corresponding to shape deformation of lifting components. The third verification case shows the capability of the approach to achieve a trim state while maintaining the low-boom characteristics of a previously untrimmed configuration. Finally, the new low-boom target generation approach is demonstrated through the early conceptual design of a demonstrator concept that is low-boom feasible, trimmed, and stable in cruise.

The light ion pulsed power induction accelerator for ETF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazarakis, M.G.; Olson, R.E.; Olson, C.L.

1994-12-31

Our Engineering Test Facility (ETF) driver concept is based on HERMES III and RHEPP technologies. Actually, it is a scaled-down version of the LMF design incorporating repetition rate capabilities of up to 10 Hz CW. The preconceptual design presented here provides 200-TW peak power to the ETF target during 10 ns, equal to 2-MJ total ion beam energy. Linear inductive voltage addition driving a self-magnetically insulated transmission line (MITL) is utilized to generate the 36-MV peak voltage needed for lithium ion beams. The {approximately} 3-MA ion current is achieved by utilizing many accelerating modules in parallel. Since the current permore » module is relatively modest ({approximately}300 kA), two-stage or one-stage extraction diodes can be utilized for the generation of singly charged lithium ions. The accelerating modules are arranged symmetrically around the fusion chamber in order to provide uniform irradiation onto the ETF target. In addition, the modules are fired in a programmed sequence in order to generate the optimum power pulse shape onto the target. This design utilizes RHEPP accelerator modules as the principal power source.« less

Design, Synthesis, and Pharmacokinetics of a Bone-Targeting Dual-Action Prodrug for the Treatment of Osteoporosis.

PubMed

Xie, Haibo; Chen, Gang; Young, Robert N

2017-08-24

A dual-action bone-targeting prodrug has been designed, synthesized, and evaluated for in vitro and in vivo metabolic stability, in vivo tissue distribution, and rates of release of the active constituents after binding to bones through the use of differentially double-labeled derivatives. The conjugate (general structure 7) embodies the merger of a very potent and proven anabolic selective agonist of the prostaglandin EP4 receptor, compound 5, and alendronic acid, a potent inhibitor of bone resorption, optimally linked through a differentially hydrolyzable linker unit, N-4-carboxymethylphenyl-methyloxycarbonyl-leucinyl-argininyl-para-aminophenylmethylalcohol (Leu-Arg-PABA). Optimized conjugate 16 was designed so that esterase activity will liberate 5 and cathepsin K cleavage of the Leu-Arg-PABA element will liberate alendronic acid. Studies with doubly radiolabeled 16 provide a proof-of-concept for the use of a cathepsin K cleavable peptide-linked conjugate for targeting of bisphosphonate prodrugs to bone and slow release liberation of the active constituents in vivo. Such conjugates are potential therapies for the treatment of bone disorders such as osteoporosis.

Advanced Communications Architecture Demonstration Made Significant Progress

NASA Technical Reports Server (NTRS)

Carek, David Andrew

2004-01-01

Simulation for a ground station located at 44.5 deg latitude. The Advanced Communications Architecture Demonstration (ACAD) is a concept architecture to provide high-rate Ka-band (27-GHz) direct-to-ground delivery of payload data from the International Space Station. This new concept in delivering data from the space station targets scientific experiments that buffer data onboard. The concept design provides a method to augment the current downlink capability through the Tracking Data Relay Satellite System (TDRSS) Ku-band (15-GHz) communications system. The ACAD concept pushes the limits of technology in high-rate data communications for space-qualified systems. Research activities are ongoing in examining the various aspects of high-rate communications systems including: (1) link budget parametric analyses, (2) antenna configuration trade studies, (3) orbital simulations (see the preceding figure), (4) optimization of ground station contact time (see the following graph), (5) processor and storage architecture definition, and (6) protocol evaluations and dependencies.

Review of Propulsion Technologies for N+3 Subsonic Vehicle Concepts

NASA Technical Reports Server (NTRS)

Ashcraft, Scott W.; Padron, Andres S.; Pascioni, Kyle A.; Stout, Gary W., Jr.; Huff, Dennis L.

2011-01-01

NASA has set aggressive fuel burn, noise, and emission reduction goals for a new generation (N+3) of aircraft targeting concepts that could be viable in the 2035 timeframe. Several N+3 concepts have been formulated, where the term "N+3" indicate aircraft three generations later than current state-of-the-art aircraft, "N". Dramatic improvements need to be made in the airframe, propulsion systems, mission design, and the air transportation system in order to meet these N+3 goals. The propulsion system is a key element to achieving these goals due to its major role with reducing emissions, fuel burn, and noise. This report provides an in-depth description and assessment of propulsion systems and technologies considered in the N+3 subsonic vehicle concepts. Recommendations for technologies that merit further research and development are presented based upon their impact on the N+3 goals and likelihood of being operational by 2035.

Development of Advanced High Lift Leading Edge Technology for Laminar Flow Wings

NASA Technical Reports Server (NTRS)

Bright, Michelle M.; Korntheuer, Andrea; Komadina, Steve; Lin, John C.

2013-01-01

This paper describes the Advanced High Lift Leading Edge (AHLLE) task performed by Northrop Grumman Systems Corporation, Aerospace Systems (NGAS) for the NASA Subsonic Fixed Wing project in an effort to develop enabling high-lift technology for laminar flow wings. Based on a known laminar cruise airfoil that incorporated an NGAS-developed integrated slot design, this effort involved using Computational Fluid Dynamics (CFD) analysis and quality function deployment (QFD) analysis on several leading edge concepts, and subsequently down-selected to two blown leading-edge concepts for testing. A 7-foot-span AHLLE airfoil model was designed and fabricated at NGAS and then tested at the NGAS 7 x 10 Low Speed Wind Tunnel in Hawthorne, CA. The model configurations tested included: baseline, deflected trailing edge, blown deflected trailing edge, blown leading edge, morphed leading edge, and blown/morphed leading edge. A successful demonstration of high lift leading edge technology was achieved, and the target goals for improved lift were exceeded by 30% with a maximum section lift coefficient (Cl) of 5.2. Maximum incremental section lift coefficients ( Cl) of 3.5 and 3.1 were achieved for a blown drooped (morphed) leading edge concept and a non-drooped leading edge blowing concept, respectively. The most effective AHLLE design yielded an estimated 94% lift improvement over the conventional high lift Krueger flap configurations while providing laminar flow capability on the cruise configuration.

Smart optical writing head design for laser-based manufacturing

NASA Astrophysics Data System (ADS)

Amin, M. Junaid; Riza, Nabeel A.

2014-03-01

Proposed is a smart optical writing head design suitable for high precision industrial laser based machining and manufacturing applications. The design uses an Electronically Controlled Variable Focus Lens (ECVFL) which enables the highest achievable spatial resolution of writing head spot sizes for axial target distances reaching 8 meters. A proof-of-concept experiment is conducted using a visible wavelength laser with a collimated beam that is coupled to beam conditioning optics which includes an electromagnetically actuated deformable membrane liquid ECVFL cascaded with a bias convex lens of fixed focal length. Electronic tuning and control of the ECVFL keeps the laser writing head far-field spot beam radii under 1 mm that is demonstrated over a target range of 20 cm to 800 cm. Applications for the proposed writing head design, which can accommodate both continuous wave and pulsed wave sources, include laser machining, high precision industrial molding of components, as well as materials processing requiring material sensitive optical power density control.

TU-A-201-01: Introduction to In-Room Imaging System Characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, J.

2016-06-15

Recent years have seen a widespread proliferation of available in-room image guidance systems for radiation therapy target localization with many centers having multiple in-room options. In this session, available imaging systems for in-room IGRT will be reviewed highlighting the main differences in workflow efficiency, targeting accuracy and image quality as it relates to target visualization. Decision-making strategies for integrating these tools into clinical image guidance protocols that are tailored to specific disease sites like H&N, lung, pelvis, and spine SBRT will be discussed. Learning Objectives: Major system characteristics of a wide range of available in-room imaging systems for IGRT. Advantagesmore » / disadvantages of different systems for site-specific IGRT considerations. Concepts of targeting accuracy and time efficiency in designing clinical imaging protocols.« less

TU-A-201-02: Treatment Site-Specific Considerations for Clinical IGRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wijesooriya, K.

2016-06-15

Recent years have seen a widespread proliferation of available in-room image guidance systems for radiation therapy target localization with many centers having multiple in-room options. In this session, available imaging systems for in-room IGRT will be reviewed highlighting the main differences in workflow efficiency, targeting accuracy and image quality as it relates to target visualization. Decision-making strategies for integrating these tools into clinical image guidance protocols that are tailored to specific disease sites like H&N, lung, pelvis, and spine SBRT will be discussed. Learning Objectives: Major system characteristics of a wide range of available in-room imaging systems for IGRT. Advantagesmore » / disadvantages of different systems for site-specific IGRT considerations. Concepts of targeting accuracy and time efficiency in designing clinical imaging protocols.« less

TU-A-201-00: Image Guidance Technologies and Management Strategies

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2016-06-15

Recent years have seen a widespread proliferation of available in-room image guidance systems for radiation therapy target localization with many centers having multiple in-room options. In this session, available imaging systems for in-room IGRT will be reviewed highlighting the main differences in workflow efficiency, targeting accuracy and image quality as it relates to target visualization. Decision-making strategies for integrating these tools into clinical image guidance protocols that are tailored to specific disease sites like H&N, lung, pelvis, and spine SBRT will be discussed. Learning Objectives: Major system characteristics of a wide range of available in-room imaging systems for IGRT. Advantagesmore » / disadvantages of different systems for site-specific IGRT considerations. Concepts of targeting accuracy and time efficiency in designing clinical imaging protocols.« less

Design and verification of a cloud field optical simulator

NASA Technical Reports Server (NTRS)

Davis, J. M.; Cox, S. K.; Mckee, T. B.

1982-01-01

A concept and an apparatus designed to investigate the reflected and transmitted distributions of light from optically thick clouds is presented. The Cloud Field Optical Simulator (CFOS) is a laboratory device which utilizes an array of incandescent lamps as a source, simulated clouds made from cotton or styrofoam as targets, and an array of silicon photodiodes as detectors. The device allows virtually any source-target-detector geometry to be examined. Similitude between real clouds and their CFOS cotton or styrofoam counterparts is established by relying on a linear relationship between optical depth and the ratio of reflected to transmitted light for a semi-infinite layer. Comparisons of principal plane radiances observed by the CFOS with Monte Carlo computations for a water cloud at 0.7 microns show excellent agreement.

Designed multiple ligands in metabolic disease research: from concept to platform.

PubMed

Gattrell, W; Johnstone, C; Patel, S; Smith, C Sambrook; Scheel, A; Schindler, M

2013-08-01

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and drug monotherapy typically results in unsatisfactory treatment outcomes for patients. Even when used in combination, existing therapies lack efficacy in the long term. Designed multiple ligands (DMLs) are compounds developed to modulate multiple targets relevant to a disease. DMLs offer the potential to yield greater efficacy over monotherapies, either by modulating different biological pathways, or by boosting a single one. However, examples of DMLs progressing into clinical trials, or onto the market are rare; DML drug discovery is challenging, and perceived by some to be almost impossible. Nevertheless, with the judicious selection of biological targets, both from a biological and chemical perspective, it is possible to develop drug-like DMLs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pressure-actuated cellular structures.

PubMed

Pagitz, M; Lamacchia, E; Hol, J M A M

2012-03-01

Shape changing structures will play an important role in future engineering designs since rigid structures are usually only optimal for a small range of service conditions. Hence, a concept for reliable and energy-efficient morphing structures that possess a large strength to self-weight ratio would be widely applicable. We propose a novel concept for morphing structures that is inspired by the nastic movement of plants. The idea is to connect prismatic cells with tailored pentagonal and/or hexagonal cross sections such that the resulting cellular structure morphs into given target shapes for certain cell pressures. An efficient algorithm for computing equilibrium shapes as well as cross-sectional geometries is presented. The potential of this novel concept is demonstrated by several examples that range from a flagellum like propulsion device to a morphing aircraft wing.

Integrating Decision Making and Mental Health Interventions Research: Research Directions

PubMed Central

Wills, Celia E.; Holmes-Rovner, Margaret

2006-01-01

The importance of incorporating patient and provider decision-making processes is in the forefront of the National Institute of Mental Health (NIMH) agenda for improving mental health interventions and services. Key concepts in patient decision making are highlighted within a simplified model of patient decision making that links patient-level/“micro” variables to services-level/“macro” variables via the decision-making process that is a target for interventions. The prospective agenda for incorporating decision-making concepts in mental health research includes (a) improved measures for characterizing decision-making processes that are matched to study populations, complexity, and types of decision making; (b) testing decision aids in effectiveness research for diverse populations and clinical settings; and (c) improving the understanding and incorporation of preference concepts in enhanced intervention designs. PMID:16724158

Comparison of different target material options for the European Spallation Source based on certain aspects related to the final disposal

NASA Astrophysics Data System (ADS)

Kókai, Zsófia; Török, Szabina; Zagyvai, Péter; Kiselev, Daniela; Moormann, Rainer; Börcsök, Endre; Zanini, Luca; Takibayev, Alan; Muhrer, Günter; Bevilacqua, Riccardo; Janik, József

2018-02-01

Different target options have been examined for the European Spallation Source, which is under construction in Lund, Sweden. During the design update phase, parameters and characteristics for the target design have been optimized not only for neutronics but also with respect to the waste characteristics related to the final disposal of the target. A rotating, solid tungsten target was eventually selected as baseline concept; the other options considered included mercury and lead-bismuth (LBE) targets suitable for a pulsed source. Since the licensee is obliged to present a decommissioning plan even before the construction phase starts, the radioactive waste category of the target after full operation time is of crucial importance. The results obtained from a small survey among project partners of 7th Framework Program granted by EU 202247 contract have been used. Waste characteristics of different potential spallation target materials were compared. Based on waste index, the tungsten target is the best alternative and the second one is the mercury target. However, all alternatives have HLW category after a 10 year cooling. Based on heat generation alone all of the options would be below the HLW limit after this cooling period. The LBE is the least advantageous alternative based on waste index and heat generation comparison. These results can be useful in compiling the licensing documents of the ESS facility as the target alternatives can be compared from various aspects related to their disposal.

LDRD Final Report: Advanced Hohlraum Concepts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, Ogden S.

Indirect drive inertial confinement fusion (ICF) experiments to date have mostly used cylindrical, laser-heated, gas-filled hohlraums to produce the radiation drive needed to symmetrically implode DT-filled fusion capsules. These hohlraums have generally been unable to produce a symmetric radiation drive through the end of the desired drive pulse, and are plagued with complications due to laser-plasma interactions (LPI) that have made it difficult to predict their performance. In this project we developed several alternate hohlraum concepts. These new hohlraums utilize different hohlraum geometries, radiation shields, and foam materials in an attempt to improve performance relative to cylindrical hohlraums. Each alternatemore » design was optimized using radiation hydrodynamic (RH) design codes to implode a reference DT capsule with a high-density carbon (HDC) ablator. The laser power and energy required to produce the desired time-dependent radiation drive, and the resulting time-dependent radiation symmetry for each new concept were compared to the results for a reference cylindrical hohlraum. Since several of the new designs needed extra laser entrance holes (LEHs), techniques to keep small LEHs open longer, including high-Z foam liners and low-Z wires at the LEH axis, were investigated numerically. Supporting experiments and target fabrication efforts were also done as part of this project. On the Janus laser facility plastic tubes open at one end (halfraums) and filled with SiO 2 or Ta 2O 5 foam were heated with a single 2w laser. Laser propagation and backscatter were measured. Generally the measured propagation was slower than calculated, and the measured laser backscatter was less than calculated. A comparable, scaled up experiment was designed for the NIF facility and four targets were built. Since low density gold foam was identified as a desirable material for lining the LEH and the hohlraum wall, a technique was developed to produce 550 mg/cc gold foam, and a sample of this material was successfully manufactured.« less

Deep Space Habitat Concept of Operations for Extended Duration Transit Missions

NASA Technical Reports Server (NTRS)

Hoffman, Stephen J.; Toups, Larry

2012-01-01

NASA's Capability-Driven Framework (CDF) describes an approach for progressively extending human exploration missions farther into the Solar System for longer periods of time as allowed by developments in technology and spacecraft systems. Within this framework design reference missions (DRMs) targeted for several specific destinations are being used to assess different combinations of vehicles, operations, and advanced technologies to help understand which combination will best support expanded human exploration both efficiently and sustainably. Several of the identified destinations have been found to require missions with a round trip duration exceeding one year. These mission durations exceed the capabilities of current human-rated spacecraft if resupply from Earth is not possible. This makes the design of an efficient and reliable Deep Space Habitat (DSH) critical for reaching these destinations. The paper will describe the current understanding of DSH capabilities and functions that must be exhibited by any future habitat design for these missions. This description of the DSH is presented in the form of a concept of operation, which focuses on the functions that any DSH must provide, as opposed to a specific DSH design concept. Development of a concept of operations, based on DRM features, provides a common basis for assessing the viability of design concepts incorporating differing configurations and technologies. A study team with representation from several NASA Centers and relevant engineering and scientific disciplines collaborated to develop this DSH concept of operations for the transit phases of these missions. The transit phase of a mission is defined as the time after leaving Earth but before arrival at the destination and the time after leaving the destination but before arriving back at Earth. These transit phases were found to have many common features across all of the destinations being assessed for the CDF and thus arguing for a common concept of operations for all of the associated DRMs. The paper first describes the CDF and potential destinations being considered within this framework. DRMs representative of those currently being assessed will then be discussed to illustrate the range of capabilities that the DSH must support. The 18 functions identified by the multi-discipline analysis team are then described at a summary level. Several specific examples of the potential use for this concept of operations are described.

Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes

PubMed Central

Justice, Jamie; Miller, Jordan D.; Newman, John C.; Hashmi, Shahrukh K.; Halter, Jeffrey; Austad, Steve N.; Barzilai, Nir

2016-01-01

Therapies targeted at fundamental processes of aging may hold great promise for enhancing the health of a wide population by delaying or preventing a range of age-related diseases and conditions—a concept dubbed the “geroscience hypothesis.” Early, proof-of-concept clinical trials will be a key step in the translation of therapies emerging from model organism and preclinical studies into clinical practice. This article summarizes the outcomes of an international meeting partly funded through the NIH R24 Geroscience Network, whose purpose was to generate concepts and frameworks for early, proof-of-concept clinical trials for therapeutic interventions that target fundamental processes of aging. The goals of proof-of-concept trials include generating preliminary signals of efficacy in an aging-related disease or outcome that will reduce the risk of conducting larger trials, contributing data and biological samples to support larger-scale research by strategic networks, and furthering a dialogue with regulatory agencies on appropriate registration indications. We describe three frameworks for proof-of-concept trials that target age-related chronic diseases, geriatric syndromes, or resilience to stressors. We propose strategic infrastructure and shared resources that could accelerate development of therapies that target fundamental aging processes. PMID:27535966

Designing artificial enzymes from scratch: Experimental study and mesoscale simulation

NASA Astrophysics Data System (ADS)

Komarov, Pavel V.; Zaborina, Olga E.; Klimova, Tamara P.; Lozinsky, Vladimir I.; Khalatur, Pavel G.; Khokhlov, Alexey R.

2016-09-01

We present a new concept for designing biomimetic analogs of enzymatic proteins; these analogs are based on the synthetic protein-like copolymers. α-Chymotrypsin is used as a prototype of the artificial catalyst. Our experimental study shows that in the course of free radical copolymerization of hydrophobic and hydrophilic monomers the target globular nanostructures of a "core-shell" morphology appear in a selective solvent. Using a mesoscale computer simulation, we show that the protein-like globules can have a large number of catalytic centers located at the hydrophobic core/hydrophilic shell interface.

Optical and Electric Multifunctional CMOS Image Sensors for On-Chip Biosensing Applications.

PubMed

Tokuda, Takashi; Noda, Toshihiko; Sasagawa, Kiyotaka; Ohta, Jun

2010-12-29

In this review, the concept, design, performance, and a functional demonstration of multifunctional complementary metal-oxide-semiconductor (CMOS) image sensors dedicated to on-chip biosensing applications are described. We developed a sensor architecture that allows flexible configuration of a sensing pixel array consisting of optical and electric sensing pixels, and designed multifunctional CMOS image sensors that can sense light intensity and electric potential or apply a voltage to an on-chip measurement target. We describe the sensors' architecture on the basis of the type of electric measurement or imaging functionalities.

Innovative divertor concept development on DIII-D and EAST

DOE PAGES

Guo, H. Y.; Allen, S.; Canik, J.; ...

2016-06-02

A critical issue facing the design and operation of next-step high-power steady-state fusion devices is the control of heat fluxes and erosion at the plasma-facing components, in particular, the divertor target plates. A new initiative has been launched on DIII-D to develop and demonstrate innovative boundary plasma-materials interface solutions. The central purposes of this new initiative are to advance scientific understanding in this critical area and develop an advanced divertor concept for application to next-step fusion devices. Finally, DIII-D will leverage strong collaborative efforts on the EAST superconducting tokamak for extending integrated high performance advanced divertor solutions to true steady-state.

TMAP - A Versatile Mobile Robot

NASA Astrophysics Data System (ADS)

Weiss, Joel A.; Simmons, Richard K.

1989-03-01

TMAP, the Teleoperated Mobile All-purpose Platform, provides the Army with a low cost, light weight, flexibly designed, modularly expandable platform for support of maneuver forces and light infantry units. The highly mobile, four wheel drive, diesel-hydraulic platform is controllable at distances of up to 4km from a portable operator control unit using either fiber optic or RF control links. The Martin Marietta TMAP system is based on a hierarchical task decomposition Real-time Control System architecture that readily supports interchange of mission packages and provides the capability for simple incorporation of supervisory control concepts leading to increased system autonomy and resulting force multiplication. TMAP has been designed to support a variety of missions including target designation, anti-armor, anti-air, countermine, and reconnaissance/surveillance. As a target designation system TMAP will provide the soldier with increased survivability and effectiveness by providing substantial combat standoff, and the firepower effectiveness of several manual designator operators. Force-on-force analysis of simulated TMAP engagements indicate that TMAP should provide significant force multiplication for the Army in Air-Land Battle 2000.

Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review.

PubMed

Mousavizadeh, Ali; Jabbari, Ali; Akrami, Mohammad; Bardania, Hassan

2017-10-01

Cell targeting peptides (CTP) are small peptides which have high affinity and specificity to a cell or tissue targets. They are typically identified by using phage display and chemical synthetic peptide library methods. CTPs have attracted considerable attention as a new class of ligands to delivery specifically therapeutic and diagnostic agents, because of the fact they have several advantages including easy synthesis, smaller physical sizes, lower immunogenicity and cytotoxicity and their simple and better conjugation to nano-carriers and therapeutic or diagnostic agents compared to conventional antibodies. In this systematic review, we will focus on the basic concepts concerning the use of cell-targeting peptides (CTPs), following the approaches of selecting them from peptide libraries. We discuss several developed strategies for cell-specific delivery of different cargos by CTPs, which are designed for drug delivery and diagnostic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Off-target model based OPC

NASA Astrophysics Data System (ADS)

Lu, Mark; Liang, Curtis; King, Dion; Melvin, Lawrence S., III

2005-11-01

Model-based Optical Proximity correction has become an indispensable tool for achieving wafer pattern to design fidelity at current manufacturing process nodes. Most model-based OPC is performed considering the nominal process condition, with limited consideration of through process manufacturing robustness. This study examines the use of off-target process models - models that represent non-nominal process states such as would occur with a dose or focus variation - to understands and manipulate the final pattern correction to a more process robust configuration. The study will first examine and validate the process of generating an off-target model, then examine the quality of the off-target model. Once the off-target model is proven, it will be used to demonstrate methods of generating process robust corrections. The concepts are demonstrated using a 0.13 μm logic gate process. Preliminary indications show success in both off-target model production and process robust corrections. With these off-target models as tools, mask production cycle times can be reduced.

Segmented beryllium target for a 2 MW super beam facility

DOE PAGES

Davenne, T.; Caretta, O.; Densham, C.; ...

2015-09-14

The Long Baseline Neutrino Facility (LBNF, formerly the Long Baseline Neutrino Experiment) is under design as a next generation neutrino oscillation experiment, with primary objectives to search for CP violation in the leptonic sector, to determine the neutrino mass hierarchy and to provide a precise measurement of θ 23. The facility will generate a neutrino beam at Fermilab by the interaction of a proton beam with a target material. At the ultimate anticipated proton beam power of 2.3 MW the target material must dissipate a heat load of between 10 and 25 kW depending on the target size. This paper presents amore » target concept based on an array of spheres and compares it to a cylindrical monolithic target such as that which currently operates at the T2K facility. Thus simulation results show that the proposed technology offers efficient cooling and lower stresses whilst delivering a neutrino production comparable with that of a conventional solid cylindrical target.« less

The Remote Observing Working Group for the Asteroid Impact and Deflection Assessment (AIDA)

NASA Astrophysics Data System (ADS)

Rivkin, A. S.; Pravec, P.; Thomas, C. A.; Thirouin, A.; Snodgrass, C.; Green, S.; Licandro, J.; Sickafoose, A. A.; Erasmus, N.; Howell, E. S.; Osip, D.; Thomas-Osip, J.; Moskovitz, N.; Scheirich, P.; Oszkiewicz, D.; Richardson, D. C.; Polishook, D.; Ryan, W. H.; Busch, M. W.

2017-09-01

The Asteroid Impact and Deflection Assessment (AIDA) is a joint US-European mission concept designed to demonstrate the effectiveness of an kinetic impactor for planetary defense. Ground-based observing is a key component to AIDA and critical for its success. We present the observing campaign we have been conducting of the asteroid Didymos, the AIDA target, and plans for future work.

DARPA Initiative in Concurrent Engineering (DICE). Phase 2

DTIC Science & Technology

1990-07-31

XS spreadsheet tool " Q-Calc spreadsheet tool " TAE+ outer wrapper for XS • Framemaker-based formal EDN (Electronic Design Notebook) " Data...shared global object space and object persistence. Technical Results Module Development XS Integration Environment A prototype of the wrapper concepts...for a spreadsheet integration environment, using an X-Windows based extensible Lotus 1-2-3 emulation called XS , and was (initially) targeted for

AFC-Enabled Simplified High-Lift System Integration Study

NASA Technical Reports Server (NTRS)

Hartwich, Peter M.; Dickey, Eric D.; Sclafani, Anthony J.; Camacho, Peter; Gonzales, Antonio B.; Lawson, Edward L.; Mairs, Ron Y.; Shmilovich, Arvin

2014-01-01

The primary objective of this trade study report is to explore the potential of using Active Flow Control (AFC) for achieving lighter and mechanically simpler high-lift systems for transonic commercial transport aircraft. This assessment was conducted in four steps. First, based on the Common Research Model (CRM) outer mold line (OML) definition, two high-lift concepts were developed. One concept, representative of current production-type commercial transonic transports, features leading edge slats and slotted trailing edge flaps with Fowler motion. The other CRM-based design relies on drooped leading edges and simply hinged trailing edge flaps for high-lift generation. The relative high-lift performance of these two high-lift CRM variants is established using Computational Fluid Dynamics (CFD) solutions to the Reynolds-Averaged Navier-Stokes (RANS) equations for steady flow. These CFD assessments identify the high-lift performance that needs to be recovered through AFC to have the CRM variant with the lighter and mechanically simpler high-lift system match the performance of the conventional high-lift system. Conceptual design integration studies for the AFC-enhanced high-lift systems were conducted with a NASA Environmentally Responsible Aircraft (ERA) reference configuration, the so-called ERA-0003 concept. These design trades identify AFC performance targets that need to be met to produce economically feasible ERA-0003-like concepts with lighter and mechanically simpler high-lift designs that match the performance of conventional high-lift systems. Finally, technical challenges are identified associated with the application of AFC-enabled highlift systems to modern transonic commercial transports for future technology maturation efforts.

TRAC performance estimates

NASA Technical Reports Server (NTRS)

Everett, L.

1992-01-01

This report documents the performance characteristics of a Targeting Reflective Alignment Concept (TRAC) sensor. The performance will be documented for both short and long ranges. For long ranges, the sensor is used without the flat mirror attached to the target. To better understand the capabilities of the TRAC based sensors, an engineering model is required. The model can be used to better design the system for a particular application. This is necessary because there are many interrelated design variables in application. These include lense parameters, camera, and target configuration. The report presents first an analytical development of the performance, and second an experimental verification of the equations. In the analytical presentation it is assumed that the best vision resolution is a single pixel element. The experimental results suggest however that the resolution is better than 1 pixel. Hence the analytical results should be considered worst case conditions. The report also discusses advantages and limitations of the TRAC sensor in light of the performance estimates. Finally the report discusses potential improvements.

Improving Conceptual Understanding and Representation Skills Through Excel-Based Modeling

NASA Astrophysics Data System (ADS)

Malone, Kathy L.; Schunn, Christian D.; Schuchardt, Anita M.

2018-02-01

The National Research Council framework for science education and the Next Generation Science Standards have developed a need for additional research and development of curricula that is both technologically model-based and includes engineering practices. This is especially the case for biology education. This paper describes a quasi-experimental design study to test the effectiveness of a model-based curriculum focused on the concepts of natural selection and population ecology that makes use of Excel modeling tools (Modeling Instruction in Biology with Excel, MBI-E). The curriculum revolves around the bio-engineering practice of controlling an invasive species. The study takes place in the Midwest within ten high schools teaching a regular-level introductory biology class. A post-test was designed that targeted a number of common misconceptions in both concept areas as well as representational usage. The results of a post-test demonstrate that the MBI-E students significantly outperformed the traditional classes in both natural selection and population ecology concepts, thus overcoming a number of misconceptions. In addition, implementing students made use of more multiple representations as well as demonstrating greater fascination for science.

Application of expert systems in project management decision aiding

NASA Technical Reports Server (NTRS)

Harris, Regina; Shaffer, Steven; Stokes, James; Goldstein, David

1987-01-01

The feasibility of developing an expert systems-based project management decision aid to enhance the performance of NASA project managers was assessed. The research effort included extensive literature reviews in the areas of project management, project management decision aiding, expert systems technology, and human-computer interface engineering. Literature reviews were augmented by focused interviews with NASA managers. Time estimation for project scheduling was identified as the target activity for decision augmentation, and a design was developed for an Integrated NASA System for Intelligent Time Estimation (INSITE). The proposed INSITE design was judged feasible with a low level of risk. A partial proof-of-concept experiment was performed and was successful. Specific conclusions drawn from the research and analyses are included. The INSITE concept is potentially applicable in any management sphere, commercial or government, where time estimation is required for project scheduling. As project scheduling is a nearly universal management activity, the range of possibilities is considerable. The INSITE concept also holds potential for enhancing other management tasks, especially in areas such as cost estimation, where estimation-by-analogy is already a proven method.

Erotic target location errors: an underappreciated paraphilic dimension.

PubMed

Lawrence, Anne A

2009-01-01

Based on studies of heterosexual male fetishists, transvestites, and transsexuals, Blanchard (1991) proposed the existence of a hitherto unrecognized paraphilic dimension, erotic target location errors (ETLEs), involving the erroneous location of erotic targets in the environment. ETLEs can involve preferential attention to a peripheral or inessential part of an erotic target, manifesting as fetishism, or mislocation of an erotic target in one's own body, manifesting as the desire to impersonate or become a facsimile of the erotic target (e.g., transvestism or transsexualism). Despite its potential clinical and heuristic value, the concept that ETLEs define a paraphilic dimension is underappreciated. This review summarizes the studies leading to the concept of ETLEs and describes how ETLEs are believed to manifest in men whose preferred erotic targets are women, children, men, amputees, plush animals, and real animals. This review also describes ETLEs in women; discusses possible etiologies of ETLEs; considers the implications of the ETLE concept for psychoanalytic theories of transvestism and male-to-female transsexualism, as well as for the forthcoming revision of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; suggests reasons why the concept of ETLEs has been underappreciated; and describes what might result if the concept were more widely appreciated.

Block Ignition Inertial Confinement Fusion (ICF) with Condensed Matter Cluster Type Targets for p-B11 Powered Space Propulsion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miley, George H.; Hora, H.; Badziak, J.

The use of laser-driven Inertial Confinement Fusion (ICF) for space propulsion has been the subject of several earlier conceptual design studies, (see: Orth, 1998; and other references therein). However, these studies were based on older ICF technology using either 'direct' or 'in-direct x-ray driven' type target irradiation. Important new directions have opened for laser ICF in recent years following the development of 'chirped' lasers capable of ultra short pulses with powers of TW up to few PW which leads to the concept of 'fast ignition (FI)' to achieve higher energy gains from target implosions. In a recent publication the authorsmore » showed that use of a modified type of FI, termed 'block ignition' (Miley et al., 2008), could meet many of the requirements anticipated (but not then available) by the designs of the Vehicle for Interplanetary Space Transport Applications (VISTA) ICF fusion propulsion ship (Orth, 2008) for deep space missions. Subsequently the first author devised and presented concepts for imbedding high density condensed matter 'clusters' of deuterium into the target to obtain ultra high local fusion reaction rates (Miley, 2008). Such rates are possible due to the high density of the clusters (over an order of magnitude above cryogenic deuterium). Once compressed by the implosion, the yet higher density gives an ultra high reaction rate over the cluster volume since the fusion rate is proportional to the square of the fuel density. Most recently, a new discovery discussed here indicates that the target matrix could be composed of B{sup 11} with proton clusters imbedded. This then makes p-B{sup 11} fusion practical, assuming all of the physics issues such as stability of the clusters during compression are resolved. Indeed, p-B{sup 11} power is ideal for fusion propulsion since it has a minimum of unwanted side products while giving most of the reaction energy to energetic alpha particles which can be directed into an exhaust (propulsion) nozzle. Power plants using p-B{sup 11} have been discussed for such applications before, but prior designs face formidable physics/technology issues, largely overcome with the present approach.« less

AlphaSpace: Fragment-Centric Topographical Mapping To Target Protein–Protein Interaction Interfaces

PubMed Central

2016-01-01

Inhibition of protein–protein interactions (PPIs) is emerging as a promising therapeutic strategy despite the difficulty in targeting such interfaces with drug-like small molecules. PPIs generally feature large and flat binding surfaces as compared to typical drug targets. These features pose a challenge for structural characterization of the surface using geometry-based pocket-detection methods. An attractive mapping strategy—that builds on the principles of fragment-based drug discovery (FBDD)—is to detect the fragment-centric modularity at the protein surface and then characterize the large PPI interface as a set of localized, fragment-targetable interaction regions. Here, we introduce AlphaSpace, a computational analysis tool designed for fragment-centric topographical mapping (FCTM) of PPI interfaces. Our approach uses the alpha sphere construct, a geometric feature of a protein’s Voronoi diagram, to map out concave interaction space at the protein surface. We introduce two new features—alpha-atom and alpha-space—and the concept of the alpha-atom/alpha-space pair to rank pockets for fragment-targetability and to facilitate the evaluation of pocket/fragment complementarity. The resulting high-resolution interfacial map of targetable pocket space can be used to guide the rational design and optimization of small molecule or biomimetic PPI inhibitors. PMID:26225450

Progress in direct-drive inertial confinement fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCrory, R. L.; Meyerhofer, D. D.; Betti, R.

Significant progress in direct-drive inertial confinement fusion (ICF) research has been made since the completion of the 60-beam, 30-kJ{sub UV} OMEGA Laser System [Boehly, Opt. Commun. 133, 495 (1997)] in 1995. A theory of ignition requirements, applicable to any ICF concept, has been developed. Detailed understanding of laser-plasma coupling, electron thermal transport, and hot-electron preheating has lead to the measurement of neutron-averaged areal densities of {approx}200 mg/cm{sup 2} in cryogenic target implosions. These correspond to an estimated peak fuel density in excess of 100 g/cm{sup 3} and are in good agreement with hydrodynamic simulations. The implosions were performed using anmore » 18-kJ drive pulse designed to put the converging fuel on an adiabat of two. The polar-drive concept will allow direct-drive-ignition research on the National Ignition Facility while it is configured for indirect drive. Advanced ICF ignition concepts - fast ignition [Tabak et al., Phys. Plasmas 1, 1626 (1994)] and shock ignition [Betti et al., Phys. Rev. Lett. 98, 155001 (2007)] - have the potential to significantly reduce ignition driver energies and/or provide higher target gain.« less

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

PubMed Central

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

2013-01-01

Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development of targeted polymeric NPs and to highlight the challenges associated with the engineering of this novel class of therapeutics, including considerations of NP design optimization, development and biophysicochemical properties. Additionally, we highlight some recent examples from the literature, which demonstrate current trends and novel concepts in both the design and utility of targeted polymeric NPs (444 references). PMID:22388185

Automatic three-dimensional measurement of large-scale structure based on vision metrology.

PubMed

Zhu, Zhaokun; Guan, Banglei; Zhang, Xiaohu; Li, Daokui; Yu, Qifeng

2014-01-01

All relevant key techniques involved in photogrammetric vision metrology for fully automatic 3D measurement of large-scale structure are studied. A new kind of coded target consisting of circular retroreflective discs is designed, and corresponding detection and recognition algorithms based on blob detection and clustering are presented. Then a three-stage strategy starting with view clustering is proposed to achieve automatic network orientation. As for matching of noncoded targets, the concept of matching path is proposed, and matches for each noncoded target are found by determination of the optimal matching path, based on a novel voting strategy, among all possible ones. Experiments on a fixed keel of airship have been conducted to verify the effectiveness and measuring accuracy of the proposed methods.

Mobile Aerial Tracking and Imaging System (MATrIS) for Aeronautical Research

NASA Technical Reports Server (NTRS)

Banks, Daniel W.; Blanchard, Robert C.; Miller, Geoffrey M.

2004-01-01

A mobile, rapidly deployable ground-based system to track and image targets of aeronautical interest has been developed. Targets include reentering reusable launch vehicles as well as atmospheric and transatmospheric vehicles. The optics were designed to image targets in the visible and infrared wavelengths. To minimize acquisition cost and development time, the system uses commercially available hardware and software where possible. The conception and initial funding of this system originated with a study of ground-based imaging of global aerothermal characteristics of reusable launch vehicle configurations. During that study the National Aeronautics and Space Administration teamed with the Missile Defense Agency/Innovative Science and Technology Experimentation Facility to test techniques and analysis on two Space Shuttle flights.

Autonomous self-navigating drug-delivery vehicles: from science fiction to reality.

PubMed

Petrenko, Valery A

2017-12-01

Low efficacy of targeted nanomedicines in biological experiments enforced us to challenge the traditional concept of drug targeting and suggest a paradigm of 'addressed self-navigating drug-delivery vehicles,' in which affinity selection of targeting peptides and vasculature-directed in vivo phage screening is replaced by the migration selection, which explores ability of 'promiscuous' phages and their proteins to migrate through the tumor-surrounding cellular barriers, using a 'hub and spoke' delivery strategy, and penetrate into the tumor affecting the diverse tumor cell population. The 'self-navigating' drug-delivery paradigm can be used as a theoretical and technical platform in design of a novel generation of molecular medications and imaging probes for precise and personal medicine. [Formula: see text].

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yewondwossen, M; Robar, J; Parsons, D

Purpose: During radiotherapy treatment, lung tumors can display substantial respiratory motion. This motion usually necessitates enlarged treatment margins to provide full tumour coverage. Unfortunately, these margins limit the dose that can be prescribed for tumour control and cause complications to normal tissue. Options for real-time methods of direct detection of tumour position, and particularly those that obviate the need for inserted fiducial markers, are limited. We propose a method of tumor tracking without implanted fiducial markers using a novel fast switching-target that toggles between a FFF copper/tungsten therapy mode and a FFF low-Z target mode for imaging. In this workmore » we demonstrate proof-of-concept of this new technology. Methods: The prototype includes two targets: i) a FFF copper/tungsten target equivalent to that in the Varian 2100 EX 6 MV, and ii) a low-Z (carbon) target with a thickness of 110% of continuous slowing down approximation range (CSDA) at 7 MeV. The two targets can be exchanged with a custom made linear slide and motor-driven actuator. The usefulness of the switching-target concept is demonstrated through experimental BEV Planar images acquired with continual treatment and imaging at a user-defined period. Results: The prototype switching-target demonstrates that two recent advances in linac technology (FFF target for therapy and low-Z target) can be combined with synergy. The switching-target approach offers the capacity for rapid switching between treatment and high-contrast imaging modes, allowing intrafractional tracking, as demonstrated in this work with dynamic breathing phantom. By using a single beam-line, the design is streamlined and may obviate the need for an auxiliary imaging system (e.g., kV OBI.) Conclusion: This switching-target approach is a feasible combination of two current advances in linac technology (FFF target for therapy and a FFF low-Z target) allowing new options in on-line IGRT.« less

Engineering Concepts in Stem Cell Research.

PubMed

Narayanan, Karthikeyan; Mishra, Sachin; Singh, Satnam; Pei, Ming; Gulyas, Balazs; Padmanabhan, Parasuraman

2017-12-01

The field of regenerative medicine integrates advancements made in stem cells, molecular biology, engineering, and clinical methodologies. Stem cells serve as a fundamental ingredient for therapeutic application in regenerative medicine. Apart from stem cells, engineering concepts have equally contributed to the success of stem cell based applications in improving human health. The purpose of various engineering methodologies is to develop regenerative and preventive medicine to combat various diseases and deformities. Explosion of stem cell discoveries and their implementation in clinical setting warrants new engineering concepts and new biomaterials. Biomaterials, microfluidics, and nanotechnology are the major engineering concepts used for the implementation of stem cells in regenerative medicine. Many of these engineering technologies target the specific niche of the cell for better functional capability. Controlling the niche is the key for various developmental activities leading to organogenesis and tissue homeostasis. Biomimetic understanding not only helped to improve the design of the matrices or scaffolds by incorporating suitable biological and physical components, but also ultimately aided adoption of designs that helped these materials/devices have better function. Adoption of engineering concepts in stem cell research improved overall achievement, however, several important issues such as long-term effects with respect to systems biology needs to be addressed. Here, in this review the authors will highlight some interesting breakthroughs in stem cell biology that use engineering methodologies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Use of concurrent mixed methods combining concept mapping and focus groups to adapt a health equity tool in Canada.

PubMed

Guichard, Anne; Tardieu, Émilie; Dagenais, Christian; Nour, Kareen; Lafontaine, Ginette; Ridde, Valéry

2017-04-01

The aim of this project was to identify and prioritize a set of conditions to be considered for incorporating a health equity tool into public health practice. Concept mapping and focus groups were implemented as complementary methods to investigate the conditions of use of a health equity tool by public health organizations in Quebec. Using a hybrid integrated research design is a richer way to address the complexity of questions emerging from intervention and planning settings. This approach provides a deeper, operational, and contextualized understanding of research results involving different professional and organizational cultures, and thereby supports the decision-making process. Concept mapping served to identify and prioritize in a limited timeframe the conditions to be considered for incorporation into a health equity tool into public health practices. Focus groups then provided a more refined understanding of the barriers, issues, and facilitating factors surrounding the tools adoption, helped distinguish among participants' perspectives based on functional roles and organizational contexts, and clarified some apparently contradictory results from the concept map. The combined use of these two techniques brought the strengths of each approach to bear, thereby overcoming some of the respective limitations of concept mapping and focus groups. This design is appropriate for investigating targets with multiple levels of complexity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Beacon Collision Avoidance System (BCAS) Alternative Concepts for Determining Target Positions

DOT National Transportation Integrated Search

1978-09-01

The (Litchford) Beacon-based Collision Avoidance System concept requires the computation of target range and bearing relative to the BCAS aircraft. Techniques for determining target range and bearing under four different assumptions about the ground ...

Heat removal capability of divertor coaxial tube assembly

NASA Astrophysics Data System (ADS)

Shibui, Masanao; Nakahira, Masataka; Tada, Eisuke; Takatsu, Hideyuki

1994-05-01

To deal with high power flowing in the divertor region, an advanced divertor concept with gas target has been proposed for use in ITER/EDA. The concept uses a divertor channel to remove the radiated power while allowing neutrals to recirculate. Candidate channel wall designs include a tube array design where many coaxial tubes are arranged in the toroidal direction to make louver. The coaxial tube consists of a Be protection tube encases many supply tubes wound helically around a return tube. V-alloy and hardened Cu-alloy have been proposed for use in the supply and return tubes. Some coolants have also been proposed for the design including pressurized He and liquid metals, because these coolants are consistent with the selection of coolants for the blanket and also meet the requirement of high temperature operation. In the coaxial tube design, the coolant area is restricted and brittle Be material is used under severe thermal cyclings. Thus, to obtain the coaxial tube with sufficient safety margin for the expected fusion power excursion, it is essential to understand its applicability limit. The paper discusses heat removal capability of the coaxial tube and recommends some design modifications.

Computer Aided Drug Design: Success and Limitations.

PubMed

Baig, Mohammad Hassan; Ahmad, Khurshid; Roy, Sudeep; Ashraf, Jalaluddin Mohammad; Adil, Mohd; Siddiqui, Mohammad Haris; Khan, Saif; Kamal, Mohammad Amjad; Provazník, Ivo; Choi, Inho

2016-01-01

Over the last few decades, computer-aided drug design has emerged as a powerful technique playing a crucial role in the development of new drug molecules. Structure-based drug design and ligand-based drug design are two methods commonly used in computer-aided drug design. In this article, we discuss the theory behind both methods, as well as their successful applications and limitations. To accomplish this, we reviewed structure based and ligand based virtual screening processes. Molecular dynamics simulation, which has become one of the most influential tool for prediction of the conformation of small molecules and changes in their conformation within the biological target, has also been taken into account. Finally, we discuss the principles and concepts of molecular docking, pharmacophores and other methods used in computer-aided drug design.

Concept and Design of the Hybrid Sensor Bus System for Telecommunication Satellites

NASA Astrophysics Data System (ADS)

Hurni, Andreas; Tiefenbeck, Christoph; Manhart, Markus; Heyer, Heinz-Volker; Plattner, Markus; Putzer, Philipp; Roßner, Max; Koch, Alexander W.; Furano, Gianluca; McKenzie, Iain; Lam, King

2012-08-01

The Hybrid Sensor Bus (HSB) is a system for sensor interrogation in telecommunication satellites, which will be developed in the frame of the ESA ARTES program. The main target of the HSB system is the replacement of classical point-to-point wired sensors by sensors connected on bus networks. This will save mass and reduces efforts in assembly, integration and testing (AIT). The HSB system is able to manage an electrical I2C and a fiber-optical sensor network. The system consists of an intelligent power module, an electrical and a fiber-optical interrogator module in cold redundancy. Additional features of the HSB system are its modularity and the adaptability to different satellite platforms. The implementation of a HSB system allows platform manufacturers to build a more cost efficient satellite.This paper presents the concept and the design status of the HSB system.

A SPR strategy for high-throughput ligand screenings based on synthetic peptides mimicking a selected subdomain of the target protein: a proof of concept on HER2 receptor.

