Science.gov

Sample records for ras design simulation

  1. Design and Performance of McRas in SCMs and GEOS I/II GCMs

    NASA Technical Reports Server (NTRS)

    Sud, Yogesh C.; Einaudi, Franco (Technical Monitor)

    2000-01-01

    The design of a prognostic cloud scheme named McRAS (Microphysics of clouds with Relaxed Arakawa-Schubert Scheme) for general circulation models (GCMs) will be discussed. McRAS distinguishes three types of clouds: (1) convective, (2) stratiform, and (3) boundary-layer types. The convective clouds transform and merge into stratiform clouds on an hourly time-scale, while the boundary-layer clouds merge into the stratiform clouds instantly. The cloud condensate converts into precipitation following the auto-conversion equations of Sundqvist that contain a parametric adaptation for the Bergeron-Findeisen process of ice crystal growth and collection of cloud condensate by precipitation. All clouds convect, advect, as well as diffuse both horizontally and vertically with a fully interactive cloud-microphysics throughout the life-cycle of the cloud, while the optical properties of clouds are derived from the statistical distribution of hydrometeors and idealized cloud geometry. An evaluation of McRAS in a single column model (SCM) with the GATE Phase III and 5-ARN CART datasets has shown that together with the rest of the model physics, McRAS can simulate the observed temperature, humidity, and precipitation without many systematic errors. The time history and time mean incloud water and ice distribution, fractional cloudiness, cloud optical thickness, origin of precipitation in the convective anvil and towers, and the convective updraft and downdraft velocities and mass fluxes all show a realistic behavior. Performance of McRAS in GEOS 11 GCM shows several satisfactory features but some of the remaining deficiencies suggest need for additional research involving convective triggers and inhibitors, provision for continuously detraining updraft, a realistic scheme for cumulus gravity wave drag, and refinements to physical conditions for ascertaining cloud detrainment level.

  2. Terahertz Gyrotrons at IAP RAS: Status and New Designs

    NASA Astrophysics Data System (ADS)

    Bratman, V. L.; Glyavin, M. Yu.; Kalynov, Yu. K.; Litvak, A. G.; Luchinin, A. G.; Savilov, A. V.; Zapevalov, V. E.

    2011-03-01

    Powerful gyrotrons with radiation frequencies in the range 0.33-0.65 THz were demonstrated at the IAP as early as in the 1970-1980s. This trend has recently been renewed in connection with a significant increase in interest in terahertz frequency range. In the course of new experiments, the radiation frequency of pulsed gyrotrons was increased up to 1.3 THz and 1 THz at the fundamental and third cyclotron harmonics, respectively. In addition, gyrotrons operated in CW regime with a frequency of 0.3 THz for technological applications (in collaboration with the University of Fukui, Japan) and 0.26 THz for the dynamic nuclear polarization at a high-field NMR were implemented. Designs of a pulsed fundamental-harmonic gyrotron with MW-level power at 0.3 THz and a CW kW-level third-harmonic gyrotron with a frequency of 0.4 THz are currently developed. Estimates show that modern techniques for the creation of strong magnetic fields now make it possible to realize gyrotrons with an operating frequency at least up to 1-1.5 THz. Such generators utilize a relatively low particle energy and can provide higher average power than the existing FELs.

  3. Flexibility of Ras Lipid Modifications Studied by 2H Solid-State NMR and Molecular Dynamics Simulations

    PubMed Central

    Vogel, Alexander; Tan, Kui-Thong; Waldmann, Herbert; Feller, Scott E.; Brown, Michael F.; Huster, Daniel