PubMed

Monfregola, Luca; Vitale, Rosa Maria; Amodeo, Pietro; De Luca, Stefania

2009-10-01

The discovery of pharmaceutical agents is a complex, lengthy and costly process, critically depending on the availability of rapid and efficient screening methods. In particular, when targets are large, multidomain proteins, their complexity may affect unfavorably technical feasibility, costs and unambiguity of binding test interpretation. A possible strategy to overcome these problems relies on molecular design of receptor fragments that are: sensible targets for ligand screenings, conformationally stable also as standalone domains, easily synthesized and immobilized on chip for Biacore experiments. An additional desirable feature for new ligands is the ability of selectively targeting alternative conformational states typical of many proteins. To test the feasibility of such approach on a case with potential applicative interest, we developed a surface plasmon resonance (SPR)-based screening method for drug candidates toward HER2, a Tyr-kinase receptor targeted in anticancer therapies. HER2 was mimicked by HER2-DIVMP, a modified fragment of it immobilized onto the sensor surface specifically modeling HER2 domain IV in its bounded form, designed by structural comparison of HER2 alone and in complex with Herceptin, a monoclonal therapeutic anti-HER2 antibody. This design and its implementation in SPR devices was validated by investigating Herceptin- HER2-DIVMP affinity, measuring its dissociation constant (K(D)=19.2 nM). An efficient synthetic procedure to prepare the HER2-DIVMP peptide was also developed. The HER2-DIVMP conformational stability suggested by experimental and computational results, makes it also a valuable candidate as a mold to design new molecules selectively targeting domain IV of HER2.

Screening studies of advanced control concepts for airbreathing engines

NASA Technical Reports Server (NTRS)

Ouzts, Peter J.; Lorenzo, Carl F.; Merrill, Walter C.

1993-01-01

The application of advanced control concepts to airbreathing engines may yield significant improvements in aircraft/engine performance and operability. Accordingly, the NASA Lewis Research Center has conducted screening studies of advanced control concepts for airbreathing engines to determine their potential impact on turbine engine performance and operability. The purpose of the studies was to identify concepts which offered high potential yet may incur high research and development risk. A target suite of proposed concepts was formulated by NASA and industry. These concepts were evaluated in a two phase study to quantify each concept's impact on desired engine characteristics. To aid in the evaluation, three target aircraft/engine combinations were considered: a military high performance fighter mission, a high speed civil transport mission, and a civil tiltrotor mission. Each of the advanced control concepts considered in the study were defined and described. The concept's potential impact on engine performance was determined. Relevant figures of merit on which to evaluate the concepts were also determined. Finally, the concepts were ranked with respect to the target aircraft/engine missions.

Optical Alignment of the JWST ISIM to the OTE Simulator (OSIM): Current Concept and Design Studies

NASA Technical Reports Server (NTRS)

Frey, Bradley J.; Davila, Pamela S.; Marsh, James M.; Ohl, Raymond G.; Sullivan, Joseph

2007-01-01

The James Webb Space Telescope's (JWST) Integrated Science Instrument Module (ISIM) is the scientific payload of the observatory and contai ns four science instruments. During alignment and test of the integrated ISIM (i.e. ISIM + science instruments) at NASA's Goddard Space Fli ght Center (GSFC), the Optical telescope element SIMulator (OSIM) wil l be used to optically stimulate the science instruments to verify their operation and performance. In this paper we present the design of two cryogenic alignment fixtures that will be used to determine and verify the proper alignment of OSIM to ISIM during testing at GSFC. The se fixtures, the Master Alignment Target Fixture (MATF) and the ISIM Alignment Target Fixture (IATF), will provide continuous, 6 degree of freedom feedback to OSIM during initial ambient alignment as well as during cryogenic vacuum testing.

Design and verification of a cloud field optical simulator

NASA Technical Reports Server (NTRS)

Davis, J. M.; Cox, S. K.; Mckee, T. B.

1983-01-01

A concept and an apparatus designed to investigate the reflected and transmitted distributions of light from optically thick clouds is presented. The Cloud Field Optical Simulator (CFOS) is a laboratory device which utilizes an array of incandescent lamps as a source, simulated clouds made from cotton or styrofoam as targets, and an array of silicon photodiodes as detectors. The device allows virtually any source-target-detector geometry to be examined. Similitude between real clouds and their CFOS cotton or styrofoam counterparts is established by relying on a linear relationship between optical depth and the ratio of reflected to transmitted light for a semiinfinite layer. Comparisons of principal plane radiances observed by the CFOS with Monte Carlo computations for a water cloud at 0.7 micron show excellent agreement. Initial applications of the CFOS are discussed.

Concepts for a Muon Accelerator Front-End

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stratakis, Diktys; Berg, Scott; Neuffer, David

2017-03-16

We present a muon capture front-end scheme for muon based applications. In this Front-End design, a proton bunch strikes a target and creates secondary pions that drift into a capture channel, decaying into muons. A series of rf cavities forms the resulting muon beams into a series of bunches of differerent energies, aligns the bunches to equal central energies, and initiates ionization cooling. We also discuss the design of a chicane system for the removal of unwanted secondary particles from the muon capture region and thus reduce activation of the machine. With the aid of numerical simulations we evaluate themore » performance of this Front-End scheme as well as study its sensitivity against key parameters such as the type of target, the number of rf cavities and the gas pressure of the channel.« less

Three dimensional calculation of thermonuclear ignition conditions for magnetized targets

NASA Astrophysics Data System (ADS)

Cortez, Ross; Cassibry, Jason; Lapointe, Michael; Adams, Robert

2017-10-01

Fusion power balance calculations, often performed using analytic methods, are used to estimate the design space for ignition conditions. In this paper, fusion power balance is calculated utilizing a 3-D smoothed particle hydrodynamics code (SPFMax) incorporating recent stopping power routines. Effects of thermal conduction, multigroup radiation emission and nonlocal absorption, ion/electron thermal equilibration, and compressional work are studied as a function of target and liner parameters and geometry for D-T, D-D, and 6LI-D fuels to identify the potential ignition design space. Here, ignition is defined as the condition when fusion particle deposition equals or exceeds the losses from heat conduction and radiation. The simulations are in support of ongoing research with NASA to develop advanced propulsion systems for rapid interplanetary space travel. Supported by NASA Innovative Advanced Concepts and NASA Marshall Space Flight Center.

Effects of priming a bipolar attribute concept on dimension versus concept-specific accessibility of semantic memory.

PubMed

Park, J W; Yoon, S O; Kim, K H; Wyer, R S

2001-09-01

In Experiment 1, participants received behavioral information about a person that could be interpreted as either honest or unkind. Priming a concept along 1 dimension (e.g., honesty) increased the likelihood of spontaneously describing the target along this dimension (i.e., as honest), regardless of whether the primed concept was directly applicable for interpreting the target's behavior ("honest") or was its bipolar opposite ("dishonest"). Experiment 2 replicated this finding in a different, product domain. It further demonstrated that when information is ambiguous, primed concepts can influence not only the dimension along which the target is described but also the value it is assigned along this dimension. The effect of priming in both experiments was reflected in participants' overall evaluations of the targets as well as in their spontaneous descriptions of it. Results were consistent with the assumption that bipolar attributes are associatively linked in memory but are stored as separate concepts rather than as values along a bipolar continuum.

Development of a Meiosis Concept Inventory

PubMed Central

Kalas, Pamela; O’Neill, Angie; Pollock, Carol; Birol, Gülnur

2013-01-01

We have designed, developed, and validated a 17-question Meiosis Concept Inventory (Meiosis CI) to diagnose student misconceptions on meiosis, which is a fundamental concept in genetics. We targeted large introductory biology and genetics courses and used published methodology for question development, which included the validation of questions by student interviews (n = 28), in-class testing of the questions by students (n = 193), and expert (n = 8) consensus on the correct answers. Our item analysis showed that the questions’ difficulty and discrimination indices were in agreement with published recommended standards and discriminated effectively between high- and low-scoring students. We foresee other institutions using the Meiosis CI as both a diagnostic tool and an instrument to assess teaching effectiveness and student progress, and invite instructors to visit http://q4b.biology.ubc.ca for more information. PMID:24297292

The Scientific Challenge of Expanding the Frontiers of Nutrition.

PubMed

Rezzi, Serge; Solari, Soren; Bouche, Nicolas; Baetge, Emmanuel E

2016-01-01

Nutritional research is entering a paradigm shift which necessitates the modeling of complex interactions between diet, genetics, lifestyle, and environmental factors. This requires the development of analytical and processing capabilities for multiple data and information sources to be able to improve targeted and personalized nutritional approaches for the maintenance of health. Ideally, such knowledge will be employed to underpin the development of concepts that combine consumer and medical nutrition with diagnostic targeting for early intervention designed to maintain proper metabolic homeostasis and delay the onset of chronic diseases. Nutritional status is fundamental to any description of health, and when combined with other data on lifestyle, environment, and genetics, it can be used to drive stratified or even personalized nutritional strategies for health maintenance and preventive medicine. In this work, we will discuss the importance of developing new nutrient assessment methods and diagnostic capabilities for nutritional status to generate scientific hypotheses and actionable concepts from which to develop targeted and eventually personalized nutritional solutions for health protection. We describe efforts to develop algorithms for dietary nutrient intake and a holistic nutritional profiling platform as the basis of understanding the complex nutrition and health interactome. © 2016 Nestec Ltd., Vevey/S. Karger AG, Basel.

Seat Capacity Selection for an Advanced Short-Haul Aircraft Design

NASA Technical Reports Server (NTRS)

Marien, Ty V.

2016-01-01

A study was performed to determine the target seat capacity for a proposed advanced short-haul aircraft concept projected to enter the fleet by 2030. This analysis projected the potential demand in the U.S. for a short-haul aircraft using a transportation theory approach, rather than selecting a target seat capacity based on recent industry trends or current market demand. A transportation systems model was used to create a point-to-point network of short-haul trips and then predict the number of annual origin-destination trips on this network. Aircraft of varying seat capacities were used to meet the demand on this network, assuming a single aircraft type for the entire short-haul fleet. For each aircraft size, the ticket revenue and operational costs were used to calculate a total market profitability metric for all feasible flights. The different aircraft sizes were compared, based on this market profitability metric and also the total number of annual round trips and markets served. Sensitivity studies were also performed to determine the effect of changing the aircraft cruise speed and maximum trip length. Using this analysis, the advanced short-haul aircraft design team was able to select a target seat capacity for their design.

Services to Multi-Problem Youth. Georgia Department of Human Resources Program and Funding Report, Vol. 2, No. 1, January 15, 1976.

ERIC Educational Resources Information Center

Schiffman, Jan; Washington, Blanche

This report focuses on a problem area which is being addressed by a consortium of agencies, and is designed to enrich the options of planners and program personnel in terms of both innovative concepts and potential resources required for program support. This report relates to the target population of "multi-problem" youth for whom no existing…

A mass filter based on an accelerating traveling wave.

PubMed

Wiedenbeck, Michael; Kasemset, Bodin; Kasper, Manfred

2008-01-01

We describe a novel mass filtering concept based on the acceleration of a pulsed ion beam through a stack of electrostatic plates. A precisely controlled traveling wave generated within such an ion guide will induce a mass-selective ion acceleration, with mass separation ultimately accomplished via a simple energy-filtering system. Crucial for successful filtering is that the velocity with which the traveling wave passes through the ion guide must be dynamically controlled in order to accommodate the acceleration of the target ion species. Mass selection is determined by the velocity and acceleration with which the wave traverses the ion guide, whereby the target species will acquire a higher kinetic energy than all other lighter as well as heaver species. Finite element simulations of this design demonstrate that for small masses a mass resolution M/DeltaM approximately 1000 can be achieved within an electrode stack containing as few as 20 plates. Some of the possible advantages and drawbacks which distinguish this concept from established mass spectrometric technologies are discussed.

Asteroid Redirect Robotic Mission: Robotic Boulder Capture Option Overview

NASA Technical Reports Server (NTRS)

Mazanek, Daniel D.; Merrill, Raymond G.; Belbin, Scott P.; Reeves, David M.; Earle, Kevin D.; Naasz, Bo J.; Abell, Paul A.

2014-01-01

The National Aeronautics and Space Administration (NASA) is currently studying an option for the Asteroid Redirect Robotic Mission (ARRM) that would capture a multi-ton boulder (typically 2-4 meters in size) from the surface of a large (is approximately 100+ meter) Near-Earth Asteroid (NEA) and return it to cislunar space for subsequent human and robotic exploration. This alternative mission approach, designated the Robotic Boulder Capture Option (Option B), has been investigated to determine the mission feasibility and identify potential differences from the initial ARRM concept of capturing an entire small NEA (4-10 meters in size), which has been designated the Small Asteroid Capture Option (Option A). Compared to the initial ARRM concept, Option B allows for centimeter-level characterization over an entire large NEA, the certainty of target NEA composition type, the ability to select the boulder that is captured, numerous opportunities for mission enhancements to support science objectives, additional experience operating at a low-gravity planetary body including extended surface contact, and the ability to demonstrate future planetary defense strategies on a hazardous-size NEA. Option B can leverage precursor missions and existing Agency capabilities to help ensure mission success by targeting wellcharacterized asteroids and can accommodate uncertain programmatic schedules by tailoring the return mass.

The Design of Clinical Trials in Portal Hypertension.

PubMed

Abraldes, Juan G; Garcia-Tsao, Guadalupe

2017-02-01

Portal hypertension (PH) is the main consequence of cirrhosis and is responsible for the majority of its complications. Gastroesophageal varices and variceal hemorrhage are direct consequences of PH; therefore, most clinical trials in PH have been directed toward treating or preventing variceal hemorrhage. However, varices and variceal hemorrhage are not isolated events; they must be considered in the context of the presence (or absence) of other complications of cirrhosis/PH. Cirrhosis progresses across different stages, each with a different prognosis and pathophysiology and hence different therapeutic targets. In this review, the authors discuss the design of proof-of-concept studies for the assessment of new drugs for the treatment of PH, that are mainly based on the drug's ability to reduce the hepatic venous pressure gradient. They further discuss the design of studies with clinical endpoints in the context of each stage of cirrhosis, specifically targets of therapy, optimal therapies in the control arm, risk stratification, and primary outcome. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

High-irradiance reactor design with practical unfolded optics

NASA Astrophysics Data System (ADS)

Feuermann, Daniel; Gordon, Jeffrey M.

2008-08-01

In the design of high-temperature chemical reactors and furnaces, as well as high-radiance light projection applications, reconstituting the ultra-high radiance of short-arc discharge lamps at maximum radiative efficiency constitutes a significant challenge. The difficulty is exacerbated by the high numerical aperture necessary at both the source and the target. Separating the optic from both the light source and the target allows practical operation, control, monitoring, diagnostics and maintenance. We present near-field unfolded aplanatic optics as a feasible solution. The concept is illustrated with a design customized to a high-temperature chemical reactor for nano-material synthesis, driven by an ultra-bright xenon short-arc discharge lamp, with near-unity numerical aperture for both light input and light output. We report preliminary optical measurements for the first prototype, which constitutes a double-ellipsoid solution. We also propose compound unfolded aplanats that collect the full angular extent of lamp emission (in lieu of light recycling optics) and additionally permit nearly full-circumference irradiation of the reactor.

Diffraction-limited lucky imaging with a 12" commercial telescope

NASA Astrophysics Data System (ADS)

Baptista, Brian J.

2014-08-01

Here we demonstrate a novel lucky imaging camera which is designed to produce diffraction-limited imaging using small telescopes similar to ones used by many academic institutions for outreach and/or student training. We present a design that uses a Meade 12" SCT paired with an Andor iXon fast readout EMCCD. The PSF of the telescope is matched to the pixel size of the EMCCD by adding a simple, custom-fabricated, intervening optical system. We demonstrate performance of the system by observing both astronomical and terrestrial targets. The astronomical application requires simpler data reconstruction techniques as compared to the terrestrial case. We compare different lucky imaging registration and reconstruction algorithms for use with this imager for both astronomical and terrestrial targets. We also demonstrate how this type of instrument would be useful for both undergraduate and graduate student training. As an instructional aide, the instrument can provide a hands-on approach for teaching instrument design, standard data reduction techniques, lucky imaging data processing, and high resolution imaging concepts.

Full-Scale Spacecraft Simulator Design for a 2D Zero Gravity Small Body Surface Sampling Validation

NASA Astrophysics Data System (ADS)

Mongelli, Marco

NASA is developing several Touch-And-Go (TAG) classes of missions. These types of missions like the OSIRIS-REx asteroid sample return [1] or a comet sample return mission (CSSR)[2], consist usually in three phases: propulsive approach to the target, sampling and propulsion to move the spacecraft away from the target. The development of TAG mission, from concept to realization, is usually divided in two phases: Phase I discusses the major trades that could affect the mission architecture; Phase II focuses in detail on the design. This project of a spacecraft emulator fits into phase II and specifically on the way the spacecraft could react in absence of gravity while the Sample Acquisition System (SAS) is collecting the sample. A full-scale spacecraft on a 2D zero-friction environment has been designed. Also a propulsion system has been implemented to re-create the full dynamics of a spacecraft in space.

RS-34 Phoenix In-Space Propulsion System Applied to Active Debris Removal Mission

NASA Technical Reports Server (NTRS)

Esther, Elizabeth A.; Burnside, Christopher G.

2014-01-01

In-space propulsion is a high percentage of the cost when considering Active Debris Removal mission. For this reason it is desired to research if existing designs with slight modification would meet mission requirements to aid in reducing cost of the overall mission. Such a system capable of rendezvous, close proximity operations, and de-orbit of Envisat class resident space objects has been identified in the existing RS-34 Phoenix. RS-34 propulsion system is a remaining asset from the de-commissioned United States Air Force Peacekeeper program; specifically the pressure-fed storable bi-propellant Stage IV Post Boost Propulsion System. The National Aeronautics and Space Administration (NASA) Marshall Space Flight Center (MSFC) gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. Subsequently, MSFC has obtained permission from the USAF to obtain all the remaining RS-34 stages for re-use opportunities. The MSFC Advanced Concepts Office (ACO) was commissioned to lead a study for evaluation of the Rocketdyne produced RS-34 propulsion system as it applies to an active debris removal design reference mission for resident space object targets including Envisat. Originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy payloads at multiple orbital locations. The RS-34 Concept Study lead by sought to further understand application for a similar orbital debris design reference mission to provide propulsive capability for rendezvous, close proximity operations to support the capture phase of the mission, and deorbit of single or multiple large class resident space objects. Multiple configurations varying the degree of modification were identified to trade for dry mass optimization and propellant load. The results of the RS-34 Phoenix Concept Study show that the system is technically sufficient to successfully support all of the missions to rendezvous, capture, and de-orbit targets including Envisat and Hubble Space Telescope. The results and benefits of the RS-34 Orbital Debris Application Concept Study are presented in this paper.

Minerva: A Dedicated Observatory for the Detection of Small Planets in the Solar Neighborhood

NASA Astrophysics Data System (ADS)

Hogstrom, Kristina; Johnson, J. A.; Wright, J.; McCrady, N.; Swift, J.; Muirhead, P.; Bottom, M.; Plavchan, P.; Zhao, M.; Riddle, R. L.

2013-01-01

Minerva is an array of 0.7m aperture robotic telescopes to be built atop Palomar Mountain outfitted for both photometry and high-resolution spectroscopy. It will be the first U.S. observatory dedicated to exoplanetary science capable of both precise radial velocimetry and transit studies. The multi-telescope concept will be implemented to either observe separate targets or a single target with a larger effective aperture. The flexibility of the observatory will maximize scientific potential and also provide ample opportunities for education and public outreach. The design and implementation of Minerva will be carried out by postdoctoral and student researchers at Caltech.

Development of a cryogenically cooled platform for the Magnetized Liner Inertial Fusion (MagLIF) Program [Development of a cryogenically-cooled platform for the Magnetized Liner Inertial Fusion (MagLIF) Concept

DOE PAGES

Awe, T. J.; Shelton, K. P.; Sefkow, A. B.; ...

2017-09-25

A cryogenically cooled hardware platform has been developed and commissioned on the Z Facility at Sandia National Laboratories in support of the Magnetized Liner Inertial Fusion (MagLIF) Program. MagLIF is a magneto-inertial fusion concept that employs a magnetically imploded metallic tube (liner) to compress and inertially confine premagnetized and preheated fusion fuel. The fuel is preheated using a ~2 kJ laser that must pass through a ~1.5-3.5-μm-thick polyimide “window” at the target’s laser entrance hole (LEH). As the terawatt-class laser interacts with the dense window, laser plasma instabilities (LPIs) can develop, which reduce the preheat energy delivered to the fuel,more » initiate fuel contamination, and degrade target performance. Cryogenically cooled targets increase the parameter space accessible to MagLIF target designs by allowing nearly 10 times thinner windows to be used for any accessible gas density. Thinner LEH windows reduce the deleterious effects of difficult to model LPIs. The Z Facility’s cryogenic infrastructure has been significantly altered to enable compatibility with the premagnetization and fuel preheat stages of MagLIF. The MagLIF cryostat brings the liquid helium coolant directly to the target via an electrically resistive conduit. This design maximizes cooling power while allowing rapid diffusion of the axial magnetic field supplied by external Helmholtz-like coils. A variety of techniques have been developed to mitigate the accumulation of ice from vacuum chamber contaminants on the cooled LEH window, as even a few hundred nanometers of ice would impact laser energy coupling to the fuel region. Here, the MagLIF cryostat has demonstrated compatibility with the premagnetization and preheat stages of MagLIF and the ability to cool targets to liquid deuterium temperatures in approximately 5 min.« less

Development of a cryogenically cooled platform for the Magnetized Liner Inertial Fusion (MagLIF) Program [Development of a cryogenically-cooled platform for the Magnetized Liner Inertial Fusion (MagLIF) Concept

DOE Office of Scientific and Technical Information (OSTI.GOV)

Awe, T. J.; Shelton, K. P.; Sefkow, A. B.

A cryogenically cooled hardware platform has been developed and commissioned on the Z Facility at Sandia National Laboratories in support of the Magnetized Liner Inertial Fusion (MagLIF) Program. MagLIF is a magneto-inertial fusion concept that employs a magnetically imploded metallic tube (liner) to compress and inertially confine premagnetized and preheated fusion fuel. The fuel is preheated using a ~2 kJ laser that must pass through a ~1.5-3.5-μm-thick polyimide “window” at the target’s laser entrance hole (LEH). As the terawatt-class laser interacts with the dense window, laser plasma instabilities (LPIs) can develop, which reduce the preheat energy delivered to the fuel,more » initiate fuel contamination, and degrade target performance. Cryogenically cooled targets increase the parameter space accessible to MagLIF target designs by allowing nearly 10 times thinner windows to be used for any accessible gas density. Thinner LEH windows reduce the deleterious effects of difficult to model LPIs. The Z Facility’s cryogenic infrastructure has been significantly altered to enable compatibility with the premagnetization and fuel preheat stages of MagLIF. The MagLIF cryostat brings the liquid helium coolant directly to the target via an electrically resistive conduit. This design maximizes cooling power while allowing rapid diffusion of the axial magnetic field supplied by external Helmholtz-like coils. A variety of techniques have been developed to mitigate the accumulation of ice from vacuum chamber contaminants on the cooled LEH window, as even a few hundred nanometers of ice would impact laser energy coupling to the fuel region. Here, the MagLIF cryostat has demonstrated compatibility with the premagnetization and preheat stages of MagLIF and the ability to cool targets to liquid deuterium temperatures in approximately 5 min.« less

The use of participant-observation protocol in an industrial engineering research.

PubMed

Silveira e Silva, Renato da; Sznelwar, Laerte Idal; D'Afonseca e Silva, Victor

2012-01-01

Based on literature, this article aims to present the "participant-observation' research protocol, and its practical application in the industrial engineering field, more specifically within the area of design development, and in the case shown by this article, of interiors' design. The main target is to identify the concept of the method, i.e., from its characteristics to structure a general sense about the subject, so that the protocol can be used in different areas of knowledge, especially those ones which are committed with the scientific research involving the expertise from researchers, and subjective feelings and opinions of the users of an engineering product, and how this knowledge can be benefic for product design, contributing since the earliest stage of design.

A supermolecular building approach for the design and construction of metal-organic frameworks.

PubMed

Guillerm, Vincent; Kim, Dongwook; Eubank, Jarrod F; Luebke, Ryan; Liu, Xinfang; Adil, Karim; Lah, Myoung Soo; Eddaoudi, Mohamed

2014-08-21

In this review, we describe two recently implemented conceptual approaches facilitating the design and deliberate construction of metal–organic frameworks (MOFs), namely supermolecular building block (SBB) and supermolecular building layer (SBL) approaches. Our main objective is to offer an appropriate means to assist/aid chemists and material designers alike to rationally construct desired functional MOF materials, made-to-order MOFs. We introduce the concept of net-coded building units (net-cBUs), where precise embedded geometrical information codes uniquely and matchlessly a selected net, as a compelling route for the rational design of MOFs. This concept is based on employing pre-selected 0-periodic metal–organic polyhedra or 2-periodic metal–organic layers, SBBs or SBLs respectively, as a pathway to access the requisite net-cBUs. In this review, inspired by our success with the original rht-MOF, we extrapolated our strategy to other known MOFs via their deconstruction into more elaborate building units (namely polyhedra or layers) to (i) elucidate the unique relationship between edge-transitive polyhedra or layers and minimal edge-transitive 3-periodic nets, and (ii) illustrate the potential of the SBB and SBL approaches as a rational pathway for the design and construction of 3-periodic MOFs. Using this design strategy, we have also identified several new hypothetical MOFs which are synthetically targetable.

Accounting for uncertainty in the historical response rate of the standard treatment in single-arm two-stage designs based on Bayesian power functions.

PubMed

Matano, Francesca; Sambucini, Valeria

2016-11-01

In phase II single-arm studies, the response rate of the experimental treatment is typically compared with a fixed target value that should ideally represent the true response rate for the standard of care therapy. Generally, this target value is estimated through previous data, but the inherent variability in the historical response rate is not taken into account. In this paper, we present a Bayesian procedure to construct single-arm two-stage designs that allows to incorporate uncertainty in the response rate of the standard treatment. In both stages, the sample size determination criterion is based on the concepts of conditional and predictive Bayesian power functions. Different kinds of prior distributions, which play different roles in the designs, are introduced, and some guidelines for their elicitation are described. Finally, some numerical results about the performance of the designs are provided and a real data example is illustrated. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A Survey of Titan Balloon Concepts and Technology Status

NASA Technical Reports Server (NTRS)

Hall, Jeffery L.

2011-01-01

This paper surveys the options for, and technology status of, balloon vehicles to explore Saturn's moon Titan. A significant amount of Titan balloon concept thinking and technology development has been performed in recent years, particularly following the spectacular results from the descent and landing of the Huygens probe and remote sensing observations by the Cassini spacecraft. There is widespread recognition that a balloon vehicle on the next Titan mission could provide an outstanding and unmatched capability for in situ exploration on a global scale. The rich variety of revealed science targets has combined with a highly favorable Titan flight environment to yield a wide diversity of proposed balloon concepts. The paper presents a conceptual framework for thinking about balloon vehicle design choices and uses it to analyze various Titan options. The result is a list of recommended Titan balloon vehicle concepts that could perform a variety of science missions, along with their projected performance metrics. Recent technology developments for these balloon concepts are discussed to provide context for an assessment of outstanding risk areas and technological maturity. The paper concludes with suggestions for technology investments needed to achieve flight readiness.

Concept Mapping Assessment of Media Assisted Learning in Interdisciplinary Science Education

NASA Astrophysics Data System (ADS)

Schaal, Steffen; Bogner, Franz X.; Girwidz, Raimund

2010-05-01

Acquisition of conceptual knowledge is a central aim in science education. In this study we monitored an interdisciplinary hypermedia assisted learning unit on hibernation and thermodynamics based on cooperative learning. We used concept mapping for the assessment, applying a pre-test/post-test design. In our study, 106 9th graders cooperated by working in pairs ( n = 53) for six lessons. As an interdisciplinary learning activity in such complex knowledge domains has to combine many different aspects, we focused on long-term knowledge. Learners working cooperatively in dyads constructed computer-supported concept maps which were analysed by specific software. The data analysis encompassed structural aspects of the knowledge corresponding to a target reference map. After the learning unit, the results showed the acquisition of higher-order domain-specific knowledge structures which indicates successful interdisciplinary learning through the hypermedia learning environment. The benefit of using a computer-assisted concept mapping assessment for research in science education, and in science classrooms is considered.

Audience reactions and receptivity to HIV prevention message concepts for people living with HIV.

PubMed

Uhrig, Jennifer D; Bann, Carla M; Wasserman, Jill; Guenther-Grey, Carolyn; Eroğlu, Doğan

2010-04-01

This study measured audience reactions and receptivity to five draft HIV prevention messages developed for people living with HIV (PLWH) to inform future HIV message choice and audience targeting decisions. Our premise was that message concepts that receive wide audience appeal constitute a strong starting point for designing future HIV prevention messages, program activities, and health communication and marketing campaigns for PLWH. The majority of participants indicated agreement with evaluative statements that expressed favorable attitudes toward all five of the message concepts we evaluated. Participants gave the lowest approval to the message promoting sero-sorting. Sociodemographic characteristics played less of a role in predicting differences in message perceptions than attitudes, beliefs and sexual behavior. The general appeal for these messages is encouraging given that messages were expressed in plain text without the support of other creative elements that are commonly used in message execution. These results confirm the utility of systematic efforts to generate and screen message concepts prior to large-scale testing.

Optical and Electric Multifunctional CMOS Image Sensors for On-Chip Biosensing Applications

PubMed Central

Tokuda, Takashi; Noda, Toshihiko; Sasagawa, Kiyotaka; Ohta, Jun

2010-01-01

In this review, the concept, design, performance, and a functional demonstration of multifunctional complementary metal-oxide-semiconductor (CMOS) image sensors dedicated to on-chip biosensing applications are described. We developed a sensor architecture that allows flexible configuration of a sensing pixel array consisting of optical and electric sensing pixels, and designed multifunctional CMOS image sensors that can sense light intensity and electric potential or apply a voltage to an on-chip measurement target. We describe the sensors’ architecture on the basis of the type of electric measurement or imaging functionalities. PMID:28879978

Improving Clinical Trial Efficiency: Thinking outside the Box.

PubMed

Mandrekar, Sumithra J; Dahlberg, Suzanne E; Simon, Richard

2015-01-01

Clinical trial design strategies have evolved over the past few years as a means to accelerate the drug development process so that the right therapies can be delivered to the right patients. Basket, umbrella, and adaptive enrichment strategies represent a class of novel designs for testing targeted therapeutics in oncology. Umbrella trials include a central infrastructure for screening and identification of patients, and focus on a single tumor type or histology with multiple subtrials, each testing a targeted therapy within a molecularly defined subset. Basket trial designs offer the possibility to include multiple molecularly defined subpopulations, often across histology or tumor types, but included in one cohesive design to evaluate the targeted therapy in question. Adaptive enrichment designs offer the potential to enrich for patients with a particular molecular feature that is predictive of benefit for the test treatment based on accumulating evidence from the trial. This review will aim to discuss the fundamentals of these design strategies, the underlying statistical framework, the logistical barriers of implementation, and, ultimately, the interpretation of the trial results. New statistical approaches, extensive multidisciplinary collaboration, and state of the art data capture technologies are needed to implement these strategies in practice. Logistical challenges to implementation arising from centralized assay testing, requirement of multiple specimens, multidisciplinary collaboration, and infrastructure requirements will also be discussed. This review will present these concepts in the context of the National Cancer Institute's precision medicine initiative trials: MATCH, ALCHEMIST, Lung MAP, as well as other trials such as FOCUS4.

Extending the Duluth Model to Workplace Bullying: A Modification and Adaptation of the Workplace Power-Control Wheel.

PubMed

Scott, Hannah S

2018-03-01

Workplace bullying (WB) is an increasingly prevalent topic in the nursing literature. Recently, a new concept has been introduced into WB research to explain the motivations of WB instigators using elements of the Power-Control Wheel (PCW). Initially, this wheel was designed to assist intimate partner violence (IPV) targets/victims identify patterns of abuse and intervene with male batterers/instigators. Research examining IPV and victims/survivors of WB demonstrate that targets often share common abusive experiences, including intimidation, coercion and threats, isolation, and economic and emotional abuse. This article demonstrates clear support for the Duluth Model and its application to WB target experiences. Applications of this model to identify WB and assist individuals to identify and describe experiences of abusive work environments are discussed.

NASA's Advanced Exploration Systems Mars Transit Habitat Refinement Point of Departure Design

NASA Technical Reports Server (NTRS)

Simon, Matthew; Latorella, Kara; Martin, John; Cerro, Jeff; Lepsch, Roger; Jefferies, Sharon; Goodliff, Kandyce; McCleskey, Carey; Smitherman, David; Stromgren, Chel

2017-01-01

This paper describes the recently developed point of departure design for a long duration, reusable Mars Transit Habitat, which was established during a 2016 NASA habitat design refinement activity supporting the definition of NASA's Evolvable Mars Campaign. As part of its development of sustainable human Mars mission concepts achievable in the 2030s, the Evolvable Mars Campaign has identified desired durations and mass/dimensional limits for long duration Mars habitat designs to enable the currently assumed solar electric and chemical transportation architectures. The Advanced Exploration Systems Mars Transit Habitat Refinement Activity brought together habitat subsystem design expertise from across NASA to develop an increased fidelity, consensus design for a transit habitat within these constraints. The resulting design and data (including a mass equipment list) contained in this paper are intended to help teams across the agency and potential commercial, academic, or international partners understand: 1) the current architecture/habitat guidelines and assumptions, 2) performance targets of such a habitat (particularly in mass, volume, and power), 3) the driving technology/capability developments and architectural solutions which are necessary for achieving these targets, and 4) mass reduction opportunities and research/design needs to inform the development of future research and proposals. Data presented includes: an overview of the habitat refinement activity including motivation and process when informative; full documentation of the baseline design guidelines and assumptions; detailed mass and volume breakdowns; a moderately detailed concept of operations; a preliminary interior layout design with rationale; a list of the required capabilities necessary to enable the desired mass; and identification of any worthwhile trades/analyses which could inform future habitat design efforts. As a whole, the data in the paper show that a transit habitat meeting the 43 metric tons launch mass/trans-Mars injection burn limits specified by the Evolvable Mars Campaign is achievable near the desired timeframe with moderate strategic investments including maintainable life support systems, repurposable structures and packaging, and lightweight exercise modalities. It also identifies operational and technological options to reduce this mass to less than 41 metric tons including staging of launch structure/packaging and alternate structural materials.

Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes

PubMed Central

2015-01-01

We report a versatile dendritic structure based platform for construction of targeted dual-modality imaging probes. The platform contains multiple copies of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out from a 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) core. The specific coordination chemistries of the NOTA and DOTA moieties offer specific loading of 68/67Ga3+ and Gd3+, respectively, into a common molecular scaffold. The platform also contains three amino groups which can potentiate targeted dual-modality imaging of PET/MRI or SPECT/MRI (PET: positron emission tomography; SPECT: single photon emission computed tomography; MRI: magnetic resonance imaging) when further functionalized by targeting vectors of interest. To validate this design concept, a bimetallic complex was synthesized with six peripheral Gd-DOTA units and one Ga-NOTA core at the center, whose ion T1 relaxivity per gadolinium atom was measured to be 15.99 mM–1 s–1 at 20 MHz. Further, the bimetallic agent demonstrated its anticipated in vivo stability, tissue distribution, and pharmacokinetic profile when labeled with 67Ga. When conjugated with a model targeting peptide sequence, the trivalent construct was able to visualize tumors in a mouse xenograft model by both PET and MRI via a single dose injection. PMID:25615011

Statistical molecular design of balanced compound libraries for QSAR modeling.

PubMed

Linusson, A; Elofsson, M; Andersson, I E; Dahlgren, M K

2010-01-01

A fundamental step in preclinical drug development is the computation of quantitative structure-activity relationship (QSAR) models, i.e. models that link chemical features of compounds with activities towards a target macromolecule associated with the initiation or progression of a disease. QSAR models are computed by combining information on the physicochemical and structural features of a library of congeneric compounds, typically assembled from two or more building blocks, and biological data from one or more in vitro assays. Since the models provide information on features affecting the compounds' biological activity they can be used as guides for further optimization. However, in order for a QSAR model to be relevant to the targeted disease, and drug development in general, the compound library used must contain molecules with balanced variation of the features spanning the chemical space believed to be important for interaction with the biological target. In addition, the assays used must be robust and deliver high quality data that are directly related to the function of the biological target and the associated disease state. In this review, we discuss and exemplify the concept of statistical molecular design (SMD) in the selection of building blocks and final synthetic targets (i.e. compounds to synthesize) to generate information-rich, balanced libraries for biological testing and computation of QSAR models.

Mercury Handling for the Target System for a Muon Collider

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graves, Van B; Mcdonald, K; Kirk, H.

2012-01-01

The baseline target concept for a Muon Collider or Neutrino Factory is a free-stream mercury jet being impacted by an 8-GeV proton beam. The target is located within a 20-T magnetic field, which captures the generated pions that are conducted to a downstream decay channel. Both the mercury and the proton beam are introduced at slight downward angles to the magnetic axis. A pool of mercury serves as a receiving reservoir for the mercury and a dump for the unexpended proton beam. The impact energy of the remaining beam and jet are substantial, and it is required that splashes andmore » waves be controlled in order to minimize the potential for interference of pion production at the target. Design issues discussed in this paper include the nozzle, splash mitigation in the mercury pool, the mercury containment vessel, and the mercury recirculation system.« less

Head-Up Auditory Displays for Traffic Collision Avoidance System Advisories: A Preliminary Investigation

NASA Technical Reports Server (NTRS)

Begault, Durand R.

1993-01-01

The advantage of a head-up auditory display was evaluated in a preliminary experiment designed to measure and compare the acquisition time for capturing visual targets under two auditory conditions: standard one-earpiece presentation and two-earpiece three-dimensional (3D) audio presentation. Twelve commercial airline crews were tested under full mission simulation conditions at the NASA-Ames Man-Vehicle Systems Research Facility advanced concepts flight simulator. Scenario software generated visual targets corresponding to aircraft that would activate a traffic collision avoidance system (TCAS) aural advisory; the spatial auditory position was linked to the visual position with 3D audio presentation. Results showed that crew members using a 3D auditory display acquired targets approximately 2.2 s faster than did crew members who used one-earpiece head- sets, but there was no significant difference in the number of targets acquired.

Exciton-controlled fluorescence: application to hybridization-sensitive fluorescent DNA probe.

PubMed

Okamoto, Akimitsu; Ikeda, Shuji; Kubota, Takeshi; Yuki, Mizue; Yanagisawa, Hiroyuki

2009-01-01

A hybridization-sensitive fluorescent probe has been designed for nucleic acid detection, using the concept of fluorescence quenching caused by the intramolecular excitonic interaction of fluorescence dyes. We synthesized a doubly thiazole orange-labeled nucleotide showing high fluorescence intensity for a hybrid with the target nucleic acid and effective quenching for the single-stranded state. This exciton-controlled fluorescent probe was applied to living HeLa cells using microinjection to visualize intracellular mRNA localization. Immediately after injection of the probe into the cell, fluorescence was observed from the probe hybridizing with the target RNA. This fluorescence rapidly decreased upon addition of a competitor DNA. Multicoloring of this probe resulted in the simple simultaneous detection of plural target nucleic acid sequences. This probe realized a large, rapid, reversible change in fluorescence intensity in sensitive response to the amount of target nucleic acid, and facilitated spatiotemporal monitoring of the behavior of intracellular RNA.

PHOBOS Exploration using Two Small Solar Electric Propulsion Spacecraft

NASA Technical Reports Server (NTRS)

Lang, Jared J.; Baker, John D.; Castillo-Rogez, Julie C.; McElrath, Timothy P.; Piacentine, Jamie S.; Snyder, J. Steve

2012-01-01

Primitive bodies are exciting targets for exploration as they provide clues to the early Solar system conditions and dynamical evolution. The two moons of Mars are particularly interesting because of their proximity to an astrobiological target. However, after four decades of Mars exploration, their origin and nature remain enigmatic. In addition, when considering the long-term objectives of the flexible path for the potential human exploration to Mars, Phobos and Deimos present exciting intermediate opportunities without the complication and expense of landing and ascending from the surface. As interest in these targets for the next frontier of human exploration grows, characterization missions designed specifically to examine surface properties, landing environments, and surface mapping prior to human exploration are becoming increasingly important. A precursor mission concept of this sort has been developed using two identical spacecraft designed from low cost, flight proven and certified off-the-shelf component and utilizing Solar Electric Propulsion (SEP) to orbit both targets as secondary payloads launched aboard any NASA or GTO launch. This precursor mission has the potential to address both precursor measurements that are strategic knowledge gaps and decadal science, including soil physical properties at the global and local (human) scale and the search for in situ resources.

Conceptual Design of In-Space Vehicles for Human Exploration of the Outer Planets

NASA Technical Reports Server (NTRS)

Adams, R. B.; Alexander, R. A.; Chapman, J. M.; Fincher, S. S.; Hopkins, R. C.; Philips, A. D.; Polsgrove, T. T.; Litchford, R. J.; Patton, B. W.; Statham, G.

2003-01-01

During FY-2002, a team of engineers from TD30/Advanced Concepts and TD40/Propulsion Research Center embarked on a study of potential crewed missions to the outer solar system. The study was conducted under the auspices of the Revolutionary Aerospace Systems Concepts activity administered by Langley Research Center (LaRC). The Marshall Space Flight Center (MSFC) team interacted heavily with teams from other Centers including Glenn Research Center, LaRC, Jet Propulsion Laboratory, and Johnson Space Center. The MSFC team generated five concept missions for this project. The concept missions use a variety of technologies, including magnetized target fusion (MTF), magnetoplasmadynamic thrusters, solid core reactors, and molten salt reactors in various combinations. The Technical Publication (TP) reviews these five concepts and the methods used to generate them. The analytical methods used are described for all significant disciplines and subsystems. The propulsion and power technologies selected for each vehicle are reviewed in detail. The MSFC team also expended considerable effort refining the MTF concept for use with this mission. The results from this effort are also contained within this TP. Finally, the lessons learned from this activity are summarized in the conclusions section.

Building Integrated Design Practice under the Concept of Sustainable Development

NASA Astrophysics Data System (ADS)

Liu, Xuexin

2018-03-01

With the continuous development of social economy, people are more demanding for architecture. Some advanced design concepts are gradually applied to the design of buildings. Under the concept of sustainable development, building integration design has also been widely used to promote the rapid development of architectural design. Integrated design concepts and sustainable development concepts play an important role to meet people’s requirements. This article will explore the concept of sustainable development under the concept of integrated architectural design and practice analysis, propose appropriate measures.

Guidance and Navigation for Rendezvous and Proximity Operations with a Non-Cooperative Spacecraft at Geosynchronous Orbit

NASA Technical Reports Server (NTRS)

Barbee, Brent William; Carpenter, J. Russell; Heatwole, Scott; Markley, F. Landis; Moreau, Michael; Naasz, Bo J.; VanEepoel, John

2010-01-01

The feasibility and benefits of various spacecraft servicing concepts are currently being assessed, and all require that the servicer spacecraft perform rendezvous, proximity, and capture operations with the target spacecraft to be serviced. Many high-value spacecraft, which would be logical targets for servicing from an economic point of view, are located in geosynchronous orbit, a regime in which autonomous rendezvous and capture operations are not commonplace. Furthermore, existing GEO spacecraft were not designed to be serviced. Most do not have cooperative relative navigation sensors or docking features, and some servicing applications, such as de-orbiting of a non-functional spacecraft, entail rendezvous and capture with a spacecraft that may be non-functional or un-controlled. Several of these challenges have been explored via the design of a notional mission in which a nonfunctional satellite in geosynchronous orbit is captured by a servicer spacecraft and boosted into super-synchronous orbit for safe disposal. A strategy for autonomous rendezvous, proximity operations, and capture is developed, and the Orbit Determination Toolbox (ODTBX) is used to perform a relative navigation simulation to assess the feasibility of performing the rendezvous using a combination of angles-only and range measurements. Additionally, a method for designing efficient orbital rendezvous sequences for multiple target spacecraft is utilized to examine the capabilities of a servicer spacecraft to service multiple targets during the course of a single mission.

Pathotropic nanoparticles for cancer gene therapy Rexin-G IV: three-year clinical experience.

PubMed

Gordon, Erlinda M; Lopez, Francisco F; Cornelio, Gerardo H; Lorenzo, Conrado C; Levy, John P; Reed, Rebecca A; Liu, Liqiong; Bruckner, Howard W; Hall, Frederick L

2006-11-01

Metastatic cancer is a life-threatening illness with a predictably fatal outcome, thereby representing a major unmet medical need. In 2003, Rexin-G became the world's first targeted injectable vector approved for clinical trials in the treatment of intractable metastatic disease. Uniquely suited, by design, to function within the context of the human circulatory system, Rexin-G is a pathotropic (disease-seeking) gene delivery system bearing a designer killer gene; in essence, a targeted nanoparticle that seeks out and selectively accumulates in metastatic sites upon intravenous infusion. The targeted delivery of the cytocidal gene to primary tumors and metastatic foci, in effective local concentrations, compels both cancer cells and tumor-associated neovasculature to self-destruct, without causing untoward collateral damage to non-target organs. In this study: i) we report the results of three distinctive clinical studies which demonstrate the initial proofs of concept, safety, and efficacy of Rexin-G when used as a single agent for advanced or metastatic cancer, ii) we introduce the quantitative foundations of an innovative personalized treatment regimen, designated the 'Calculus of Parity', based on a patient's calculated tumor burden, iii) we propose a refinement of surrogate end-points commonly used for defining success in cancer therapy, and iv) we map out a strategic plan for the accelerated approval of Rexin-G based on the oncologic Threshold of Credibility paradigm being developed by the Food and Drug Administration.

Dual-acting of Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches.

PubMed

Abdolmaleki, Azizeh; Ghasemi, Jahan B

2017-01-01

Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as selective multitarget chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group's participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mtdrugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Surface target-tracking guidance by self-organizing formation flight of fixed-wing UAV

NASA Astrophysics Data System (ADS)

Regina, N.; Zanzi, M.

This paper presents a new concept of ground target surveillance based on a formation flight of two Unmanned Aerial Vehicles (UAVs) of fixed-wing type. Each UAV considered in this work has its own guidance law specifically designed for two different aims. A self organizing non-symmetric collaborative surveying scheme has been developed based on pursuers with different roles: the close-up-pursuer and the distance-pursuer. The close-up-pursuer behaves according to a guidance law which takes it to continually over-fly the target, also optimizing flight endurance. On the other hand, the distancepursuer behaves so as to circle around the target by flying at a certain distance and altitude from it; moreover, its motion ensures the maximum “ seeability” of the ground based target. In addition, the guidance law designed for the distance-pursuer also implements a collision avoidance feature in order to prevent possible risks of collision with the close-up-pursuer during the tracking maneuvers. The surveying scheme is non-symmetric in the sense that the collision avoidance feature is accomplished by a guidance law implemented only on one of the two pursuers; moreover, it is collaborative because the surveying is performed by different tasks of two UAVs and is self-organizing because, due to the collision avoidance feature, target tracking does not require pre-planned collision-risk-free trajectories but trajectories are generated in real time.

Efficient Mitochondrial Glutamine Targeting Prevails Over Glioblastoma Metabolic Plasticity.

PubMed

Oizel, Kristell; Chauvin, Cynthia; Oliver, Lisa; Gratas, Catherine; Geraldo, Fanny; Jarry, Ulrich; Scotet, Emmanuel; Rabe, Marion; Alves-Guerra, Marie-Clotilde; Teusan, Raluca; Gautier, Fabien; Loussouarn, Delphine; Compan, Vincent; Martinou, Jean-Claude; Vallette, François M; Pecqueur, Claire

2017-10-15

Purpose: Glioblastoma (GBM) is the most common and malignant form of primary human brain tumor in adults, with an average survival at diagnosis of 18 months. Metabolism is a new attractive therapeutic target in cancer; however, little is known about metabolic heterogeneity and plasticity within GBM tumors. We therefore aimed to investigate metabolic phenotyping of primary cultures in the context of molecular tumor heterogeneity to provide a proof of concept for personalized metabolic targeting of GBM. Experimental Design: We have analyzed extensively several primary GBM cultures using transcriptomics, metabolic phenotyping assays, and mitochondrial respirometry. Results: We found that metabolic phenotyping clearly identifies 2 clusters, GLN High and GLN Low , mainly based on metabolic plasticity and glutamine (GLN) utilization. Inhibition of glutamine metabolism slows the in vitro and in vivo growth of GLN High GBM cultures despite metabolic adaptation to nutrient availability, in particular by increasing pyruvate shuttling into mitochondria. Furthermore, phenotypic and molecular analyses show that highly proliferative GLN High cultures are CD133 neg and display a mesenchymal signature in contrast to CD133 pos GLN Low GBM cells. Conclusions: Our results show that metabolic phenotyping identified an essential metabolic pathway in a GBM cell subtype, and provide a proof of concept for theranostic metabolic targeting. Clin Cancer Res; 23(20); 6292-304. ©2017 AACR . ©2017 American Association for Cancer Research.

Progress Toward Attractive Stellarators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neilson, G H; Brown, T G; Gates, D A

The quasi-axisymmetric stellarator (QAS) concept offers a promising path to a more compact stellarator reactor, closer in linear dimensions to tokamak reactors than previous stellarator designs. Concept improvements are needed, however, to make it more maintainable and more compatible with high plant availability. Using the ARIES-CS design as a starting point, compact stellarator designs with improved maintenance characteristics have been developed. While the ARIES-CS features a through-the-port maintenance scheme, we have investigated configuration changes to enable a sector-maintenance approach, as envisioned for example in ARIES AT. Three approaches are reported. The first is to make tradeoffs within the QAS designmore » space, giving greater emphasis to maintainability criteria. The second approach is to improve the optimization tools to more accurately and efficiently target the physics properties of importance. The third is to employ a hybrid coil topology, so that the plasma shaping functions of the main coils are shared more optimally, either with passive conductors made of high-temperature superconductor or with local compensation coils, allowing the main coils to become simpler. Optimization tools are being improved to test these approaches.« less

Multidisciplinary conceptual design optimization of aircraft using a sound-matching-based objective function

NASA Astrophysics Data System (ADS)

Diez, Matteo; Iemma, Umberto

2012-05-01

The article presents a novel approach to include community noise considerations based on sound quality in the Multidisciplinary Conceptual Design Optimization (MCDO) of civil transportation aircraft. The novelty stems from the use of an unconventional objective function, defined as a measure of the difference between the noise emission of the aircraft under analysis and a reference 'weakly annoying' noise, the target sound. The minimization of such a merit factor yields an aircraft concept with a noise signature as close as possible to the given target. The reference sound is one of the outcomes of the European Research Project SEFA (Sound Engineering For Aircraft, VI Framework Programme, 2004-2007), and used here as an external input. The aim of the present work is to address the definition and the inclusion of the sound-matching-based objective function in the MCDO of aircraft.

The effect of spatial organization of targets and distractors on the capacity to selectively memorize objects in visual short-term memory.

PubMed

Abbes, Aymen Ben; Gavault, Emmanuelle; Ripoll, Thierry

2014-01-01

We conducted a series of experiments to explore how the spatial configuration of objects influences the selection and the processing of these objects in a visual short-term memory task. We designed a new experiment in which participants had to memorize 4 targets presented among 4 distractors. Targets were cued during the presentation of distractor objects. Their locations varied according to 4 spatial configurations. From the first to the last configuration, the distance between targets' locations was progressively increased. The results revealed a high capacity to select and memorize targets embedded among distractors even when targets were extremely distant from each other. This capacity is discussed in relation to the unitary conception of attention, models of split attention, and the competitive interaction model. Finally, we propose that the spatial dispersion of objects has different effects on attentional allocation and processing stages. Thus, when targets are extremely distant from each other, attentional allocation becomes more difficult while processing becomes easier. This finding implicates that these 2 aspects of attention need to be more clearly distinguished in future research.

Development of the Biological Experimental Design Concept Inventory (BEDCI).

PubMed

Deane, Thomas; Nomme, Kathy; Jeffery, Erica; Pollock, Carol; Birol, Gülnur

2014-01-01

Interest in student conception of experimentation inspired the development of a fully validated 14-question inventory on experimental design in biology (BEDCI) by following established best practices in concept inventory (CI) design. This CI can be used to diagnose specific examples of non-expert-like thinking in students and to evaluate the success of teaching strategies that target conceptual changes. We used BEDCI to diagnose non-expert-like student thinking in experimental design at the pre- and posttest stage in five courses (total n = 580 students) at a large research university in western Canada. Calculated difficulty and discrimination metrics indicated that BEDCI questions are able to effectively capture learning changes at the undergraduate level. A high correlation (r = 0.84) between responses by students in similar courses and at the same stage of their academic career, also suggests that the test is reliable. Students showed significant positive learning changes by the posttest stage, but some non-expert-like responses were widespread and persistent. BEDCI is a reliable and valid diagnostic tool that can be used in a variety of life sciences disciplines. © 2014 T. Deane et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

A Hierarchical Visualization Analysis Model of Power Big Data

NASA Astrophysics Data System (ADS)

Li, Yongjie; Wang, Zheng; Hao, Yang

2018-01-01

Based on the conception of integrating VR scene and power big data analysis, a hierarchical visualization analysis model of power big data is proposed, in which levels are designed, targeting at different abstract modules like transaction, engine, computation, control and store. The regularly departed modules of power data storing, data mining and analysis, data visualization are integrated into one platform by this model. It provides a visual analysis solution for the power big data.

The New Intelligence, Surveillance, and Reconnaissance Cockpit: Examining the Contributions of Emerging Unmanned Aircraft Systems

DTIC Science & Technology

2010-04-25

similar to the architecture of the right hemisphere of the brain. 169 The other method involves the development of software-based pheromones ...borrowing from the genetic behaviors employed by ants and termites . 170 UAVs and UCAVs employing this theoretical technique can essentially mark...coverage areas and targets with “digital pheromones .” 171 Both concepts are being designed to allow relatively inexpensive unmanned aircraft to cue

A Bayesian paradigm for decision-making in proof-of-concept trials.

PubMed

Pulkstenis, Erik; Patra, Kaushik; Zhang, Jianliang

2017-01-01

Decision-making is central to every phase of drug development, and especially at the proof of concept stage where risk and evidence must be weighed carefully, often in the presence of significant uncertainty. The decision to proceed or not to large expensive Phase 3 trials has significant implications to both patients and sponsors alike. Recent experience has shown that Phase 3 failure rates remain high. We present a flexible Bayesian quantitative decision-making paradigm that evaluates evidence relative to achieving a multilevel target product profile. A framework for operating characteristics is provided that allows the drug developer to design a proof-of-concept trial in light of its ability to support decision-making rather than merely achieve statistical significance. Operating characteristics are shown to be superior to traditional p-value-based methods. In addition, discussion related to sample size considerations, application to interim futility analysis and incorporation of prior historical information is evaluated.

Modeling of microjoule and millijoule energy LIDARs with PMT/SiPM/APD detectors: a sensitivity analysis.

PubMed

Agishev, Ravil

2018-05-10

This paper demonstrates a renewed concept and applications of the generalized methodology for atmospheric light detection and ranging (LIDAR) capability prediction as a continuation of a series of our previous works, where the dimensionless parameterization appeared as a tool for comparing systems of a different scale, design, and applications. The modernized concept applied to microscale and milliscale LIDARs with relatively new silicon photomultiplier detectors and traditional photomultiplier tube and avalanche photodiode detectors allowed prediction of the remote sensing instruments' performance and limitations. Such a generalized, uniform, and objective concept is applied for evaluation of the increasingly popular class of limited-energy LIDARs using the best optical detectors, operating on different targets (back-scatter or topographic, static or dynamic) and under intense sky background conditions. It can be used in the LIDAR community to compare different instruments and select the most suitable and effective ones for specific applications.

Experiments and simulation of a net closing mechanism for tether-net capture of space debris

NASA Astrophysics Data System (ADS)

Sharf, Inna; Thomsen, Benjamin; Botta, Eleonora M.; Misra, Arun K.

2017-10-01

This research addresses the design and testing of a debris containment system for use in a tether-net approach to space debris removal. The tether-net active debris removal involves the ejection of a net from a spacecraft by applying impulses to masses on the net, subsequent expansion of the net, the envelopment and capture of the debris target, and the de-orbiting of the debris via a tether to the chaser spacecraft. To ensure a debris removal mission's success, it is important that the debris be successfully captured and then, secured within the net. To this end, we present a concept for a net closing mechanism, which we believe will permit consistently successful debris capture via a simple and unobtrusive design. This net closing system functions by extending the main tether connecting the chaser spacecraft and the net vertex to the perimeter and around the perimeter of the net, allowing the tether to actuate closure of the net in a manner similar to a cinch cord. A particular embodiment of the design in a laboratory test-bed is described: the test-bed itself is comprised of a scaled-down tether-net, a supporting frame and a mock-up debris. Experiments conducted with the facility demonstrate the practicality of the net closing system. A model of the net closure concept has been integrated into the previously developed dynamics simulator of the chaser/tether-net/debris system. Simulations under tether tensioning conditions demonstrate the effectiveness of the closure concept for debris containment, in the gravity-free environment of space, for a realistic debris target. The on-ground experimental test-bed is also used to showcase its utility for validating the dynamics simulation of the net deployment, and a full-scale automated setup would make possible a range of validation studies of other aspects of a tether-net debris capture mission.

Linking climate change mitigation and coastal eutrophication management through biogas technology: Evidence from a new Danish bioenergy concept.

PubMed

Kaspersen, Bjarke Stoltze; Christensen, Thomas Budde; Fredenslund, Anders Michael; Møller, Henrik Bjarne; Butts, Michael Brian; Jensen, Niels H; Kjaer, Tyge

2016-01-15

The interest in sustainable bioenergy solutions has gained great importance in Europe due to the need to reduce GHG emissions and to meet environmental policy targets, not least for the protection of groundwater and surface water quality. In the Municipality of Solrød in Denmark, a novel bioenergy concept for anaerobic co-digestion of food industry residues, manure and beach-cast seaweed has been developed and tested in order to quantify the potential for synergies between climate change mitigation and coastal eutrophication management in the Køge Bay catchment. The biogas plant, currently under construction, was designed to handle an annual input of up to 200,000 t of biomass based on four main fractions: pectin wastes, carrageenan wastes, manure and beach-cast seaweed. This paper describes how this bioenergy concept can contribute to strengthening the linkages between climate change mitigation strategies and Water Framework Directive (WFD) action planning. Our assessments of the projected biogas plant indicate an annual reduction of GHG emissions of approx. 40,000 t CO2 equivalents, corresponding to approx. 1/3 of current total GHG emissions in the Municipality of Solrød. In addition, nitrogen and phosphorous loads to Køge Bay are estimated to be reduced by approx. 63 t yr.(-1) and 9 tyr.(-1), respectively, contributing to the achievement of more than 70% of the nutrient reduction target set for Køge Bay in the first WFD river basin management plan. This study shows that anaerobic co-digestion of the specific food industry residues, pig manure and beach-cast seaweed is feasible and that there is a very significant, cost-effective GHG and nutrient loading mitigation potential for this bioenergy concept. Our research demonstrates how an integrated planning process where considerations about the total environment are integrated into the design and decision processes can support the development of this kind of holistic bioenergy solutions. Copyright © 2015 Elsevier B.V. All rights reserved.

Imbalance in chemical space: How to facilitate the identification of protein-protein interaction inhibitors.

PubMed

Kuenemann, Mélaine A; Labbé, Céline M; Cerdan, Adrien H; Sperandio, Olivier

2016-04-01

Protein-protein interactions (PPIs) play vital roles in life and provide new opportunities for therapeutic interventions. In this large data analysis, 3,300 inhibitors of PPIs (iPPIs) were compared to 17 reference datasets of collectively ~566,000 compounds (including natural compounds, existing drugs, active compounds on conventional targets, etc.) using a chemoinformatics approach. Using this procedure, we showed that comparable classes of PPI targets can be formed using either the similarity of their ligands or the shared properties of their binding cavities, constituting a proof-of-concept that not only can binding pockets be used to group PPI targets, but that these pockets certainly condition the properties of their corresponding ligands. These results demonstrate that matching regions in both chemical space and target space can be found. Such identified classes of targets could lead to the design of PPI-class-specific chemical libraries and therefore facilitate the development of iPPIs to the stage of drug candidates.

Probing and improving student's understanding of protein α-helix structure using targeted assessment and classroom interventions in collaboration with a faculty community of practice.

PubMed

Loertscher, Jennifer; Villafañe, Sachel M; Lewis, Jennifer E; Minderhout, Vicky

2014-01-01

The increasing availability of concept inventories and other assessment tools in the molecular life sciences provides instructors with myriad avenues to probe student understanding. For example, although molecular visualization is central to the study of biochemistry, a growing body of evidence suggests that students have substantial limitations in their ability to recognize and interpret basic features of biological macromolecules. In this study, a pre/posttest administered to students at diverse institutions nationwide revealed a robust incorrect idea about the location of the amino acid side chains in the protein α-helix structure. Because this incorrect idea was present even after a semester of biochemistry instruction at a range of institutions, an intervention was necessary. A community of expert biochemistry instructors collaborated to design two active learning classroom activities that systematically examine α-helix structure and function. Several participating faculty used one or both of the activities in their classrooms and some improvement of student understanding of this concept was observed. This study provides a model of how a community of instructors can work together using assessment data to inform targeted changes in instruction with the goal of improving student understanding of fundamental concepts. Copyright © 2014 by The International Union of Biochemistry and Molecular Biology.

Pandemic controllability: a concept to guide a proportionate and flexible operational response to future influenza pandemics.

PubMed

McCaw, J M; Glass, K; Mercer, G N; McVernon, J

2014-03-01

The 2009 H1N1 influenza pandemic posed challenges for governments worldwide. Strategies designed to limit community transmission, such as antiviral deployment, were largely ineffective due to both feasibility constraints and the generally mild nature of disease, resulting in incomplete case ascertainment. Reviews of national pandemic plans have identified pandemic impact, primarily linked to measures of transmissibility and severity, as a key concept to incorporate into the next generation of plans. While an assessment of impact provides the rationale under which interventions may be warranted, it does not directly provide an assessment on whether particular interventions may be effective. Such considerations motivate our introduction of the concept of pandemic controllability. For case-targeted interventions, such as antiviral treatment and post-exposure prophylaxis, we identify the visibility and transmissibility of a pandemic as the key drivers of controllability. Taking a case-study approach, we suggest that high-impact pandemics, for which control is most desirable, are likely uncontrollable with case-targeted interventions. Strategies that do not rely on the identification of cases may prove relatively more effective. By introducing a pragmatic framework for relating the assessment of impact to the ability to mitigate an epidemic (controllability), we hope to address a present omission identified in pandemic response plans.

Application of Magnetized Target Fusion to High-Energy Space Propulsion

NASA Technical Reports Server (NTRS)

Thio, Y. C. F.; Schmidt, G. R.; Kirkpatrick, R. C.; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

Most fusion propulsion concepts that have been investigated in the past employ some form of inertial or magnetic confinement. Although the prospective performance of these concepts is excellent, the fusion processes on which these concepts are based still require considerable development before they can be seriously considered for actual applications. Furthermore, these processes are encumbered by the need for sophisticated plasma and power handling systems that are generally quite inefficient and have historically resulted in large, massive spacecraft designs. Here we present a comparatively new approach, Magnetized Target Fusion (MTF), which offers a nearer-term avenue for realizing the tremendous performance benefits of fusion propulsion'. The key advantage of MTF is its less demanding requirements for driver energy and power processing. Additional features include: 1) very low system masses and volumes, 2) high gain and relatively low waste heat, 3) substantial utilization of energy from product neutrons, 4) efficient, low peak-power drivers based on existing pulsed power technology, and 5) very high Isp, specific power and thrust. MTF overcomes many of the problems associated with traditional fusion techniques, thus making it particularly attractive for space applications. Isp greater than 50,000 seconds and specific powers greater than 50 kilowatts/kilogram appear feasible using relatively near-term pulse power and plasma gun technology.

What does systems biology mean for drug development?

PubMed

Schrattenholz, André; Soskić, Vukić

2008-01-01

The complexity and flexibility of cellular architectures is increasingly recognized by impressive progress on the side of molecular analytics, i.e. proteomics, genomics and metabolomics. One of the messages from systems biology is that the number of molecular species in cellular networks is orders of magnitude bigger than anticipated by genomic analysis, in particular by fast posttranslational modifications of proteins. The requirements to manage external signals, integrate spatiotemporal signal transduction inside an organism and at the same time optimizing networks of biochemical and chemical reactions result in chemically extremely fine tuned molecular entities. Chemical side reactions of enzymatic activity, like e.g. random oxidative damage of proteins by free radicals during aging constantly introduce epigenetic alterations of protein targets. These events gradually and on an individual stochastic scale, keep modifying activities of these targets, and their affinities and selectivities towards biological and pharmacological ligands. One further message is that many of the key reactions in living systems are essentially based on interactions of low affinities and even low selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. So, in complex disorders like cancer or neurodegenerative diseases, which are rooted in relatively subtle and multimodal dysfunction of important physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which still dominate the pharmaceutical industry increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade and the treatment of "complex diseases" remains a most pressing medical need. Currently a change of paradigm can be observed with regard to a new focus on agents that modulate multiple targets simultaneously. Targeting cellular function as a system rather than on the level of the single protein molecule significantly increases the size of the drugable proteome and is expected to introduce novel classes of multi-target drugs with fewer adverse effects and toxicity. Multiple target approaches have recently been used to design medications against atherosclerosis, cancer, depression, psychosis and neurodegenerative diseases. A focussed approach towards "systemic" drugs will certainly require the development of novel computational and mathematical concepts for appropriate modelling of complex data and extraction of "screenable" information from biological systems essentially ruled by deterministic chaotic processes on a background of individual stochasticity.

Twitter's tweet method modelling and simulation

NASA Astrophysics Data System (ADS)

Sarlis, Apostolos S.; Sakas, Damianos P.; Vlachos, D. S.

2015-02-01

This paper seeks to purpose the concept of Twitter marketing methods. The tools that Twitter provides are modelled and simulated using iThink in the context of a Twitter media-marketing agency. The paper has leveraged the system's dynamic paradigm to conduct Facebook marketing tools and methods modelling, using iThink™ system to implement them. It uses the design science research methodology for the proof of concept of the models and modelling processes. The following models have been developed for a twitter marketing agent/company and tested in real circumstances and with real numbers. These models were finalized through a number of revisions and iterators of the design, develop, simulate, test and evaluate. It also addresses these methods that suit most organized promotion through targeting, to the Twitter social media service. The validity and usefulness of these Twitter marketing methods models for the day-to-day decision making are authenticated by the management of the company organization. It implements system dynamics concepts of Twitter marketing methods modelling and produce models of various Twitter marketing situations. The Tweet method that Twitter provides can be adjusted, depending on the situation, in order to maximize the profit of the company/agent.

Active 3D camera design for target capture on Mars orbit

NASA Astrophysics Data System (ADS)

Cottin, Pierre; Babin, François; Cantin, Daniel; Deslauriers, Adam; Sylvestre, Bruno

2010-04-01

During the ESA Mars Sample Return (MSR) mission, a sample canister launched from Mars will be autonomously captured by an orbiting satellite. We present the concept and the design of an active 3D camera supporting the orbiter navigation system during the rendezvous and capture phase. This camera aims at providing the range and bearing of a 20 cm diameter canister from 2 m to 5 km within a 20° field-of-view without moving parts (scannerless). The concept exploits the sensitivity and the gating capability of a gated intensified camera. It is supported by a pulsed source based on an array of laser diodes with adjustable amplitude and pulse duration (from nanoseconds to microseconds). The ranging capability is obtained by adequately controlling the timing between the acquisition of 2D images and the emission of the light pulses. Three modes of acquisition are identified to accommodate the different levels of ranging and bearing accuracy and the 3D data refresh rate. To come up with a single 3D image, each mode requires a different number of images to be processed. These modes can be applied to the different approach phases. The entire concept of operation of this camera is detailed with an emphasis on the extreme lighting conditions. Its uses for other space missions and terrestrial applications are also highlighted. This design is implemented in a prototype with shorter ranging capabilities for concept validation. Preliminary results obtained with this prototype are also presented. This work is financed by the Canadian Space Agency.

Conceptual design of fast-ignition laser fusion reactor FALCON-D

NASA Astrophysics Data System (ADS)

Goto, T.; Someya, Y.; Ogawa, Y.; Hiwatari, R.; Asaoka, Y.; Okano, K.; Sunahara, A.; Johzaki, T.

2009-07-01

A new conceptual design of the laser fusion power plant FALCON-D (Fast-ignition Advanced Laser fusion reactor CONcept with a Dry wall chamber) has been proposed. The fast-ignition method can achieve sufficient fusion gain for a commercial operation (~100) with about 10 times smaller fusion yield than the conventional central ignition method. FALCON-D makes full use of this property and aims at designing with a compact dry wall chamber (5-6 m radius). 1D/2D simulations by hydrodynamic codes showed a possibility of achieving sufficient gain with a laser energy of 400 kJ, i.e. a 40 MJ target yield. The design feasibility of the compact dry wall chamber and the solid breeder blanket system was shown through thermomechanical analysis of the dry wall and neutronics analysis of the blanket system. Moderate electric output (~400 MWe) can be achieved with a high repetition (30 Hz) laser. This dry wall reactor concept not only reduces several difficulties associated with a liquid wall system but also enables a simple cask maintenance method for the replacement of the blanket system, which can shorten the maintenance period. The basic idea of the maintenance method for the final optics system has also been proposed. Some critical R&D issues required for this design are also discussed.

First steps in designing an all-in-one ICT-based device for persons with cognitive impairment: evaluation of the first mock-up.

PubMed

Boman, Inga-Lill; Persson, Ann-Christine; Bartfai, Aniko

2016-03-07

This project Smart Assisted Living involving Informal careGivers++ (SALIG) intends to develop an ICT-based device for persons with cognitive impairment combined with remote support possibilities for significant others and formal caregivers. This paper presents the identification of the target groups' needs and requirements of such device and the evaluation of the first mock-up, demonstrated in a tablet. The inclusive design method that includes end-users in the design process was chosen. First, a scoping review was conducted in order to examine the target group's need of an ICT-based device, and to gather recommendations regarding its design and functionalities. In order to capture the users' requirements of the design and functionalities of the device three targeted focus groups were conducted. Based on the findings from the publications and the focus groups a user requirement specification was developed. After that a design concept and a first mock-up was developed in an iterative process. The mock-up was evaluated through interviews with persons with cognitive impairment, health care professionals and significant others. Data were analysed using content analysis. Several useful recommendations of the design and functionalities of the SALIG device for persons with cognitive impairment were identified. The main benefit of the mock-up was that it was a single device with a set of functionalities installed on a tablet and designed for persons with cognitive impairment. An additional benefit was that it could be used remotely by significant others and formal caregivers. The SALIG device has the potentials to facilitate everyday life for persons with cognitive impairment, their significant others and the work situation for formal caregivers. The results may provide guidance in the development of different types of technologies for the target population and for people with diverse disabilities. Further work will focus on developing a prototype to be empirically tested by persons with cognitive impairment, their significant others and formal caregivers.

Rational design of peptide affinity ligands for the purification of therapeutic enzymes.

PubMed

Trasatti, John P; Woo, James; Ladiwala, Asif; Cramer, Steven; Karande, Pankaj

2018-04-25

Non-mAb biologics represent a growing class of therapeutics under clinical development. Although affinity chromatography is a potentially attractive approach for purification, the development of platform technologies, such as Protein A for mAbs, has been challenging due to the inherent chemical and structural diversity of these molecules. Here, we present our studies on the rapid development of peptide affinity ligands for the purification of biologics using a prototypical enzyme therapeutic in clinical use. Employing a suite of de novo rational and combinatorial design strategies we designed and screened a library of peptides on microarray platforms for their ability to bind to the target with high affinity and selectivity in cell culture fluid. Lead peptides were evaluated on resin in batch conditions and compared with a commercially available resin to evaluate their efficacy. Two lead candidates identified from microarray studies provided high binding capacity to the target while demonstrating high selectivity against culture contaminants and product variants compared to a commercial resin system. These findings provide a proof-of-concept for developing affinity peptide-based bioseparations processes for a target biologic. Peptide affinity ligand design and screening approaches presented in this work can also be easily translated to other biologics of interest. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

MMWR/FLIR/ATR sensor fusion: Proof of concept

NASA Astrophysics Data System (ADS)

Woolett, Jerry F.

1988-06-01

To improve the relocatable target capabilities of strategic aircraft a sensor fusion concept using a millimeter-wave radar (MMWR) and a forward-looking infrared (FLIR) system providing inputs to an auto target recognizer (ATR) has been developed. To prove this concept, a cooperative research effort is being conducted by a group of industry leaders in bomber avionics, MMWR, and ATR technologies. The author discusses the concept and the plan developed to test, evaluate, and demonstrate the expected performance.

Reimagining Game Design: Exploring the Design of Constructible Authentic Representations for Science Reasoning

NASA Astrophysics Data System (ADS)

Holbert, Nathan Ryan

Video games have recently become a popular space for educational design due to their interactive and engaging nature and the ubiquity of the gaming experience among youth. Though many researchers argue video games can provide opportunities for learning, educational game design has focused on the classroom rather than the informal settings where games are typically played. Educational games have been moderately successful at achieving learning gains on standardized items, but have failed to show improvements on related but distal problems. In this dissertation I develop and assess a new design principle, called constructible authentic representations for creating informal gaming experiences that players will actively draw on when reasoning in formal and real world contexts. These games provide players with opportunities to engage in meaningful construction with components that integrate relevant concepts to create in-game representations that visually and epistemologically align with related tools and representations utilized in the target domain. In the first phase of the dissertation, I observed children playing popular video games to better understand what in-game representations children attend to and how interactions with these representations contribute to intuitive ideas of encountered STEM content. Results from this study fed into the iterative design of two prototype video games, FormulaT Racing and Particles!, intending to give players useful knowledge resources for reasoning about kinematics and the particulate nature of matter respectively. Designed games encourage players to utilize and refine intuitive ideas about target content through the construction of domain relevant representations. To assess the effectiveness of these designs I conducted two studies of children ages 7-14 playing prototype games in informal settings. An analysis of pre- and post-game clinical interviews, domain specific tasks, and video and logging data of gameplay suggests players developed useful knowledge resources, likely gained and/or refined from experiences in-game, that are employed to solve non-game problems and tasks. Furthermore, players utilized in-game representations as objects-to-think-with when explaining real world phenomena and formal concepts. The results suggest that games designed to include constructible authentic representations can provide players with powerful and useful knowledge resources accessible when thinking and reasoning in a variety of contexts.

Design Study for a Mars Geyser Hopper

NASA Technical Reports Server (NTRS)

Landis, Geoffrey A.; Oleson, Steven J.; McGuire, Melissa

2012-01-01

The Mars Geyser Hopper is a design reference missions (DRMs) for a Discovery-class spacecraft using Advanced Stirling Radioisotope Generator (ASRG) power source. The Geyser Hopper is a mission concept that will investigate the springtime carbon-dioxide geysers found in regions around the south pole of Mars. The Geyser Hopper design uses Phoenix heritage systems and approach, but uses a single ASRG as the power source, rather than twin solar arrays, and is designed to last over a one-year stay on the South Pole. The spacecraft will land at a target landing area near the south pole of Mars, and have the ability to "hop" after a summertime landing to reposition itself close to a geyser site, and wait through the winter until the first sunlight of spring to witness first-hand the geyser phenomenon.

Static Performance of Six Innovative Thrust Reverser Concepts for Subsonic Transport Applications: Summary of the NASA Langley Innovative Thrust Reverser Test Program

NASA Technical Reports Server (NTRS)

Asbury, Scott C.; Yetter, Jeffrey A.

2000-01-01

The NASA Langley Configuration Aerodynamics Branch has conducted an experimental investigation to study the static performance of innovative thrust reverser concepts applicable to high-bypass-ratio turbofan engines. Testing was conducted on a conventional separate-flow exhaust system configuration, a conventional cascade thrust reverser configuration, and six innovative thrust reverser configurations. The innovative thrust reverser configurations consisted of a cascade thrust reverser with porous fan-duct blocker, a blockerless thrust reverser, two core-mounted target thrust reversers, a multi-door crocodile thrust reverser, and a wing-mounted thrust reverser. Each of the innovative thrust reverser concepts offer potential weight savings and/or design simplifications over a conventional cascade thrust reverser design. Testing was conducted in the Jet-Exit Test Facility at NASA Langley Research Center using a 7.9%-scale exhaust system model with a fan-to-core bypass ratio of approximately 9.0. All tests were conducted with no external flow and cold, high-pressure air was used to simulate core and fan exhaust flows. Results show that the innovative thrust reverser concepts achieved thrust reverser performance levels which, when taking into account the potential for system simplification and reduced weight, may make them competitive with, or potentially more cost effective than current state-of-the-art thrust reverser systems.

Microsputterer with integrated ion-drag focusing for additive manufacturing of thin, narrow conductive lines

NASA Astrophysics Data System (ADS)

Kornbluth, Y. S.; Mathews, R. H.; Parameswaran, L.; Racz, L. M.; Velásquez-García, L. F.

2018-04-01

We report the design, modelling, and proof-of-concept demonstration of a continuously fed, atmospheric-pressure microplasma metal sputterer that is capable of printing conductive lines narrower than the width of the target without the need for post-processing or lithographic patterning. Ion drag-induced focusing is harnessed to print narrow lines; the focusing mechanism is modelled via COMSOL Multiphysics simulations and validated with experiments. A microplasma sputter head with gold target is constructed and used to deposit imprints with minimum feature sizes as narrow as 9 µm, roughness as small as 55 nm, and electrical resistivity as low as 1.1 µΩ · m.

Design of a line-VISAR interferometer system for the Sandia Z Machine

NASA Astrophysics Data System (ADS)

Galbraith, J.; Austin, K.; Baker, J.; Bettencourt, R.; Bliss, E.; Celeste, J.; Clancy, T.; Cohen, S.; Crosley, M.; Datte, P.; Fratanduono, D.; Frieders, G.; Hammer, J.; Jackson, J.; Johnson, D.; Jones, M.; Koen, D.; Lusk, J.; Martinez, A.; Massey, W.; McCarville, T.; McLean, H.; Raman, K.; Rodriguez, S.; Spencer, D.; Springer, P.; Wong, J.

2017-08-01

A joint team comprised of Lawrence Livermore National Laboratory (LLNL) and Sandia National Laboratory (SNL) personnel is designing a line-VISAR (Velocity Interferometer System for Any Reflector) for the Sandia Z Machine, Z Line-VISAR. The diagnostic utilizes interferometry to assess current delivery as a function of radius during a magnetically-driven implosion. The Z Line-VISAR system is comprised of the following: a two-leg line-VISAR interferometer, an eight-channel Gated Optical Imager (GOI), and a fifty-meter transport beampath to/from the target of interest. The Z Machine presents unique optomechanical design challenges. The machine utilizes magnetically driven pulsed power to drive a target to elevated temperatures and pressures useful for high energy density science. Shock accelerations exceeding 30g and a strong electromagnetic pulse (EMP) are generated during the shot event as the machine discharges currents of over 25 million amps. Sensitive optical components must be protected from shock loading, and electrical equipment must be adequately shielded from the EMP. The optical design must accommodate temperature and humidity fluctuations in the facility as well as airborne hydrocarbons from the pulsed power components. We will describe the engineering design and concept of operations of the Z Line-VISAR system. Focus will be on optomechanical design.

ILC TARGET WHEEL RIM FRAGMENT/GUARD PLATE IMPACT ANALYSIS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hagler, L

2008-07-17

A positron source component is needed for the International Linear Collider Project. The leading design concept for this source is a rotating titanium alloy wheel whose spokes rotate through an intense localized magnetic field. The system is composed of an electric motor, flexible motor/drive-shaft coupling, stainless steel drive-shaft, two Plumber's Block tapered roller bearings, a titanium alloy target wheel, and electromagnet. Surrounding the target wheel and magnet is a steel frame with steel guarding plates intended to contain shrapnel in case of catastrophic wheel failure. Figure 1 is a layout of this system (guard plates not shown for clarity). Thismore » report documents the FEA analyses that were performed at LLNL to help determine, on a preliminary basis, the required guard plate thickness for three potential plate steels.« less

Automation of the targeting and reflective alignment concept

NASA Technical Reports Server (NTRS)

Redfield, Robin C.

1992-01-01

The automated alignment system, described herein, employs a reflective, passive (requiring no power) target and includes a PC-based imaging system and one camera mounted on a six degree of freedom robot manipulator. The system detects and corrects for manipulator misalignment in three translational and three rotational directions by employing the Targeting and Reflective Alignment Concept (TRAC), which simplifies alignment by decoupling translational and rotational alignment control. The concept uses information on the camera and the target's relative position based on video feedback from the camera. These relative positions are converted into alignment errors and minimized by motions of the robot. The system is robust to exogenous lighting by virtue of a subtraction algorithm which enables the camera to only see the target. These capabilities are realized with relatively minimal complexity and expense.

US Army remotely piloted vehicle supporting technology program

NASA Technical Reports Server (NTRS)

Gossett, T. D.

1981-01-01

Essential technology programs that lead to the full scale engineering development of the Aquila Remotely Piloted Vehicle system for U.S. Army are described. The Aquila system uses a small recoverable and reusable RPV to provide target acquisition, designation, and aerial reconnaissance mission support for artillery and smart munitions. Developments that will provide growth capabilities to the Aquila RPV system, as well as future RPV mission concepts being considered by the U.S. Army are presented.

Crewed Mission to Callisto Using Advanced Plasma Propulsion Systems

NASA Technical Reports Server (NTRS)

Adams, R. B.; Statham, G.; White, S.; Patton, B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Fincher, S.; Polsgrove, T.; Chapman, J.

2003-01-01

This paper describes the engineering of several vehicles designed for a crewed mission to the Jovian satellite Callisto. Each subsystem is discussed in detail. Mission and trajectory analysis for each mission concept is described. Crew support components are also described. Vehicles were developed using both fission powered magneto plasma dynamic (MPD) thrusters and magnetized target fusion (MTF) propulsion systems. Conclusions were drawn regarding the usefulness of these propulsion systems for crewed exploration of the outer solar system.

Small Solar Electric Propulsion Spacecraft Concept for Near Earth Object and Inner Solar System Missions

NASA Technical Reports Server (NTRS)

Lang, Jared J.; Randolph, Thomas M.; McElrath, Timothy P.; Baker, John D.; Strange, Nathan J.; Landau, Damon; Wallace, Mark S.; Snyder, J. Steve; Piacentine, Jamie S.; Malone, Shane;

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

PubMed Central

Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; Cristini, Vittorio; Brinker, Lina M.; Staquicini, Fernanda I.; Cardó-Vila, Marina; D’Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R.; Dogra, Prashant; Melancon, Marites P.; Stafford, R. Jason; Miyazono, Kohei; Gelovani, Juri G.; Kataoka, Kazunori; Brinker, C. Jeffrey; Sidman, Richard L.; Arap, Wadih; Pasqualini, Renata

2016-01-01

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications. PMID:26839407

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release.

PubMed

Hosoya, Hitomi; Dobroff, Andrey S; Driessen, Wouter H P; Cristini, Vittorio; Brinker, Lina M; Staquicini, Fernanda I; Cardó-Vila, Marina; D'Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R; Dogra, Prashant; Melancon, Marites P; Stafford, R Jason; Miyazono, Kohei; Gelovani, Juri G; Kataoka, Kazunori; Brinker, C Jeffrey; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2016-02-16

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

DOE PAGES

Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; ...

2016-02-02

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared,more » thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.« less

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared,more » thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.« less

Capabilities of a FOXSI Small Explorer

NASA Astrophysics Data System (ADS)

Inglis, A. R.; Christe, S.; Glesener, L.; Krucker, S.; Dennis, B. R.; Shih, A.; Wilson-Hodge, C.; Gubarev, M.; Hudson, H. S.; Kontar, E.; Buitrago Casas, J. C.; Drake, J. F.; Caspi, A.; Holman, G.; Allred, J. C.; Ryan, D.; Alaoui, M.; White, S. M.; Saint-Hilaire, P.; Klimchuk, J. A.; Hannah, I. G.; Antiochos, S. K.; Grefenstette, B.; Ramsey, B.; Jeffrey, N. L. S.; Reep, J. W.; Schwartz, R. A.; Ireland, J.

2015-12-01

We present the FOXSI (Focusing Optics X-ray Solar Imager) small explorer (SMEX) concept, a mission dedicated to studying particle acceleration and energy release on the Sun. FOXSI is designed as a 3-axis stabilized spacecraft in low-Earth orbit making use of state-of-the-art grazing incidence focusing optics, allowing for direct imaging of solar X-rays. The current design being studied features three telescope modules deployed in a low-inclination low-earth orbit (LEO). With a 15 meter focal length enabled by a deployable boom, FOXSI will observe the Sun in the 3-50 keV energe range. The FOXSI imaging concept has already been tested on two sounding rocket flights, in 2012 and 2014 and on the HEROES balloon payload flight in 2013. FOXSI will image the Sun with an angular resolution of 5'', a spectral resolution of 0.5 keV, and sub-second temporal resolution using CdTe detectors. In this presentation we investigate the science objectives and targets which can be accessed from this mission. Because of the defining characteristic of FOXSI is true imaging spectroscopy with high dynamic range and sensitivity, a brand-new perspective on energy release on the Sun is possible. Some of the science targets discussed here include; flare particle acceleration processes, electron beams, return currents, sources of solar energetic particles (SEPs), as well as understanding X-ray emission from active region structures and the quiescent corona.

Impact Testing and Analysis of Composites for Aircraft Engine Fan Cases

NASA Technical Reports Server (NTRS)

Roberts, Gary D.; Revilock, Duane M.; Binienda, Wieslaw K.; Nie, Walter Z.; Mackenzie, S. Ben; Todd, Kevin B.

2002-01-01

The fan case in a jet engine is a heavy structure because of its size and because of the requirement that it contain a blade released during engine operation. Composite materials offer the potential for reducing the weight of the case. Efficient design, test, and analysis methods are needed to efficiently evaluate the large number of potential composite materials and design concepts. The type of damage expected in a composite case under blade-out conditions was evaluated using a subscale test in which a glass/epoxy composite half-ring target was impacted with a wedge-shaped titanium projectile. Fiber shearing occurred near points of contact between the projectile and target. Delamination and tearing occurred on a larger scale. These damage modes were reproduced in a simpler test in which flat glass/epoxy composites were impacted with a blunt cylindrical projectile. A surface layer of ceramic eliminated fiber shear fracture but did not reduce delamination. Tests on 3D woven carbon/epoxy composites indicated that transverse reinforcement is effective in reducing delamination. A 91 cm (36 in.) diameter full-ring sub-component was proposed for larger scale testing of these and other composite concepts. Explicit, transient, finite element analyses indicated that a full-ring test is needed to simulate complete impact dynamics, but simpler tests using smaller ring sections are adequate when evaluation of initial impact damage is the primary concern.

Design and interpretation of microRNA-reporter gene activity.

PubMed

Carroll, Adam P; Tooney, Paul A; Cairns, Murray J

2013-06-15

MicroRNAs (miRNAs) are small noncoding RNA molecules that act as sequence specificity guides to direct post-transcriptional gene silencing. In doing so, miRNAs regulate many critical developmental processes, including cellular proliferation, differentiation, migration, and apoptosis, as well as more specialized biological functions such as dendritic spine development and synaptogenesis. Interactions between miRNAs and their miRNA recognition elements occur via partial complementarity, rendering tremendous redundancy in targeting such that miRNAs are predicted to regulate 60% of the genome, with each miRNA estimated to regulate more than 200 genes. Because these predictions are prone to false positives and false negatives, there is an ever present need to provide material support to these assertions to firmly establish the biological function of specific miRNAs in both normal and pathophysiological contexts. Using schizophrenia-associated miR-181b as an example, we present detailed guidelines and novel insights for the rapid establishment of a streamlined miRNA-reporter gene assay and explore various design concepts for miRNA-reporter gene applications, including bidirectional miRNA modulation. In exemplifying this approach, we report seven novel miR-181b target sites for five schizophrenia candidate genes (DISC1, BDNF, ENKUR, GRIA1, and GRIK1) and dissect a number of vital concepts regarding future developments for miRNA-reporter gene assays and the interpretation of their results. Copyright © 2013 Elsevier Inc. All rights reserved.

Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation.

PubMed

Pallagi, Edina; Ambrus, Rita; Szabó-Révész, Piroska; Csóka, Ildikó

2015-08-01

Regulatory science based pharmaceutical development and product manufacturing is highly recommended by the authorities nowadays. The aim of this study was to adapt regulatory science even in the nano-pharmaceutical early development. Authors applied the quality by design (QbD) concept in the early development phase of nano-systems, where the illustration material was meloxicam. The meloxicam nanoparticles produced by co-grinding method for nasal administration were studied according to the QbD policy and the QbD based risk assessment (RA) was performed. The steps were implemented according to the relevant regulatory guidelines (quality target product profile (QTPP) determination, selection of critical quality attributes (CQAs) and critical process parameters (CPPs)) and a special software (Lean QbD Software(®)) was used for the RA, which represents a novelty in this field. The RA was able to predict and identify theoretically the factors (e.g. sample composition, production method parameters, etc.) which have the highest impact on the desired meloxicam-product quality. The results of the practical research justified the theoretical prediction. This method can improve pharmaceutical nano-developments by achieving shorter development time, lower cost, saving human resource efforts and more effective target-orientation. It makes possible focusing the resources on the selected parameters and area during the practical product development. Copyright © 2015 Elsevier B.V. All rights reserved.

Moving belt metal detector

NASA Astrophysics Data System (ADS)

Nelson, Carl V.; Mendat, Deborah P.; Huynh, Toan B.

2006-05-01

The Johns Hopkins University Applied Physics Laboratory (APL) has developed a prototype metal detection survey system that will increase the search speed of conventional technology while maintaining high sensitivity. Higher search speeds will reduce the time to clear roads of landmines and improvised explosive devices (IED) and to locate unexploded ordnance (UXO) at Base Realignment and Closure (BRAC) sites, thus reducing remediation costs. The new survey sensor system is called the moving belt metal detector (MBMD) and operates by both increasing sensor speed over the ground while maintaining adequate sensor dwell time over the target for good signal-to-noise ratio (SNR) and reducing motion-induced sensor noise. The MBMD uses an array of metal detection sensors mounted on a flexible belt similar to a tank track. The belt motion is synchronized with the forward survey speed so individual sensor elements remain stationary relative to the ground. A single pulsed transmitter coil is configured to provide a uniform magnetic field along the length of the receivers in ground contact. Individual time-domain electromagnetic induction (EMI) receivers are designed to sense a single time-gate measurement of the total metal content. Each sensor module consists of a receiver coil, amplifier, digitizing electronics and a low power UHF wireless transmitter. This paper presents the survey system design concepts and metal detection data from various targets at several survey speeds. Although the laboratory prototype is designed to demonstrate metal detection survey speeds up to 10 m/s, higher speeds are achievable with a larger sensor array. In addition, the concept can be adapted to work with other sensor technologies not previously considered for moving platforms.

Improving comprehension and recall of information for an HIV vaccine trial among women at risk for HIV: reading level simplification and inclusion of pictures to illustrate key concepts.

PubMed

Murphy, D A; O'Keefe, Z H; Kaufman, A H

1999-10-01

A simplified version of the prototype HIV vaccine material was developed through (a) reducing reading grade level, (b) restructuring of the organization and categorization of the material, (c) adding pictures designed to emphasize key concepts, and (d) obtaining feedback on the simplified version through focus groups with the target population. Low-income women at risk for HIV (N = 141) recruited from a primary care clinic were randomly assigned to be presented the standard or the simplified version. There were no significant differences between the groups in terms of education or Vocabulary, Block Design, and Passage Comprehension scores. Women who received the simplified version had significantly higher comprehension scores immediately following presentation of the material than did women who received the standard version and were also significantly more likely to recall study benefits and risks. These findings were maintained at 3-month follow-up. Implications for informed consent are discussed.

Hardware test program for evaluation of baseline range/range rate sensor concept

NASA Technical Reports Server (NTRS)

1985-01-01

The Hardware Test Program for evaluation of the baseline range/range rate sensor concept was initiated 11 September 1984. This ninth report covers the period 12 May through 11 June 1885. A contract amendment adding a second phase has extended the Hardware Test Program through 10 December 1985. The objective of the added program phase is to establish range and range measurement accuracy and radar signature characteristics for a typical spacecraft target. Phase I of the Hardware Test Program was designed to reduce the risks associated with the Range/Range Rate (R/R) Sensor baseline design approach. These risks are associated with achieving the sensor performance required for the two modes of operation, the Interrupted CW (ICW) mode for initial acquisition and tracking to close-in ranges, and the CW mode, providing coverage during the final docking maneuver. The risks associated with these modes of operation have to do with the realization of adequate sensitivity to operate to their individual maximum ranges.

Color associations among designers and non-designers for common warning and operation concepts.

PubMed

Ng, Annie W Y; Chan, Alan H S

2018-07-01

This study examined color-concept associations among designers and non-designers with commonly used warning and operation concepts. This study required 199 designers and 175 non-designers to indicate their choice among nine colors to associate with each of the 38 concepts in a color-concept table. The results showed that the designers and non-designers had the same color associations and similar strengths of stereotypes for 17 concepts. The strongest color-concept stereotypes for both groups were red-danger, red-fire, and red-hot. However, the designers and non-designers had different color associations for the concepts of escape (green, red), increase (green, red), potential hazard (red, orange), fatal (black, red), and normal (white, green), while the strengths of the 16 remaining associations for both groups were not at equivalent levels. These findings provide ergonomists and design practitioners with a better understanding of population stereotypes for color coding, and consequently to effectively use colors in their user-centered designs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Macromolecular target prediction by self-organizing feature maps.