    2007-01-01

    Human posttranslationally modified N-ras oncogenes are known to be implicated in numerous human cancers. Here, we applied a combination of experimental and computational techniques to determine structural and dynamical details of the lipid chain modifications of an N-ras heptapeptide in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) membranes. Experimentally, 2H NMR spectroscopy was used to study oriented membranes that incorporated ras heptapeptides with two covalently attached perdeuterated hexadecyl chains. Atomistic molecular dynamics simulations of the same system were carried out over 100 ns including 60 DMPC and 4 ras molecules. Several structural and dynamical experimental parameters could be directly compared to the simulation. Experimental and simulated 2H NMR order parameters for the methylene groups of the ras lipid chains exhibited a systematic difference attributable to the absence of collective motions in the simulation and to geometrical effects. In contrast, experimental 2H NMR spin-lattice relaxation rates for Zeeman order were well reproduced in the simulation. The lack of slower collective motions in the simulation did not appreciably influence the relaxation rates at a Larmor frequency of 115.1 MHz. The experimental angular dependence of the 2H NMR relaxation rates with respect to the external magnetic field was also relatively well simulated. These relaxation rates showed a weak angular dependence, suggesting that the lipid modifications of ras are very flexible and highly mobile in agreement with the low order parameters. To quantify these results, the angular dependence of the 2H relaxation rates was calculated by an analytical model considering both molecular and collective motions. Peptide dynamics in the membrane could be modeled by an anisotropic diffusion tensor with principal values of D‖ = 2.1 × 109 s−1 and D⊥ = 4.5 × 105 s−1. A viscoelastic fitting parameter describing the membrane elasticity, viscosity, and temperature

  4. RAS Insight

    Cancer.gov

    David Heimbrook, now CEO of the Frederick National Laboratory for Cancer Research, played a major role in a large pharma as it tried to develop an anti-RAS drug. Lessons from that failure inform the RAS Initiative today.

  5. Design, dimensioning, and performance of a research facility for studies on the requirements of fish in RAS environments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recirculating aquaculture systems (RAS) are increasingly being used for Atlantic salmon smolt production. However, knowledge of how the RAS environment affects welfare and performance of Atlantic salmon is limited. For instance, safe limits for chronic exposure to typical compounds in RAS, such as N...

  6. Mutation-Specific RAS Oncogenicity Explains N-RAS Codon 61 Selection in Melanoma

    PubMed Central

    Burd, Christin E.; Liu, Wenjin; Huynh, Minh V.; Waqas, Meriam A.; Gillahan, James E.; Clark, Kelly S.; Fu, Kailing; Martin, Brit L.; Jeck, William R.; Souroullas, George P.; Darr, David B.; Zedek, Daniel C.; Miley, Michael J.; Baguley, Bruce C.; Campbell, Sharon L.

    2014-01-01

    N-RAS mutation at codon 12, 13 or 61 is associated with transformation; yet, in melanoma, such alterations are nearly exclusive to codon 61. Here, we compared the melanoma susceptibility of an N-RasQ61R knock-in allele to similarly designed K-RasG12D and N-RasG12D alleles. With concomitant p16INK4a inactivation, K-RasG12D or N-RasQ61R expression efficiently promoted melanoma in vivo, whereas N-RasG12D did not. Additionally, N-RasQ61R mutation potently cooperated with Lkb1/Stk11 loss to induce highly metastatic disease. Functional comparisons of N-RasQ61R and N-RasG12D revealed little difference in the ability of these proteins to engage PI3K or RAF. Instead, N-RasQ61R showed enhanced nucleotide binding, decreased intrinsic GTPase activity and increased stability when compared to N-RasG12D. This work identifies a faithful model of human N-RAS mutant melanoma, and suggests that the increased melanomagenecity of N-RasQ61R over N-RasG12D is due to heightened abundance of the active, GTP-bound form rather than differences in the engagement of downstream effector pathways. PMID:25252692

  7. Ras and GTPase-activating protein (GAP) drive GTP into a precatalytic state as revealed by combining FTIR and biomolecular simulations.

    PubMed

    Rudack, Till; Xia, Fei; Schlitter, Jürgen; Kötting, Carsten; Gerwert, Klaus

    2012-09-18

    Members of the Ras superfamily regulate many cellular processes. They are down-regulated by a GTPase reaction in which GTP is cleaved into GDP and P(i) by nucleophilic attack of a water molecule. Ras proteins accelerate GTP hydrolysis by a factor of 10(5) compared to GTP in water. GTPase-activating proteins (GAPs) accelerate hydrolysis by another factor of 10(5) compared to Ras alone. Oncogenic mutations in Ras and GAPs slow GTP hydrolysis and are a factor in many cancers. Here, we elucidate in detail how this remarkable catalysis is brought about. We refined the protein-bound GTP structure and protein-induced charge shifts within GTP beyond the current resolution of X-ray structural models by combining quantum mechanics and molecular mechanics simulations with time-resolved Fourier-transform infrared spectroscopy. The simulations were validated by comparing experimental and theoretical IR difference spectra. The reactant structure of GTP is destabilized by Ras via a conformational change from a staggered to an eclipsed position of the nonbridging oxygen atoms of the γ- relative to the β-phosphates and the further rotation of the nonbridging oxygen atoms of α- relative to the β- and γ-phosphates by GAP. Further, the γ-phosphate becomes more positive although two of its oxygen atoms remain negative. This facilitates the nucleophilic attack by the water oxygen at the phosphate and proton transfer to the oxygen. Detailed changes in geometry and charge distribution in the ligand below the resolution of X-ray structure analysis are important for catalysis. Such high resolution appears crucial for the understanding of enzyme catalysis.