PubMed

Schneider, Gisbert; Schneider, Petra

2017-03-01

Rational drug discovery would greatly benefit from a more nuanced appreciation of the activity of pharmacologically active compounds against a diverse panel of macromolecular targets. Already, computational target-prediction models assist medicinal chemists in library screening, de novo molecular design, optimization of active chemical agents, drug re-purposing, in the spotting of potential undesired off-target activities, and in the 'de-orphaning' of phenotypic screening hits. The self-organizing map (SOM) algorithm has been employed successfully for these and other purposes. Areas covered: The authors recapitulate contemporary artificial neural network methods for macromolecular target prediction, and present the basic SOM algorithm at a conceptual level. Specifically, they highlight consensus target-scoring by the employment of multiple SOMs, and discuss the opportunities and limitations of this technique. Expert opinion: Self-organizing feature maps represent a straightforward approach to ligand clustering and classification. Some of the appeal lies in their conceptual simplicity and broad applicability domain. Despite known algorithmic shortcomings, this computational target prediction concept has been proven to work in prospective settings with high success rates. It represents a prototypic technique for future advances in the in silico identification of the modes of action and macromolecular targets of bioactive molecules.

Conceptual Design of a Hypervelocity Asteroid Intercept Vehicle (HAIV) Flight Validation Mission

NASA Technical Reports Server (NTRS)

Barbee, Brent W.; Wie, Bong; Steiner, Mark; Getzandanner, Kenneth

2013-01-01

In this paper we present a detailed overview of the MDL study results and subsequent advances in the design of GNC algorithms for accurate terminal guidance during hypervelocity NEO intercept. The MDL study produced a conceptual con guration of the two-body HAIV and its subsystems; a mission scenario and trajectory design for a notional flight validation mission to a selected candidate target NEO; GNC results regarding the ability of the HAIV to reliably intercept small (50 m) NEOs at hypervelocity (typically greater than 10 km/s); candidate launch vehicle selection; a notional operations concept and cost estimate for the flight validation mission; and a list of topics to address during the remainder of our NIAC Phase II study.

Phage display: concept, innovations, applications and future.

PubMed

Pande, Jyoti; Szewczyk, Magdalena M; Grover, Ashok K

2010-01-01

Phage display is the technology that allows expression of exogenous (poly)peptides on the surface of phage particles. The concept is simple in principle: a library of phage particles expressing a wide diversity of peptides is used to select those that bind the desired target. The filamentous phage M13 is the most commonly used vector to create random peptide display libraries. Several methods including recombinant techniques have been developed to increase the diversity of the library. On the other extreme, libraries with various biases can be created for specific purposes. For instance, when the sequence of the peptide that binds the target is known, its affinity and selectivity can be increased by screening libraries created with limited mutagenesis of the peptide. Phage libraries are screened for binding to synthetic or native targets. The initial screening of library by basic biopanning has been extended to column chromatography including negative screening and competition between selected phage clones to identify high affinity ligands with greater target specificity. The rapid isolation of specific ligands by phage display is advantageous in many applications including selection of inhibitors for the active and allosteric sites of the enzymes, receptor agonists and antagonists, and G-protein binding modulatory peptides. Phage display has been used in epitope mapping and analysis of protein-protein interactions. The specific ligands isolated from phage libraries can be used in therapeutic target validation, drug design and vaccine development. Phage display can also be used in conjunction with other methods. The past innovations and those to come promise a bright future for this field. Copyright © 2010 Elsevier Inc. All rights reserved.

Hybrid nanoporous silicon optical biosensor architectures for biological sample analysis

NASA Astrophysics Data System (ADS)

Bonanno, Lisa M.; Zheng, Hong; DeLouise, Lisa A.

2010-02-01

This work focuses on demonstrating proof-of-concept for a novel nanoparticle optical signal amplification scheme employing hybrid porous silicon (PSi) sensors. We are investigating the development of target responsive hydrogels integrated with PSi optical transducers. These hybrid-PSi sensors can be designed to provide a tunable material response to target concentration ranging from swelling to complete chain dissolution. The corresponding refractive index changes are significant and readily detected by the PSi transducer. However, to increase signal to noise, lower the limit of detection, and provide a visual read out capability, we are investigating the incorporation of high refractive index nanoparticles (NP) into the hydrogel for optical signal amplification. These NPs can be nonspecifically encapsulated, or functionalized with bioactive ligands to bind polymer chains or participate in cross linking. In this work, we demonstrate encapsulation of high refractive index QD nanoparticles into a 5wt% polyacrylamide hydrogel crosslinked with N,N'-methylenebisacrylamide (BIS) and N,N Bis-acryloyl cystamine (BAC). A QD loading (~0.29 wt%) produced a 2X larger optical shift compared to the control. Dissolution of disulphide crosslinks, using Tris[2-carboxyethyl] phosphine (TCEP) reducing agent, induced gel swelling and efficient QD release. We believe this hybrid sensor concept constitutes a versatile technology platform capable of detecting a wide range of bio/chemical targets provided target analogs can be linked to the polymer backbone and crosslinks can be achieved with target responsive multivalent receptors, such a antibodies. The optical signal amplification scheme will enable a lower limit of detection sensitivity not yet demonstrated with PSi technology and colorimetric readout visible to the naked eye.

Workplace incivility: a concept analysis.

PubMed

Abolfazl Vagharseyyedin, Seyyed

2015-01-01

This study aimed to describe the meaning of the concept 'workplace incivility' and promote consistency in its application in nursing research and practice. The methodology introduced by Walker and Avant was used to analyze this concept. A total number of 50 studies that had essentially addressed the concept of incivility in employees' work environment was selected. Ambiguous intent, violation of mutual respect, low intensity and lack of physical assault were identified as the defining attributes of workplace incivility. The necessary antecedent of workplace incivility consisted of the presence of two or more people, with one or more as the source of the incivility, and another or others as its target in the workplace. Moreover, certain individual and organisational factors were the potential antecedents of workplace incivility. Possible negative outcomes for victims, witnesses, organisations, society and perpetrators of such behaviours, such as increased cost for the organisation, reduced citizenship performance, psychological distress and anxiety were identified as outcomes of workplace incivility. Results of the current concept analysis can guide nurse managers to design interventions so that the occurrence of workplace incivility can be reduced. Further studies can focus on testing the psychometric properties of the existing workplace incivility scales, especially uncivil behaviours experienced by nurses across different societies or cultures.

Aligning Goals, Assessments, and Activities: An Approach to Teaching PCR and Gel Electrophoresis

PubMed Central

Robertson, Amber L.; Batzli, Janet; Harris, Michelle; Miller, Sarah

2008-01-01

Polymerase chain reaction (PCR) and gel electrophoresis have become common techniques used in undergraduate molecular and cell biology labs. Although students enjoy learning these techniques, they often cannot fully comprehend and analyze the outcomes of their experiments because of a disconnect between concepts taught in lecture and experiments done in lab. Here we report the development and implementation of novel exercises that integrate the biological concepts of DNA structure and replication with the techniques of PCR and gel electrophoresis. Learning goals were defined based on concepts taught throughout the cell biology lab course and learning objectives specific to the PCR and gel electrophoresis lab. Exercises developed to promote critical thinking and target the underlying concepts of PCR, primer design, gel analysis, and troubleshooting were incorporated into an existing lab unit based on the detection of genetically modified organisms. Evaluative assessments for each exercise were aligned with the learning goals and used to measure student learning achievements. Our analysis found that the exercises were effective in enhancing student understanding of these concepts as shown by student performance across all learning goals. The new materials were particularly helpful in acquiring relevant knowledge, fostering critical-thinking skills, and uncovering prevalent misconceptions. PMID:18316813

Adaptive tight frame based medical image reconstruction: a proof-of-concept study for computed tomography

NASA Astrophysics Data System (ADS)

Zhou, Weifeng; Cai, Jian-Feng; Gao, Hao

2013-12-01

A popular approach for medical image reconstruction has been through the sparsity regularization, assuming the targeted image can be well approximated by sparse coefficients under some properly designed system. The wavelet tight frame is such a widely used system due to its capability for sparsely approximating piecewise-smooth functions, such as medical images. However, using a fixed system may not always be optimal for reconstructing a variety of diversified images. Recently, the method based on the adaptive over-complete dictionary that is specific to structures of the targeted images has demonstrated its superiority for image processing. This work is to develop the adaptive wavelet tight frame method image reconstruction. The proposed scheme first constructs the adaptive wavelet tight frame that is task specific, and then reconstructs the image of interest by solving an l1-regularized minimization problem using the constructed adaptive tight frame system. The proof-of-concept study is performed for computed tomography (CT), and the simulation results suggest that the adaptive tight frame method improves the reconstructed CT image quality from the traditional tight frame method.

Parameter Study of the LIFE Engine Nuclear Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kramer, K J; Meier, W R; Latkowski, J F

2009-07-10

LLNL is developing the nuclear fusion based Laser Inertial Fusion Energy (LIFE) power plant concept. The baseline design uses a depleted uranium (DU) fission fuel blanket with a flowing molten salt coolant (flibe) that also breeds the tritium needed to sustain the fusion energy source. Indirect drive targets, similar to those that will be demonstrated on the National Ignition Facility (NIF), are ignited at {approx}13 Hz providing a 500 MW fusion source. The DU is in the form of a uranium oxycarbide kernel in modified TRISO-like fuel particles distributed in a carbon matrix forming 2-cm-diameter pebbles. The thermal power ismore » held at 2000 MW by continuously varying the 6Li enrichment in the coolants. There are many options to be considered in the engine design including target yield, U-to-C ratio in the fuel, fission blanket thickness, etc. Here we report results of design variations and compare them in terms of various figures of merit such as time to reach a desired burnup, full-power years of operation, time and maximum burnup at power ramp down and the overall balance of plant utilization.« less

Beliefs Alter Holistic Face Processing…If Response Bias is not Taken into Account

PubMed Central

Richler, Jennifer J.; Cheung, Olivia S.; Gauthier, Isabel

2012-01-01

The composite paradigm is widely used to quantify holistic processing (HP) of faces, but there is debate regarding the appropriate design (partial vs. complete) and measures in this task. Here, we argue that some operational definitions of HP are problematic because they are sensitive to top-down influences, even though the underlying concept is assumed to be cognitively impenetrable. In Experiment 1, we told one group of participants that the target face half would remain the same on 75% of trials, and another group that it would change on 75% of trials. The true proportion of same/different trials was 50% - groups only differed in their beliefs about the target halves. In Experiment 2, we manipulated the actual proportion of same/different trials in the experiment (75% of trials were same for one group, 75% of trials were different for another group), but did not give explicit instructions about proportions. In both experiments these manipulations influenced response biases that altered partial design measures of HP while the complete design measure was unaffected. We argue that the partial design should be abandoned because it has poor construct validity. PMID:22101018

LWST Phase I Project Conceptual Design Study: Evaluation of Design and Construction Approaches for Economical Hybrid Steel/Concrete Wind Turbine Towers; June 28, 2002 -- July 31, 2004

DOE Office of Scientific and Technical Information (OSTI.GOV)

LaNier, M. W.

The United States Department of Energy (DOE) Wind Energy Research Program has begun a new effort to partner with U.S. industry to develop wind technology that will allow wind systems to compete in regions of low wind speed. The Class 4 and 5 sites targeted by this effort have annual average wind speeds of 5.8 m/s (13 mph), measured at 10 m (33 ft) height. Such sites are abundant in the United States and would increase the land area available for wind energy production twenty-fold. The new program is targeting a levelized cost of energy of 3 cents/kWh at thesemore » sites by 2010. A three-element approach has been initiated. These efforts are concept design, component development, and system development. This work builds on previous activities under the WindPACT program and the Next Generation Turbine program. If successful, DOE estimates that his new technology could result in 35 to 45 gigawatts of additional wind capacity being installed by 2020.« less

Candidate molten salt investigation for an accelerator driven subcritical core

NASA Astrophysics Data System (ADS)

Sooby, E.; Baty, A.; Beneš, O.; McIntyre, P.; Pogue, N.; Salanne, M.; Sattarov, A.

2013-09-01

We report a design for accelerator-driven subcritical fission in a molten salt core (ADSMS) that utilizes a fuel salt composed of NaCl and transuranic (TRU) chlorides. The ADSMS core is designed for fast neutronics (28% of neutrons >1 MeV) to optimize TRU destruction. The choice of a NaCl-based salt offers benefits for corrosion, operating temperature, and actinide solubility as compared with LiF-based fuel salts. A molecular dynamics (MD) code has been used to estimate properties of the molten salt system which are important for ADSMS design but have never been measured experimentally. Results from the MD studies are reported. Experimental measurements of fuel salt properties and studies of corrosion and radiation damage on candidate metals for the core vessel are anticipated. A special thanks is due to Prof. Paul Madden for introducing the ADSMS group to the concept of using the molten salt as the spallation target, rather than a conventional heavy metal spallation target. This feature helps to optimize this core as a Pu/TRU burner.

Demonstration of the CDMA-mode CAOS smart camera.

PubMed

Riza, Nabeel A; Mazhar, Mohsin A

2017-12-11

Demonstrated is the code division multiple access (CDMA)-mode coded access optical sensor (CAOS) smart camera suited for bright target scenarios. Deploying a silicon CMOS sensor and a silicon point detector within a digital micro-mirror device (DMD)-based spatially isolating hybrid camera design, this smart imager first engages the DMD starring mode with a controlled factor of 200 high optical attenuation of the scene irradiance to provide a classic unsaturated CMOS sensor-based image for target intelligence gathering. Next, this CMOS sensor provided image data is used to acquire a focused zone more robust un-attenuated true target image using the time-modulated CDMA-mode of the CAOS camera. Using four different bright light test target scenes, successfully demonstrated is a proof-of-concept visible band CAOS smart camera operating in the CDMA-mode using up-to 4096 bits length Walsh design CAOS pixel codes with a maximum 10 KHz code bit rate giving a 0.4096 seconds CAOS frame acquisition time. A 16-bit analog-to-digital converter (ADC) with time domain correlation digital signal processing (DSP) generates the CDMA-mode images with a 3600 CAOS pixel count and a best spatial resolution of one micro-mirror square pixel size of 13.68 μm side. The CDMA-mode of the CAOS smart camera is suited for applications where robust high dynamic range (DR) imaging is needed for un-attenuated un-spoiled bright light spectrally diverse targets.

The eyes of LITENING

NASA Astrophysics Data System (ADS)

Moser, Eric K.

2016-05-01

LITENING is an airborne system-of-systems providing long-range imaging, targeting, situational awareness, target tracking, weapon guidance, and damage assessment, incorporating a laser designator and laser range finders, as well as non-thermal and thermal imaging systems, with multi-sensor boresight. Robust operation is at a premium, and subsystems are partitioned to modular, swappable line-replaceable-units (LRUs) and shop-replaceable-units (SRUs). This presentation will explore design concepts for sensing, data storage, and presentation of imagery associated with the LITENING targeting pod. The "eyes" of LITENING are the electro-optic sensors. Since the initial LITENING II introduction to the US market in the late 90s, as the program has evolved and matured, a series of spiral functional improvements and sensor upgrades have been incorporated. These include laser-illuminated imaging, and more recently, color sensing. While aircraft displays are outside of the LITENING system, updates to the available viewing modules have also driven change, and resulted in increasingly effective ways of utilizing the targeting system. One of the latest LITENING spiral upgrades adds a new capability to display and capture visible-band color imagery, using new sensors. This is an augmentation to the system's existing capabilities, which operate over a growing set of visible and invisible colors, infrared bands, and laser line wavelengths. A COTS visible-band camera solution using a CMOS sensor has been adapted to meet the particular needs associated with the airborne targeting use case.

Making the Venus Concept Watch 1.0

NASA Astrophysics Data System (ADS)

Balint, Tibor S.; Melchiorri, Julian P.

2014-08-01

Over the past year we have celebrated the 50th anniversary of planetary exploration, which started with the Venus flyby of Mariner-2; and the 35th anniversary of the Pioneer-Venus multi-probe mission where one large and three small probes descended to the surface of Venus, encountering extreme environmental conditions. At the surface of Venus the temperature is about 460 °C, and the pressure is 92 bar, with a highly corrosive super-critical CO2 atmosphere. At a Venusian altitude of 50 km the pressure and temperature conditions are near Earth-like, but the clouds carry sulfuric acid droplets. Deep probe missions to Jupiter and Saturn, targeting the 100 bar pressure depth encounter similar pressure and temperature conditions as the Pioneer-Venus probes did. Mitigating these environments is highly challenging and requires special considerations for designs and materials. While assessing such space mission concepts, we have found that there is an overlap between the extreme environments in planetary atmospheres and the environments experienced by deep-sea explorers back on Earth. Consequently, the mitigation approaches could be also similar between planetary probes and diver watches. For example, both need to tolerate about 100 bar of pressure-although high temperatures are not factors on Earth. Mitigating these environments, the potential materials are: titanium for the probe and the watch housing; sapphire for the window and glass; resin impregnated woven carbon fiber for the aeroshell's thermal protection system and for the face of the watch; and nylon ribbon for the parachute and for the watch band. Planetary probes also utilize precision watches; thus there is yet another crosscutting functionality with diver watches. Our team, from the Innovation Design Engineering Program of the Royal College of Art, has designed and built a concept watch to commemorate these historical events, while highlighting advances in manufacturing processes over the past three to five decades, relevant to both future planetary mission designs and can be used to produce deep diver watches. In this paper we describe our design considerations; give a brief overview of the extreme environments these components would experience on both Venus and Earth; the manufacturing techniques and materials we used to build the Venus Watch; and its outreach potential to bring a distant concept of planetary exploration closer to Earth. We will also address lessons learned from this project and new ideas forward, for the next generation of this concept design.

Combined Structural and Trajectory Control of Variable-Geometry Planetary Entry Systems

NASA Technical Reports Server (NTRS)

Quadrelli, Marco B.; Pellegrino, Sergio; Kwok, Kawai

2011-01-01

Some of the key challenges of planetary entry are to dissipate the large kinetic energy of the entry vehicle and to land with precision. Past missions to Mars were based on unguided entry, where entry vehicles carried payloads of less than 0.6 T and landed within 100 km of the designated target. The Mars Science Laboratory (MSL) is expected to carry a mass of almost 1 T to within 20 km of the target site. Guided lifting entry is needed to meet these higher deceleration and targeting demands. If the aerodynamic characteristics of the decelerator are variable during flight, more trajectory options are possible, and can be tailored to specific mission requirements. In addition to the entry trajectory modulation, having variable aerodynamic properties will also favor maneuvering of the vehicle prior to descent. For proper supersonic parachute deployment, the vehicle needs to turn to a lower angle of attack. One approach to entry trajectory improvement and angle of attack control is to embed a variable geometry decelerator in the design of the vehicle. Variation in geometry enables the vehicle to adjust its aerodynamic performance continuously without additional fuel cost because only electric power is needed for actuating the mechanisms that control the shape change. Novel structural and control concepts have been developed that enable the decelerator to undergo variation in geometry. Changing the aerodynamic characteristics of a flight vehicle by active means can potentially provide a mechanically simple, affordable, and enabling solution for entry, descent, and landing across a wide range of mission types, sample capture and return, and reentry to Earth, Titan, Venus, or Mars. Unguided ballistic entry is not sufficient to meet this more stringent deceleration, heating, and targeting demands. Two structural concepts for implementing the cone angle variation, a segmented shell, and a corrugated shell, have been presented.

Microfine coal firing results from a retrofit gas/oil-designed industrial boiler

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, R.; Borio, R.W.; Liljedahl, G.

1995-12-31

The development of a High Efficiency Advanced Coal Combustor (HEACC) has been in progress since 1987 and the ABB Power Plant Laboratories. The initial work on this concept produced an advanced coal firing system that was capable of firing both water-based and dry pulverized coal in an industrial boiler environment. Economics may one day dictate that it makes sense to replace oil or natural gas with coal in boilers that were originally designed to burn these fuels. The objective of the current program is to demonstrate the technical and economic feasibility of retrofitting a gas/oil designed boiler to burn micronizedmore » coal. In support of this overall objective, the following specific areas were targeted: A coal handling/preparation system that can meet the technical requirements for retrofitting microfine coal on a boiler designed for burning oil or natural gas; Maintaining boiler thermal performance in accordance with specifications when burning oil or natural gas; Maintaining NOx emissions at or below 0.6 lb/MBtu; Achieving combustion efficiencies of 98% or higher; and Calculating economic payback periods as a function of key variables. The overall program has consisted of five major tasks: (1) A review of current state-of-the-art coal firing system components; (2) Design and experimental testing of a prototype HEACC burner; (3) Installation and testing of a HEACC system in a commercial retrofit application; (4) Economic evaluation of the HEACC concept for retrofit applications; and (5) Long term demonstration under commercial user demand conditions. This paper will summarize the latest key experimental results (Task 3) and the economic evaluation (Task 4) of the HEACC concept for retrofit applications. 28 figs., 6 tabs.« less

RchyOptimyx: Cellular Hierarchy Optimization for Flow Cytometry

PubMed Central

Aghaeepour, Nima; Jalali, Adrin; O’Neill, Kieran; Chattopadhyay, Pratip K.; Roederer, Mario; Hoos, Holger H.; Brinkman, Ryan R.

2013-01-01

Analysis of high-dimensional flow cytometry datasets can reveal novel cell populations with poorly understood biology. Following discovery, characterization of these populations in terms of the critical markers involved is an important step, as this can help to both better understand the biology of these populations and aid in designing simpler marker panels to identify them on simpler instruments and with fewer reagents (i.e., in resource poor or highly regulated clinical settings). However, current tools to design panels based on the biological characteristics of the target cell populations work exclusively based on technical parameters (e.g., instrument configurations, spectral overlap, and reagent availability). To address this shortcoming, we developed RchyOptimyx (cellular hieraRCHY OPTIMization), a computational tool that constructs cellular hierarchies by combining automated gating with dynamic programming and graph theory to provide the best gating strategies to identify a target population to a desired level of purity or correlation with a clinical outcome, using the simplest possible marker panels. RchyOptimyx can assess and graphically present the trade-offs between marker choice and population specificity in high-dimensional flow or mass cytometry datasets. We present three proof-of-concept use cases for RchyOptimyx that involve 1) designing a panel of surface markers for identification of rare populations that are primarily characterized using their intracellular signature; 2) simplifying the gating strategy for identification of a target cell population; 3) identification of a non-redundant marker set to identify a target cell population. PMID:23044634

Countering MANPADS: study of new concepts and applications: part two

NASA Astrophysics Data System (ADS)

Maltese, Dominique; Vergnolle, Jean-François; Aragones, Julien; Renaudat, Mathieu

2007-04-01

The latest events of ground-to-air Man Portable Air Defense (MANPAD) attacks against aircraft have revealed a new threat both for military and civilian aircraft. Consequently, the implementation of protecting systems (i.e. Directed Infra Red Counter Measure - DIRCM) in order to face IR guided missiles turns out to be now inevitable. In a near future, aircraft will have to possess detection, tracking, identification, targeting and jamming capabilities to face MANPAD threats. Besides, Multiple Missiles attacks become more and more current scenarios to deal with. In this paper, a practical example of DIRCM systems under study at SAGEM DEFENSE & SECURITY Company is presented. The article is the continuation of a previous SPIE one. Self-protection solutions include built-in and automatic locking-on, tracking, identification and laser jamming capabilities, including defeat assessment. Target Designations are provided by a Missile Warning System. Targets scenarios including multiple threats are considered to design systems architectures. In a first step, the article reminds the context, current and future threats (IR seekers of different generations...), and scenarios for system definition. Then, it focuses on potential self-protection systems under study at SAGEM DEFENSE & SECURITY Company. Different strategies including target identification, multi band laser and active imagery have been previously studied in order to design DIRCM System solutions. Thus, results of self-protection scenarios are provided for different MANPAD scenarios to highlight key problems to solve. Data have been obtained from simulation software modeling full DIRCM systems architectures on technical and operational scenarios (parametric studies).

A mRNA-Responsive G-Quadruplex-Based Drug Release System

PubMed Central

Yaku, Hidenobu; Murashima, Takashi; Miyoshi, Daisuke; Sugimoto, Naoki

2015-01-01

G-quadruplex-based drug delivery carriers (GDDCs) were designed to capture and release a telomerase inhibitor in response to a target mRNA. Hybridization between a loop on the GDDC structure and the mRNA should cause the G-quadruplex structure of the GDDC to unfold and release the bound inhibitor, anionic copper(II) phthalocyanine (CuAPC). As a proof of concept, GDDCs were designed with a 10-30-mer loop, which can hybridize with a target sequence in epidermal growth factor receptor (EGFR) mRNA. Structural analysis using circular dichroism (CD) spectroscopy showed that the GDDCs form a (3 + 1) type G-quadruplex structure in 100 mM KCl and 10 mM MgCl2 in the absence of the target RNA. Visible absorbance titration experiments showed that the GDDCs bind to CuAPC with Ka values of 1.5 × 105 to 5.9 × 105 M−1 (Kd values of 6.7 to 1.7 μM) at 25 °C, depending on the loop length. Fluorescence titration further showed that the G-quadruplex structure unfolds upon binding to the target RNA with Ka values above 1.0 × 108 M−1 (Kd values below 0.01 μM) at 25 °C. These results suggest the carrier can sense and bind to the target RNA, which should result in release of the bound drug. Finally, visible absorbance titration experiments demonstrated that the GDDC release CuAPC in response to the target RNA. PMID:25905703

Controllability in Multi-Stage Laser Ion Acceleration

NASA Astrophysics Data System (ADS)

Kawata, S.; Kamiyama, D.; Ohtake, Y.; Barada, D.; Ma, Y. Y.; Kong, Q.; Wang, P. X.; Gu, Y. J.; Li, X. F.; Yu, Q.

2015-11-01

The present paper shows a concept for a future laser ion accelerator, which should have an ion source, ion collimators, ion beam bunchers and ion post acceleration devices. Based on the laser ion accelerator components, the ion particle energy and the ion energy spectrum are controlled, and a future compact laser ion accelerator would be designed for ion cancer therapy or for ion material treatment. In this study each component is designed to control the ion beam quality. The energy efficiency from the laser to ions is improved by using a solid target with a fine sub-wavelength structure or a near-critical density gas plasma. The ion beam collimation is performed by holes behind the solid target or a multi-layered solid target. The control of the ion energy spectrum and the ion particle energy, and the ion beam bunching are successfully realized by a multi-stage laser-target interaction. A combination of each component provides a high controllability of the ion beam quality to meet variable requirements in various purposes in the laser ion accelerator. The work was partly supported by MEXT, JSPS, ASHULA project/ ILE, Osaka University, CORE (Center for Optical Research and Education, Utsunomiya University, Japan), Fudan University and CDI (Creative Dept. for Innovation) in CCRD, Utsunomiya University.

A nested array of rRNA targeted probes for the detection and identification of enterococci by reverse hybridization.

PubMed

Behr, T; Koob, C; Schedl, M; Mehlen, A; Meier, H; Knopp, D; Frahm, E; Obst, U; Schleifer, K; Niessner, R; Ludwig, W

2000-12-01

Complete 23S and almost complete 16S rRNA gene sequences were determined for the type strains of the validly described Enterococcus species, Melissococcus pluton and Tetragenococcus halophilus. A comprehensive set of rRNA targeted specific oligonucleotide hybridization probes was designed according to the multiple probe concept. In silico probe design and evaluation was performed using the respective tools of the ARB program package in combination with the ARB databases comprising the currently available 16S as well as 23S rRNA primary structures. The probes were optimized with respect to their application for reverse hybridization in microplate format. The target comprising 16S and 23S rDNA was amplified and labeled by PCR (polymerase chain reaction) using general primers targeting a wide spectrum of bacteria. Alternatively, amplification of two adjacent rDNA fragments of enterococci was performed by using specific primers. In vitro evaluation of the probe set was done including all Enterococcus type strains, and a selection of other representatives of the gram-positive bacteria with a low genomic DNA G+C content. The optimized probe set was used to analyze enriched drinking water samples as well as original samples from waste water treatment plants.

Space Environments and Spacecraft Effects Organization Concept

NASA Technical Reports Server (NTRS)

Edwards, David L.; Burns, Howard D.; Miller, Sharon K.; Porter, Ron; Schneider, Todd A.; Spann, James F.; Xapsos, Michael

2012-01-01

The National Aeronautics and Space Administration (NASA) is embarking on a course to expand human presence beyond Low Earth Orbit (LEO) while also expanding its mission to explore the solar system. Destinations such as Near Earth Asteroids (NEA), Mars and its moons, and the outer planets are but a few of the mission targets. Each new destination presents an opportunity to increase our knowledge of the solar system and the unique environments for each mission target. NASA has multiple technical and science discipline areas specializing in specific space environments disciplines that will help serve to enable these missions. To complement these existing discipline areas, a concept is presented focusing on the development of a space environments and spacecraft effects (SENSE) organization. This SENSE organization includes disciplines such as space climate, space weather, natural and induced space environments, effects on spacecraft materials and systems and the transition of research information into application. This space environment and spacecraft effects organization will be composed of Technical Working Groups (TWG). These technical working groups will survey customers and users, generate products, and provide knowledge supporting four functional areas: design environments, engineering effects, operational support, and programmatic support. The four functional areas align with phases in the program mission lifecycle and are briefly described below. Design environments are used primarily in the mission concept and design phases of a program. Engineering effects focuses on the material, component, sub-system and system-level selection and the testing to verify design and operational performance. Operational support provides products based on real time or near real time space weather to mission operators to aid in real time and near-term decision-making. The programmatic support function maintains an interface with the numerous programs within NASA, other federal government agencies, and the commercial sector to ensure that communications are well established and the needs of the programs are being met. The programmatic support function also includes working in coordination with the program in anomaly resolution and generation of lessons learned documentation. The goal of this space environment and spacecraft effects organization is to develop decision-making tools and engineering products to support all mission phases from mission concept through operations by focusing on transitioning research to application. Products generated by this space environments and effects application are suitable for use in anomaly investigations. This paper will describe the scope of the TWGs and their relationship to the functional areas, and discuss an organizational structure for this space environments and spacecraft effects organization.

An Overview of the Space Environments and Spacecraft Effects Organization Concept

NASA Technical Reports Server (NTRS)

Edwards, David L.; Burns, Howard D.; Garrett, Henry B.; Miller, Sharon K.; Peddie, Darilyn; Porter Ron; Spann, James F.; Xapsos, Michael A.

2012-01-01

The National Aeronautics and Space Administration (NASA) is embarking on a course to expand human presence beyond Low Earth Orbit (LEO) while also expanding its mission to explore our Earth, and the solar system. Destinations such as Near Earth Asteroids (NEA), Mars and its moons, and the outer planets are but a few of the mission targets. Each new destination presents an opportunity to increase our knowledge on the solar system and the unique environments for each mission target. NASA has multiple technical and science discipline areas specializing in specific space environments fields that will serve to enable these missions. To complement these existing discipline areas, a concept is presented focusing on the development of a space environment and spacecraft effects (SESE) organization. This SESE organization includes disciplines such as space climate, space weather, natural and induced space environments, effects on spacecraft materials and systems, and the transition of research information into application. This space environment and spacecraft effects organization will be composed of Technical Working Groups (TWG). These technical working groups will survey customers and users, generate products, and provide knowledge supporting four functional areas: design environments, engineering effects, operational support, and programmatic support. The four functional areas align with phases in the program mission lifecycle and are briefly described below. Design environments are used primarily in the mission concept and design phases of a program. Environment effects focuses on the material, component, sub-system, and system-level response to the space environment and include the selection and testing to verify design and operational performance. Operational support provides products based on real time or near real time space weather to mission operators to aid in real time and near-term decision-making. The programmatic support function maintains an interface with the numerous programs within NASA, other federal government agencies, and the commercial sector to ensure that communications are well established and the needs of the programs are being met. The programmatic support function also includes working in coordination with the program in anomaly resolution and generation of lessons learned documentation. The goal of this space environment and spacecraft effects organization is to develop decision-making tools and engineering products to support all mission phases from mission concept through operations by focusing on transitioning research to application. Products generated by this space environments and effects application are suitable for use in anomaly investigations. This paper will describe the scope and purpose of the space environments and spacecraft effects organization and describe the TWG's and their relationship to the functional areas.

A lightweight vibro-acoustic metamaterial demonstrator: Numerical and experimental investigation

NASA Astrophysics Data System (ADS)

Claeys, C.; Deckers, E.; Pluymers, B.; Desmet, W.

2016-03-01

In recent years metamaterials gained a lot of attention due to their superior noise and vibration insulation properties, be it at least in some targeted and tuneable frequency ranges, referred to as stopbands. These are frequency zones for which free wave propagation is prevented throughout the metamaterial, resulting in frequency zones of pronounced wave attenuation. Metamaterials are achieved due to addition of an, often periodic, grid of resonant structures to a host material or structure. The interaction between resonant inclusions and host structure can lead to a performance which is superior to the ones of any of the constituent materials. A key element in this concept is that waves can be affected by incorporating structural resonant elements of sub-wavelength sizes, i.e. features that are actually smaller than the wavelength of the waves to be affected. This paves the way towards compact and light vibro-acoustic solutions in the lower frequency ranges. This paper discusses the numerical design and experimental validation of acoustic insulation based on the concept of metamaterials: a hollow core periodic sandwich structure with added local resonant structures. In order to investigate the sensitivity to specific parameters in the metamaterial design and the robustness of the design, a set of variations on the nominal design are investigated. The stop bands are numerically predicted through unit cell modelling after which a full vibro-acoustic finite element model is applied to predict the insertion loss of the demonstrator. The results of these analyses are compared with measurements; both indicate that this metamaterials concept can be applied to combine light weight, compact volume and good acoustic behaviour.

Demonstrations of bio-inspired perching landing gear for UAVs

NASA Astrophysics Data System (ADS)

Tieu, Mindy; Michael, Duncan M.; Pflueger, Jeffery B.; Sethi, Manik S.; Shimazu, Kelli N.; Anthony, Tatiana M.; Lee, Christopher L.

2016-04-01

Results are presented which demonstrate the feasibility and performance of two concepts of biologically-inspired landing-gear systems that enable bird-sized, unmanned aerial vehicles (UAV's) to land, perch, and take-off from branchlike structures and/or ledges. The first concept follows the anatomy of birds that can grasp ahold of a branch and perch as tendons in their legs are tensioned. This design involves a gravity-activated, cable-driven, underactuated, graspingfoot mechanism. As the UAV lands, its weight collapses a four-bar linkage pulling a cable which curls two opposing, multi-segmented feet to grasp the landing target. Each foot is a single, compliant mechanism fabricated by simultaneouly 3D-printing a flexible thermo-plastic and a stiffer ABS plastic. The design is optimized to grasp structures over a range of shapes and sizes. Quasi-static and flight tests of this landing gear affixed to RC rotorcraft (24 cm to 550 cm in diameter) demonstrate that the aircraft can land, perch, and take-off from a tree branch, rectangular wood board, PVC pipe, metal hand rail, chair armrest, and in addition, a stone wall ledge. Stability tests show that perching is maintained under base and wind disturbances. The second design concept, inspired by roosting bats, is a two-material, 3D-printed hooking mechanism that enables the UAV to stably suspend itself from a wire or small-diameter branch. The design balances structural stiffness for support and flexibility for the perching process. A flight-test demonstrates the attaching and dis-engaging of a small, RC quadcopter from a suspended line.

Early aggressive intraocular pressure lowering, target intraocular pressure, and a novel concept for glaucoma care.

PubMed

Singh, Kuldev; Shrivastava, Anurag

2008-11-01

Early diagnosis of glaucomatous optic nerve damage offers the potential for early treatment which may prevent vision loss from this neurodegenerative disease. Even in patients who do not begin early treatment, early diagnosis allows for better monitoring of disease at a stage where the stakes are lower relative to later stages of the disease. For these reasons, early diagnosis of glaucomatous optic nerve disease is desirable and opens the door for appropriately aggressive therapy. The target intraocular pressure (IOP) concept is widely employed by glaucoma practitioners. Although there have been no randomized clinical trials or other high-quality studies showing the benefits of setting a target IOP versus not using this approach, there is ample evidence that lowering IOP slows glaucoma progression and, in general, lower is better, regardless of disease stage and baseline IOP level. We propose an alternative approach to managing glaucoma without the use of the target IOP concept and suggest that this market IOP concept should be compared with the target IOP approach in an appropriately powered comparative clinical trial.

Evaluation of 6-chloro-N-[3,4-disubstituted-1,3-thiazol-2(3H)-ylidene]-1,3-benzothiazol-2-amine Using Drug Design Concept for Their Targeted Activity Against Colon Cancer Cell Lines HCT-116, HCT15, and HT29.

PubMed

Zhu, Ming-Li; Wang, Cui-Yue; Xu, Cheng-Mian; Bi, Wei-Ping; ZHou, Xiu-Ying

2017-03-05

BACKGROUND Colorectal adenocarcinoma is the second leading cause of cancer-related death in the world. The stage of the disease is related to the survival of the patient, and in early phases surgery is the main modality of treatment. The main aim of modern medicinal chemistry is to synthesize small molecules via drug designing, especially by targeting tumor cells. MATERIAL AND METHODS A new series of 19 compounds containing benzothiazole and thiazole were designed. Molecular docking studies were performed on the designed series of molecules. Compounds showing good binding affinity towards the EGFR receptor were selected for synthetic studies. Characterization of the synthesized compounds was done by FTIR, 1HNMR, Mass and C, H, N, analysis. RESULTS The anticancer evaluation of the synthesized compounds was done at NIC, USA at a single dose against colon cancer cell lines HCT 116, HCT15, and HC 29. The active compounds were further evaluated for the 5-dose testing. Compounds were designed by using docking analysis. To ascertain the interaction of EGFR tyrosine kinase binding, energy calculation was used. CONCLUSIONS The results of the present study indicate that the designed compounds show good activity against colon cancer cell lines, which may be further studied to design new potential molecules.

Balancing novelty with confined chemical space in modern drug discovery.

PubMed

Medina-Franco, José L; Martinez-Mayorga, Karina; Meurice, Nathalie

2014-02-01

The concept of chemical space has broad applications in drug discovery. In response to the needs of drug discovery campaigns, different approaches are followed to efficiently populate, mine and select relevant chemical spaces that overlap with biologically relevant chemical spaces. This paper reviews major trends in current drug discovery and their impact on the mining and population of chemical space. We also survey different approaches to develop screening libraries with confined chemical spaces balancing physicochemical properties. In this context, the confinement is guided by criteria that can be divided in two broad categories: i) library design focused on a relevant therapeutic target or disease and ii) library design focused on the chemistry or a desired molecular function. The design and development of chemical libraries should be associated with the specific purpose of the library and the project goals. The high complexity of drug discovery and the inherent imperfection of individual experimental and computational technologies prompt the integration of complementary library design and screening approaches to expedite the identification of new and better drugs. Library design approaches including diversity-oriented synthesis, biological-oriented synthesis or combinatorial library design, to name a few, and the design of focused libraries driven by target/disease, chemical structure or molecular function are more efficient if they are guided by multi-parameter optimization. In this context, consideration of pharmaceutically relevant properties is essential for balancing novelty with chemical space in drug discovery.

TanCAR: A Novel Bispecific Chimeric Antigen Receptor for Cancer Immunotherapy

PubMed Central

Grada, Zakaria; Hegde, Meenakshi; Byrd, Tiara; Shaffer, Donald R; Ghazi, Alexia; Brawley, Vita S; Corder, Amanda; Schönfeld, Kurt; Koch, Joachim; Dotti, Gianpietro; Heslop, Helen E; Gottschalk, Stephen; Wels, Winfried S; Baker, Matthew L; Ahmed, Nabil

2013-01-01

Targeted T cells are emerging as effective non-toxic therapies for cancer. Multiple elements, however, contribute to the overall pathogenesis of cancer through both distinct and redundant mechanisms. Hence, targeting multiple cancer-specific markers simultaneously could result in better therapeutic efficacy. We created a functional chimeric antigen receptor—the TanCAR, a novel artificial molecule that mediates bispecific activation and targeting of T cells. We demonstrate the feasibility of cumulative integration of structure and docking simulation data using computational tools to interrogate the design and predict the functionality of such a complex bispecific molecule. Our prototype TanCAR induced distinct T cell reactivity against each of two tumor restricted antigens, and produced synergistic enhancement of effector functions when both antigens were simultaneously encountered. Furthermore, the TanCAR preserved the cytolytic ability of T cells upon loss of one of the target molecules and better controlled established experimental tumors by recognition of both targets in an animal disease model. This proof-of-concept approach can be used to increase the specificity of effector cells for malignant versus normal target cells, to offset antigen escape or to allow for targeting the tumor and its microenvironment. PMID:23839099

Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands.

PubMed

Sancineto, Luca; Iraci, Nunzio; Barreca, Maria Letizia; Massari, Serena; Manfroni, Giuseppe; Corazza, Gianmarco; Cecchetti, Violetta; Marcello, Alessandro; Daelemans, Dirk; Pannecouque, Christophe; Tabarrini, Oriana

2014-09-01

It is getting clearer that many drugs effective in different therapeutic areas act on multiple rather than single targets. The application of polypharmacology concepts might have numerous advantages especially for disease such as HIV/AIDS, where the rapid emergence of resistance requires a complex combination of more than one drug. In this paper, we have designed three hybrid molecules combining WM5, a quinolone derivative we previously identified as HIV Tat-mediated transcription (TMT) inhibitor, with the tricyclic core of nevirapine and BILR 355BS (BILR) non-nucleoside reverse transcriptase inhibitors (NNRTIs) to investigate whether it could be possible to obtain molecules acting on both transcription steps of the HIV replicative cycle. One among the three designed multiple ligands, reached this goal. Indeed, compound 1 inhibited both TMT and reverse transcriptase (RT) activity. Unexpectedly, while the anti-TMT activity exerted by compound 1 resulted into a selective inhibition of HIV-1 reactivation from latently infected OM10.1 cells, the anti-RT properties shown by all of the synthesized compounds did not translate into an anti-HIV activity in acutely infected cells. Thus, we have herein produced the proof of concept that the design of dual TMT-RT inhibitors is indeed possible, but optimization efforts are needed to obtain more potent derivatives. Copyright © 2014 Elsevier Ltd. All rights reserved.

Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications.

PubMed

Bian, Yuemin; Xie, Xiang-Qun Sean

2018-04-09

Fragment-based drug design (FBDD) has become an effective methodology for drug development for decades. Successful applications of this strategy brought both opportunities and challenges to the field of Pharmaceutical Science. Recent progress in the computational fragment-based drug design provide an additional approach for future research in a time- and labor-efficient manner. Combining multiple in silico methodologies, computational FBDD possesses flexibilities on fragment library selection, protein model generation, and fragments/compounds docking mode prediction. These characteristics provide computational FBDD superiority in designing novel and potential compounds for a certain target. The purpose of this review is to discuss the latest advances, ranging from commonly used strategies to novel concepts and technologies in computational fragment-based drug design. Particularly, in this review, specifications and advantages are compared between experimental and computational FBDD, and additionally, limitations and future prospective are discussed and emphasized.

Compact Polarimetry Potentials

NASA Technical Reports Server (NTRS)

Truong-Loi, My-Linh; Dubois-Fernandez, Pascale; Pottier, Eric

2011-01-01

The goal of this study is to show the potential of a compact-pol SAR system for vegetation applications. Compact-pol concept has been suggested to minimize the system design while maximize the information and is declined as the ?/4, ?/2 and hybrid modes. In this paper, the applications such as biomass and vegetation height estimates are first presented, then, the equivalence between compact-pol data simulated from full-pol data and compact-pol data processed from raw data as such is shown. Finally, a calibration procedure using external targets is proposed.

The FIELDS Instrument Suite for Solar Probe Plus

NASA Technical Reports Server (NTRS)

Bale, S. D.; Goetz, K.; Harvey, P. R.; Turin, P.; Bonnell, J. W.; Dudok de Wit, T.; Ergun, R. E.; MacDowall, R. J.; Pulupa, M.; Andre, M.;

The ALPACA Project

NASA Astrophysics Data System (ADS)

Takita, Masato

2017-06-01

We have started up the ALPACA (Andes Large area PArticle detector for Cosmic ray physics and Astronomy) project. The ALPACA experiment is composed of an 83,000 m2 air shower array and a 5,400 m2 underground muon detector array to make wide field-of-view high-sensitivity observations of high-energy cosmic rays/cosmic gamma rays on the Cerro Estuqueria highland, 4,740 m above sea level around Mount Chacaltaya, Bolivia. We briefly report on the design concept of the new project and its physics targets.

Architectural design and support for knowledge sharing across heterogeneous MAST systems

NASA Astrophysics Data System (ADS)

Arkin, Ronald C.; Garcia-Vergara, Sergio; Lee, Sung G.

2012-06-01

A novel approach for the sharing of knowledge between widely heterogeneous robotic agents is presented, drawing upon Gardenfors Conceptual Spaces approach [4]. The target microrobotic platforms considered are computationally, power, sensor, and communications impoverished compared to more traditional robotics platforms due to their small size. This produces novel challenges for the system to converge on an interpretation of events within the world, in this case specifically focusing on the task of recognizing the concept of a biohazard in an indoor setting.

The FIELDS Instrument Suite for Solar Probe Plus

PubMed Central

Goetz, K.; Harvey, P.R.; Turin, P.; Bonnell, J.W.; de Wit, T. Dudok; Ergun, R.E.; MacDowall, R.J.; Pulupa, M.; Andre, M.; Bolton, M.; Bougeret, J.-L.; Bowen, T.A.; Burgess, D.; Cattell, C.A.; Chandran, B.D.G.; Chaston, C.C.; Chen, C.H.K.; Choi, M.K.; Connerney, J.E.; Cranmer, S.; Diaz-Aguado, M.; Donakowski, W.; Drake, J.F.; Farrell, W.M.; Fergeau, P.; Fermin, J.; Fischer, J.; Fox, N.; Glaser, D.; Goldstein, M.; Gordon, D.; Hanson, E.; Harris, S.E.; Hayes, L.M.; Hinze, J.J.; Hollweg, J.V.; Horbury, T.S.; Howard, R. A.; Hoxie, V.; Jannet, G.; Karlsson, M.; Kasper, J.C.; Kellogg, P.J.; Kien, M.; Klimchuk, J.A.; Krasnoselskikh, V.V.; Krucker, S.; Lynch, J.J.; Maksimovic, M.; Malaspina, D.M.; Marker, S.; Martin, P.; Martinez-Oliveros, J.; McCauley, J.; McComas, D.J.; McDonald, T.; Meyer-Vernet, N.; Moncuquet, M.; Monson, S.J.; Mozer, F.S.; Murphy, S.D.; Odom, J.; Oliverson, R.; Olson, J.; Parker, E.N.; Pankow, D.; Phan, T.; Quataert, E.; Quinn, T.; Ruplin, S.W.; Salem, C.; Seitz, D.; Sheppard, D.A.; Siy, A.; Stevens, K.; Summers, D.; Szabo, A.; Timofeeva, M.; Vaivads, A.; Velli, M.; Yehle, A.; Werthimer, D.; Wygant, J.R.

2018-01-01

NASA’s Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products. PMID:29755144

In Situ Surveying of Saturn's Rings

NASA Technical Reports Server (NTRS)

Clark, P. E.; Curtis, S. A.; Rilee, M. L.; Cheung, C.

2004-01-01

The Saturn Autonomous Ring Array (SARA) mission concept is a new application for the Autonomous Nano-Technology Swarm (ANTS) architecture, a paradigm being developed for exploration of high surface area and/or multibody targets to minimize costs and maximize effectiveness of survey operations. Systems designed with ANTS architecture are built from potentially very large numbers of highly autonomous, yet socially interactive, specialists, in approximately ten specialist classes. Here, we analyze requirements for such a mission as well as specialized autonomous operations which would support this application.

Space Environments and Effects Concept: Transitioning Research to Operations and Applications

NASA Technical Reports Server (NTRS)

Edwards, David L.; Spann, James; Burns, Howard D.; Schumacher, Dan

2012-01-01

The National Aeronautics and Space Administration (NASA) is embarking on a course to expand human presence beyond Low Earth Orbit (LEO) while expanding its mission to explore the solar system. Destinations such as Near Earth Asteroids (NEA), Mars and its moons, and the outer planets are but a few of the mission targets. NASA has established numerous offices specializing in specific space environments disciplines that will serve to enable these missions. To complement these existing discipline offices, a concept focusing on the development of space environment and effects application is presented. This includes space climate, space weather, and natural and induced space environments. This space environment and effects application is composed of 4 topic areas; characterization and modeling, engineering effects, prediction and operation, and mitigation and avoidance. These topic areas are briefly described below. Characterization and modeling of space environments will primarily focus on utilization during Program mission concept, planning, and design phases. Engineering effects includes materials testing and flight experiments producing data to be used in mission planning and design phases. Prediction and operation pulls data from existing sources into decision-making tools and empirical data sets to be used during the operational phase of a mission. Mitigation and avoidance will develop techniques and strategies used in the design and operations phases of the mission. The goal of this space environment and effects application is to develop decision-making tools and engineering products to support the mission phases of mission concept through operations by focusing on transitioning research to operations. Products generated by this space environments and effects application are suitable for use in anomaly investigations. This paper will outline the four topic areas, describe the need, and discuss an organizational structure for this space environments and effects application.

Current progress of immunoinformatics approach harnessed for cellular- and antibody-dependent vaccine design.

PubMed

Kazi, Ada; Chuah, Candy; Majeed, Abu Bakar Abdul; Leow, Chiuan Herng; Lim, Boon Huat; Leow, Chiuan Yee

2018-03-12

Immunoinformatics plays a pivotal role in vaccine design, immunodiagnostic development, and antibody production. In the past, antibody design and vaccine development depended exclusively on immunological experiments which are relatively expensive and time-consuming. However, recent advances in the field of immunological bioinformatics have provided feasible tools which can be used to lessen the time and cost required for vaccine and antibody development. This approach allows the selection of immunogenic regions from the pathogen genomes. The ideal regions could be developed as potential vaccine candidates to trigger protective immune responses in the hosts. At present, epitope-based vaccines are attractive concepts which have been successfully trailed to develop vaccines which target rapidly mutating pathogens. In this article, we provide an overview of the current progress of immunoinformatics and their applications in the vaccine design, immune system modeling and therapeutics.

A New Optical Design for Imaging Spectroscopy

NASA Astrophysics Data System (ADS)

Thompson, K. L.

2002-05-01

We present an optical design concept for imaging spectroscopy, with some advantages over current systems. The system projects monochromatic images onto the 2-D array detector(s). Faint object and crowded field spectroscopy can be reduced first using image processing techniques, then building the spectrum, unlike integral field units where one must first extract the spectra, build data cubes from these, then reconstruct the target's integrated spectral flux. Like integral field units, all photons are detected simultaneously, unlike tunable filters which must be scanned through the wavelength range of interest and therefore pay a sensitivity pentalty. Several sample designs are presented, including an instrument optimized for measuring intermediate redshift galaxy cluster velocity dispersions, one designed for near-infrared ground-based adaptive optics, and one intended for space-based rapid follow-up of transient point sources such as supernovae and gamma ray bursts.

A Dynamic Navigation Model for Unmanned Aircraft Systems and an Application to Autonomous Front-On Environmental Sensing and Photography Using Low-Cost Sensor Systems.

PubMed

Cooper, Andrew James; Redman, Chelsea Anne; Stoneham, David Mark; Gonzalez, Luis Felipe; Etse, Victor Kwesi

2015-08-28

This paper presents an unmanned aircraft system (UAS) that uses a probabilistic model for autonomous front-on environmental sensing or photography of a target. The system is based on low-cost and readily-available sensor systems in dynamic environments and with the general intent of improving the capabilities of dynamic waypoint-based navigation systems for a low-cost UAS. The behavioural dynamics of target movement for the design of a Kalman filter and Markov model-based prediction algorithm are included. Geometrical concepts and the Haversine formula are applied to the maximum likelihood case in order to make a prediction regarding a future state of a target, thus delivering a new waypoint for autonomous navigation. The results of the application to aerial filming with low-cost UAS are presented, achieving the desired goal of maintained front-on perspective without significant constraint to the route or pace of target movement.

Compression Dynamics of an Indirect Drive Fast Ignition Target

NASA Astrophysics Data System (ADS)

Stephens, R. B.; Hatchett, S. A.; Turner, R. E.; Tanaka, K. A.; Kodama, R.; Soures, J.

2002-11-01

We have compared the compression of an indirectly driven cone-in-shell target, a type proposed for the fast ignition concept, with models. The experimental parameters -500 μm diameter plastic shell with 60 μm thick wall were a 1/5 scale realization of a fast ignition target designed for NIF (absorbing 180 kJ for compression and ˜30 kJ for ignition, and yielding ˜30 MJ) [1]. The implosion was backlit with 6.4 keV x-rays, and observed with a framing camera which captured the implosion from ˜2.6 to 3.3 ns after the onset. The collapsing structure was very similar to model predictions except that non-thermal m-band emissions from the hohlraum penetrated the shell and vaporized gold off the reentrant cone. This could be eliminated by changing the hohlraum composition. [1] S. Hatchett, et al., 5th Wkshp on Fast Ignition of Fusion Targets (Satellite Wkshp, 28th EPS Conf. on Contr. Fusion and Plasma Phys.), Madeira, Portugal (2001).

A Dynamic Navigation Model for Unmanned Aircraft Systems and an Application to Autonomous Front-On Environmental Sensing and Photography Using Low-Cost Sensor Systems

PubMed Central

Cooper, Andrew James; Redman, Chelsea Anne; Stoneham, David Mark; Gonzalez, Luis Felipe; Etse, Victor Kwesi

2015-01-01

This paper presents an unmanned aircraft system (UAS) that uses a probabilistic model for autonomous front-on environmental sensing or photography of a target. The system is based on low-cost and readily-available sensor systems in dynamic environments and with the general intent of improving the capabilities of dynamic waypoint-based navigation systems for a low-cost UAS. The behavioural dynamics of target movement for the design of a Kalman filter and Markov model-based prediction algorithm are included. Geometrical concepts and the Haversine formula are applied to the maximum likelihood case in order to make a prediction regarding a future state of a target, thus delivering a new waypoint for autonomous navigation. The results of the application to aerial filming with low-cost UAS are presented, achieving the desired goal of maintained front-on perspective without significant constraint to the route or pace of target movement. PMID:26343680

Ultrasound-Targeted Microbubble Destruction to Deliver siRNA Cancer Therapy

PubMed Central

Carson, Andrew R; McTiernan, Charles F; Lavery, Linda; Grata, Michelle; Leng, Xiaoping; Wang, Jianjun; Chen, Xucai; Villanueva, Flordeliza S

2012-01-01

Microbubble contrast agents can specifically deliver nucleic acids to target tissues when exposed to ultrasound treatment parameters that mediate microbubble destruction. In this study, we evaluated whether microbubbles and ultrasound targeted microbubble destruction (UTMD) could be used to enhance delivery of EGFR-directed small inhibitory RNA (siRNA) to murine squamous cell carcinomas. Custom designed microbubbles efficiently bound siRNA and mediated RNAse protection. UTMD-mediated delivery of microbubbles loaded with EGFR-directed siRNA to murine squamous carcinoma cells in vitro reduced EGFR expression and EGF-dependent growth, relative to delivery of control siRNA. Similarly, serial UTMD-mediated delivery of EGFR siRNA to squamous cell carcinoma in vivo decreased EGFR expression and increased tumor doubling times, relative to controls receiving EGFR siRNA loaded microbubbles but not ultrasound or control siRNA loaded microbubbles and UTMD. Taken together, our results offer a preclinical proof of concept for customized microbubbles and UTMD to deliver gene-targeted siRNA for cancer therapy. PMID:23010078

EEG character identification using stimulus sequences designed to maximize mimimal hamming distance.

PubMed

Fukami, Tadanori; Shimada, Takamasa; Forney, Elliott; Anderson, Charles W

2012-01-01

In this study, we have improved upon the P300 speller Brain-Computer Interface paradigm by introducing a new character encoding method. Our concept in detection of the intended character is not based on a classification of target and nontarget responses, but based on an identifaction of the character which maximize the difference between P300 amplitudes in target and nontarget stimuli. Each bit included in the code corresponds to flashing character, '1', and non-flashing, '0'. Here, the codes were constructed in order to maximize the minimum hamming distance between the characters. Electroencephalography was used to identify the characters using a waveform calculated by adding and subtracting the response of the target and non-target stimulus according the codes respectively. This stimulus presentation method was applied to a 3×3 character matrix, and the results were compared with that of a conventional P300 speller of the same size. Our method reduced the time until the correct character was obtained by 24%.

Solvatochromic and Fluorogenic Dyes as Environment-Sensitive Probes: Design and Biological Applications.

PubMed

Klymchenko, Andrey S

2017-02-21

Fluorescent environment-sensitive probes are specially designed dyes that change their fluorescence intensity (fluorogenic dyes) or color (e.g., solvatochromic dyes) in response to change in their microenvironment polarity, viscosity, and molecular order. The studies of the past decade, including those of our group, have shown that these molecules become universal tools in fluorescence sensing and imaging. In fact, any biomolecular interaction or change in biomolecular organization results in modification of the local microenvironment, which can be directly monitored by these types of probes. In this Account, the main examples of environment-sensitive probes are summarized according to their design concepts. Solvatochromic dyes constitute a large class of environment-sensitive probes which change their color in response to polarity. Generally, they are push-pull dyes undergoing intramolecular charge transfer. Emission of their highly polarized excited state shifts to the red in more polar solvents. Excited-state intramolecular proton transfer is the second key concept to design efficient solvatochromic dyes, which respond to the microenvironment by changing relative intensity of the two emissive tautomeric forms. Due to their sensitivity to polarity and hydration, solvatochromic dyes have been successfully applied to biological membranes for studying lipid domains (rafts), apoptosis and endocytosis. As fluorescent labels, solvatochromic dyes can detect practically any type of biomolecular interactions, involving proteins, nucleic acids and biomembranes, because the binding event excludes local water molecules from the interaction site. On the other hand, fluorogenic probes usually exploit intramolecular rotation (conformation change) as a design concept, with molecular rotors being main representatives. These probes were particularly efficient for imaging viscosity and lipid order in biomembranes as well as to light up biomolecular targets, such as antibodies, aptamers and receptors. The emerging concepts to achieve fluorogenic response to the microenvironment include ground-state isomerization, aggregation-caused quenching, and aggregation-induced emission. The ground-state isomerization exploits, for instance, polarity-dependent spiro-lactone formation in silica-rhodamines. The aggregation-caused quenching uses disruption of the self-quenched dimers and nanoassemblies of dyes in less polar environments of lipid membranes and biomolecules. The aggregation-induced emission couples target recognition with formation of highly fluorescent dye aggregates. Overall, solvatochromic and fluorogenic probes enable background-free bioimaging in wash-free conditions as well as quantitative analysis when combined with advanced microscopy, such as fluorescence lifetime (FLIM) and ratiometric imaging. Further development of fluorescent environment-sensitive probes should address some remaining problems: (i) improving their optical properties, especially brightness, photostability, and far-red to near-infrared operating range; (ii) minimizing nonspecific interactions of the probes in biological systems; (iii) their adaptation for advanced microscopies, notably for superresolution and in vivo imaging.

The Cost of Economic Literacy: How Well Does a Literacy-Targeted Principles of Economics Course Prepare Students for Intermediate Theory Courses?

ERIC Educational Resources Information Center

Gilleskie, Donna B.; Salemi, Michael K.

2012-01-01

In a typical economics principles course, students encounter a large number of concepts. In a literacy-targeted course, students study a "short list" of concepts that they can use for the rest of their lives. While a literacy-targeted principles course provides better education for nonmajors, it may place economic majors at a…

Optimization of a Lunar Pallet Lander Reinforcement Structure Using a Genetic Algorithm

NASA Technical Reports Server (NTRS)

Burt, Adam O.; Hull, Patrick V.

2014-01-01

This paper presents a design automation process using optimization via a genetic algorithm to design the conceptual structure of a Lunar Pallet Lander. The goal is to determine a design that will have the primary natural frequencies at or above a target value as well as minimize the total mass. Several iterations of the process are presented. First, a concept optimization is performed to determine what class of structure would produce suitable candidate designs. From this a stiffened sheet metal approach was selected leading to optimization of beam placement through generating a two-dimensional mesh and varying the physical location of reinforcing beams. Finally, the design space is reformulated as a binary problem using 1-dimensional beam elements to truncate the design space to allow faster convergence and additional mechanical failure criteria to be included in the optimization responses. Results are presented for each design space configuration. The final flight design was derived from these results.

Integrated process modeling for the laser inertial fusion energy (LIFE) generation system

NASA Astrophysics Data System (ADS)

Meier, W. R.; Anklam, T. M.; Erlandson, A. C.; Miles, R. R.; Simon, A. J.; Sawicki, R.; Storm, E.

2010-08-01

A concept for a new fusion-fission hybrid technology is being developed at Lawrence Livermore National Laboratory. The primary application of this technology is base-load electrical power generation. However, variants of the baseline technology can be used to "burn" spent nuclear fuel from light water reactors or to perform selective transmutation of problematic fission products. The use of a fusion driver allows very high burn-up of the fission fuel, limited only by the radiation resistance of the fuel form and system structures. As a part of this process, integrated process models have been developed to aid in concept definition. Several models have been developed. A cost scaling model allows quick assessment of design changes or technology improvements on cost of electricity. System design models are being used to better understand system interactions and to do design trade-off and optimization studies. Here we describe the different systems models and present systems analysis results. Different market entry strategies are discussed along with potential benefits to US energy security and nuclear waste disposal. Advanced technology options are evaluated and potential benefits from additional R&D targeted at the different options is quantified.

Passive millimeter-wave imaging polarimeter system

NASA Astrophysics Data System (ADS)

Persons, Christopher M.; Martin, Christopher A.; Jones, Michael W.; Kolinko, Vladimir; Lovberg, John A.

2009-05-01

The Army has identified a need to rapidly identify, map, and classify natural and manmade features to aid situational awareness as well as mission and tactical planning. To address these needs, Digital Fusion and Trex Enterprises have designed a full Stokes, passive MMW imaging polarimeter that is capable of being deployed on an unmanned aerial vehicle. Results of a detailed trade study are presented, where an architecture, waveband and target platform are selected. The selected architecture is a pushbroom phased-array system, which allows the system to collect a wide fieldof- view image with minimal components and weight. W band is chosen as a trade-off between spatial resolution, weather penetration, and component availability. The trade study considers several unmanned aerial system (UAS) platforms that are capable of low-level flight and that can support the MMW antenna. The utility of the passive Stokes imager is demonstrated through W band phenomenology data collections at horizontal and vertical polarization using a variety of natural and manmade materials. The concept design is detailed, along with hardware and procedures for both radiometric and polarimetric calibration. Finally, a scaled version of the concept design is presented, which is being fabricated for an upcoming demonstration on a small, manned aircraft.

Generic repository design concepts and thermal analysis (FY11).

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howard, Robert; Dupont, Mark; Blink, James A.

2011-08-01

Reference concepts for geologic disposal of used nuclear fuel and high-level radioactive waste in the U.S. are developed, including geologic settings and engineered barriers. Repository thermal analysis is demonstrated for a range of waste types from projected future, advanced nuclear fuel cycles. The results show significant differences among geologic media considered (clay/shale, crystalline rock, salt), and also that waste package size and waste loading must be limited to meet targeted maximum temperature values. In this study, the UFD R&D Campaign has developed a set of reference geologic disposal concepts for a range of waste types that could potentially be generatedmore » in advanced nuclear FCs. A disposal concept consists of three components: waste inventory, geologic setting, and concept of operations. Mature repository concepts have been developed in other countries for disposal of spent LWR fuel and HLW from reprocessing UNF, and these serve as starting points for developing this set. Additional design details and EBS concepts will be considered as the reference disposal concepts evolve. The waste inventory considered in this study includes: (1) direct disposal of SNF from the LWR fleet, including Gen III+ advanced LWRs being developed through the Nuclear Power 2010 Program, operating in a once-through cycle; (2) waste generated from reprocessing of LWR UOX UNF to recover U and Pu, and subsequent direct disposal of used Pu-MOX fuel (also used in LWRs) in a modified-open cycle; and (3) waste generated by continuous recycling of metal fuel from fast reactors operating in a TRU burner configuration, with additional TRU material input supplied from reprocessing of LWR UOX fuel. The geologic setting provides the natural barriers, and establishes the boundary conditions for performance of engineered barriers. The composition and physical properties of the host medium dictate design and construction approaches, and determine hydrologic and thermal responses of the disposal system. Clay/shale, salt, and crystalline rock media are selected as the basis for reference mined geologic disposal concepts in this study, consistent with advanced international repository programs, and previous investigations in the U.S. The U.S. pursued deep geologic disposal programs in crystalline rock, shale, salt, and volcanic rock in the years leading up to the Nuclear Waste Policy Act, or NWPA (Rechard et al. 2011). The 1987 NWPA amendment act focused the U.S. program on unsaturated, volcanic rock at the Yucca Mountain site, culminating in the 2008 license application. Additional work on unsaturated, crystalline rock settings (e.g., volcanic tuff) is not required to support this generic study. Reference disposal concepts are selected for the media listed above and for deep borehole disposal, drawing from recent work in the U.S. and internationally. The main features of the repository concepts are discussed in Section 4.5 and summarized in Table ES-1. Temperature histories at the waste package surface and a specified distance into the host rock are calculated for combinations of waste types and reference disposal concepts, specifying waste package emplacement modes. Target maximum waste package surface temperatures are identified, enabling a sensitivity study to inform the tradeoff between the quantity of waste per disposal package, and decay storage duration, with respect to peak temperature at the waste package surface. For surface storage duration on the order of 100 years or less, waste package sizes for direct disposal of SNF are effectively limited to 4-PWR configurations (or equivalent size and output). Thermal results are summarized, along with recommendations for follow-on work including adding additional reference concepts, verification and uncertainty analysis for thermal calculations, developing descriptions of surface facilities and other system details, and cost estimation to support system-level evaluations.« less

Kinase inhibitors for CNS diseases: an analysis of the recent patent literature.

PubMed

Amigoni, Federica; Legnaghi, Elena; Pevarello, Paolo

2012-05-01

Protein kinases (PKs), as members of an important target class in current pharmaceutical research, have been mostly exploited so far in therapeutic areas such as oncology and inflammation. However, basic research on some PKs as key components of molecular mechanisms underlying neurodegeneration and neuroprotection may translate into new medicines for CNS diseases in the next few years. This review is an account of recent patents dealing with kinase inhibitors primarily designed for CNS indications. CNS-directed patents on kinase modulators published after 2008 were surveyed using SciFinder(®) and public patent search engines. Some PK targets, such as GSK-3β, CDK5, ROCK and p38α MAPK, continue to attract interest even though a clinical proof-of-concept is yet to be attained in a CNS setting. Less established PKs such as LRRK2, MLK, PAK and DAPK-1 hold promise as valuable targets of the future.

Self-assembling toxin-based nanoparticles as self-delivered antitumoral drugs.

PubMed

Sánchez-García, Laura; Serna, Naroa; Álamo, Patricia; Sala, Rita; Céspedes, María Virtudes; Roldan, Mònica; Sánchez-Chardi, Alejandro; Unzueta, Ugutz; Casanova, Isolda; Mangues, Ramón; Vázquez, Esther; Villaverde, Antonio

2018-03-28

Loading capacity and drug leakage from vehicles during circulation in blood is a major concern when developing nanoparticle-based cell-targeted cytotoxics. To circumvent this potential issue it would be convenient the engineering of drugs as self-delivered nanoscale entities, devoid of any heterologous carriers. In this context, we have here engineered potent protein toxins, namely segments of the diphtheria toxin and the Pseudomonas aeruginosa exotoxin as self-assembling, self-delivered therapeutic materials targeted to CXCR4 + cancer stem cells. The systemic administration of both nanostructured drugs in a colorectal cancer xenograft mouse model promotes efficient and specific local destruction of target tumor tissues and a significant reduction of the tumor volume. This observation strongly supports the concept of intrinsically functional protein nanoparticles, which having a dual role as drug and carrier, are designed to be administered without the assistance of heterologous vehicles. Copyright © 2018 Elsevier B.V. All rights reserved.

Indirubin core structure of glycogen synthase kinase-3 inhibitors as novel chemotype for intervention with 5-lipoxygenase.

PubMed

Pergola, Carlo; Gaboriaud-Kolar, Nicolas; Jestädt, Nadine; König, Stefanie; Kritsanida, Marina; Schaible, Anja M; Li, Haokun; Garscha, Ulrike; Weinigel, Christina; Barz, Dagmar; Albring, Kai F; Huber, Otmar; Skaltsounis, Alexios L; Werz, Oliver

2014-05-08

The enzymes 5-lipoxygenase (5-LO) and glycogen synthase kinase (GSK)-3 represent promising drug targets in inflammation. We made use of the bisindole core of indirubin, present in GSK-3 inhibitors, to innovatively target 5-LO at the ATP-binding site for the design of dual 5-LO/GSK-3 inhibitors. Evaluation of substituted indirubin derivatives led to the identification of (3Z)-6-bromo-3-[(3E)-3-hydroxyiminoindolin-2-ylidene]indolin-2-one (15) as a potent, direct, and reversible 5-LO inhibitor (IC50 = 1.5 μM), with comparable cellular effectiveness on 5-LO and GSK-3. Together, we present indirubins as novel chemotypes for the development of 5-LO inhibitors, the interference with the ATP-binding site as a novel strategy for 5-LO targeting, and dual 5-LO/GSK-3 inhibition as an unconventional and promising concept for anti-inflammatory intervention.

Structural Overview of the Nuclear Receptor Superfamily: Insights into Physiology and Therapeutics

PubMed Central

Huang, Pengxiang; Chandra, Vikas; Rastinejad, Fraydoon

2013-01-01

As ligand-regulated transcription factors, the nuclear hormone receptors are nearly ideal drug targets, with internal pockets that bind to hydrophobic, drug-like molecules and well-characterized ligand-induced conformational changes that recruit transcriptional coregulators to promoter elements. Yet, due to the multitude of genes under the control of a single receptor, the major challenge has been the identification of ligands with gene-selective actions, impacting disease outcomes through a narrow subset of target genes and not across their entire gene-regulatory repertoire. Here, we summarize the concepts and work to date underlying the development of steroidal and nonsteroidal receptor ligands, including the use of crystal structures, high-throughput screens, and rational design approaches for finding useful therapeutic molecules. Difficulties in finding selective receptor modulators require a more complete understanding of receptor interdomain communications, posttranslational modifications, and receptor-protein interactions that could be exploited for target gene selectivity. PMID:20148675

Iterative Design and Testing for the Development of a Game-Based Chlamydia Awareness Intervention: A Pilot Study.

PubMed

Jiang, Rui; McKanna, James; Calabrese, Samantha; Seif El-Nasr, Magy

2017-08-01

Herein we describe a methodology for developing a game-based intervention to raise awareness of Chlamydia and other sexually transmitted infections among youth in Boston's underserved communities. We engaged in three design-based experiments. These utilized mixed methods, including playtesting and assessment methods, to examine the overall effectiveness of the game. In this case, effectiveness is defined as (1) engaging the target group, (2) increasing knowledge about Chlamydia, and (3) changing attitudes toward Chlamydia testing. These three experiments were performed using participants from different communities and with slightly different versions of the game, as we iterated through the design/feedback process. Overall, participants who played the game showed a significant increase in participants' knowledge of Chlamydia compared with those in the control group (P = 0.0002). The version of the game, including elements specifically targeting systemic thinking, showed significant improvement in participants' intent to get tested compared with the version of the game without such elements (Stage 2: P > 0.05; Stage 3: P = 0.0045). Furthermore, during both Stage 2 and Stage 3, participants showed high levels of enjoyment, mood, and participation and moderate levels of game engagement and social engagement. During Stage 3, however, participants' game engagement (P = 0.0003), social engagement (P = 0.0003), and participation (P = 0.0003) were significantly higher compared with those of Stage 2. Thus, we believe that motivation improvements from Stage 2 to 3 were also effective. Finally, participants' overall learning effectiveness was correlated with their prepositive affect (r = 0.52) and their postproblem hierarchy (r = -0.54). The game improved considerably from its initial conception through three stages of iterative design and feedback. Our assessment methods for each stage targeted and integrated learning, health, and engagement outcomes. Lessons learned through this iterative design process are a great contribution to the games for health community, especially in targeting the development of health and learning goals through game design.

Green Infrastructure Design Based on Spatial Conservation Prioritization and Modeling of Biodiversity Features and Ecosystem Services.

PubMed

Snäll, Tord; Lehtomäki, Joona; Arponen, Anni; Elith, Jane; Moilanen, Atte

2016-02-01

There is high-level political support for the use of green infrastructure (GI) across Europe, to maintain viable populations and to provide ecosystem services (ES). Even though GI is inherently a spatial concept, the modern tools for spatial planning have not been recognized, such as in the recent European Environment Agency (EEA) report. We outline a toolbox of methods useful for GI design that explicitly accounts for biodiversity and ES. Data on species occurrence, habitats, and environmental variables are increasingly available via open-access internet platforms. Such data can be synthesized by statistical species distribution modeling, producing maps of biodiversity features. These, together with maps of ES, can form the basis for GI design. We argue that spatial conservation prioritization (SCP) methods are effective tools for GI design, as the overall SCP goal is cost-effective allocation of conservation efforts. Corridors are currently promoted by the EEA as the means for implementing GI design, but they typically target the needs of only a subset of the regional species pool. SCP methods would help to ensure that GI provides a balanced solution for the requirements of many biodiversity features (e.g., species, habitat types) and ES simultaneously in a cost-effective manner. Such tools are necessary to make GI into an operational concept for combating biodiversity loss and promoting ES.

Green Infrastructure Design Based on Spatial Conservation Prioritization and Modeling of Biodiversity Features and Ecosystem Services

NASA Astrophysics Data System (ADS)

Snäll, Tord; Lehtomäki, Joona; Arponen, Anni; Elith, Jane; Moilanen, Atte

2016-02-01

There is high-level political support for the use of green infrastructure (GI) across Europe, to maintain viable populations and to provide ecosystem services (ES). Even though GI is inherently a spatial concept, the modern tools for spatial planning have not been recognized, such as in the recent European Environment Agency (EEA) report. We outline a toolbox of methods useful for GI design that explicitly accounts for biodiversity and ES. Data on species occurrence, habitats, and environmental variables are increasingly available via open-access internet platforms. Such data can be synthesized by statistical species distribution modeling, producing maps of biodiversity features. These, together with maps of ES, can form the basis for GI design. We argue that spatial conservation prioritization (SCP) methods are effective tools for GI design, as the overall SCP goal is cost-effective allocation of conservation efforts. Corridors are currently promoted by the EEA as the means for implementing GI design, but they typically target the needs of only a subset of the regional species pool. SCP methods would help to ensure that GI provides a balanced solution for the requirements of many biodiversity features (e.g., species, habitat types) and ES simultaneously in a cost-effective manner. Such tools are necessary to make GI into an operational concept for combating biodiversity loss and promoting ES.

AXTAR: Mission Design Concept

NASA Technical Reports Server (NTRS)

Ray, Paul S.; Chakrabarty, Deepto; Wilson-Hodge, Colleen A.; Philips, Bernard F.; Remillard, Ronald A.; Levine, Alan M.; Wood, Kent S.; Wolff, Michael T.; Gwon, Chul S.; Strohmayer, Tod E.;

Crafting biochars to reduce N2O and CO2 emissions while also improving soil quality

NASA Astrophysics Data System (ADS)

Novak, Jeff; Ippolito, Jim; Spokas, Kurt; Sigua, Gilbert; Kammann, Claudia; Wrage-Monnig, Nicole; Borchard, Nils; Schirrmann, Michael; Estavillo, Jose Maria; Fuertes-Mendizabal, Teresa; Menendez, Sergio; Cayuela, Maria Luz

2017-04-01

Biochar used as an amendment has been linked to nitrous oxide (N2O) emission reductions, a decrease in nitrogen (N) leaching, and soil quality improvements (e.g., soil carbon sequestration, pH, etc.). While numerous articles will support these three facts, conversely, there are reports of no to marginal influences. One reason for the mixed biochar performance could be related to applying biochar with incorrect chemical and physical characteristics. As a means to increase biochar efficiency, we introduced the concept of crafting biochars with properties attuned to specific soil deficiencies. Implementing this concept requires a literature review to identify salient biochar characteristics that reduces N2O emissions, impacts N availability, while also improving soil quality. Thus, scientists from the USDA-ARS and through a coalition of European scientists under the FACCE-JPI umbrella have conceived the DesignChar4food (d4f) project. In this project, scientists are working collaboratively to further this concept to match the appropriate biochar for selective soil quality improvement, retain N for crops, and promote greenhouse gas reductions. This presentation will highlight results from the d4f team compromising a meta-analysis of articles on biochar:N2O dynamics, N availability, and how designer biochars can target specific soil quality improvements.

Environmental Control and Life Support (ECLS) Hardware Commonality for Exploration Vehicles

NASA Technical Reports Server (NTRS)

Carrasquillo, Robyn; Anderson, Molly

2012-01-01

In August 2011, the Environmental Control and Life Support Systems (ECLSS) technical community, along with associated stakeholders, held a workshop to review NASA s plans for Exploration missions and vehicles with two objectives: revisit the Exploration Atmospheres Working Group (EAWG) findings from 2006, and discuss preliminary ECLSS architecture concepts and technology choices for Exploration vehicles, identifying areas for potential common hardware or technologies to be utilized. Key considerations for selection of vehicle design total pressure and percent oxygen include operational concepts for extravehicular activity (EVA) and prebreathe protocols, materials flammability, and controllability within pressure and oxygen ranges. New data for these areas since the 2006 study were presented and discussed, and the community reached consensus on conclusions and recommendations for target design pressures for each Exploration vehicle concept. For the commonality study, the workshop identified many areas of potential commonality across the Exploration vehicles as well as with heritage International Space Station (ISS) and Shuttle hardware. Of the 36 ECLSS functions reviewed, 16 were considered to have strong potential for commonality, 13 were considered to have some potential commonality, and 7 were considered to have limited potential for commonality due to unique requirements or lack of sufficient heritage hardware. These findings, which will be utilized in architecture studies and budget exercises going forward, are presented in detail.

ATD-2 Surface Scheduling and Metering Concept

NASA Technical Reports Server (NTRS)

Coppenbarger, Richard A.; Jung, Yoon Chul; Capps, Richard Alan; Engelland, Shawn A.

2017-01-01

This presentation describes the concept of ATD-2 tactical surface scheduling and metering. The concept is composed of several elements, including data exchange and integration; surface modeling; surface scheduling; and surface metering. The presentation explains each of the elements. Surface metering is implemented to balance demand and capacity• When surface metering is on, target times from surface scheduler areconverted to advisories for throttling demand• Through the scheduling process, flights with CTOTs will not get addedmetering delay (avoids potential for ‘double delay’)• Carriers can designate certain flights as exempt from metering holds• Demand throttle in Phase 1 at CLT is through advisories sent to rampcontrollers for pushback instructions to the flight deck– Push now– Hold for an advised period of time (in minutes)• Principles of surface metering can be more generally applied to otherairports in the NAS to throttle demand via spot-release times (TMATs Strong focus on optimal use of airport resources• Flexibility enables stakeholders to vary the amount of delay theywould like transferred to gate• Addresses practical aspects of executing surface metering in aturbulent real world environment• Algorithms designed for both short term demand/capacityimbalances (banks) or sustained metering situations• Leverage automation to enable surface metering capability withoutrequiring additional positions• Represents first step in Tactical/Strategic fusion• Provides longer look-ahead calculations to enable analysis ofstrategic surface metering potential usage

Mission Design and Simulation Considerations for ADReS-A

NASA Astrophysics Data System (ADS)

Peters, S.; Förstner, R.; Fiedler, H.

2016-09-01

Space debris in general has become a major problem for modern space activities. Guidelines to mitigate the threat have been recommended, better prediction models are developed and an advanced observation of objects orbiting Earth is in progress. And still - without the implementation of active debris removal (ADR), the number of debris in space will exponentially increase. To support the ongoing research on ADR-missions, this paper presents the updated mission design of ADReS-A (Autonomous Debris Removal Satellite - #A) - one possible concept for the multiple active removal of large debris in Low Earth orbit, in this case especially of rocket bodies of the SL-8-type. ADReS-A as chaser satellite is supported by at least 5 de-orbit kits, allowing for the same number of targets to be removed. While ADReS-A is conceived for handling of the target, the kit's task is the controlled re-entry of the designated rocket body. The presented mission design forms the basis for the simulation environment in progress. The simulation shall serve as testbed to test multiple scenarios in terms of approach and abort optimization or different tumbling modes of the target. The ultimate goal is the test of autonomous behaviors of the spacecraft in case of unforeseen failures during the approach phase. Considerations to create a simulation for the described mission are presented and discussed. A first visualization of pre-calculated aboard trajectories can be found at the end of this paper.

Design, Synthesis of Novel Platinum(II) Glycoconjugates, and Evaluation of Their Antitumor Effects.

PubMed

Han, Jianbin; Gao, Xiangqian; Liu, Ran; Yang, Jinna; Zhang, Menghua; Mi, Yi; Shi, Ying; Gao, Qingzhi

2016-06-01

A new series of sugar-conjugated (trans-R, R-cyclohexane-1, 2-diamine)-2-halo-malonato-platinum(II) complexes were designed and synthesized to target tumor-specific glucose transporters (GLUTs). The water solubility of the sugar-conjugated platinum (II) complexes was greatly improved by average of 570-fold, 33-fold, and 94-fold, respectively, compared to cisplatin (1.0 mg/mL), carboplatin (17.1 mg/mL), and the newest generation of clinical drug oxaliplatin (6.0 mg/mL). Despite the high water solubility, the platinum(II) glycoconjugates exhibited a notable increase in cytotoxicity by a margin of 1.5- to 6.0-fold in six different human cancer cell lines with respect to oxaliplatin. The potential GLUT1 transportability of the complexes was investigated through a molecular docking study and was confirmed with GLUT1 inhibitor-mediated cytotoxicity dependency evaluation. The results showed that the sugar-conjugated platinum(II) complexes can be recognized by the glucose recognition binding site of GLUT1 and their cell killing effect depends highly on the GLUT1 inhibitor, quercetin. The research presenting a prospective concept for targeted therapy anticancer drug design, and with the analysis of the synthesis, water solubility, antitumor activity, and the transportability of the platinum(II) glycoconjugates, this study provides fundamental data supporting the inherent potential of these designed conjugates as lead compounds for GLUT-mediated tumor targeting. © 2016 John Wiley & Sons A/S.

Application of computer assisted combinatorial chemistry in antivirial, antimalarial and anticancer agents design

NASA Astrophysics Data System (ADS)

Burello, E.; Bologa, C.; Frecer, V.; Miertus, S.

Combinatorial chemistry and technologies have been developed to a stage where synthetic schemes are available for generation of a large variety of organic molecules. The innovative concept of combinatorial design assumes that screening of a large and diverse library of compounds will increase the probability of finding an active analogue among the compounds tested. Since the rate at which libraries are screened for activity currently constitutes a limitation to the use of combinatorial technologies, it is important to be selective about the number of compounds to be synthesized. Early experience with combinatorial chemistry indicated that chemical diversity alone did not result in a significant increase in the number of generated lead compounds. Emphasis has therefore been increasingly put on the use of computer assisted combinatorial chemical techniques. Computational methods are valuable in the design of virtual libraries of molecular models. Selection strategies based on computed physicochemical properties of the models or of a target compound are introduced to reduce the time and costs of library synthesis and screening. In addition, computational structure-based library focusing methods can be used to perform in silico screening of the activity of compounds against a target receptor by docking the ligands into the receptor model. Three case studies are discussed dealing with the design of targeted combinatorial libraries of inhibitors of HIV-1 protease, P. falciparum plasmepsin and human urokinase as potential antivirial, antimalarial and anticancer drugs. These illustrate library focusing strategies.

Multi-Organization Multi-Discipline Effort Developing a Mitigation Concept for Planetary Defense

NASA Technical Reports Server (NTRS)

Leung, Ronald Y.; Barbee, Brent W.; Seery, Bernard D.; Bambacus, Myra; Finewood, Lee; Greenaugh, Kevin C.; Lewis, Anthony; Dearborn, David; Miller, Paul L.; Weaver, Robert P.;

Core-shell nanosized assemblies mediated by the alpha-beta cyclodextrin dimer with a tumor-triggered targeting property.

PubMed

Quan, Chang-Yun; Chen, Jing-Xiao; Wang, Hui-Yuan; Li, Cao; Chang, Cong; Zhang, Xian-Zheng; Zhuo, Ren-Xi

2010-07-27

In this paper, the alpha-beta cyclodextrin dimer is designed via "click" chemistry to connect the hydrophilic and hydrophobic segments to form self-assembled noncovalently connected micelles (NCCMs) through host-guest interactions. A peptide containing the Arg-Gly-Asp (RGD) sequence was introduced to NCCMs as a target ligand to improve the cell uptake efficacy, while PEGylated technology was employed via benzoic-imine bonds to protect the ligands in normal tissues and body fluid. In addition, two fluorescent dyes were conjugated to different segments to track the formation of the micelles as well as the assemblies. It was found that the targeting property of NCCMs was switched off before reaching the tumor sites and switched on after removing the poly(ethylene glycol) (PEG) segment in the tumor sites, which was called "tumor-triggered targeting". With deshielding of the PEG segment, the drugs loaded in NCCMs could be released rapidly due to the thermoinduced phase transition. The new concept of "tumor-triggered targeting" proposed here has great potential for cancer treatment.

To be targeted: is the magic bullet concept a viable option for synthetic nucleic acid therapeutics?

PubMed

Ogris, Manfred; Wagner, Ernst

2011-07-01

Nucleic acids offer the possibility of tailor-made, individualized treatments for genetic disorders, infectious diseases, and cancer. As an alternative to viral vectors, synthetic delivery systems have a potentially improved safety profile, but often lack sufficient efficiency especially when applied in vivo. Receptor targeting of synthetic vectors can improve the specificity of the vector and increase the efficiency of nucleic acid delivery to the target site. This review covers recent concepts for targeted DNA and RNA delivery to organs like liver and lung, and also to solid cancers. Syntheses and applications of delivery systems targeted with proteins, peptides, and small molecules as ligands coupled to polymeric or lipidic nucleic acid carriers are reviewed. Therapeutic concepts for treatment of genetic and infectious diseases are explained. Systemic treatment regimens of metastasized malignancies in combination with chemotherapy and radiation have already been successfully applied in preclinical studies. In addition, a first clinical study in the human application of a targeted synthetic carrier has been performed.

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

NASA Astrophysics Data System (ADS)

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

2014-09-01

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

Preliminary studies for a beam-generated plasma neutralizer test in NIO1

NASA Astrophysics Data System (ADS)

Sartori, E.; Veltri, P.; Balbinot, L.; Cavenago, M.; Veranda, M.; Antoni, V.; Serianni, G.

2017-08-01

The deployment of neutral beam injectors in future fusion plants is beset by the particularly poor efficiency of the neutralization process. Beam-generated plasma neutralizers were proposed as a passive and intrinsically safe scheme of efficient plasma neutralizers. The concept is based on the natural ionization of the gas target by the beam, and on a suitable confinement of the secondary plasma. The technological challenge of such a concept is the magnetic confinement of the secondary plasma: a proof-of-principle for the concept is needed. The possibility to test of such a system in the small negative ion beam system NIO1 is discussed in this paper. The constraints given by the facility are first discussed. A model of beam-gas interaction is developed to provide the charge-state of beam particles along the neutralizer, and to provide the source terms of plasma generation. By using a cylindrical model of plasma diffusion in magnetic fields, the ionization degree of the target is estimated. In the absence of magnetic fields the diffusion model is validated against experimental measurements of the space-charge compensation plasma in the drift region of NIO1. Finally, the feasibility study for a beam-generated plasma neutralizer in NIO is presented. The neutralizer length, required gas target thickness, and a very simple magnetic setup were considered, taking into account the integration in NIO1. For the basic design a low ionization degree (1%) is obtained, however a promising plasma density up to hundred times the beam density was calculated. The proposed test in NIO1 can be the starting point for studying advanced schemes of magnetic confinement aiming at ionization degrees in the order of 10%.

Geoscience Laser Ranging System design and performance predictions

NASA Technical Reports Server (NTRS)

Anderson, Kent L.

1991-01-01

The Geoscience Laser System (GLRS) will be a high-precision distance-measuring instrument planned for deployment on the EOS-B platform. Its primary objectives are to perform ranging measurements to ground targets to monitor crustal deformation and tectonic plate motions, and nadir-looking altimetry to determine ice sheet thicknesses, surface topography, and vertical profiles of clouds and aerosols. The system uses a mode-locked, 3-color Nd:YAG laser source, a Microchannel Plate-PMT for absolute time-of-flight (TOF) measurement (at 532 nm), a streak camera for TOF 2-color dispersion measurement (532 nm and 355 nm), and a Si avalanche photodiode for altimeter waveform detection (1064 nm). The performance goals are to make ranging measurements to ground targets with about 1 cm accuracy, and altimetry height measurements over ice with 10 cm accuracy. This paper presents an overview of the design concept developed during a phase B study. System engineering issues and trade studies are discussed, with particular attention to error budgets and performance predictions.

Pulsed-coil magnet systems for applying 10-30 Tesla Fields to cm-scale targets on Sandia's Z facility

DOE PAGES

Rovang, Dean C.; Lamppa, Derek C.; Cuneo, Michael Edward; ...

2014-12-04

We have successfully integrated the capability to apply uniform, high magnetic fields (10–30 T) to high energy density experiments on the Z facility. This system uses an 8-mF, 15-kV capacitor bank to drive large-bore (5 cm diameter), high-inductance (1–3 mH) multi-turn, multi-layer electromagnets that slowly magnetize the conductive targets used on Z over several milliseconds (time to peak field of 2–7 ms). This system was commissioned in February 2013 and has been used successfully to magnetize more than 30 experiments up to 10 T that have produced exciting and surprising physics results. These experiments used split-magnet topologies to maintain diagnosticmore » lines of sight to the target. We then describe the design, integration, and operation of the pulsed coil system into the challenging and harsh environment of the Z Machine. We also describe our plans and designs for achieving fields up to 20 T with a reduced-gap split-magnet configuration, and up to 30 T with a solid magnet configuration in pursuit of the Magnetized Liner Inertial Fusion concept.« less

Pulsed-coil magnet systems for applying uniform 10-30 T fields to centimeter-scale targets on Sandia's Z facility

NASA Astrophysics Data System (ADS)

Rovang, D. C.; Lamppa, D. C.; Cuneo, M. E.; Owen, A. C.; McKenney, J.; Johnson, D. W.; Radovich, S.; Kaye, R. J.; McBride, R. D.; Alexander, C. S.; Awe, T. J.; Slutz, S. A.; Sefkow, A. B.; Haill, T. A.; Jones, P. A.; Argo, J. W.; Dalton, D. G.; Robertson, G. K.; Waisman, E. M.; Sinars, D. B.; Meissner, J.; Milhous, M.; Nguyen, D. N.; Mielke, C. H.

2014-12-01

Sandia has successfully integrated the capability to apply uniform, high magnetic fields (10-30 T) to high energy density experiments on the Z facility. This system uses an 8-mF, 15-kV capacitor bank to drive large-bore (5 cm diameter), high-inductance (1-3 mH) multi-turn, multi-layer electromagnets that slowly magnetize the conductive targets used on Z over several milliseconds (time to peak field of 2-7 ms). This system was commissioned in February 2013 and has been used successfully to magnetize more than 30 experiments up to 10 T that have produced exciting and surprising physics results. These experiments used split-magnet topologies to maintain diagnostic lines of sight to the target. We describe the design, integration, and operation of the pulsed coil system into the challenging and harsh environment of the Z Machine. We also describe our plans and designs for achieving fields up to 20 T with a reduced-gap split-magnet configuration, and up to 30 T with a solid magnet configuration in pursuit of the Magnetized Liner Inertial Fusion concept.

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

PubMed

Schrattenholz, André; Groebe, Karlfried; Soskic, Vukic

2010-01-01

Systems biology is essentially a proteomic and epigenetic exercise because the relatively condensed information of genomes unfolds on the level of proteins. The flexibility of cellular architectures is not only mediated by a dazzling number of proteinaceous species but moreover by the kinetics of their molecular changes: The time scales of posttranslational modifications range from milliseconds to years. The genetic framework of an organism only provides the blue print of protein embodiments which are constantly shaped by external input. Indeed, posttranslational modifications of proteins represent the scope and velocity of these inputs and fulfil the requirements of integration of external spatiotemporal signal transduction inside an organism. The optimization of biochemical networks for this type of information processing and storage results in chemically extremely fine tuned molecular entities. The huge dynamic range of concentrations, the chemical diversity and the necessity of synchronisation of complex protein expression patterns pose the major challenge of systemic analysis of biological models. One further message is that many of the key reactions in living systems are essentially based on interactions of moderate affinities and moderate selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. In complex disorders such as cancer or neurodegenerative diseases, which initially appear to be rooted in relatively subtle dysfunctions of multimodal physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which has been dominating the pharmaceutical industry for a long time, increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade, and the treatment of "complex diseases" remains a most pressing medical need. Currently, a change of paradigm can be observed with regard to a new interest in agents that modulate multiple targets simultaneously, essentially "dirty drugs." Targeting cellular function as a system rather than on the level of the single target, significantly increases the size of the drugable proteome and is expected to introduce novel classes of multi-target drugs with fewer adverse effects and toxicity. Multiple target approaches have recently been used to design medications against atherosclerosis, cancer, depression, psychosis and neurodegenerative diseases. A focussed approach towards "systemic" drugs will certainly require the development of novel computational and mathematical concepts for appropriate modelling of complex data. But the key is the extraction of relevant molecular information from biological systems by implementing rigid statistical procedures to differential proteomic analytics.

Simulation of the target creation through FRC merging for a magneto-inertial fusion concept

NASA Astrophysics Data System (ADS)

Li, Chenguang; Yang, Xianjun

2017-04-01

A two-dimensional magnetohydrodynamics model has been used to simulate the target creation process in a magneto-inertial fusion concept named Magnetized Plasma Fusion Reactor (MPFR) [C. Li and X. Yang, Phys. Plasmas 23, 102702 (2016)], where the target plasma created through Field reversed configuration (FRC) merging was compressed by an imploding liner driven by the pulsed-power driver. In the scheme, two initial FRCs (Field reversed configurations) are translated into the region where FRC merging occurs, bringing out the target plasma ready for compression. The simulations cover the three stages of the target creation process: formation, translation, and merging. The factors affecting the achieved target are analyzed numerically. The magnetic field gradient produced by the conical coils is found to determine how fast the FRC is accelerated to peak velocity and the collision merging occurs. Moreover, it is demonstrated that FRC merging can be realized by real coils with gaps showing nearly identical performance, and the optimized target by FRC merging shows larger internal energy and retained flux, which is more suitable for the MPFR concept.

Implementation of "Quality by Design (QbD)" Approach for the Development of 5-Fluorouracil Loaded Thermosensitive Hydrogel.

PubMed

Dalwadi, Chintan; Patel, Gayatri

2016-01-01

The purpose of this study was to investigate Quality by Design (QbD) principle for the preparation of hydrogel products to prove both practicability and utility of executing QbD concept to hydrogel based controlled release systems. Product and process understanding will help in decreasing the variability of critical material and process parameters, which give quality product output and reduce the risk. This study includes the identification of the Quality Target Product Profiles (QTPPs) and Critical Quality Attributes (CQAs) from literature or preliminary studies. To identify and control the variability in process and material attributes, two tools of QbD was utilized, Quality Risk Management (QRM) and Experimental Design. Further, it helps to identify the effect of these attributes on CQAs. Potential risk factors were identified from fishbone diagram and screened by risk assessment and optimized by 3-level 2- factor experimental design with center points in triplicate, to analyze the precision of the target process. This optimized formulation was further characterized by gelling time, gelling temperature, rheological parameters, in-vitro biodegradation and in-vitro drug release. Design space was created using experimental design tool that gives the control space and working within this controlled space reduces all the failure modes below the risk level. In conclusion, QbD approach with QRM tool provides potent and effectual pyramid to enhance the quality into the hydrogel.

Design of a multisensor data fusion system for target detection

NASA Astrophysics Data System (ADS)

Thomopoulos, Stelios C.; Okello, Nickens N.; Kadar, Ivan; Lovas, Louis A.

1993-09-01

The objective of this paper is to discuss the issues that are involved in the design of a multisensor fusion system and provide a systematic analysis and synthesis methodology for the design of the fusion system. The system under consideration consists of multifrequency (similar) radar sensors. However, the fusion design must be flexible to accommodate additional dissimilar sensors such as IR, EO, ESM, and Ladar. The motivation for the system design is the proof of the fusion concept for enhancing the detectability of small targets in clutter. In the context of down-selecting the proper configuration for multisensor (similar and dissimilar, and centralized vs. distributed) data fusion, the issues of data modeling, fusion approaches, and fusion architectures need to be addressed for the particular application being considered. Although the study of different approaches may proceed in parallel, the interplay among them is crucial in selecting a fusion configuration for a given application. The natural sequence for addressing the three different issues is to begin from the data modeling, in order to determine the information content of the data. This information will dictate the appropriate fusion approach. This, in turn, will lead to a global fusion architecture. Both distributed and centralized fusion architectures are used to illustrate the design issues along with Monte-Carlo simulation performance comparison of a single sensor versus a multisensor centrally fused system.

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

NASA Astrophysics Data System (ADS)

Sykes, Edward Alexander

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

Application of the Deming management method to equipment-inspection processes.

PubMed

Campbell, C A

1996-01-01

The Biomedical Engineering staff at the Washington Hospital Center has designed an inspection process that optimizes timely completion of scheduled equipment inspections. The method used to revise the process was primarily Deming, but certainly the method incorporates the re-engineering concept of questioning the basic assumptions around which the original process was designed. This effort involved a review of the existing process in its entirety by task groups made up of representatives from all involved departments. Complete success in all areas has remained elusive. However, the lower variability of inspection completion ratios follows Deming's description of a successfully revised process. Further CQI efforts targeted at specific areas with low completion ratios will decrease this variability even further.

Broadband Liner Optimization for the Source Diagnostic Test Fan

NASA Technical Reports Server (NTRS)

Nark, Douglas M.; Jones, Michael G.

2012-01-01

The broadband component of fan noise has grown in relevance with the utilization of increased bypass ratio and advanced fan designs. Thus, while the attenuation of fan tones remains paramount, the ability to simultaneously reduce broadband fan noise levels has become more appealing. This paper describes a broadband acoustic liner optimization study for the scale model Source Diagnostic Test fan. Specifically, in-duct attenuation predictions with a statistical fan source model are used to obtain optimum impedance spectra over a number of flow conditions for three liner locations in the bypass duct. The predicted optimum impedance information is then used with acoustic liner modeling tools to design liners aimed at producing impedance spectra that most closely match the predicted optimum values. Design selection is based on an acceptance criterion that provides the ability to apply increased weighting to specific frequencies and/or operating conditions. Typical tonal liner designs targeting single frequencies at one operating condition are first produced to provide baseline performance information. These are followed by multiple broadband design approaches culminating in a broadband liner targeting the full range of frequencies and operating conditions. The broadband liner is found to satisfy the optimum impedance objectives much better than the tonal liner designs. In addition, the broadband liner is found to provide better attenuation than the tonal designs over the full range of frequencies and operating conditions considered. Thus, the current study successfully establishes a process for the initial design and evaluation of novel broadband liner concepts for complex engine configurations.

Effects of the use of thematic organizers in conjunction with concept mapping on learning, misconceptions, and retention in middle school science class

NASA Astrophysics Data System (ADS)

Keown, Sandra L.

This study was devised to determine effects of the use of interactive thematic organizers and concept maps in middle school science classes during a unit study on minerals. The design, a pretest-posttest control group, consisted of matched groups (three experimental groups and one comparison group). It also included a student survey assessing qualitative aspects of the investigation. The 67 6th-grade students and one science teacher who participated in the study were from an independent K-12 school. Students represented a normal, well-distributed range of abilities. Group I (control) proceeded with their usual method of studying a unit---reading aloud the text and answering workbook questions. Group II worked with interactive thematic organizers, designed to activate prior knowledge and help students make inferences about target concepts in three treatments. Group III created three interactive concept maps, which represented both understandings and misconceptions. Concept maps were reviewed and repaired as students completed each treatment. Group IV participated in both thematic organizer and concept map treatments. Statistical analyses were determined through a pretest and a delayed recall posttest essay for all four groups. Two scores were assigned---one quantitative raw score of correct explicit answers and one rubric score based on the quality of interpretive responses. Group II also received scores for thematic organizer responses. Group III received rubric scores for concept maps. Group IV received all possible scores. Paired t-tests reported comparisons of scores across the treatment groups. A linear regression indicated whether or not concept map misconceptions affected posttest scores. Finally, an ANCOVA reported statistical significance across the four treatment groups. Findings of data analysis indicated statistically significant improvement in posttest scores among students in the three experimental groups. Students who participated in both treatments represented the highest scores among the four groups. Results of the ANCOVA indicated there was statistically significant difference in scores among the four treatments. Recommendations were made to further investigate development of interactive thematic organizers with student-chosen hyperlinks to concepts, as well as a recommendation that researchers investigate teacher understandings of interpretive purpose and form in the creation of thematic organizers.

Enhancing the response rate of strand displacement-based electrochemical aptamer sensors using bivalent binding aptamer-cDNA probes.

PubMed

Zhang, Ziping; Tao, Cancan; Yin, Jungang; Wang, Yunhui; Li, Yanshen

2018-04-30

Electrochemical aptamer (EA) sensors based on aptamer-cDNA duplex probes (cDNA: complementary DNA) and target induced strand displacement (TISD) recognition are sensitive, selective and capable of detecting a wide variety of target analytes. While substantial research efforts have focused on engineering of new signaling mechanisms for the improvement of sensor sensitivity, little attention was paid to the enhancement of sensor response rate. Typically, the previous TISD based EA sensors exhibited relatively long response times larger than 30min, which mainly resulted from the suboptimal aptamer-cDNA probe structure in which most of aptamer bases were paired to the cDNA bases. In an effort to improve the response rate of this type of sensors, we report here the rational engineering of a quickly responsive and sensitive aptamer-cDNA probe by employing the conception of bivalent interaction in supramolecular chemistry. We design a bivalent cDNA strand through linking two short monovalent cDNA sequences, and it is simultaneously hybridized to two electrode-immobilized aptamer probes to form a bivalent binding (BB) aptamer-cDNA probe. This class of BB probe possesses the advantages of less aptamer bases paired to the cDNA bases for quick response rate and good structural stability for high sensor sensitivity. By use of the rationally designed BB aptamer-cDNA probe, a TISD based EA sensor against ATP with significantly enhanced response rate (with a displacement equilibrium time of 4min) and high sensitivity was successfully constructed. We believe that our BB probe conception will help guide future designs and applications of TISD based EA sensors. Copyright © 2017 Elsevier B.V. All rights reserved.

Constrained target controllability of complex networks

NASA Astrophysics Data System (ADS)

Guo, Wei-Feng; Zhang, Shao-Wu; Wei, Ze-Gang; Zeng, Tao; Liu, Fei; Zhang, Jingsong; Wu, Fang-Xiang; Chen, Luonan

2017-06-01

It is of great theoretical interest and practical significance to study how to control a system by applying perturbations to only a few driver nodes. Recently, a hot topic of modern network researches is how to determine driver nodes that allow the control of an entire network. However, in practice, to control a complex network, especially a biological network, one may know not only the set of nodes which need to be controlled (i.e. target nodes), but also the set of nodes to which only control signals can be applied (i.e. constrained control nodes). Compared to the general concept of controllability, we introduce the concept of constrained target controllability (CTC) of complex networks, which concerns the ability to drive any state of target nodes to their desirable state by applying control signals to the driver nodes from the set of constrained control nodes. To efficiently investigate the CTC of complex networks, we further design a novel graph-theoretic algorithm called CTCA to estimate the ability of a given network to control targets by choosing driver nodes from the set of constrained control nodes. We extensively evaluate the CTC of numerous real complex networks. The results indicate that biological networks with a higher average degree are easier to control than biological networks with a lower average degree, while electronic networks with a lower average degree are easier to control than web networks with a higher average degree. We also show that our CTCA can more efficiently produce driver nodes for target-controlling the networks than existing state-of-the-art methods. Moreover, we use our CTCA to analyze two expert-curated bio-molecular networks and compare to other state-of-the-art methods. The results illustrate that our CTCA can efficiently identify proven drug targets and new potentials, according to the constrained controllability of those biological networks.

Discussion of thermal extraction chamber concepts for Lunar ISRU

NASA Astrophysics Data System (ADS)

Pfeiffer, Matthias; Hager, Philipp; Parzinger, Stephan; Dirlich, Thomas; Spinnler, Markus; Sattelmayer, Thomas; Walter, Ulrich

The Exploration group of the Institute of Astronautics (LRT) of the Technische Universitüt a München focuses on long-term scenarios and sustainable human presence in space. One of the enabling technologies in this long-term perspective is in-situ resource utilization (ISRU). When dealing with the prospect of future manned missions to Moon and Mars the use of ISRU seems useful and intended. The activities presented in this paper focus on Lunar ISRU. This basically incorporates both the exploitation of Lunar oxygen from natural rock and the extraction of solar wind implanted particles (SWIP) from regolith dust. Presently the group at the LRT is examining possibilities for the extraction of SWIPs, which may provide several gaseous components (such as H2 and N2) valuable to a human presence on the Moon. As a major stepping stone in the near future a Lunar demonstrator/ verification experiment payload is being designed. This experiment, LUISE (LUnar ISru Experiment), will comprise a thermal process chamber for heating regolith dust (grain size below 500m), a solar thermal power supply, a sample distribution unit and a trace gas analysis. The first project stage includes the detailed design and analysis of the extraction chamber concepts and the thermal process involved in the removal of SWIP from Lunar Regolith dust. The technique of extracting Solar Wind volatiles from Regolith has been outlined by several sources. Heating the material to a threshold value seems to be the most reasonable approach. The present paper will give an overview over concepts for thermal extraction chambers to be used in the LUISE project and evaluate in detail the pros and cons of each concept. The special boundary conditions set by solar thermal heating of the chambers as well as the material properties of Regolith in a Lunar environment will be discussed. Both greatly influence the design of the extraction chamber. The performance of the chamber concepts is discussed with respect to the desired target temperature using ESARAD/ESATAN software. Additionally a value for the homogeneity of heating the sample, as a measure for the effectiveness of the concept, will be presented and discussed.

Safety Guided Design of Crew Return Vehicle in Concept Design Phase Using STAMP/STPA

NASA Astrophysics Data System (ADS)

Nakao, H.; Katahira, M.; Miyamoto, Y.; Leveson, N.

2012-01-01

In the concept development and design phase of a new space system, such as a Crew Vehicle, designers tend to focus on how to implement new technology. Designers also consider the difficulty of using the new technology and trade off several system design candidates. Then they choose an optimal design from the candidates. Safety should be a key aspect driving optimal concept design. However, in past concept design activities, safety analysis such as FTA has not used to drive the design because such analysis techniques focus on component failure and component failure cannot be considered in the concept design phase. The solution to these problems is to apply a new hazard analysis technique, called STAMP/STPA. STAMP/STPA defines safety as a control problem rather than a failure problem and identifies hazardous scenarios and their causes. Defining control flow is the essential in concept design phase. Therefore STAMP/STPA could be a useful tool to assess the safety of system candidates and to be part of the rationale for choosing a design as the baseline of the system. In this paper, we explain our case study of safety guided concept design using STPA, the new hazard analysis technique, and model-based specification technique on Crew Return Vehicle design and evaluate benefits of using STAMP/STPA in concept development phase.

Advancing Porous Silicon Biosensor Technology for Use in Clinical Diagnostics

NASA Astrophysics Data System (ADS)

Bonanno, Lisa Marie

Inexpensive and robust analytical techniques for detecting molecular recognition events are in great demand in healthcare, food safety, and environmental monitoring. Despite vast research in this area, challanges remain to develop practical biomolecular platforms that, meet the rigorous demands of real-world applications. This includes maintaining low-cost devices that are sensitive and specific in complex test specimens, are stable after storage, have short assay time, and possess minimal complexity of instrumentation for readout. Nanostructured porous silicon (PSi) material has been identified as an ideal candidate towards achieving these goals and the past decade has seen diverse proof-of-principle studies developing optical-based sensing techniques. In Part 1 of this thesis, the impact of surface chemistry and PSi morphology on detection sensitivity of target molecules is investigated. Initial proof-of-concept that PSi devices facilitate detection of protein in whole blood is demonstrated. This work highlights the importance of material stability and blocking chemistry for sensor use in real world biological samples. In addition, the intrinisic filtering capability of the 3-D PSi morphology is shown as an advantage in complex solutions, such as whole blood. Ultimately, this initial work identified a need to improve detection sensitivity of the PSI biosensor technique to facilitate clinical diagnostic use over relevant target concentration ranges. The second part of this thesis, builds upon sensitivity challenges that are highlighted in the first part of the thesis and development of a surface-bound competitive inhibition immunoassay facilitated improved detection sensitivity of small molecular weight targets (opiates) over a relevant clinical concentration range. In addition, optimization of assay protocol addressed issues of maintaining stability of sensors after storage. Performance of the developed assay (specificity and sensitivity) was then validated in a blind clinical study that screened real patient urine samples (n=70) for opiates in collaboration with Strong Memorial Hospital Clinical Toxicology Laboratory. PSI sensor results showed improved clinical specificity over current commercial opiate immunoassay techniques and therefore, identified potential for a reduction in false-negative and false-positive screening results. Here, we demonstrate for the first time, successful clinical capability of a PSi sensor to detect opiates as a model target in real-world patient samples. The final part of this thesis explores novel sensor designs to leverage the tunable optical properties of PSi photonic devices and facilitate colorimetric readout of molecular recognition events by the unaided eye. Such a design is ideal for uncomplicated diagnostic screening at point-of-care as no instrumentation is needed for result readout. The photonic PSi transducers were integrated with target analyte-responsive hydrogels (TRAP-gels) that upon exposure to a target solution would swell and dissolute, inducing material property changes that were optically detected by the incorporated PSi transducer. This strategy extends target detection throughout the 3-ll internal volume of the PSi, improving upon current techniques that limit detection to the surface area (2-ll) of PSi. Work to acheive this approach involved design of TRAP-gel networks, polymer synthesis and characterization techniques, and optical characterization of the hybrid hydrogel-PSi material sensor. Successful implementation of a hybrid sensor design was exhibited for a. model chemical target (reducing agent), in which visual colorimetric change from red to green was observed for above-threshold exposure to the chemical target. In addition, initial proof-of-concept of an opiate responsive TRAP-gel is also demonstrated where cross-links are formed between antibody-antigen interactions and exposure to opiates induces bulk gel dissolution.

Safety Guided Design Based on Stamp/STPA for Manned Vehicle in Concept Design Phase

NASA Astrophysics Data System (ADS)

Ujiie, Ryo; Katahira, Masafumi; Miyamoto, Yuko; Umeda, Hiroki; Leveson, Nancy; Hoshino, Nobuyuki

2013-09-01

In manned vehicles, such as the Soyuz and the Space Shuttle, the crew and computer system cooperate to succeed in returning to the earth. While computers increase the functionality of system, they also increase the complexity of the interaction between the controllers (human and computer) and the target dynamics. In some cases, the complexity can produce a serious accident. To prevent such losses, traditional hazard analysis such as FTA has been applied to system development, however it can be used after creating a detailed system because it focuses on detailed component failures. As a result, it's more difficult to eliminate hazard cause early in the process when it is most feasible.STAMP/STPA is a new hazard analysis that can be applied from the early development phase, with the analysis being refined as more detailed decisions are made. In essence, the analysis and design decisions are intertwined and go hand-in-hand. We have applied STAMP/STPA to a concept design of a new JAXA manned vehicle and tried safety guided design of the vehicle. As a result of this trial, it has been shown that STAMP/STPA can be accepted easily by system engineers and the design has been made more sophisticated from a safety viewpoint. The result also shows that the consequences of human errors on system safety can be analysed in the early development phase and the system designed to prevent them. Finally, the paper will discuss an effective way to harmonize this safety guided design approach with system engineering process based on the result of this experience in this project.

Targeting Future Customers: An Introductory Biobanking Course for Undergraduate Students of Life Sciences.

PubMed

Abdelhafiz, Ahmed Samir; Fouda, Merhan Ahmed; El-Jaafary, Shaimaa Ibrahim; Farghly, Maysa Ibrahim; Salem, Mazen; Tammam, Ahmed; Gabr, Hala

2017-08-01

Biobanking is a relatively new concept in the Arab region. Targeting different stakeholders to introduce the concept of biobanking and develop an acceptance of it among them is important for the growth of biobanking in the region. Undergraduate students of life sciences represent an important segment of stakeholders, since they constitute potential future biobank customers. Limited funding, lack of awareness of the existence of the term "biobanking" itself among these students, and questions regarding best marketing strategies presented challenges to planning for the most effective message delivery to this target group. A specific course was designed for undergraduate students of life sciences, which was conducted at the Faculty of Medicine, Cairo University, Egypt. The course was conducted twice in 2016 and included lectures covering biobanking, quality, ethics, information technology, and translational research. Facebook and word-of-mouth were used for marketing and advertising. A total number of 125 participants attended both courses cumulatively. Facebook appeared to have been an effective marketing outlet, especially when paid advertisements were used. Evaluation of knowledge, measured using a pretest and posttest, demonstrated some improvement in knowledge of participants. Evaluation forms filled after the course showed positive attitude toward content and message delivery by a majority of participants. Facebook was also used as an evaluation method through analysis of engagement with posts created after course completion. Biobanking education can be carried out effectively with limited resources. Understanding the needs of the target group and using appropriate methods of communication are essential prerequisites to a well-tailored curriculum and effective message delivery. Using Facebook appears to be an effective and affordable method of communication and advertising. Targeting undergraduate students of life sciences interested in research is a good investment and can be very effective in increasing awareness about biobanking inside the research community.

Human Centered Autonomous and Assistant Systems Testbed for Exploration Operations

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Mount, Frances; Carreon, Patricia; Torney, Susan E.

2001-01-01

The Engineering and Mission Operations Directorates at NASA Johnson Space Center are combining laboratories and expertise to establish the Human Centered Autonomous and Assistant Systems Testbed for Exploration Operations. This is a testbed for human centered design, development and evaluation of intelligent autonomous and assistant systems that will be needed for human exploration and development of space. This project will improve human-centered analysis, design and evaluation methods for developing intelligent software. This software will support human-machine cognitive and collaborative activities in future interplanetary work environments where distributed computer and human agents cooperate. We are developing and evaluating prototype intelligent systems for distributed multi-agent mixed-initiative operations. The primary target domain is control of life support systems in a planetary base. Technical approaches will be evaluated for use during extended manned tests in the target domain, the Bioregenerative Advanced Life Support Systems Test Complex (BIO-Plex). A spinoff target domain is the International Space Station (ISS) Mission Control Center (MCC). Prodl}cts of this project include human-centered intelligent software technology, innovative human interface designs, and human-centered software development processes, methods and products. The testbed uses adjustable autonomy software and life support systems simulation models from the Adjustable Autonomy Testbed, to represent operations on the remote planet. Ground operations prototypes and concepts will be evaluated in the Exploration Planning and Operations Center (ExPOC) and Jupiter Facility.

Techniques for Conducting Effective Concept Design and Design-to-Cost Trade Studies

NASA Technical Reports Server (NTRS)

Di Pietro, David A.

2015-01-01

Concept design plays a central role in project success as its product effectively locks the majority of system life cycle cost. Such extraordinary leverage presents a business case for conducting concept design in a credible fashion, particularly for first-of-a-kind systems that advance the state of the art and that have high design uncertainty. A key challenge, however, is to know when credible design convergence has been achieved in such systems. Using a space system example, this paper characterizes the level of convergence needed for concept design in the context of technical and programmatic resource margins available in preliminary design and highlights the importance of design and cost evaluation learning curves in determining credible convergence. It also provides techniques for selecting trade study cases that promote objective concept evaluation, help reveal unknowns, and expedite convergence within the trade space and conveys general practices for conducting effective concept design-to-cost studies.

Cortical hot spots and labyrinths: why cortical neuromodulation for episodic migraine with aura should be personalized

PubMed Central

Dahlem, Markus A.; Schmidt, Bernd; Bojak, Ingo; Boie, Sebastian; Kneer, Frederike; Hadjikhani, Nouchine; Kurths, Jürgen

2015-01-01

Stimulation protocols for medical devices should be rationally designed. For episodic migraine with aura we outline model-based design strategies toward preventive and acute therapies using stereotactic cortical neuromodulation. To this end, we regard a localized spreading depression (SD) wave segment as a central element in migraine pathophysiology. To describe nucleation and propagation features of the SD wave segment, we define the new concepts of cortical hot spots and labyrinths, respectively. In particular, we firstly focus exclusively on curvature-induced dynamical properties by studying a generic reaction-diffusion model of SD on the folded cortical surface. This surface is described with increasing level of details, including finally personalized simulations using patient's magnetic resonance imaging (MRI) scanner readings. At this stage, the only relevant factor that can modulate nucleation and propagation paths is the Gaussian curvature, which has the advantage of being rather readily accessible by MRI. We conclude with discussing further anatomical factors, such as areal, laminar, and cellular heterogeneity, that in addition to and in relation to Gaussian curvature determine the generalized concept of cortical hot spots and labyrinths as target structures for neuromodulation. Our numerical simulations suggest that these target structures are like fingerprints, they are individual features of each migraine sufferer. The goal in the future will be to provide individualized neural tissue simulations. These simulations should predict the clinical data and therefore can also serve as a test bed for exploring stereotactic cortical neuromodulation. PMID:25798103

Meeting forest restoration challenges: Using the Target Plant Concept

Treesearch

Kas Dumroese; Thomas D. Landis; Jeremy Pinto; Diane L. Haase; Kim W. Wilkinson; Anthony S. Davis

2016-01-01

Meeting forest restoration challenges relies on successful establishment of plant materials (e.g., seeds, cuttings, rooted cuttings, or seedlings, etc.; hereafter simply "seedlings"). The Target Plant Concept (TPC) provides a flexible framework that nursery managers and their clients can use to improve the survival and growth of these seedlings. The...

Time Critical Targeting Concept of Operations (CONOPS) Interactions

DTIC Science & Technology

2011-05-01

range of topics in force development and employment. Carl has participated in projects examining the interdiction of armoured ground forces , long...Critical Targeting Concept of Operations (CONOPS) Interactions Executive Summary In 2003, RAND Project Air Force examined the...Attack. ____________________ ________________________________________________ Carl Rhodes Project Air Force , RAND Corporation Carl Rhodes is the

The effect of spatial organization of targets and distractors on the capacity to selectively memorize objects in visual short-term memory

PubMed Central

Abbes, Aymen Ben; Gavault, Emmanuelle; Ripoll, Thierry

2014-01-01

We conducted a series of experiments to explore how the spatial configuration of objects influences the selection and the processing of these objects in a visual short-term memory task. We designed a new experiment in which participants had to memorize 4 targets presented among 4 distractors. Targets were cued during the presentation of distractor objects. Their locations varied according to 4 spatial configurations. From the first to the last configuration, the distance between targets’ locations was progressively increased. The results revealed a high capacity to select and memorize targets embedded among distractors even when targets were extremely distant from each other. This capacity is discussed in relation to the unitary conception of attention, models of split attention, and the competitive interaction model. Finally, we propose that the spatial dispersion of objects has different effects on attentional allocation and processing stages. Thus, when targets are extremely distant from each other, attentional allocation becomes more difficult while processing becomes easier. This finding implicates that these 2 aspects of attention need to be more clearly distinguished in future research. PMID:25339978

New approach of delivering cytotoxic drugs towards CAIX expressing cells: A concept of dual-target drugs.

PubMed

van Kuijk, Simon J A; Parvathaneni, Nanda Kumar; Niemans, Raymon; van Gisbergen, Marike W; Carta, Fabrizio; Vullo, Daniela; Pastorekova, Silvia; Yaromina, Ala; Supuran, Claudiu T; Dubois, Ludwig J; Winum, Jean-Yves; Lambin, Philippe

2017-02-15

Carbonic anhydrase IX (CAIX) is a hypoxia-regulated and tumor-specific protein that maintains the pH balance of cells. Targeting CAIX might be a valuable approach for specific delivery of cytotoxic drugs, thereby reducing normal tissue side-effects. A series of dual-target compounds were designed and synthesized incorporating a sulfonamide, sulfamide, or sulfamate moiety combined with several different anti-cancer drugs, including the chemotherapeutic agents chlorambucil, tirapazamine, and temozolomide, two Ataxia Telangiectasia and Rad3-related protein inhibitors (ATRi), and the anti-diabetic biguanide agent phenformin. An ATRi derivative (12) was the only compound to show a preferred efficacy in CAIX overexpressing cells versus cells without CAIX expression when combined with radiation. Its efficacy might however not solely depend on binding to CAIX, since all described compounds generally display low activity as carbonic anhydrase inhibitors. The hypothesis that dual-target compounds specifically target CAIX expressing tumor cells was therefore not confirmed. Even though dual-target compounds remain an interesting approach, alternative options should also be investigated as novel treatment strategies. Copyright © 2016 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Development of a Recombinant Multifunctional Biomacromolecule for Targeted Gene Transfer to Prostate Cancer Cells.

PubMed

Hatefi, Arash; Karjoo, Zahra; Nomani, Alireza

2017-09-11

The objective of this study was to genetically engineer a fully functional single chain fusion peptide composed of motifs from diverse biological and synthetic origins that can perform multiple tasks including DNA condensation, cell targeting, cell transfection, particle shielding from immune system and effective gene transfer to prostate tumors. To achieve the objective, a single chain biomacromolecule (vector) consisted of four repeatative units of histone H2A peptide, fusogenic peptide GALA, short elastin-like peptide, and PC-3 cell targeting peptide was designed. To examine the functionality of each motif in the vector sequence, it was characterized in terms of size and zeta potential by Zetasizer, PC-3 cell targeting and transfection by flowcytometry, IgG induction by immunogenicity assay, and PC-3 tumor transfection by quantitative live animal imaging. Overall, the results of this study showed the possibility of using genetic engineering techniques to program various functionalities into one single chain vector and create a multifunctional nonimmunogenic biomacromolecule for targeted gene transfer to prostate cancer cells. This proof-of-concept study is a significant step forward toward creating a library of vectors for targeted gene transfer to any cancer cell type at both in vitro and in vivo levels.

Unintended Embodiment of Concepts into Percepts: Sensory Activation Boosts Attention for Same-Modality Concepts in the Attentional Blink Paradigm

ERIC Educational Resources Information Center

Vermeulen, Nicolas; Mermillod, Martial; Godefroid, Jimmy; Corneille, Olivier

2009-01-01

This study shows that sensory priming facilitates reports of same-modality concepts in an attentional blink paradigm. Participants had to detect and report two target words (T1 and T2) presented for 53 ms each among a series of nonwords distractors at a frequency of up to 19 items per second. SOA between target words was set to 53 ms or 213 ms,…

Current Highlights on ESA's Planetary Technology Reference Studies

NASA Astrophysics Data System (ADS)

Falkner, P.

The concept of Technology Reference Studies has been introduced already at EGU05, where the Venus Entry Probe (VEP), the Jupiter Minisat Explorer (JME), the Deimos Sample Return (DSR) and the Interstellar Heliopause Probe (IHP) have been presented in detail. At the EGU06 the new studies in reaction to the Cosmic Vision exercise have been introduced. The formulation of themes and mapping into potential future missions has been taken as basis in the planning of additional new and adaptation of existing TRS's to cover areas, which have not yet been addressed by any TRS. These new ongoing studies are progressing well and current highlights will be presented in the paper in further detail as well as an overview on supporting technology studies and Concurrent Design Facility (CDF) sessions. The Jupiter System Explorer (JSE) study investigates mission concepts with up to two Magnetospheric Orbiters placed in a highly elliptical Jovian orbit and the possibility to deploy a Jovian Entry Probe. The mission profile is based on a solar powered concept launched on a Soyuz-Fregat launcher. Mission analysis and the application of a new Jovian radiation model are supporting the study activities. The Near-Earth Asteroid Sample Return (NEA-SR) concept explores the possibilities of sample return or in-situ mission profiles with visits to up to two NEA targets. Due to the assumed low cost cap a trade between a sample return and remote/in-situ exploration concept has a high attention in the study. The Cross Scale TRS (CS-TRS) is intended to simultaneously investigate magnetospheric and plasma processes in three spatial scales with a formation flight of up to 12 spacecraft, orbiting on deep elliptical orbits around Earth. One of the major challenges is the launch of that number of spacecraft on a single launcher and the collisionless deployment of the formation at the target orbit. The scope if the GeoSail TRS is to demonstrate deployment, attitude control and navigation concepts for a solar sailing mission as required by Interstellar Heliopause Probe (IHP) or Solar Polar Orbiter (SPO) mission concepts and to investigate the potential influence of the extended sail for science measurements.

The concept of crosstalk-directed embryological target mining and its application to essential hypertension treatment failures.

PubMed

Sag, Alan Alper; Sal, Oguzhan; Kilic, Yagmur; Onal, Emine Meltem; Kanbay, Mehmet

2017-05-01

This review aims to introduce the novel concept of embryological target mining applied to interorgan crosstalk network genesis, and applies embryological target mining to multidrug-resistant essential hypertension (a prototype, complex, undertreated, multiorgan systemic syndrome) to uncover new treatment targets and critique why existing strategies fail. Briefly, interorgan crosstalk pathways represent the next frontier for target mining in molecular medicine. This is because stereotyped stepwise organogenesis presents a unique opportunity to infer interorgan crosstalk pathways that may be crucial to discovering novel treatment targets. Insights gained from this review will be applied to patient management in a clinician-directed fashion. ©2017 Wiley Periodicals, Inc.

Innovative Strategies for Asteroid Precursor Exploration

NASA Astrophysics Data System (ADS)

Klaus, K.; Lawrence, S.; Elsperman, M. S.; Smith, D. B.

2011-12-01

Introduction: Our ambitions for space exploration have outpaced our ability to afford frequent visits to targets of interest. Launch costs and development times continue to increase for getting large space craft to deep space. This particularly affects workforce development and imperils opportunities for new development starts. The time has come to leverage technology advances (including advances in autonomous operation and propulsion technology) to reduce the cost and increase the flight rate of planetary missions, while actively developing a scientific and engineering workforce to achieve national space objectives. Background: As demonstrated by the 1994 Clementine mission, planetary exploration missions maximizing off-the-shelf components to obtain a focused set of measurement objectives can make meaningful contributions to advancing the frontiers of space exploration by achieving numerous science and exploration objectives. Near Earth Objects [NEOs] are interesting candidates for missions of this nature. While results from recent missions (i.e., Hayabusa, NEAR, Dawn) have dramatically increased our understanding of asteroids, important questions remain. For example, characterizing the properties of asteroid regolith is an important consideration for understanding telescopic observations of asteroids, as well as preparing for future asteroid human exploration. Spacecraft Concepts: There are many candidate target asteroids that are attainable with our concept. We envision a "mothership" carrying 2-3 nanosats to the target. The nanosats would serve as in-situ explorers. The spacecraft is notionally designed for launch on a Taurus II. Our study intends on validating the concept and our notional spacecraft design will be refined and presented. The current dry mass with nanosats is estimated to be 750kg. The 1999 JU3 mission concept is a rendezvous with a 950 kg of initial spacecraft mass, launched to a C3 of 4 km2/s2. Subtracting the spacecraft dry mass from the initial mass gives a propellant loading of 200 kg. The solution for this case required 115.3 kg of propellant, leaving a 42% propellant margin. Science Instrumentation: Key objectives of this notional asteroid explorer would include: (1) high-resolution surface topography; (2) characterization surface composition and mineralogy; (3) quantification of the radiation environment near an NEO; and (4) mechanical properties of surface, if a touchdown takes place. Each nanosat would notionally contain a stereo camera for navigation, an alpha proton x-ray spectrometer to make measurements of the surface chemistry, and a microscopic imaging system to characterize the particle size distribution of asteroid regolith; multiple nanosats would provided redundancy for the in-situ surface characterization phase of the mission and enable a rudimentary gravity map through radio signal tracking.

Swingbed Amine Carbon Dioxide Removal Flight Experiment - Feasibility Study and Concept Development for Cost-Effective Exploration Technology Maturation on The International Space Station

NASA Technical Reports Server (NTRS)

Hodgson, Edward; Papale, William; Nalette, Timothy; Graf, John; Sweterlitsch, Jeffery; Hayley, Elizabeth; Williams, Antony; Button, Amy

2011-01-01

The completion of International Space Station Assembly and transition to a full six person crew has created the opportunity to create and implement flight experiments that will drive down the ultimate risks and cost for human space exploration by maturing exploration technologies in realistic space environments that are impossible or incredibly costly to duplicate in terrestrial laboratories. An early opportunity for such a technology maturation experiment was recognized in the amine swingbed technology baselined for carbon dioxide and humidity control on the Orion spacecraft and Constellation Spacesuit System. An experiment concept using an existing high fidelity laboratory swing bed prototype has been evaluated in a feasibility and concept definition study leading to the conclusion that the envisioned flight experiment can be both feasible and of significant value for NASA s space exploration technology development efforts. Based on the results of that study NASA has proceeded with detailed design and implementation for the flight experiment. The study effort included the evaluation of technology risks, the extent to which ISS provided unique opportunities to understand them, and the implications of the resulting targeted risks for the experiment design and operational parameters. Based on those objectives and characteristics, ISS safety and integration requirements were examined, experiment concepts developed to address them and their feasibility assessed. This paper will describe the analysis effort and conclusions and present the resulting flight experiment concept. The flight experiment, implemented by NASA and launched in two packages in January and August 2011, integrates the swing bed with supporting elements including electrical power and controls, sensors, cooling, heating, fans, air- and water-conserving functionality, and mechanical packaging structure. It is now on board the ISS awaiting installation and activation.

Direct-drive inertial confinement fusion research at the Laboratory for Laser Energetics: charting the path to thermonuclear ignition

NASA Astrophysics Data System (ADS)

McCrory, R. L.; Regan, S. P.; Loucks, S. J.; Meyerhofer, D. D.; Skupsky, S.; Betti, R.; Boehly, T. R.; Craxton, R. S.; Collins, T. J. B.; Delettrez, J. A.; Edgell, D.; Epstein, R.; Fletcher, K. A.; Freeman, C.; Frenje, J. A.; Glebov, V. Yu.; Goncharov, V. N.; Harding, D. R.; Igumenshchev, I. V.; Keck, R. L.; Kilkenny, J. D.; Knauer, J. P.; Li, C. K.; Marciante, J.; Marozas, J. A.; Marshall, F. J.; Maximov, A. V.; McKenty, P. W.; Myatt, J.; Padalino, S.; Petrasso, R. D.; Radha, P. B.; Sangster, T. C.; Séguin, F. H.; Seka, W.; Smalyuk, V. A.; Soures, J. M.; Stoeckl, C.; Yaakobi, B.; Zuegel, J. D.

2005-10-01

Significant theoretical and experimental progress continues to be made at the University of Rochester's Laboratory for Laser Energetics (LLE), charting the path to direct-drive inertial confinement fusion (ICF) ignition. Direct drive offers the potential for higher-gain implosions than x-ray drive and is a leading candidate for an inertial fusion energy power plant. LLE's direct-drive ICF ignition target designs for the National Ignition Facility (NIF) are based on hot-spot ignition. A cryogenic target with a spherical DT-ice layer, within or without a foam matrix, enclosed by a thin plastic shell, will be directly irradiated with ~1.5 MJ of laser energy. Cryogenic and plastic/foam (surrogate-cryogenic) targets that are hydrodynamically scaled from these ignition target designs are imploded on the 60-beam, 30 kJ, UV OMEGA laser system to validate the key target physics issues, including energy coupling, hydrodynamic instabilities and implosion symmetry. Prospects for direct-drive ignition on the NIF are extremely favourable, even while it is in its x-ray-drive irradiation configuration, with the development of the polar-direct-drive concept. A high-energy petawatt capability is being constructed at LLE next to the existing 60-beam OMEGA compression facility. This OMEGA EP (extended performance) laser will add two short-pulse, 2.6 kJ beams to the OMEGA laser system to backlight direct-drive ICF implosions and study fast-ignition physics with focused intensities up to 6 × 1020 W cm-2.

Self-efficacy with application to adolescent smoking cessation: a concept analysis.

PubMed

Heale, Roberta; Griffin, Mary T Q

2009-04-01

This paper is a report of a concept analysis of adolescent smoking cessation self-efficacy. Smoking cessation is a key preventive care/health promotion strategy offered by nurses worldwide. Most programming is tailored to adults although the reasons for smoking, along with coping strategies, resources and developmental stage, differ in adolescence. Understanding of the concept of self-efficacy as it relates to the adolescent population will assist nurses in addressing smoking cessation behaviours with this population. The CINAHL and Proquest Nursing databases were searched for papers published between 1977 and 2007 using the keywords self-efficacy, adolescents and smoking cessation. The Walker and Avant method of concept analysis was applied. Adolescent smoking cessation self-efficacy is the confidence, perceived capacity and perceived ability that the teen possesses to quit smoking. Identified antecedents include developmental stage, past life support, emotional support, coping strategies, resources and emotional status. Consequences are smoking cessation: positive or negative. Empirical measures are identified. Levels of self-efficacy have been shown to be an important consideration in the approach of nurses to smoking cessation counselling with the adolescent client. The theoretical definition for this concept will provide the basis for nurses to design appropriate interventions for use in smoking cessation programmes targeted to adolescents. This definition identifies the key attributes of this concept that should be addressed when caring for this population.

DARPin-Based Crystallization Chaperones Exploit Molecular Geometry as a Screening Dimension in Protein Crystallography.

PubMed

Batyuk, Alexander; Wu, Yufan; Honegger, Annemarie; Heberling, Matthew M; Plückthun, Andreas

2016-04-24

DARPin libraries, based on a Designed Ankyrin Repeat Protein consensus framework, are a rich source of binding partners for a wide variety of proteins. Their modular structure, stability, ease of in vitro selection and high production yields make DARPins an ideal starting point for further engineering. The X-ray structures of around 30 different DARPin complexes demonstrate their ability to facilitate crystallization of their target proteins by restricting flexibility and preventing undesired interactions of the target molecule. However, their small size (18 kDa), very hydrophilic surface and repetitive structure can limit the DARPins' ability to provide essential crystal contacts and their usefulness as a search model for addressing the crystallographic phase problem in molecular replacement. To optimize DARPins for their application as crystallization chaperones, rigid domain-domain fusions of the DARPins to larger proteins, proven to yield high-resolution crystal structures, were generated. These fusions were designed in such a way that they affect only one of the terminal capping repeats of the DARPin and do not interfere with residues involved in target binding, allowing to exchange at will the binding specificities of the DARPin in the fusion construct. As a proof of principle, we designed rigid fusions of a stabilized version of Escherichia coli TEM-1 β-lactamase to the C-terminal capping repeat of various DARPins in six different relative domain orientations. Five crystal structures representing four different fusion constructs, alone or in complex with the cognate target, show the predicted relative domain orientations and prove the validity of the concept. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modeling and design of a tendon actuated soft robotic exoskeleton for hemiparetic upper limb rehabilitation.

PubMed

Nycz, Christopher J; Delph, Michael A; Fischer, Gregory S

2015-01-01

Robotic technology has recently been explored as a means to rehabilitate and assist individuals suffering from hemiparesis of their upper limbs. Robotic approaches allow for targeted rehabilitation routines which are more personalized and adaptable while providing quantitative measurements of patient outcomes. Development of these technologies into inherently safe and portable devices has the potential to extend the therapy outside of the clinical setting and into the patient's home with benefits to the cost and accessibility of care. To this end, a soft, cable actuated robotic glove and sleeve was designed, modeled, and constructed to provide assistance of finger and elbow movements in a way that mimics the biological function of the tendons. The resulting design increases safety through greater compliance as well as greater tolerance for misalignment with the user's skeletal frame over traditional rigid exoskeletons. Overall this design provides a platform to expand and study the concepts around soft robotic rehabilitation.

A comparison of Stirling engines for use with a 25 kW dish-electric conversion system

NASA Technical Reports Server (NTRS)

Shaltens, Richard K.

1987-01-01

Two designs for an advanced Stirling conversion system (ASCS) are described. The objective of the ASCS is to generate about 25 kW of electric power to an electric utility grid at an engine/alternator target cost of $300.00/kW at the manufacturing rate of 10,000 unit/yr. Both designs contain a free-piston Stirling engine (FPSE), a heat transport system, solar receiver, a means to generate electric power, the necessary auxiliaries, and a control system. The major differences between the two concepts are: one uses a 25 kWe single-piston FPSE which incorporates a linear alternator to directly convert the energy to electricity on the utility grid; and in the second design, electrical power is generated indirectly using a hydraulic output to a ground based hydraulic motor coupled to a rotating alternator. Diagrams of the two designs are presented.

Targeted Structural Optimization with Additive Manufacturing of Metals

NASA Technical Reports Server (NTRS)

Burt, Adam; Hull, Patrick

2015-01-01

The recent advances in additive manufacturing (AM) of metals have now improved the state-of-the-art such that traditionally non-producible parts can be readily produced in a cost-effective way. Because of these advances in manufacturing technology, structural optimization techniques are well positioned to supplement and advance this new technology. The goal of this project is to develop a structural design, analysis, and optimization framework combined with AM to significantly light-weight the interior of metallic structures while maintaining the selected structural properties of the original solid. This is a new state-of-the-art capability to significantly reduce mass, while maintaining the structural integrity of the original design, something that can only be done with AM. In addition, this framework will couple the design, analysis, and fabrication process, meaning that what has been designed directly represents the produced part, thus closing the loop on the design cycle and removing human iteration between design and fabrication. This fundamental concept has applications from light-weighting launch vehicle components to in situ resource fabrication.

A Summary Description of a Computer Program Concept for the Design and Simulation of Solar Pond Electric Power Generation Systems

NASA Technical Reports Server (NTRS)

1984-01-01

A solar pond electric power generation subsystem, an electric power transformer and switch yard, a large solar pond, a water treatment plant, and numerous storage and evaporation ponds. Because a solar pond stores thermal energy over a long period of time, plant operation at any point in time is dependent upon past operation and future perceived generation plans. This time or past history factor introduces a new dimension in the design process. The design optimization of a plant must go beyond examination of operational state points and consider the seasonal variations in solar, solar pond energy storage, and desired plant annual duty-cycle profile. Models or design tools will be required to optimize a plant design. These models should be developed in order to include a proper but not excessive level of detail. The model should be targeted to a specific objective and not conceived as a do everything analysis tool, i.e., system design and not gradient-zone stability.

Moly99 Production Facility: Report on Beamline Components, Requirements, Costs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bishofberger, Kip A.

2015-12-23

In FY14 we completed the design of the beam line for the linear accelerator production design concept. This design included a set of three bending magnets, quadrupole focusing magnets, and octopoles to flatten the beam on target. This design was generic and applicable to multiple different accelerators if necessary. In FY15 we built on that work to create specifications for the individual beam optic elements, including power supply requirements. This report captures the specification of beam line components with initial cost estimates for the NorthStar production facility.This report is organized as follows: The motivation of the beamline design is introducedmore » briefly, along with renderings of the design. After that, a specific list is provided, which accounts for each beamline component, including part numbers and costs, to construct the beamline. After that, this report details the important sections of the beamline and individual components. A final summary and list of follow-on activities completes this report.« less

Ultra Low Power, Radiation Tolerant UHF Radio Technologies for In Situ Communication Applications

NASA Technical Reports Server (NTRS)

Lay, N. E.

2001-01-01

For future deep space missions, significant reductions in the mass and power requirements for short-range telecommunication systems will be critical in enabling a wide variety of new mission concepts. These possibilities include penetrators, gliders, miniature rovers, and sensor networks. Under joint funding from NASA's Cross Enterprise and JPL's Telecommunications and Mission technology programs, recent development activity has focused on the design of ultralow mass and power transceiver systems and subsystems suitable for operation in a flight environment. For these efforts, the functionality of the transceiver has been targeted towards a specific Mars communications scenario. However, the overall architecture is well suited to any short or medium range application where a remote probe will aperiodically communicate with a base station, possibly an orbiter, for the eventual purpose of relaying science information back to Earth. In 2001, these sponsors have been augmented with collaborative expertise and funding from JPL's Center for Integrated Space Microsystems in order to migrate existing concepts and designs to a System on a Chip (SOAC) solution. Additional information is contained in the original extended abstract.

ThermoData Engine (TDE): software implementation of the dynamic data evaluation concept. 5. Experiment planning and product design.

PubMed

Diky, Vladimir; Chirico, Robert D; Kazakov, Andrei F; Muzny, Chris D; Magee, Joseph W; Abdulagatov, Ilmutdin; Kang, Jeong Won; Kroenlein, Kenneth; Frenkel, Michael

2011-01-24

ThermoData Engine (TDE) is the first full-scale software implementation of the dynamic data evaluation concept, as reported recently in this journal. In the present paper, we describe development of an algorithmic approach to assist experiment planning through assessment of the existing body of knowledge, including availability of experimental thermophysical property data, variable ranges studied, associated uncertainties, state of prediction methods, and parameters for deployment of prediction methods and how these parameters can be obtained using targeted measurements, etc., and, indeed, how the intended measurement may address the underlying scientific or engineering problem under consideration. A second new feature described here is the application of the software capabilities for aid in the design of chemical products through identification of chemical systems possessing desired values of thermophysical properties within defined ranges of tolerance. The algorithms and their software implementation to achieve this are described. Finally, implementation of a new data validation and weighting system is described for vapor-liquid equilibrium (VLE) data, and directions for future enhancements are outlined.

Early warning smartphone diagnostics for water security and analysis using real-time pH mapping

NASA Astrophysics Data System (ADS)

Hossain, Md. Arafat; Canning, John; Ast, Sandra; Rutledge, Peter J.; Jamalipour, Abbas

2015-12-01

Early detection of environmental disruption, unintentional or otherwise, is increasingly desired to ensure hazard minimization in many settings. Here, using a field-portable, smartphone fluorimeter to assess water quality based on the pH response of a designer probe, a map of pH of public tap water sites has been obtained. A custom designed Android application digitally processed and mapped the results utilizing the global positioning system (GPS) service of the smartphone. The map generated indicates no disruption in pH for all sites measured, and all the data are assessed to fall inside the upper limit of local government regulations, consistent with authority reported measurements. This implementation demonstrates a new security concept: network environmental forensics utilizing the potential of novel smartgrid analysis with wireless sensors for the detection of potential disruption to water quality at any point in the city. This concept is applicable across all smartgrid strategies within the next generation of the Internet of Things and can be extended on national and global scales to address a range of target analytes, both chemical and biological.

Tailoring Systems Engineering Processes in a Conceptual Design Environment: A Case Study at NASA Marshall Spaceflight Center's ACO

NASA Technical Reports Server (NTRS)

Mulqueen, John; Maples, C. Dauphne; Fabisinski, Leo, III

2012-01-01

This paper provides an overview of Systems Engineering as it is applied in a conceptual design space systems department at the National Aeronautics and Space Administration (NASA) Marshall Spaceflight Center (MSFC) Advanced Concepts Office (ACO). Engineering work performed in the NASA MFSC's ACO is targeted toward the Exploratory Research and Concepts Development life cycle stages, as defined in the International Council on Systems Engineering (INCOSE) System Engineering Handbook. This paper addresses three ACO Systems Engineering tools that correspond to three INCOSE Technical Processes: Stakeholder Requirements Definition, Requirements Analysis, and Integration, as well as one Project Process Risk Management. These processes are used to facilitate, streamline, and manage systems engineering processes tailored for the earliest two life cycle stages, which is the environment in which ACO engineers work. The role of systems engineers and systems engineering as performed in ACO is explored in this paper. The need for tailoring Systems Engineering processes, tools, and products in the ever-changing engineering services ACO provides to its customers is addressed.

Improving late life depression and cognitive control through the use of therapeutic video game technology: A proof-of-concept randomized trial.

PubMed

Anguera, Joaquin A; Gunning, Faith M; Areán, Patricia A

2017-06-01

Existing treatments for depression are known to have only modest effects, are insufficiently targeted, and are inconsistently utilized, particularly in older adults. Indeed, older adults with impaired cognitive control networks tend to demonstrate poor response to a majority of existing depression interventions. Cognitive control interventions delivered using entertainment software have the potential to not only target the underlying cerebral dysfunction associated with depression, but to do so in a manner that is engaging and engenders adherence to treatment protocol. In this proof-of-concept trial (Clinicaltrials.gov #: NCT02229188), individuals with late life depression (LLD) (22; 60+ years old) were randomized to either problem solving therapy (PST, n = 10) or a neurobiologically inspired digital platform designed to enhance cognitive control faculties (Project: EVO™, n = 12). Given the overlapping functional neuroanatomy of mood disturbances and executive dysfunction, we explored the impact of an intervention targeting cognitive control abilities, functional disability, and mood in older adults suffering from LLD, and how those outcomes compare to a therapeutic gold standard. EVO participants demonstrated similar improvements in mood and self-reported function after 4 weeks of treatment to PST participants. The EVO participants also showed generalization to untrained measures of working memory and attention, as well as negativity bias, a finding not evident in the PST condition. Individuals assigned to EVO demonstrated 100% adherence. This study provides preliminary findings that this therapeutic video game targeting cognitive control deficits may be an efficacious LLD intervention. Future research is needed to confirm these findings. © 2016 Wiley Periodicals, Inc.

Bioengineering of Bacteria To Assemble Custom-Made Polyester Affinity Resins

PubMed Central

Hay, Iain D.; Du, Jinping; Burr, Natalie

2014-01-01

Proof of concept for the in vivo bacterial production of a polyester resin displaying various customizable affinity protein binding domains is provided. This was achieved by engineering various protein binding domains into a bacterial polyester-synthesizing enzyme. Affinity binding domains based on various structural folds and derived from molecular libraries were used to demonstrate the potential of this technique. Designed ankyrin repeat proteins (DARPins), engineered OB-fold domains (OBodies), and VHH domains from camelid antibodies (nanobodies) were employed. The respective resins were produced in a single bacterial fermentation step, and a simple purification protocol was developed. Purified resins were suitable for most lab-scale affinity chromatography purposes. All of the affinity domains tested produced polyester beads with specific affinity for the target protein. The binding capacity of these affinity resins ranged from 90 to 600 nmol of protein per wet gram of polyester affinity resin, enabling purification of a recombinant protein target from a complex bacterial cell lysate up to a purity level of 96% in one step. The polyester resin was efficiently produced by conventional lab-scale shake flask fermentation, resulting in bacteria accumulating up to 55% of their cellular dry weight as polyester. A further proof of concept demonstrating the practicality of this technique was obtained through the intracellular coproduction of a specific affinity resin and its target. This enables in vivo binding and purification of the coproduced “target protein.” Overall, this study provides evidence for the use of molecular engineering of polyester synthases toward the microbial production of specific bioseparation resins implementing previously selected binding domains. PMID:25344238

Curtailing the high rate of late-stage attrition of investigational therapeutics against unprecedented targets in patients with lung and other malignancies.

PubMed

Rowinsky, Eric K

2004-06-15

A greater understanding of the pathogenesis and biology of cancer coupled with major advances in biotechnology has resulted in the identification of rationally designed, target-based (RDTB) anticancer therapeutics, ushering in new therapeutic opportunities and high expectations for the future as well as developmental challenges. Because these agents appear to principally target malignant cells, it is expected that they will produce less toxicity at clinically effective doses than nonspecific cytotoxic agents, but their target requirements are likely to be much more stringent. The innate complexity of the networks that contain elements targeted by these agents also decreases the probability that any single therapeutic manipulation will result in robust clinical activity and success when used alone, particularly in patients with solid malignancies that have multiple relevant signaling aberrations. In contrast, proof of principle and robust antitumor activity may be most efficiently demonstrated in nonrandomized evaluations involving tumors that are principally driven by aberrations of the specific target. The predominant therapeutic manifestation of RDTB agents in preclinical studies is due to decreased tumor growth rates and will likely be similar in the clinic; however, such manifestations are not readily detectable and quantifiable using nonrandomized clinical evaluations. To curtail the increasing rate of late-stage attrition of RDTB agents, which, if maintained, will stymie progress in cancer therapy, the design of initial nonrandomized evaluations, particularly the selection of tumors and patients, must be guided by the principal biological features of the agents. Next, evaluations, some of which must be randomized, can be performed in a wide range of tumor types, depending on the presence and relevance of the target. To validate the concept of RDTB therapeutics and to realize their full potential, radically different development, evaluation, and regulatory paradigms must be adopted.

Efficient Receptor Mediated siRNA Delivery in Vitro by Folic Acid Targeted Pentablock Copolymer-Based Micelleplexes.

PubMed

Lehner, Roman; Liu, Kegang; Wang, Xueya; Hunziker, Patrick

2017-08-14

Novel, biocompatible polyplexes, based on the combination of cationic pentablock copolymers with folic acid functionalized copolymers, were designed and developed for target-specific siRNA delivery. The resulting micelleplexes spontaneously formed polymeric micelles with a hydrophobic core surrounded directly by a cationic poly-2-(4-aminobutyl)-oxazole (PABOXA) and subsequently shielded by hydrophilic poly-2-methyl-oxazole (PMOXA) layer. The described micelleplexes form highly stable particles even in complete serum after 24 h compared with the highly cationic polymer PEI, which show aggregate formation in serum containing buffer solution. Targeted siRNA delivery and gene knockdown could be shown using green fluorescent protein (GFP) expressing HeLa cells, resulting in ∼31% and ∼8% suppression of the expression of GFP for targeted and nontargeted micelleplexes, respectively. Comparison studies of folic-receptor positive HeLa cells with normal folic-receptor-negative HEK293 cells revealed involvement of receptor mediated cellular uptake of fluorescently labeled siRNA. The new designed nanocarrier showed no cytotoxicity, having a potential application. The presented concept of shielding a nucleic-acid complexing cationic chains with a stealth layer and combining it with receptor ligand overcomes typical problems with undesired protein and cell interactions in delivery of nucleic acids using polymeric systems, opening new doors for application if RNA inhibition in the organism.

Advanced drug and gene delivery systems based on functional biodegradable polycarbonates and copolymers.

PubMed

Chen, Wei; Meng, Fenghua; Cheng, Ru; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan

2014-09-28

Biodegradable polymeric nanocarriers are one of the most promising systems for targeted and controlled drug and gene delivery. They have shown several unique advantages such as excellent biocompatibility, prolonged circulation time, passive tumor targeting via the enhanced permeability and retention (EPR) effect, and degradation in vivo into nontoxic products after completing their tasks. The current biodegradable drug and gene delivery systems exhibit, however, typically low in vivo therapeutic efficacy, due to issues of low loading capacity, inadequate in vivo stability, premature cargo release, poor uptake by target cells, and slow release of therapeutics inside tumor cells. To overcome these problems, a variety of advanced drug and gene delivery systems has recently been designed and developed based on functional biodegradable polycarbonates and copolymers. Notably, polycarbonates and copolymers with diverse functionalities such as hydroxyl, carboxyl, amine, alkene, alkyne, halogen, azido, acryloyl, vinyl sulfone, pyridyldisulfide, and saccharide, could be readily obtained by controlled ring-opening polymerization. In this paper, we give an overview on design concepts and recent developments of functional polycarbonate-based nanocarriers including stimuli-sensitive, photo-crosslinkable, or active targeting polymeric micelles, polymersomes and polyplexes for enhanced drug and gene delivery in vitro and in vivo. These multifunctional biodegradable nanosystems might be eventually developed for safe and efficient cancer chemotherapy and gene therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Bumper and grille airbags concept for enhanced vehicle compatibility in side impact: phase II.

PubMed

Barbat, Saeed; Li, Xiaowei; Prasad, Priya

2013-01-01

Fundamental physics and numerous field studies have shown a higher injury and fatality risk for occupants in smaller and lighter vehicles when struck by heavier, taller and higher vehicles. The consensus is that the significant parameters influencing compatibility in front-to-side crashes are geometric interaction, vehicle stiffness, and vehicle mass. The objective of this research is to develop a concept of deployable bumper and grille airbags for improved vehicle compatibility in side impact. The external airbags, deployed upon signals from sensors, may help mitigate the effect of weight, geometry and stiffness differences and reduce side intrusions. However, a highly reliable pre-crash sensing system is required to enable the reliable deployment, which is currently not technologically feasible. Analytical and numerical methods and hardware testing were used to help develop the deployable external airbags concept. Various Finite Element (FE) models at different stages were developed and an extensive number of iterations were conducted to help optimize airbag and inflator parameters to achieve desired targets. The concept development was executed and validated in two phases. This paper covers Phase II ONLY, which includes: (1) Re-design of the airbag geometry, pressure, and deployment strategies; (2) Further validation using a Via sled test of a 48 kph perpendicular side impact of an SUV-type impactor against a stationary car with US-SID-H3 crash dummy in the struck side; (3) Design of the reaction surface necessary for the bumper airbag functionality. The concept was demonstrated through live deployment of external airbags with a reaction surface in a full-scale perpendicular side impact of an SUV against a stationary passenger car at 48 kph. This research investigated only the concept of the inflatable devices since pre-crash sensing development was beyond the scope of this research. The concept design parameters of the bumper and grille airbags are presented in this paper. Full vehicle-to-vehicle crash test results, Via sled test, and simulation results are also presented. Head peak acceleration, Head Injury Criteria (HIC), Thoracic Trauma Index (TTI), and Pelvic acceleration for the SID-H3 dummy and structural intrusion profiles were used as performance metrics for the bumper and grille airbags. Results obtained from the Via sled tests and the full vehicle-to-vehicle tests with bumper and grille airbags were compared to those of baseline test results with no external airbags.

Optical design of MEMS-based infrared multi-object spectrograph concept for the Gemini South Telescope

NASA Astrophysics Data System (ADS)

Chen, Shaojie; Sivanandam, Suresh; Moon, Dae-Sik

2016-08-01

We discuss the optical design of an infrared multi-object spectrograph (MOS) concept that is designed to take advantage of the multi-conjugate adaptive optics (MCAO) corrected field at the Gemini South telescope. This design employs a unique, cryogenic MEMS-based focal plane mask to select target objects for spectroscopy by utilizing the Micro-Shutter Array (MSA) technology originally developed for the Near Infrared Spectrometer (NIRSpec) of the James Webb Space Telescope (JWST). The optical design is based on all spherical refractive optics, which serves both imaging and spectroscopic modes across the wavelength range of 0.9-2.5 μm. The optical system consists of a reimaging system, MSA, collimator, volume phase holographic (VPH) grisms, and spectrograph camera optics. The VPH grisms, which are VPH gratings sandwiched between two prisms, provide high dispersing efficiencies, and a set of several VPH grisms provide the broad spectral coverage at high throughputs. The imaging mode is implemented by removing the MSA and the dispersing unit out of the beam. We optimize both the imaging and spectrographic modes simultaneously, while paying special attention to the performance of the pupil imaging at the cold stop. Our current design provides a 1' ♢ 1' and a 0.5' ♢ 1' field of views for imaging and spectroscopic modes, respectively, on a 2048 × 2048 pixel HAWAII-2RG detector array. The spectrograph's slit width and spectral resolving power are 0.18'' and 3,000, respectively, and spectra of up to 100 objects can be obtained simultaneously. We present the overall results of simulated performance using optical model we designed.

From orbital debris capture systems through internal combustion engines on Mars

NASA Technical Reports Server (NTRS)

1991-01-01

The investigation and conceptualization of an orbital debris collector was the primary area of design. In addition, an alternate structural design for Space Station Freedom and systems supporting resource utilization at Mars and the moon were studied. Hardware for production of oxygen from simulate Mars atmosphere was modified to permit more reliable operation at low pressures (down to 10 mb). An internal combustion engine was altered to study how Mars atmosphere could be used as a diluent to control combustion temperatures and avoid excess Mars propellant production requirements that would result from either methane-rich or oxygen-rich, methane-oxygen combustion. An elastic loop traction system that could be used for lunar construction vehicles was refined to permit testing. A parabolic heat rejection radiator system was designed and built to determine whether it was capable of increasing heat rejection rates during lunar daytime operation. In addition, an alternate space station truss design, utilizing a pre-integrated concept, was studied and found to reduce estimate extravehicular activity (EVA) time and increase the structural integrity when compared to the original Warren truss concept. An orbital-debris-capturing spacecraft design which could be mated with the Orbital Maneuvering Vehicle was studied. The design identified Soviet C-1B boosters as the best targets of opportunity in Earth orbits between an altitude of 900 km and 1100 km and at an inclination of 82.9 deg. A dual robot pallet, which could be spun to match the tumbling rate of the C-1B booster, was developed as the conceptual design.

Progress in Direct-Drive Inertial Confinement Fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCrory, R.L.; Meyerhofer, D.D.; Betti, R.

Significant progress in direct-drive inertial confinement fusion (ICF) research has been made since the completion of the 60-beam, 30-kJ UV OMEGA Laser System [T. R. Boehly, Opt. Commun. 133, 495 (1997)] in 1995. A theory of ignition requirements, applicable to any ICF concept, has been developed. Detailed understanding of laser-plasma coupling, electron thermal transport, and hot-electron preheating has lead to the measurement of neutron-averaged areal densities of ~200 mg/cm^2 in cryogenic target implosions. These correspond to an estimated peak fuel density in excess of 100 g/cm^3 and are in good agreement with hydrodynamic simulations. The implosions were performed using anmore » 18-kJ drive pulse designed to put the converging fuel on an adiabat of two. The polar-drive concept will allow direct-drive-ignition research on the National Ignition Facility while it is configured for indirect drive. Advanced ICF ignition concepts—fast ignition [Tabak et al., Phys. Plasmas 1, 1626 (1994)] and shock ignition [R. Betti et al., Phys. Rev. Lett. 98, 155001 (2007)]—have the potential to significantly reduce ignition driver energies and/or provide higher target gain.« less

Plasma photonics in ICF & HED conditions

NASA Astrophysics Data System (ADS)

Michel, Pierre; Turnbull, David; Divol, Laurent; Pollock, Bradley; Chen, Cecilia Y.; Tubman, Eleanor; Goyon, Clement S.; Moody, John D.

2015-11-01

Interactions between multiple high-energy laser beams and plasma can be used to imprint refractive micro-structures in plasmas via the lasers' ponderomotive force. For example, Inertial confinement fusion (ICF) experiments at the National Ignition Facility already rely on the use of plasma gratings to redirect laser light inside an ICF target and tune the symmetry of the imploded core. More recently, we proposed new concepts of plasma polarizer and waveplate, based on two-wave mixing schemes and laser-induced plasma birefringence. In this talk, we will present new experimental results showing the first demonstration of a fully tunable plasma waveplate, which achieved near-perfect circular laser polarization. We will discuss further prospects for novel ``plasma photonics'' concepts based on two- and four-wave mixing, such as optical switches, bandpass filters, anti-reflection blockers etc. These might find applications in ICF and HED experiments by allowing to manipulate the lasers directly in-situ (i.e. inside the targets), as well as for the design of high power laser systems. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Applying the target plant concept to nursery stock quality

Treesearch

T.D. Landis; R.K. Dumroese

2007-01-01

The basic tenet of the target plant concept is thatthe quality of nursery stock is determined byoutplanting performance (survival and growth),rather than characteristics or standardsmeasured at the nursery. This means that there isno all-purpose plant, but that each outplantingproject will require different species and stocktypes. In this paper, we discuss the...

Operator vision aids for space teleoperation assembly and servicing

NASA Technical Reports Server (NTRS)

Brooks, Thurston L.; Ince, Ilhan; Lee, Greg

1992-01-01

This paper investigates concepts for visual operator aids required for effective telerobotic control. Operator visual aids, as defined here, mean any operational enhancement that improves man-machine control through the visual system. These concepts were derived as part of a study of vision issues for space teleoperation. Extensive literature on teleoperation, robotics, and human factors was surveyed to definitively specify appropriate requirements. This paper presents these visual aids in three general categories of camera/lighting functions, display enhancements, and operator cues. In the area of camera/lighting functions concepts are discussed for: (1) automatic end effector or task tracking; (2) novel camera designs; (3) computer-generated virtual camera views; (4) computer assisted camera/lighting placement; and (5) voice control. In the technology area of display aids, concepts are presented for: (1) zone displays, such as imminent collision or indexing limits; (2) predictive displays for temporal and spatial location; (3) stimulus-response reconciliation displays; (4) graphical display of depth cues such as 2-D symbolic depth, virtual views, and perspective depth; and (5) view enhancements through image processing and symbolic representations. Finally, operator visual cues (e.g., targets) that help identify size, distance, shape, orientation and location are discussed.

[The concept of social marketing--potential and limitations for health promotion and prevention in Germany].

PubMed

Loss, J; Lang, K; Ultsch, S; Eichhorn, C; Nagel, E

2006-07-01

"Social marketing" is the use of marketing principles to design and implement programmes to promote socially beneficial behaviour changes. In the field of health promotion and prevention, the systematic planning process of social marketing can offer new ideas and perspectives to the traditions of social science. Major characteristics of social marketing encompass continuous market research focussing on attitudes, motives and behavioural patterns of the target group, an integrated mix of strategic key elements, and the perpetual evaluation of all procedures. So far, however, it is unclear in how far social marketing is actually more effective than other concepts of programme planning. Furthermore, it has to be discussed whether the underlying philosophy of social marketing and its implicit understanding of relationships to the public are reconcilable with health promotion principles. In Anglo-Saxon countries, the social marketing concept has achieved widespread application and is subject to controversial scientific discussions, whereas this approach is hardly considered in German health promotion research and practice. Given the increasing call for quality management and evaluation of health promotion interventions, the social marketing concept may contribute useful insights at an operational level and thus add to a discussion on effective approaches for programme planning.

A qualitative study of conceptions and attitudes regarding maternal mortality among traditional birth attendants in rural Guatemala.

PubMed

Rööst, Mattias; Johnsdotter, Sara; Liljestrand, Jerker; Essén, Birgitta

2004-12-01

To explore conceptions of obstetric emergency care among traditional birth attendants in rural Guatemala, elucidating social and cultural factors. design Qualitative in-depth interview study. Rural Guatemala. Thirteen traditional birth attendants from 11 villages around San Miguel Ixtahuacán, Guatemala. Interviews with semi-structured, thematic, open-ended questions. Interview topics were: traditional birth attendants' experiences and conceptions as to the causes of complications, attitudes towards hospital care and referral of obstetric complications. Conceptions of obstetric complications, hospital referrals and maternal mortality among traditional birth attendants. Pregnant women rather than traditional birth attendants appear to make the decision on how to handle a complication, based on moralistically and fatalistically influenced thoughts about the nature of complications, in combination with a fear of caesarean section, maltreatment and discrimination at a hospital level. There is a discrepancy between what traditional birth attendants consider appropriate in cases of complications, and the actions they implement to handle them. Parameters in the referral system, such as logistics and socio-economic factors, are sometimes subordinated to cultural values by the target group. To have an impact on maternal mortality, bilateral culture-sensitive education should be included in maternal health programs.

Head-Worn Displays for NextGen

NASA Technical Reports Server (NTRS)

Bailey, Randall E.; Shelton, Kevin J.; Arthur, J. J.

2011-01-01

The operating concepts emerging under the Next Generation air transportation system (NextGen) require new technology and procedures - not only on the ground-side - but also on the flight deck. Flight deck display and decision support technologies are specifically targeted to overcome aircraft safety barriers that might otherwise constrain the full realization of NextGen. One such technology is the very lightweight, unobtrusive head-worn display (HWD). HWDs with an integrated head-tracking system are being researched as they offer significant potential benefit under emerging NextGen operational concepts. Two areas of benefit for NextGen are defined. First, the HWD may be designed to be equivalent to the Head-Up Display (HUD) using Virtual HUD concepts. As such, these operational credits may be provided to significantly more aircraft for which HUD installation is neither practical nor possible. Second, the HWD provides unique display capabilities, such as an unlimited field-of-regard. These capabilities may be integral to emerging NextGen operational concepts, eliminating safety issues which might otherwise constrain the full realization of NextGen. The paper details recent research results, current HWD technology limitations, and future technology development needed to realize HWDs as a enabling technology for NextGen.

[Concepts in anticoagulant therapy - past, present, and future].

PubMed

Graf, L

2012-11-01

The understanding of the clotting system emerged in parallel to the development of anticoagulants. In contrast to vitamin K-antagonists and heparins that where discovered by chance, new anticoagulants have been systematically designed to specifically inhibit single clotting factors. Both clotting factors Xa (FXa) and thrombin play a crucial role within the new cell-based model of hemostasis. Thus it is obvious that FXa and thrombin turned out to be ideal targets for anticoagulation. The proof of the concept of selective inhibition of thrombin and FXa has been provided by hirudin and fondaparinux, respectively. By now, a whole group of new oral anticoagulants has been licensed: the direct FXa-inhibitors rivaroxaban, apixaban, and edoxaban as well as the direct thrombin dabigatran etexilate. Furthermore, a bundle of FXa- and thrombin-inhibitors that differ from the so far licensed products mainly in pharmacokinetics are in an advanced phase of development. A further innovative concept of anticoagulation that entered its clinical phase of development is the inhibition of factor VIII. Other new concepts such as inhibition of initiation of coagulation by blocking factor VIIa, inhibition of contact factor XII, or inhibition of factor IX are in an early phase of development.

What works with worked examples: Extending self-explanation and analogical comparison to synthesis problems

NASA Astrophysics Data System (ADS)

Badeau, Ryan; White, Daniel R.; Ibrahim, Bashirah; Ding, Lin; Heckler, Andrew F.

2017-12-01

The ability to solve physics problems that require multiple concepts from across the physics curriculum—"synthesis" problems—is often a goal of physics instruction. Three experiments were designed to evaluate the effectiveness of two instructional methods employing worked examples on student performance with synthesis problems; these instructional techniques, analogical comparison and self-explanation, have previously been studied primarily in the context of single-concept problems. Across three experiments with students from introductory calculus-based physics courses, both self-explanation and certain kinds of analogical comparison of worked examples significantly improved student performance on a target synthesis problem, with distinct improvements in recognition of the relevant concepts. More specifically, analogical comparison significantly improved student performance when the comparisons were invoked between worked synthesis examples. In contrast, similar comparisons between corresponding pairs of worked single-concept examples did not significantly improve performance. On a more complicated synthesis problem, self-explanation was significantly more effective than analogical comparison, potentially due to differences in how successfully students encoded the full structure of the worked examples. Finally, we find that the two techniques can be combined for additional benefit, with the trade-off of slightly more time on task.

Comparison of continuous and discontinuous collisional bumpers: Dimensionally scaled impact experiments into single wire meshes

NASA Technical Reports Server (NTRS)

Hoerz, Friedrich; Cintala, Mark; See, Thomas; Bernhard, Ronald; Cardenas, Frank; Davidson, William; Haynes, Jerry

1992-01-01

An experimental inquiry into the utility of discontinuous bumpers was conducted to investigate the collisional outcomes of impacts into single grid-like targets and to compare the results with more traditional bumper designs that employ continuous sheet stock. We performed some 35 experiments using 6.3 and 3.2 mm diameter spherical soda-lime glass projectiles at low velocities (less than 2.5 km/s) and 13 at velocities between 5 and 6 km/s, using 3.2 mm spheres only. The thrust of the experiments related to the characterization of collisional fragments as a function of target thickness or areal shield mass of both bumper designs. The primary product of these experiments was witness plates that record the resulting population of collisional fragments. Substantial interpretive and predictive insights into bumper performance were obtained. All qualitative observations (on the witness plates) and detailed measurements of displaced masses seem simply and consistently related only to bumper mass available for interaction with the impactor. This renders the grid bumper into the superior shield design. These findings present evidence that discontinuous bumpers are a viable concept for collisional shields, possibly superior to continuous geometries.

Acquiring concepts and features of novel words by two types of learning: direct mapping and inference.

PubMed

Chen, Shuang; Wang, Lin; Yang, Yufang

2014-04-01

This study examined the semantic representation of novel words learnt in two conditions: directly mapping a novel word to a concept (Direct mapping: DM) and inferring the concept from provided features (Inferred learning: IF). A condition where no definite concept could be inferred (No basic-level meaning: NM) served as a baseline. The semantic representation of the novel word was assessed via a semantic-relatedness judgment task. In this task, the learned novel word served as a prime, while the corresponding concept, an unlearned feature of the concept, and an unrelated word served as targets. ERP responses to the targets, primed by the novel words in the three learning conditions, were compared. For the corresponding concept, smaller N400s were elicited in the DM and IF conditions than in the NM condition, indicating that the concept could be obtained in both learning conditions. However, for the unlearned feature, the targets in the IF condition produced an N400 effect while in the DM condition elicited an LPC effect relative to the NM learning condition. No ERP difference was observed among the three learning conditions for the unrelated words. The results indicate that conditions of learning affect the semantic representation of novel word, and that the unlearned feature was only activated by the novel word in the IF learning condition. Copyright © 2014 Elsevier Ltd. All rights reserved.

Using the Concept Attainment Strategy to Enhance Reading Comprehension

ERIC Educational Resources Information Center

Boulware, Beverly J.; Crow, Mary Lynn

2008-01-01

The Concept Attainment Strategy is an instructional technique proposed by Jerome Bruner that targets the "big idea" or concept underlining concrete or abstract examples. This strategy focuses on the developing comprehension of words and ideas associated with a concept rather than on its name or what the concept is called. Specifically it develops…

Concept Car Design and Ability Training

NASA Astrophysics Data System (ADS)

Lv, Jiefeng; Lu, Hairong

The concept design as a symbol of creative design thinking, reflecting on the future design of exploratory and prospective, as a vehicle to explore the notion of future car design, design inspiration and creativity is not only a bold display, more through demonstrate the concept, reflects the company's technological strength and technological progress, and thus enhance their brand image. Present Chinese automobile design also has a very big disparity with world level, through cultivating students' concept design ability, to establish native design features and self-reliant brand image is practical and effective ways, also be necessary and pressing.

A Tool Supporting Collaborative Data Analytics Workflow Design and Management

NASA Astrophysics Data System (ADS)

Zhang, J.; Bao, Q.; Lee, T. J.

2016-12-01

Collaborative experiment design could significantly enhance the sharing and adoption of the data analytics algorithms and models emerged in Earth science. Existing data-oriented workflow tools, however, are not suitable to support collaborative design of such a workflow, to name a few, to support real-time co-design; to track how a workflow evolves over time based on changing designs contributed by multiple Earth scientists; and to capture and retrieve collaboration knowledge on workflow design (discussions that lead to a design). To address the aforementioned challenges, we have designed and developed a technique supporting collaborative data-oriented workflow composition and management, as a key component toward supporting big data collaboration through the Internet. Reproducibility and scalability are two major targets demanding fundamental infrastructural support. One outcome of the project os a software tool, supporting an elastic number of groups of Earth scientists to collaboratively design and compose data analytics workflows through the Internet. Instead of recreating the wheel, we have extended an existing workflow tool VisTrails into an online collaborative environment as a proof of concept.

Impact of organ shape variations on margin concepts for cervix cancer ART.

PubMed

Seppenwoolde, Yvette; Stock, Markus; Buschmann, Martin; Georg, Dietmar; Bauer-Novotny, Kwei-Yuang; Pötter, Richard; Georg, Petra

2016-09-01

Target and organ movement motivate adaptive radiotherapy for cervix cancer patients. We investigated the dosimetric impact of margin concepts with different levels of complexity on both organ at risk (OAR) sparing and PTV coverage. Weekly CT and daily CBCT scans were delineated for 10 patients. The dosimetric impact of organ shape variations were evaluated for four (isotropic) margin concepts: two static PTVs (PTV 6mm and PTV 15mm ), a PTV based on ITV of the planning CT and CBCTs of the first treatment week (PTV ART ITV ) and an adaptive PTV based on a library approach (PTV ART Library ). Using static concepts, OAR doses increased with large margins, while smaller margins compromised target coverage. ART PTVs resulted in comparable target coverage and better sparing of bladder (V40Gy: 15% and 7% less), rectum (V40Gy: 18 and 6cc less) and bowel (V40Gy: 106 and 15cc less) compared to PTV 15mm . Target coverage evaluation showed that for elective fields a static 5mm margin sufficed. PTV ART Library achieved the best dosimetric results. However when weighing clinical benefit against workload, ITV margins based on repetitive movement evaluation during the first week also provide improvements over static margin concepts. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cognitive training and plasticity: Theoretical perspective and methodological consequences

PubMed Central

Willis, Sherry L.; Schaie, K. Warner

2013-01-01

Purpose To provide an overview of cognitive plasticity concepts and findings from a lifespan developmental perspective. Methods After an evaluation of the general concept of cognitive plasticity, the most important approaches to study behavioral and brain plasticity are reviewed. This includes intervention studies, experimental approaches, cognitive trainings, the study of facilitating factors for strategy learning and strategy use, practice, and person-environment interactions. Transfer and durability of training-induced plasticity is discussed. Results The review indicates that methodological and conceptual advances are needed to improve the match between levels of behavioral and brain plasticity targeted in current developmental research and study designs. Conclusions The results suggest that the emphasis of plasticity studies on treatment effectiveness needs to be complemented by a strong commitment to the grounding of the intervention in a conceptual framework. PMID:19847065

Reduction of gaseous pollutant emissions from gas turbine combustors using hydrogen-enriched jet fuel

NASA Technical Reports Server (NTRS)

Clayton, R. M.

1976-01-01

Recent progress in an evaluation of the applicability of the hydrogen enrichment concept to achieve ultralow gaseous pollutant emission from gas turbine combustion systems is described. The target emission indexes for the program are 1.0 for oxides of nitrogen and carbon monoxide, and 0.5 for unburned hydrocarbons. The basic concept utilizes premixed molecular hydrogen, conventional jet fuel, and air to depress the lean flammability limit of the mixed fuel. This is shown to permit very lean combustion with its low NOx production while simulataneously providing an increased flame stability margin with which to maintain low CO and HC emission. Experimental emission characteristics and selected analytical results are presented for a cylindrical research combustor designed for operation with inlet-air state conditions typical for a 30:1 compression ratio, high bypass ratio, turbofan commercial engine.

IDIOPATHIC PULMONARY FIBROSIS: NEW CONCEPTS IN PATHOGENESIS AND IMPLICATIONS FOR DRUG THERAPY

PubMed Central

Horowitz, Jeffrey C.; Thannickal, Victor J.

2008-01-01

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually fatal pulmonary disease for which there are no proven or approved drug therapies. Anti-inflammatory and immunosuppressive agents have been largely ineffective. The precise relationship of IPF to other idiopathic interstitial pneumonias (IIPs) is not known, despite the observation that different histopathological patterns of IIP may co-exist in the same patient. We propose that these different histopathological “reaction” patterns may be determined by complex interactions between host and environmental factors that alter the local alveolar milieu. Recent paradigms in IPF pathogenesis have focused on dysregulated epithelial-mesenchymal interactions, an imbalance in TH1/TH2 cytokines and potential roles for aberrant angiogenesis. In this review, we discuss these evolving concepts in disease pathogenesis and emerging therapies designed to target pro-fibrogenic pathways in IPF. PMID:16928146

Molecular genetics made simple

PubMed Central

Kassem, Heba Sh.; Girolami, Francesca; Sanoudou, Despina

2012-01-01

Abstract Genetics have undoubtedly become an integral part of biomedical science and clinical practice, with important implications in deciphering disease pathogenesis and progression, identifying diagnostic and prognostic markers, as well as designing better targeted treatments. The exponential growth of our understanding of different genetic concepts is paralleled by a growing list of genetic terminology that can easily intimidate the unfamiliar reader. Rendering genetics incomprehensible to the clinician however, defeats the very essence of genetic research: its utilization for combating disease and improving quality of life. Herein we attempt to correct this notion by presenting the basic genetic concepts along with their usefulness in the cardiology clinic. Bringing genetics closer to the clinician will enable its harmonious incorporation into clinical care, thus not only restoring our perception of its simple and elegant nature, but importantly ensuring the maximal benefit for our patients. PMID:25610837

Rationally designed mineralization for selective recovery of the rare earth elements

NASA Astrophysics Data System (ADS)

Hatanaka, Takaaki; Matsugami, Akimasa; Nonaka, Takamasa; Takagi, Hideki; Hayashi, Fumiaki; Tani, Takao; Ishida, Nobuhiro

2017-05-01

The increasing demand for rare earth (RE) elements in advanced materials for permanent magnets, rechargeable batteries, catalysts and lamp phosphors necessitates environmentally friendly approaches for their recovery and separation. Here, we propose a mineralization concept for direct extraction of RE ions with Lamp (lanthanide ion mineralization peptide). In aqueous solution containing various metal ions, Lamp promotes the generation of RE hydroxide species with which it binds to form hydrophobic complexes that accumulate spontaneously as insoluble precipitates, even under physiological conditions (pH ~6.0). This concept for stabilization of an insoluble lanthanide hydroxide complex with an artificial peptide also works in combination with stable scaffolds like synthetic macromolecules and proteins. Our strategy opens the possibility for selective separation of target metal elements from seawater and industrial wastewater under mild conditions without additional energy input.

Rationally designed mineralization for selective recovery of the rare earth elements

PubMed Central

Hatanaka, Takaaki; Matsugami, Akimasa; Nonaka, Takamasa; Takagi, Hideki; Hayashi, Fumiaki; Tani, Takao; Ishida, Nobuhiro

2017-01-01

The increasing demand for rare earth (RE) elements in advanced materials for permanent magnets, rechargeable batteries, catalysts and lamp phosphors necessitates environmentally friendly approaches for their recovery and separation. Here, we propose a mineralization concept for direct extraction of RE ions with Lamp (lanthanide ion mineralization peptide). In aqueous solution containing various metal ions, Lamp promotes the generation of RE hydroxide species with which it binds to form hydrophobic complexes that accumulate spontaneously as insoluble precipitates, even under physiological conditions (pH ∼6.0). This concept for stabilization of an insoluble lanthanide hydroxide complex with an artificial peptide also works in combination with stable scaffolds like synthetic macromolecules and proteins. Our strategy opens the possibility for selective separation of target metal elements from seawater and industrial wastewater under mild conditions without additional energy input. PMID:28548098

Rationally designed mineralization for selective recovery of the rare earth elements.

PubMed

Hatanaka, Takaaki; Matsugami, Akimasa; Nonaka, Takamasa; Takagi, Hideki; Hayashi, Fumiaki; Tani, Takao; Ishida, Nobuhiro

2017-05-26

The increasing demand for rare earth (RE) elements in advanced materials for permanent magnets, rechargeable batteries, catalysts and lamp phosphors necessitates environmentally friendly approaches for their recovery and separation. Here, we propose a mineralization concept for direct extraction of RE ions with Lamp (lanthanide ion mineralization peptide). In aqueous solution containing various metal ions, Lamp promotes the generation of RE hydroxide species with which it binds to form hydrophobic complexes that accumulate spontaneously as insoluble precipitates, even under physiological conditions (pH ∼6.0). This concept for stabilization of an insoluble lanthanide hydroxide complex with an artificial peptide also works in combination with stable scaffolds like synthetic macromolecules and proteins. Our strategy opens the possibility for selective separation of target metal elements from seawater and industrial wastewater under mild conditions without additional energy input.

Extraordinary Matter: Visualizing Space Plasmas and Particles

NASA Astrophysics Data System (ADS)

Barbier, S. B.; Bartolone, L.; Christian, E. R.; Eastman, T.; Lewis, E.; Thieman, J.

2010-08-01

We present an online NASA multimedia library, now in development, designed to assist educators with explaining concepts of basic particle and plasma physics. Such resources are few in number and/or difficult to locate, and most do not provide suitable context. On our Extraordinary Matter site, each product will be accompanied by an explanation at a reading level matching the concept's educational level, link to the source, educational standards addressed, file size, use restrictions, credits, format(s), creation date and, optionally, associated educational activities and other relevant information and links. The site will target grades 9-14 and the equivalent in informal education and outreach. Products are intended to stand alone, making them adaptable to the widest range of uses. This project is funded by the NASA EPOESS Program in response to NRA NNH08ZDA001N for ROSES-2008.

Application of green concept in mechanical design and manufacture

NASA Astrophysics Data System (ADS)

Liu, Xing ping

2017-11-01

With the development of productive forces, the relationship between human and nature is becoming tight increasingly, especially environmental pollution and resource consumption that comes from equipment manufacturing industry mainly. Green development concept is a new concept which can solve the current ecological environment. The philosophical foundation and theoretical basis of green idea are expounded through the study of scientific development and green concept. The difference between the traditional design and the green design is analyzed; the meaning and content of the mechanical design for green concept are discussed. And the evaluation method of green design is discussed too. The significance of green development concept in the mechanical design and manufacturing science is pinpointed clearly. The results show that the implementation of green design under the mechanical design, from the source of pollution control to achieve green manufacturing, is the only way to achieve sustainable development.

Associated Particle Tagging (APT) in Magnetic Spectrometers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jordan, David V.; Baciak, James E.; Stave, Sean C.

2012-10-16

Summary In Brief The Associated Particle Tagging (APT) project, a collaboration of Pacific Northwest National Laboratory (PNNL), Idaho National Laboratory (INL) and the Idaho State University (ISU)/Idaho Accelerator Center (IAC), has completed an exploratory study to assess the role of magnetic spectrometers as the linchpin technology in next-generation tagged-neutron and tagged-photon active interrogation (AI). The computational study considered two principle concepts: (1) the application of a solenoidal alpha-particle spectrometer to a next-generation, large-emittance neutron generator for use in the associated particle imaging technique, and (2) the application of tagged photon beams to the detection of fissile material via active interrogation.more » In both cases, a magnetic spectrometer momentum-analyzes charged particles (in the neutron case, alpha particles accompanying neutron generation in the D-T reaction; in the tagged photon case, post-bremsstrahlung electrons) to define kinematic properties of the relevant neutral interrogation probe particle (i.e. neutron or photon). The main conclusions of the study can be briefly summarized as follows: Neutron generator: • For the solenoidal spectrometer concept, magnetic field strengths of order 1 Tesla or greater are required to keep the transverse size of the spectrometer smaller than 1 meter. The notional magnetic spectrometer design evaluated in this feasibility study uses a 5-T magnetic field and a borehole radius of 18 cm. • The design shows a potential for 4.5 Sr tagged neutron solid angle, a factor of 4.5 larger than achievable with current API neutron-generator designs. • The potential angular resolution for such a tagged neutron beam can be less than 0.5o for modest Si-detector position resolution (3 mm). Further improvement in angular resolution can be made by using Si-detectors with better position resolution. • The report documents several features of a notional generator design incorporating the alpha-particle spectrometer concept, and outlines challenges involved in the magnetic field design. Tagged photon interrogation: • We investigated a method for discriminating fissile from benign cargo-material response to an energy-tagged photon beam. The method relies upon coincident detection of the tagged photon and a photoneutron or photofission neutron produced in the target material. The method exploits differences in the shape of the neutron production cross section as a function of incident photon energy in order to discriminate photofission yield from photoneutrons emitted by non-fissile materials. Computational tests of the interrogation method as applied to material composition assay of a simple, multi-layer target suggest that the tagged-photon information facilitates precise (order 1% thickness uncertainty) reconstruction of the constituent thicknesses of fissile (uranium) and high-Z (Pb) constituents of the test targets in a few minutes of photon-beam exposure. We assumed an 18-MeV endpoint tagged photon beam for these simulations. • The report addresses several candidate design and data analysis issues for beamline infrastructure required to produce a tagged photon beam in a notional AI-dedicated facility, including the accelerator and tagging spectrometer.« less

Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side.

PubMed

Lin, Kuan-Hung; Ali, Akbar; Rusere, Linah; Soumana, Djade I; Kurt Yilmaz, Nese; Schiffer, Celia A

2017-05-15

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein with high affinity for DENV protease. In this study, we designed a series of cyclic peptides interacting with both sides of the active site as inhibitors of dengue virus protease. The design was based on two aprotinin loops and aimed to leverage both key specific interactions of substrate sequences and the entropic advantage driving aprotinin's high affinity. By optimizing the cyclization linker, length, and amino acid sequence, the tightest cyclic peptide achieved a K i value of 2.9 μM against DENV3 wild-type (WT) protease. These inhibitors provide proof of concept that both sides of DENV protease active site can be exploited to potentially achieve specificity and lower hydrophilicity in the design of inhibitors targeting DENV. IMPORTANCE Viruses of the flaviviral family, including DENV and Zika virus transmitted by Aedes aegypti , continue to be a threat to global health by causing major outbreaks in tropical and subtropical regions, with no available direct-acting antivirals for treatment. A better understanding of the molecular requirements for the design of potent and specific inhibitors against flaviviral proteins will contribute to the development of targeted therapies for infections by these viruses. The cyclic peptides reported here as DENV protease inhibitors provide novel scaffolds that enable exploiting the prime side of the protease active site, with the aim of achieving better specificity and lower hydrophilicity than those of current scaffolds in the design of antiflaviviral inhibitors. Copyright © 2017 American Society for Microbiology.

IVTS-CEV (Interactive Video Tape System-Combat Engineer Vehicle) Gunnery Trainer.

DTIC Science & Technology

1981-07-01

video game technology developed for and marketed in consumer video games. The IVTS/CEV is a conceptual/breadboard-level classroom interactive training system designed to train Combat Engineer Vehicle (CEV) gunners in target acquisition and engagement with the main gun. The concept demonstration consists of two units: a gunner station and a display module. The gunner station has optics and gun controls replicating those of the CEV gunner station. The display module contains a standard large-screen color video monitor and a video tape player. The gunner’s sight

High temperature NASP engine seals: A technology review

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Dellacorte, Christopher; Tong, Mike

1991-01-01

Progress in developing advanced high temperature engine seal concepts and related sealing technologies for advanced hypersonic engines are reviewed. Design attributes and issues requiring further development for both the ceramic wafer seal and the braided ceramic rope seal are examined. Leakage data are presented for these seals for engine simulated pressure and temperature conditions and compared to a target leakage limit. Basic elements of leakage flow models to predict leakage rates for each of these seals over the wide range of pressure and temperature conditions anticipated in the engine are also presented.

Adamantane in Drug Delivery Systems and Surface Recognition.

PubMed

Štimac, Adela; Šekutor, Marina; Mlinarić-Majerski, Kata; Frkanec, Leo; Frkanec, Ruža

2017-02-16

The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in the lipid bilayer of liposomes has promising applications in the field of targeted drug delivery and surface recognition. The results reported here encourage the development of novel adamantane-based structures and self-assembled supramolecular systems for basic chemical investigations as well as for biomedical application.

A systems-level approach for metabolic engineering of yeast cell factories.

PubMed

Kim, Il-Kwon; Roldão, António; Siewers, Verena; Nielsen, Jens

2012-03-01

The generation of novel yeast cell factories for production of high-value industrial biotechnological products relies on three metabolic engineering principles: design, construction, and analysis. In the last two decades, strong efforts have been put on developing faster and more efficient strategies and/or technologies for each one of these principles. For design and construction, three major strategies are described in this review: (1) rational metabolic engineering; (2) inverse metabolic engineering; and (3) evolutionary strategies. Independent of the selected strategy, the process of designing yeast strains involves five decision points: (1) choice of product, (2) choice of chassis, (3) identification of target genes, (4) regulating the expression level of target genes, and (5) network balancing of the target genes. At the construction level, several molecular biology tools have been developed through the concept of synthetic biology and applied for the generation of novel, engineered yeast strains. For comprehensive and quantitative analysis of constructed strains, systems biology tools are commonly used and using a multi-omics approach. Key information about the biological system can be revealed, for example, identification of genetic regulatory mechanisms and competitive pathways, thereby assisting the in silico design of metabolic engineering strategies for improving strain performance. Examples on how systems and synthetic biology brought yeast metabolic engineering closer to industrial biotechnology are described in this review, and these examples should demonstrate the potential of a systems-level approach for fast and efficient generation of yeast cell factories. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

The Solar Probe mission - Mission design concepts and requirements

NASA Technical Reports Server (NTRS)

Ayon, Juan A.

1992-01-01

The Solar Probe concept as studied by the Jet Propulsion Laboratory represents the first mission to combine out-of-the-ecliptic scientific coverage with multiple, close solar encounters (at 4 solar radii). The scientific objectives of the mission have driven the investigation and analysis of several mission design concepts, all optimized to meet the science/mission requirements. This paper reviews those mission design concepts developed, the science objectives that drive the mission design, and the principle mission requirements associated with these various concepts.

Advanced Concept Studies for Supersonic Commercial Transports Entering Service in the 2018 to 2020 Period

NASA Technical Reports Server (NTRS)

Morgenstern, John; Norstrud, Nicole; Sokhey, Jack; Martens, Steve; Alonso, Juan J.

2013-01-01

Lockheed Martin Aeronautics Company (LM), working in conjunction with General Electric Global Research (GE GR), Rolls-Royce Liberty Works (RRLW), and Stanford University, herein presents results from the "N+2 Supersonic Validations" contract s initial 22 month phase, addressing the NASA solicitation "Advanced Concept Studies for Supersonic Commercial Transports Entering Service in the 2018 to 2020 Period." This report version adds documentation of an additional three month low boom test task. The key technical objective of this effort was to validate integrated airframe and propulsion technologies and design methodologies. These capabilities aspired to produce a viable supersonic vehicle design with environmental and performance characteristics. Supersonic testing of both airframe and propulsion technologies (including LM3: 97-023 low boom testing and April-June nozzle acoustic testing) verified LM s supersonic low-boom design methodologies and both GE and RRLW's nozzle technologies for future implementation. The N+2 program is aligned with NASA s Supersonic Project and is focused on providing system-level solutions capable of overcoming the environmental and performance/efficiency barriers to practical supersonic flight. NASA proposed "Initial Environmental Targets and Performance Goals for Future Supersonic Civil Aircraft". The LM N+2 studies are built upon LM s prior N+3 100 passenger design studies. The LM N+2 program addresses low boom design and methodology validations with wind tunnel testing, performance and efficiency goals with system level analysis, and low noise validations with two nozzle (GE and RRLW) acoustic tests.

The US ICF Ignition Program and the Inertial Fusion Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lindl, J D; Hammel, B A; Logan, B G

2003-07-02

There has been rapid progress in inertial fusion in the past few years. This progress spans the construction of ignition facilities, a wide range of target concepts, and the pursuit of integrated programs to develop fusion energy using lasers, ion beams and z-pinches. Two ignition facilities are under construction (NIF in the U.S. and LMJ in France) and both projects are progressing toward an initial experimental capability. The LIL prototype beamline for LMJ and the first 4 beams of NIF will be available for experiments in 2003. The full 192 beam capability of NIF will be available in 2009 andmore » ignition experiments are expected to begin shortly after that time. There is steady progress in the target science and target fabrication in preparation for indirect drive ignition experiments on NIF. Advanced target designs may lead to 5-10 times more yield than initial target designs. There has also been excellent progress on the science of ion beam and z-pinch driven indirect drive targets. Excellent progress on direct-drive targets has been obtained on the Omega laser at the University of Rochester. This includes improved performance of targets with a pulse shape predicted to result in reduced hydrodynamic instability. Rochester has also obtained encouraging results from initial cryogenic implosions. There is widespread interest in the science of fast ignition because of its potential for achieving higher target gain with lower driver energy and relaxed target fabrication requirements. Researchers from Osaka have achieved outstanding implosion and heating results from the Gekko XII Petawatt facility and implosions suitable for fast ignition have been tested on the Omega laser. A broad based program to develop lasers and ions beams for IFE is under way with excellent progress in drivers, chambers, target fabrication and target injection. KrF and Diode Pumped Solid-State lasers (DPSSL) are being developed in conjunction with drywall chambers and direct drive targets. Induction accelerators for heavy ions are being developed in conjunction with thick-liquid protected wall chambers and indirect-drive targets.« less

Structured oligonucleotides for target indexing to allow single-vessel PCR amplification and solid support microarray hybridization

PubMed Central

Girard, Laurie D.; Boissinot, Karel; Peytavi, Régis; Boissinot, Maurice; Bergeron, Michel G.

2014-01-01

The combination of molecular diagnostic technologies is increasingly used to overcome limitations on sensitivity, specificity or multiplexing capabilities, and provide efficient lab-on-chip devices. Two such techniques, PCR amplification and microarray hybridization are used serially to take advantage of the high sensitivity and specificity of the former combined with high multiplexing capacities of the latter. These methods are usually performed in different buffers and reaction chambers. However, these elaborate methods have a high complexity cost related to reagent requirements, liquid storage and the number of reaction chambers to integrate into automated devices. Furthermore, microarray hybridizations have a sequence dependent efficiency not always predictable. In this work, we have developed the concept of a structured oligonucleotide probe which is activated by cleavage from polymerase exonuclease activity. This technology is called SCISSOHR for Structured Cleavage Induced Single-Stranded Oligonucleotide Hybridization Reaction. The SCISSOHR probes enable indexing the target sequence to a tag sequence. The SCISSOHR technology also allows the combination of nucleic acid amplification and microarray hybridization in a single vessel in presence of the PCR buffer only. The SCISSOHR technology uses an amplification probe that is irreversibly modified in presence of the target, releasing a single-stranded DNA tag for microarray hybridization. Each tag is composed of a 3-nucleotidesequence-dependent segment and a unique “target sequence-independent” 14-nucleotide segment allowing for optimal hybridization with minimal cross-hybridization. We evaluated the performance of five (5) PCR buffers to support microarray hybridization, compared to a conventional hybridization buffer. Finally, as a proof of concept, we developed a multiplexed assay for the amplification, detection, and identification of three (3) DNA targets. This new technology will facilitate the design of lab-on-chip microfluidic devices, while also reducing consumable costs. At term, it will allow the cost-effective automation of highly multiplexed assays for detection and identification of genetic targets. PMID:25489607

Structured oligonucleotides for target indexing to allow single-vessel PCR amplification and solid support microarray hybridization.

PubMed

Girard, Laurie D; Boissinot, Karel; Peytavi, Régis; Boissinot, Maurice; Bergeron, Michel G

2015-02-07

The combination of molecular diagnostic technologies is increasingly used to overcome limitations on sensitivity, specificity or multiplexing capabilities, and provide efficient lab-on-chip devices. Two such techniques, PCR amplification and microarray hybridization are used serially to take advantage of the high sensitivity and specificity of the former combined with high multiplexing capacities of the latter. These methods are usually performed in different buffers and reaction chambers. However, these elaborate methods have high complexity and cost related to reagent requirements, liquid storage and the number of reaction chambers to integrate into automated devices. Furthermore, microarray hybridizations have a sequence dependent efficiency not always predictable. In this work, we have developed the concept of a structured oligonucleotide probe which is activated by cleavage from polymerase exonuclease activity. This technology is called SCISSOHR for Structured Cleavage Induced Single-Stranded Oligonucleotide Hybridization Reaction. The SCISSOHR probes enable indexing the target sequence to a tag sequence. The SCISSOHR technology also allows the combination of nucleic acid amplification and microarray hybridization in a single vessel in presence of the PCR buffer only. The SCISSOHR technology uses an amplification probe that is irreversibly modified in presence of the target, releasing a single-stranded DNA tag for microarray hybridization. Each tag is composed of a 3-nucleotide sequence-dependent segment and a unique "target sequence-independent" 14-nucleotide segment allowing for optimal hybridization with minimal cross-hybridization. We evaluated the performance of five (5) PCR buffers to support microarray hybridization, compared to a conventional hybridization buffer. Finally, as a proof of concept, we developed a multiplexed assay for the amplification, detection, and identification of three (3) DNA targets. This new technology will facilitate the design of lab-on-chip microfluidic devices, while also reducing consumable costs. At term, it will allow the cost-effective automation of highly multiplexed assays for detection and identification of genetic targets.

Direct target NOTES: prospective applications for next generation robotic platforms.

PubMed

Atallah, S; Hodges, A; Larach, S W

2018-05-01

A new era in surgical robotics has centered on alternative access to anatomic targets and next generation designs include flexible, single-port systems which follow circuitous rather than straight pathways. Such systems maintain a small footprint and could be utilized for specialized operations based on direct organ target natural orifice transluminal endoscopic surgery (NOTES), of which transanal total mesorectal excision (taTME) is an important derivative. During two sessions, four direct target NOTES operations were conducted on a cadaveric model using a flexible robotic system to demonstrate proof-of-concept of the application of a next generation robotic system to specific types of NOTES operations, all of which required removal of a direct target organ through natural orifice access. These four operations were (a) robotic taTME, (b) robotic transvaginal hysterectomy in conjunction with (c) robotic transvaginal salpingo-oophorectomy, and in an ex vivo model, (d) trans-cecal appendectomy. Feasibility was demonstrated in all cases using the Flex ® Robotic System with Colorectal Drive. During taTME, the platform excursion was 17 cm along a non-linear path; operative time was 57 min for the transanal portion of the dissection. Robotic transvaginal hysterectomy was successfully completed in 78 min with transvaginal extraction of the uterus, although laparoscopic assistance was required. Robotic transvaginal unilateral salpingo-oophorectomy with transvaginal extraction of the ovary and fallopian tube was performed without laparoscopic assistance in 13.5 min. In an ex vivo model, a robotic trans-cecal appendectomy was also successfully performed for the purpose of demonstrating proof-of-concept only; this was completed in 24 min. A flexible robotic system has the potential to access anatomy along circuitous paths, making it a suitable platform for direct target NOTES. The conceptual operations posed could be considered suitable for next generation robotics once the technology is optimized, and after further preclinical validation.

Design and development of a family of explosive ordnance disposal (EOD) robots

NASA Astrophysics Data System (ADS)

Reichard, Karl; Simpson, Tim; Rogan, Chris; Merenich, John; Brennan, Sean; Crow, Ed

2008-10-01

Across many consumer product industries, the prevailing practice is to design families of product variants that exploit commonality to provide the ability to easily customize a base platform for particular uses and to take advantage of commonality for streamlining design, manufacturing, maintenance and logistic; examples include Black & Decker, Seagate, and Volkswagen. This paper describes the application of product family concepts to the design and development of a family of robots to satisfy requirements for explosive ordnance disposal. To facilitate this process, we have developed a market segmentation grid that plots the desired capabilities and cost versus the target use cases. The product family design trade space is presented using a multi-dimensional trade space visualization tool which helps identify dependencies between different design variables and identify Pareto frontiers along which optimal design choices will lie. The EOD robot product family designs share common components and subsystems yet are modularized and scalable to provide functionality to satisfy a range of user requirements. This approach has been shown to significantly reduce development time and costs, manufacturing costs, maintenance and spare parts inventory, and operator and maintainer training.

Advanced composites structural concepts and materials technologies for primary aircraft structures: Design/manufacturing concept assessment

NASA Technical Reports Server (NTRS)

Chu, Robert L.; Bayha, Tom D.; Davis, HU; Ingram, J. ED; Shukla, Jay G.

1992-01-01

Composite Wing and Fuselage Structural Design/Manufacturing Concepts have been developed and evaluated. Trade studies were performed to determine how well the concepts satisfy the program goals of 25 percent cost savings, 40 percent weight savings with aircraft resizing, and 50 percent part count reduction as compared to the aluminum Lockheed L-1011 baseline. The concepts developed using emerging technologies such as large scale resin transfer molding (RTM), automatic tow placed (ATP), braiding, out-of-autoclave and automated manufacturing processes for both thermoset and thermoplastic materials were evaluated for possible application in the design concepts. Trade studies were used to determine which concepts carry into the detailed design development subtask.

Hexcrete Tower for Harvesting Wind Energy at Taller Hub Heights - Budget Period 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sritharan, Sri

Interest in designing taller towers for wind energy production in the United States (U.S.) has been steadily growing. In May 2015, it was revealed that taller towers will make wind energy production a reality in all 50 states, including some states that have nearly zero renewables in their energy portfolio. Facilitating wind energy production feasibility in all 50 states will no doubt contribute to increasing the electricity produced by wind from 4.5% in 2013 to a targeted scenario of 35% by 2050 in the Wind Vision report. This project focuses on the Hexcrete tower concept developed for tall towers usingmore » High Strength Concrete (HSC) and/or Ultra-High Performance Concrete (UHPC). Among other benefits, the Hexcrete concept overcomes transportation and logistical challenges, thus facilitating construction of towers with hub heights of 100-m (328-ft) and higher. The goal of this project is to facilitate widespread deployment of Hexcrete towers for harvesting wind energy at 120 to 140-m (394 to 459-ft) hub heights and reduce the Levelized Cost of Energy (LCOE) of wind energy production in the U.S. The technical scope of the project includes detailed design and optimization of at least three wind turbine towers using the Hexcrete concept together with experimental validation and LCOE analyses and development of a commercialization plan.« less

Development and characterization of plasma targets for controlled injection of electrons into laser-driven wakefields

NASA Astrophysics Data System (ADS)

Kleinwaechter, Tobias; Goldberg, Lars; Palmer, Charlotte; Schaper, Lucas; Schwinkendorf, Jan-Patrick; Osterhoff, Jens

2012-10-01

Laser-driven wakefield acceleration within capillary discharge waveguides has been used to generate high-quality electron bunches with GeV-scale energies. However, owing to fluctuations in laser and plasma conditions in combination with a difficult to control self-injection mechanism in the non-linear wakefield regime these bunches are often not reproducible and can feature large energy spreads. Specialized plasma targets with tailored density profiles offer the possibility to overcome these issues by controlling the injection and acceleration processes. This requires precise manipulation of the longitudinal density profile. Therefore our target concept is based on a capillary structure with multiple gas in- and outlets. Potential target designs are simulated using the fluid code OpenFOAM and those meeting the specified criteria are fabricated using femtosecond-laser machining of structures into sapphire plates. Density profiles are measured over a range of inlet pressures utilizing gas-density profilometry via Raman scattering and pressure calibration with longitudinal interferometry. In combination these allow absolute density mapping. Here we report the preliminary results.

Recent trends in drug delivery system using protein nanoparticles.

PubMed

Sripriyalakshmi, S; Jose, Pinkybel; Ravindran, Aswathy; Anjali, C H

2014-09-01

Engineered nanoparticles that can facilitate drug formulation and passively target tumours have been under extensive research in recent years. These successes have driven a new wave of significant innovation in the generation of advanced particles. The fate and transport of diagnostic nanoparticles would significantly depend on nonselective drug delivery, and hence the use of high drug dosage is implemented. In this perspective, nanocarrier-based drug targeting strategies can be used which improve the selective delivery of drugs to the site of action, i.e. drug targeting. Pharmaceutical industries majorly focus on reducing the toxicity and side effects of drugs but only recently it has been realised that carrier systems themselves may pose risks to the patient. Proteins are compatible with biological systems and they are biodegradable. They offer a multitude of moieties for modifications to tailor drug binding, imaging or targeting entities. Thus, protein nanoparticles provide outstanding contributions as a carrier for drug delivery systems. This review summarises recent progress in particle-based therapeutic delivery and discusses important concepts in particle design and biological barriers for developing the next generation of particles drug delivery systems.

Programmed serial stereochemical relay and its application in the synthesis of morphinans† †Electronic supplementary information (ESI) available. CCDC 1526432. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc03189k Click here for additional data file. Click here for additional data file.

PubMed Central

Ho (Kenny) Park, Kun; Chen, Rui

2017-01-01

Herein we report a rationally designed, serial point-to-axial and axial-to-point stereoinduction and its integration into multi-step and target-oriented organic synthesis. In this proof-of-concept study, the configurational stability of several carefully designed atropisomeric intermediates and the fidelity of their unconventional stereoinductions were systematically investigated. The highly functionalized prepared synthetic intermediate was further applied in a novel chemical method to access the morphinans and it is potentially applicable to other structurally related alkaloids. PMID:29147530

Touring the Saturnian system

NASA Astrophysics Data System (ADS)

Wolf, Aron A.

1996-10-01

The Cassini mission to Saturn employs a Saturn orbiter and a Titan probe to conduct an intensive investigation of the Saturnian system. The Cassini orbiter flies a series of obits, incorporating flybys of the Saturnian satellites, called the 'satellite tour'. During the tour, the gravitational fields of the satellites are used to modify and control the orbit, targeting from one satellite flyby to the next. The tour trajectory must also be designed to maximize opportunities for science observations, subject to mission-imposed constraints. Tour design studies have been conducted for Cassini to identify trades and strategies for achieving these sometimes conflicting goals. Concepts, strategies, and techniques previously developed for the Galileo mission to Jupiter have been modified, and new ones have been developed, to meet the requirements of the Cassini mission.

Creating and virtually screening databases of fluorescently-labelled compounds for the discovery of target-specific molecular probes

NASA Astrophysics Data System (ADS)

Kamstra, Rhiannon L.; Dadgar, Saedeh; Wigg, John; Chowdhury, Morshed A.; Phenix, Christopher P.; Floriano, Wely B.

2014-11-01

Our group has recently demonstrated that virtual screening is a useful technique for the identification of target-specific molecular probes. In this paper, we discuss some of our proof-of-concept results involving two biologically relevant target proteins, and report the development of a computational script to generate large databases of fluorescence-labelled compounds for computer-assisted molecular design. The virtual screening of a small library of 1,153 fluorescently-labelled compounds against two targets, and the experimental testing of selected hits reveal that this approach is efficient at identifying molecular probes, and that the screening of a labelled library is preferred over the screening of base compounds followed by conjugation of confirmed hits. The automated script for library generation explores the known reactivity of commercially available dyes, such as NHS-esters, to create large virtual databases of fluorescence-tagged small molecules that can be easily synthesized in a laboratory. A database of 14,862 compounds, each tagged with the ATTO680 fluorophore was generated with the automated script reported here. This library is available for downloading and it is suitable for virtual ligand screening aiming at the identification of target-specific fluorescent molecular probes.

Experimental Demonstration of Adaptive Infrared Multispectral Imaging using Plasmonic Filter Array.

PubMed

Jang, Woo-Yong; Ku, Zahyun; Jeon, Jiyeon; Kim, Jun Oh; Lee, Sang Jun; Park, James; Noyola, Michael J; Urbas, Augustine

2016-10-10

In our previous theoretical study, we performed target detection using a plasmonic sensor array incorporating the data-processing technique termed "algorithmic spectrometry". We achieved the reconstruction of a target spectrum by extracting intensity at multiple wavelengths with high resolution from the image data obtained from the plasmonic array. The ultimate goal is to develop a full-scale focal plane array with a plasmonic opto-coupler in order to move towards the next generation of versatile infrared cameras. To this end, and as an intermediate step, this paper reports the experimental demonstration of adaptive multispectral imagery using fabricated plasmonic spectral filter arrays and proposed target detection scenarios. Each plasmonic filter was designed using periodic circular holes perforated through a gold layer, and an enhanced target detection strategy was proposed to refine the original spectrometry concept for spatial and spectral computation of the data measured from the plasmonic array. Both the spectrum of blackbody radiation and a metal ring object at multiple wavelengths were successfully reconstructed using the weighted superposition of plasmonic output images as specified in the proposed detection strategy. In addition, plasmonic filter arrays were theoretically tested on a target at extremely high temperature as a challenging scenario for the detection scheme.

A Concept Transformation Learning Model for Architectural Design Learning Process

ERIC Educational Resources Information Center

Wu, Yun-Wu; Weng, Kuo-Hua; Young, Li-Ming

2016-01-01

Generally, in the foundation course of architectural design, much emphasis is placed on teaching of the basic design skills without focusing on teaching students to apply the basic design concepts in their architectural designs or promoting students' own creativity. Therefore, this study aims to propose a concept transformation learning model to…

KiwiSpec - an advanced spectrograph for high resolution spectroscopy: prototype design and performance

NASA Astrophysics Data System (ADS)

Gibson, Steve; Barnes, Stuart I.; Hearnshaw, John; Nield, Kathryn; Cochrane, Dave; Grobler, Deon

2012-09-01

A new advanced high resolution spectrograph has been developed by Kiwistar Optics of Industrial Research Ltd., New Zealand. The instrument, KiwiSpec R4-100, is bench-mounted, bre-fed, compact (0.75m by 1.5m footprint), and is well-suited for small to medium-sized telescopes. The instrument makes use of several advanced concepts in high resolution spectrograph design. The basic design follows the classical white pupil concept in an asymmetric implementation and employs an R4 echelle grating illuminated by a 100mm diameter collimated beam for primary dispersion. A volume phase holographic grating (VPH) based grism is used for cross-dispersion. The design also allows for up to four camera and detector channels to allow for extended wavelength coverage at high eciency. A single channel prototype of the instrument has been built and successfully tested with a 1m telescope. Targets included various spectrophotometric standard stars and several radial velocity standard stars to measure the instrument's light throughput and radial velocity capabilities. The prototype uses a 725 lines/mm VPH grism, an off-the-shelf camera objective, and a 2k×2k CCD. As such, it covers the wavelength range from 420nm to 660nm and has a resolving power of R ≍ 40,000. Spectrophotometric and precision radial velocity results from the on-sky testing period will be reported, as well as results of laboratory-based measurements. The optical design of KiwiSpec, and the various multi-channel design options, will be presented elsewhere in these proceedings.

International Design Concepts for the SKA

NASA Astrophysics Data System (ADS)

Tarter, J.

2001-12-01

In August of 2000, representatives of eleven countries signed a Memorandum of Understanding to Establish the International Square Kilometre Array Steering Committee (ISSC). Arguably, the SKA could be built today, but without question it would be unaffordable. Increasing collecting area by a factor of 100 beyond today's largest array cannot be done cost effectively by simple extensions of what has been done before. New concepts, new designs, and new technologies will be required, as well as a paradigm shift. It will be necessary to heavily exploit emerging communications and consumer market technologies; to "hammer" them into shapes required to solve the SKA challenges, rather than inventing our own solutions from scratch. Or if we do invent ab initio solutions, we should look at creating consumer markets to embrace them, so that the full benefits of mass production and manufacturing can be realized. The strawman science goals of the SKA are extremely ambitious. Today there are six primary design concepts being studied that attempt to meet some or all of these goals; phased arrays of active elements embedded into flat tiles, "super Arecibo" antennas constructed in individual limestone karst sinkholes and arrayed together, large arrays of small, spherical (or hemispherical) Luneberg lenses, large deformable apertures with long focal ratios and aerostat-borne focal plane array receivers, arrays of large parabolic antennas constructed from steel "ropes," and large arrays of small parabolic dishes derived from the TVRO industry. This talk summarizes the strengths and weaknesses of these various designs in their current, incomplete state. In the US, the US SKA Consortium of 10 academic and research organizations has generated a roadmap to guide and assess the technology development that will be required to produce a successful SKA design, with well understood costs, performance, and minimal risk. The design and construction efforts for the ATA, LOFAR and the EVLA will provide essential opportunities for proofs-of-concept for portions of the preferred US design; a very large number of small elements configured into a Large-N number of stations. An aggressive timetable has been adopted for choosing a final (hybrid?) SKA design and the selection of a site, with a target date of 2005. The first, tentative steps have been taken to create an international project office capable of overseeing the development and construction of this facility, negotiating creative solutions to problems of radio frequency interference, and along the way, inventing the infrastructure and management appropriate to this "born international" venture.

Progress in Fast Ignition Studies with Electrons and Protons

NASA Astrophysics Data System (ADS)

MacKinnon, A. J.; Akli, K. U.; Bartal, T.; Beg, F. N.; Chawla, S.; Chen, C. D.; Chen, H.; Chen, S.; Chowdhury, E.; Fedosejevs, R.; Freeman, R. R.; Hey, D.; Higginson, D.; Key, M. H.; King, J. A.; Link, A.; Ma, T.; MacPhee, A. G.; Offermann, D.; Ovchinnikov, V.; Pasley, J.; Patel, P. K.; Ping, Y.; Schumacher, D. W.; Stephens, R. B.; Tsui, Y. Y.; Wei, M. S.; Van Woerkom, L. D.

2009-09-01

Isochoric heating of inertially confined fusion plasmas by laser driven MeV electrons or protons is an area of great topical interest in the inertial confinement fusion community, particularly with respect to the fast ignition (FI) concept for initiating burn in a fusion capsule. In order to investigate critical aspects needed for a FI point design, experiments were performed to study 1) laser-to-electrons or protons conversion issues and 2) laser-cone interactions including prepulse effects. A large suite of diagnostics was utilized to study these important parameters. Using cone—wire surrogate targets it is found that pre-pulse levels on medium scale lasers such as Titan at Lawrence Livermore National Laboratory produce long scale length plasmas that strongly effect coupling of the laser to FI relevant electrons inside cones. The cone wall thickness also affects coupling to the wire. Conversion efficiency to protons has also been measured and modeled as a function of target thickness, material. Conclusions from the proton and electron source experiments will be presented. Recent advances in modeling electron transport and innovative target designs for reducing igniter energy and increasing gain curves will also be discussed. In conclusion, a program of study will be presented based on understanding the fundamental physics of the electron or proton source relevant to FI.

Breast cancer: updates and advances in 2016.

PubMed

Giordano, Sara B; Gradishar, William

2017-02-01

Approximately 1 in 8 US women (12%) will develop invasive breast cancer over the course of her lifetime. In 2016, an estimated 246,660 new cases of invasive breast cancer are expected to be diagnosed and approximately 40,450 would die as a result of it. The global burden of breast cancer exceeds all other cancers and the incidence is increasing. The heterogeneity of breast cancer makes it a challenging solid tumor to diagnose and treat. This review focuses on the recent advances in breast cancer therapy including hormonal treatment of metastatic breast cancer, targeting cyclin-dependent kinases (CDK) 4/6 in breast cancer, updates in targeting human epidermal growth factor receptor 2 (HER2) positive breast cancer, adaptive randomization trial design and cancer genetic risk assessment. Breast cancer is a heterogeneous disease and targeted therapy is improving the outcomes of women. The use of cyclin-dependent kinase inhibitors (CDK) 4/6 have demonstrated a substantial improvement in progression-free survival in the first line setting of metastatic hormone receptor positive breast cancer. And newer agents directed at HER2 continue to revolutionize HER2-positive breast cancer treatment. This review highlights the recent updates in breast cancer treatment, new concepts in clinical trial design and provides a current overview of cancer genetic risk assessment.

Versatile and Programmable DNA Logic Gates on Universal and Label-Free Homogeneous Electrochemical Platform.

PubMed

Ge, Lei; Wang, Wenxiao; Sun, Ximei; Hou, Ting; Li, Feng

2016-10-04

Herein, a novel universal and label-free homogeneous electrochemical platform is demonstrated, on which a complete set of DNA-based two-input Boolean logic gates (OR, NAND, AND, NOR, INHIBIT, IMPLICATION, XOR, and XNOR) is constructed by simply and rationally deploying the designed DNA polymerization/nicking machines without complicated sequence modulation. Single-stranded DNA is employed as the proof-of-concept target/input to initiate or prevent the DNA polymerization/nicking cyclic reactions on these DNA machines to synthesize numerous intact G-quadruplex sequences or binary G-quadruplex subunits as the output. The generated output strands then self-assemble into G-quadruplexes that render remarkable decrease to the diffusion current response of methylene blue and, thus, provide the amplified homogeneous electrochemical readout signal not only for the logic gate operations but also for the ultrasensitive detection of the target/input. This system represents the first example of homogeneous electrochemical logic operation. Importantly, the proposed homogeneous electrochemical logic gates possess the input/output homogeneity and share a constant output threshold value. Moreover, the modular design of DNA polymerization/nicking machines enables the adaptation of these homogeneous electrochemical logic gates to various input and output sequences. The results of this study demonstrate the versatility and universality of the label-free homogeneous electrochemical platform in the design of biomolecular logic gates and provide a potential platform for the further development of large-scale DNA-based biocomputing circuits and advanced biosensors for multiple molecular targets.

Synthesis of a multi-functional DNA nanosphere barcode system for direct cell detection.

PubMed

Han, Sangwoo; Lee, Jae Sung; Lee, Jong Bum

2017-09-28

Nucleic acid-based technologies have been applied to numerous biomedical applications. As a novel material for target detection, DNA has been used to construct a barcode system with a range of structures. This paper reports multi-functionalized DNA nanospheres (DNANSs) by rolling circle amplification (RCA) with several functionalized nucleotides. DNANSs with a barcode system were designed to exhibit fluorescence for coding enhanced signals and contain biotin for more functionalities, including targeting through the biotin-streptavidin (biotin-STA) interaction. Functionalized deoxynucleotide triphosphates (dNTPs) were mixed in the RCA process and functional moieties can be expressed on the DNANSs. The anti-epidermal growth factor receptor antibodies (anti-EGFR Abs) can be conjugated on DNANSs for targeting cancer cells specifically. As a proof of concept, the potential of the multi-functional DNANS barcode was demonstrated by direct cell detection as a simple detection method. The DNANS barcode provides a new route for the simple and rapid selective recognition of cancer cells.

Video camera system for locating bullet holes in targets at a ballistics tunnel

NASA Technical Reports Server (NTRS)

Burner, A. W.; Rummler, D. R.; Goad, W. K.

1990-01-01

A system consisting of a single charge coupled device (CCD) video camera, computer controlled video digitizer, and software to automate the measurement was developed to measure the location of bullet holes in targets at the International Shooters Development Fund (ISDF)/NASA Ballistics Tunnel. The camera/digitizer system is a crucial component of a highly instrumented indoor 50 meter rifle range which is being constructed to support development of wind resistant, ultra match ammunition. The system was designed to take data rapidly (10 sec between shoots) and automatically with little operator intervention. The system description, measurement concept, and procedure are presented along with laboratory tests of repeatability and bias error. The long term (1 hour) repeatability of the system was found to be 4 microns (one standard deviation) at the target and the bias error was found to be less than 50 microns. An analysis of potential errors and a technique for calibration of the system are presented.

A Network-Biology Informed Computational Drug Repositioning Strategy to Target Disease Risk Trajectories and Comorbidities of Peripheral Artery Disease.

PubMed

Shameer, Khader; Dow, Garrett; Glicksberg, Benjamin S; Johnson, Kipp W; Ze, Yi; Tomlinson, Max S; Readhead, Ben; Dudley, Joel T; Kullo, Iftikhar J

2018-01-01

Currently, drug discovery approaches focus on the design of therapies that alleviate an index symptom by reengineering the underlying biological mechanism in agonistic or antagonistic fashion. For example, medicines are routinely developed to target an essential gene that drives the disease mechanism. Therapeutic overloading where patients get multiple medications to reduce the primary and secondary side effect burden is standard practice. This single-symptom based approach may not be scalable, as we understand that diseases are more connected than random and molecular interactions drive disease comorbidities. In this work, we present a proof-of-concept drug discovery strategy by combining network biology, disease comorbidity estimates, and computational drug repositioning, by targeting the risk factors and comorbidities of peripheral artery disease, a vascular disease associated with high morbidity and mortality. Individualized risk estimation and recommending disease sequelae based therapies may help to lower the mortality and morbidity of peripheral artery disease.

Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women’s Health

PubMed Central

Thomas, Mark P.; Potter, Barry V. L.

2016-01-01

In 1994, following work from this laboratory, it was reported that estrone-3-O-sulfamate irreversibly inhibits a new potential hormone-dependent cancer target steroid sulfatase (STS). Subsequent drug discovery projects were initiated to develop the core aryl O-sulfamate pharmacophore that, over some twenty years, have led to steroidal and non-steroidal drugs in numerous pre-clinical and clinical trials, with promising results in oncology and women’s health, including endometriosis. Drugs have been designed to inhibit STS e.g. Irosustat, as innovative dual-targeting aromatase-steroid sulfatase inhibitors (DASIs) and as multi-targeting agents for hormone-independent tumors, such as the steroidal STX140 and non-steroidal counterparts, acting inter alia through microtubule disruption. The aryl sulfamate pharmacophore is highly versatile, operating via three distinct mechanisms of action and imbues attractive pharmaceutical properties. This Perspectives article gives a personal view of the work leading both to the therapeutic concepts and these drugs, their current status and how they might develop in the future. PMID:25992880

A Network-Biology Informed Computational Drug Repositioning Strategy to Target Disease Risk Trajectories and Comorbidities of Peripheral Artery Disease

PubMed Central

Shameer, Khader; Dow, Garrett; Glicksberg, Benjamin S.; Johnson, Kipp W.; Ze, Yi; Tomlinson, Max S.; Readhead, Ben; Dudley, Joel T.; Kullo, Iftikhar J.

2018-01-01

Currently, drug discovery approaches focus on the design of therapies that alleviate an index symptom by reengineering the underlying biological mechanism in agonistic or antagonistic fashion. For example, medicines are routinely developed to target an essential gene that drives the disease mechanism. Therapeutic overloading where patients get multiple medications to reduce the primary and secondary side effect burden is standard practice. This single-symptom based approach may not be scalable, as we understand that diseases are more connected than random and molecular interactions drive disease comorbidities. In this work, we present a proof-of-concept drug discovery strategy by combining network biology, disease comorbidity estimates, and computational drug repositioning, by targeting the risk factors and comorbidities of peripheral artery disease, a vascular disease associated with high morbidity and mortality. Individualized risk estimation and recommending disease sequelae based therapies may help to lower the mortality and morbidity of peripheral artery disease. PMID:29888052

Advanced controls for airbreathing engines, volume 3: Allison gas turbine

NASA Technical Reports Server (NTRS)

Bough, R. M.

1993-01-01

The application of advanced control concepts to airbreathing engines may yield significant improvements in aircraft/engine performance and operability. Screening studies of advanced control concepts for airbreathing engines were conducted by three major domestic aircraft engine manufacturers to determine the potential impact of concepts on turbine engine performance and operability. The purpose of the studies was to identify concepts which offered high potential yet may incur high research and development risk. A target suite of proposed advanced control concepts was formulated and evaluated in a two-phase study to quantify each concept's impact on desired engine characteristics. To aid in the evaluation specific aircraft/engine combinations were considered: a Military High Performance Fighter mission, a High Speed Civil Transport mission, and a Civil Tiltrotor mission. Each of the advanced control concepts considered in the study are defined and described. The concept potential impact on engine performance was determined. Relevant figures of merit on which to evaluate the concepts are determined. Finally, the concepts are ranked with respect to the target aircraft/engine missions. A final report describing the screening studies was prepared by each engine manufacturer. Volume 3 of these reports describes the studies performed by the Allison Gas Turbine Division.

Advanced control for airbreathing engines, volume 1: Pratt and Whitney

NASA Technical Reports Server (NTRS)

Ralph, J. A.

1993-01-01

The application of advanced control concepts to air breathing engines may yield significant improvements in aircraft/engine performance and operability. Screening studies of advanced control concepts for air breathing engines were conducted by three major domestic aircraft engine manufacturers to determine the potential impact of concepts on turbine engine performance and operability. The purpose of the studies was to identify concepts which offered high potential yet may incur high research and development risk. A target suite of proposed advanced control concepts was formulated and evaluated in a two phase study to quantify each concept's impact on desired engine characteristics. To aid in the evaluation specific aircraft/engine combinations were considered: a Military High Performance Fighter mission, a High Speed Civil Transport mission, and a Civil Tiltrotor mission. Each of the advanced control concepts considered in the study are defined and described. The concept potential impact on engine performance was determined. Relevant figures of merit on which to evaluate the concepts are determined. Finally, the concepts are ranked with respect to the target aircraft/engine missions. A final report describing the screening studies was prepared by each engine manufacturer. Volume 1 of these reports describes the studies performed by Pratt & Whitney.

Advanced control for airbreathing engines, volume 2: General Electric aircraft engines

NASA Technical Reports Server (NTRS)

Bansal, Indar

1993-01-01

The application of advanced control concepts to air breathing engines may yield significant improvements in aircraft/engine performance and operability. Screening studies of advanced control concepts for air breathing engines were conducted by three major domestic aircraft engine manufacturers to determine the potential impact of concepts on turbine engine performance and operability. The purpose of the studies was to identify concepts which offered high potential yet may incur high research and development risk. A target suite of proposed advanced control concepts was formulated and evaluated in a two phase study to quantify each concept's impact on desired engine characteristics. To aid in the evaluation specific aircraft/engine combinations were considered: a Military High Performance Fighter mission, a High Speed Civil Transport mission, and a Civil Tiltrotor mission. Each of the advanced control concepts considered in the study are defined and described. The concept potential impact on engine performance was determined. Relevant figures of merit on which to evaluate the concepts are determined. Finally, the concepts are ranked with respect to the target aircraft/engine missions. A final report describing the screening studies was prepared by each engine manufacturer. Volume 2 of these reports describes the studies performed by GE Aircraft Engines.

Reduction in bearing size due to superconductors in magnetic bearings

NASA Technical Reports Server (NTRS)

Rao, Dantam K.; Lewis, Paul; Dill, James F.

1991-01-01

A design concept that reduces the size of magnetic bearings is assessed. The small size will enable magnetic bearings to fit into limited available bearing volume of cryogenic machinery. The design concept, called SUPERC, uses (high Tc) superconductors or high-purity aluminum conductors in windings instead of copper. The relatively high-current density of these conductors reduces the slot radial thickness for windings, which reduces the size of the bearings. MTI developed a sizing program called SUPERC that translates the high-current density of these conductors into smaller sized bearings. This program was used to size a superconducting bearing to carry a 500 lb. load. The sizes of magnetic bearings needed by various design concepts are as follows: SUPERC design concept = 3.75 in.; magnet-bias design concept = 5.25 in.; and all electromagnet design concept = 7.0 in. These results indicate that the SUPERC design concept can significantly reduce the size of the bearing. This reduction, in turn, reduces the weight and yields a lighter bearing. Since the superconductors have inherently near-zero resistance, they are also expected to save power needed for operation considerably.

Peer Instruction Materials for Light and Spectra

NASA Astrophysics Data System (ADS)

Lee, Kevin M.; Siedell, C. M.; Prather, E. E.

2008-05-01

This poster will describe a new set of materials from the ClassAction project focusing on light and spectra. We will identify the concepts covered in the Light and Spectroscopy Concept Inventory (LSCI) which include the electromagnetic spectrum, Doppler shift, Wien's Law, Stefan-Boltzmann Law, and Kirchhoff's Laws. We will then specifically address how these concepts are targeted by the questions and resources of the ClassAction module. ClassAction is a collection of materials designed to enhance the metacognitive skills of college and high school introductory astronomy students by promoting interactive engagement and providing rapid feedback. The main focus is dynamic peer instruction questions that can be projected in the classroom. Instructors have the capability to recast these questions into alternate permutations based on their own preferences and formative feedback from the class. The questions can be easily selected from a FLASH computer database and are accompanied by outlines, graphics, and simulations which the instructor can utilize to provide feedback. These materials are publicly available at http://astro.unl.edu and are funded by NSF grant #0404988.

Clinical Impact Research – how to choose experimental or observational intervention study?

PubMed Central

Malmivaara, Antti

2016-01-01

Abstract Background: Interventions directed to individuals by health and social care systems should increase health and welfare of patients and customers. Aims: This paper aims to present and define a new concept Clinical Impact Research (CIR) and suggest which study design, either randomized controlled trial (RCT) (experimental) or benchmarking controlled trial (BCT) (observational) is recommendable and to consider the feasibility, validity, and generalizability issues in CIR. Methods: The new concept is based on a narrative review of the literature and on author’s idea that in intervention studies, there is a need to cover comprehensively all the main impact categories and their respective outcomes. The considerations on how to choose the most appropriate study design (RCT or BCT) were based on previous methodological studies on RCTs and BCTs and on author’s previous work on the concepts benchmarking controlled trial and system impact research (SIR). Results: The CIR covers all studies aiming to assess the impact for health and welfare of any health (and integrated social) care or public health intervention directed to an individual. The impact categories are accessibility, quality, equality, effectiveness, safety, and efficiency. Impact is the main concept, and within each impact category, both generic- and context-specific outcome measures are needed. CIR uses RCTs and BCTs. Conclusions: CIR should be given a high priority in medical, health care, and health economic research. Clinicians and leaders at all levels of health care can exploit the evidence from CIR. Key messagesThe new concept of Clinical Impact Research (CIR) is defined as a research field aiming to assess what are the impacts of healthcare and public health interventions targeted to patients or individuals.The term impact refers to all effects caused by the interventions, with particular emphasis on accessibility, quality, equality, effectiveness, safety, and efficiency. CIR uses two study designs: randomized controlled trials (RCTs) (experimental) and benchmarking controlled trials (BCTs) (observational). Suggestions on how to choose between RCT and BCT as the most suitable study design are presented.Simple way of determining the study question in CIR based on the PICO (patient, intervention, control intervention, outcome) framework is presented.CIR creates the scientific basis for clinical decisions. Clinicians and leaders at all levels of health care and those working for public health can use the evidence from CIR for the benefit of patients and the population. PMID:27494394

Clinical Impact Research - how to choose experimental or observational intervention study?

PubMed

Malmivaara, Antti

2016-11-01

Interventions directed to individuals by health and social care systems should increase health and welfare of patients and customers. This paper aims to present and define a new concept Clinical Impact Research (CIR) and suggest which study design, either randomized controlled trial (RCT) (experimental) or benchmarking controlled trial (BCT) (observational) is recommendable and to consider the feasibility, validity, and generalizability issues in CIR. The new concept is based on a narrative review of the literature and on author's idea that in intervention studies, there is a need to cover comprehensively all the main impact categories and their respective outcomes. The considerations on how to choose the most appropriate study design (RCT or BCT) were based on previous methodological studies on RCTs and BCTs and on author's previous work on the concepts benchmarking controlled trial and system impact research (SIR). The CIR covers all studies aiming to assess the impact for health and welfare of any health (and integrated social) care or public health intervention directed to an individual. The impact categories are accessibility, quality, equality, effectiveness, safety, and efficiency. Impact is the main concept, and within each impact category, both generic- and context-specific outcome measures are needed. CIR uses RCTs and BCTs. CIR should be given a high priority in medical, health care, and health economic research. Clinicians and leaders at all levels of health care can exploit the evidence from CIR. Key messages The new concept of Clinical Impact Research (CIR) is defined as a research field aiming to assess what are the impacts of healthcare and public health interventions targeted to patients or individuals. The term impact refers to all effects caused by the interventions, with particular emphasis on accessibility, quality, equality, effectiveness, safety, and efficiency. CIR uses two study designs: randomized controlled trials (RCTs) (experimental) and benchmarking controlled trials (BCTs) (observational). Suggestions on how to choose between RCT and BCT as the most suitable study design are presented. Simple way of determining the study question in CIR based on the PICO (patient, intervention, control intervention, outcome) framework is presented. CIR creates the scientific basis for clinical decisions. Clinicians and leaders at all levels of health care and those working for public health can use the evidence from CIR for the benefit of patients and the population.

A label-free DNA hairpin biosensor for colorimetric detection of target with suitable functional DNA partners.

PubMed

Nie, Ji; Zhang, De-Wen; Tie, Cai; Zhou, Ying-Lin; Zhang, Xin-Xiang

2013-11-15

The combination of aptamer and peroxidase-mimicking DNAzyme within a hairpin structure can form a functional DNA probe. The activities of both aptamer (as biorecognition element) and DNAzyme (as signal amplification element) are blocked via base pairing in the hairpin structure. The presence of target triggers the opening of the hairpin to form target/aptamer complex and releases G-quadruplex sequence which can generate amplified colorimetric signals. In this work, we elaborated a universal and simple procedure to design an efficient and sensitive hairpin probe with suitable functional DNA partners. A fill-in-the-blank process was developed for sequence design, and two key points including the pretreatment of the hairpin probe and the selection of suitable signal transducer sequence were proved to enhance the detection sensitivity. Cocaine was chosen as a model target for a proof of concept. A series of hairpins with different numbers of base pairs in the stem region were prepared. Hairpin-C10 with ten base pairs was screened out and a lowest detectable cocaine concentration of 5 μM by colorimetry was obtained. The proposed functional DNA hairpin showed good selectivity and satisfactory analysis in spiked biologic fluid. The whole "mix-and-measure" detection based on DNA hairpin without the need of immobilization and labeling was indicated to be time and labor saving. The strategy has potential to be transplanted into more smart hairpins toward other targets for general application in bioanalytical chemistry. Copyright © 2013 Elsevier B.V. All rights reserved.

In Vivo Tumor Targeting and Image-Guided Drug Delivery with Antibody-Conjugated, Radiolabeled Mesoporous Silica Nanoparticles

PubMed Central

Chen, Feng; Hong, Hao; Zhang, Yin; Valdovinos, Hector F.; Shi, Sixiang; Kwon, Glen S.; Theuer, Charles P.; Barnhart, Todd E.; Cai, Weibo

2013-01-01

Since the first use of biocompatible mesoporous silica (mSiO2) nanoparticles as drug delivery vehicles, in vivo tumor targeted imaging and enhanced anti-cancer drug delivery has remained a major challenge. In this work, we describe the development of functionalized mSiO2 nanoparticles for actively targeted positron emission tomography (PET) imaging and drug delivery in 4T1 murine breast tumor-bearing mice. Our structural design involves the synthesis, surface functionalization with thiol groups, PEGylation, TRC105 antibody (specific for CD105/endoglin) conjugation, and 64Cu-labeling of uniform 80 nm sized mSiO2 nanoparticles. Systematic in vivo tumor targeting studies clearly demonstrated that 64Cu-NOTA-mSiO2-PEG-TRC105 could accumulate prominently at the 4T1 tumor site via both the enhanced permeability and retention effect and TRC105-mediated binding to tumor vasculature CD105. As a proof-of-concept, we also demonstrated successful enhanced tumor targeted delivery of doxorubicin (DOX) in 4T1 tumor-bearing mice after intravenous injection of DOX-loaded NOTA-mSiO2-PEG-TRC105, which holds great potential for future image-guided drug delivery and targeted cancer therapy. PMID:24083623