  8. The specific vibrational modes of GTP in solution and bound to Ras: a detailed theoretical analysis by QM/MM simulations.

    PubMed

    Xia, Fei; Rudack, Till; Kötting, Carsten; Schlitter, Jürgen; Gerwert, Klaus

    2011-12-28

    The hydrolysis of guanosine triphosphate (GTP) in general, and especially by GTPases like the Ras protein, is in the focus of biological investigations. A huge amount of experimental data from Fourier-transformed infrared studies is currently available, and many vibrational bands of free GTP, GTP·Mg(2+), and Ras·GTP·Mg(2+) in solution have been assigned by isotopic labeling. In the Ras environment, bands between 800 cm(-1) and 1300 cm(-1) have already been assigned, but not those below 800 cm(-1). The combination of quantum and molecular mechanics (QM/MM) methods takes the quantum effects for selected relevant atoms into account. This provides structural details, vibrational frequencies and electron distributions of the region of interest. We therefore used MM and QM/MM simulations to investigate the normal vibrational modes of GTP, GTP·Mg(2+), and Ras·GTP·Mg(2+) in solution, and assigned the vibrational frequencies for each normal vibration mode. In this study, the quantum box contains the nucleoside and the Mg(2+). The comparison of calculated and experimental vibrational spectra provides a very good control for the quality of the calculations. Structurally, MM and QM/MM simulations reveal a stable tridentate coordination of the Mg(2+) by GTP in water, and a stable bidentate coordination by GTP in complex with Ras. For validation, we compare the calculated frequencies and isotopic shifts with the experimental results available in the range of 800 cm(-1) to 1300 cm(-1). For the first time we suggest band assignments of the vibrational modes below 800 cm(-1) by comparison of calculated and experimental spectra.

  9. The RAS Initiative

    Cancer.gov

    NCI established the RAS Initiative to explore innovative approaches for attacking the proteins encoded by mutant forms of RAS genes and to ultimately create effective, new therapies for RAS-related cancers.

  10. Design, Evaluation and GCM-Performance of a New Parameterization for Microphysics of Clouds with Relaxed Arakawa-Schubert Scheme (McRas)

    NASA Technical Reports Server (NTRS)

    Sud, Y. C.; Walker, G. K.

    1998-01-01

    A prognostic cloud scheme named McRAS (Microphysics of clouds with Relaxed Arakawa-Schubert Scheme) was developed with the aim of improving cloud-microphysics, and cloud-radiation interactions in GCMs. McRAS distinguishes convective, stratiform, and boundary-layer clouds. The convective clouds merge into stratiform clouds on an hourly time-scale, while the boundary-layer clouds do so instantly. The cloud condensate transforms into precipitation following the auto-conversion relations of Sundqvist that contain a parametric adaptation for the Bergeron-Findeisen process of ice crystal growth and collection of cloud condensate by precipitation. All clouds convect, advect, and diffuse both horizontally and vertically with a fully active cloud-microphysics throughout its life-cycle, while the optical properties of clouds are derived from the statistical distribution of hydrometeors and idealized cloud geometry. An evaluation of McRAS in a single column model (SCM) with the GATE Phase III data has shown that McRAS can simulate the observed temperature, humidity, and precipitation without discernible systematic errors. An evaluation with the ARM-CART SCM data in a cloud model intercomparison exercise shows reasonable but not an outstanding accurate simulation. Such a discrepancy is common to almost all models and is related, in part, to the input data quality. McRAS was implemented in the GEOS II GCM. A 50 month integration that was initialized with the ECMWF analysis of observations for January 1, 1987 and forced with the observed sea-surface temperatures and sea-ice distribution and vegetation properties (biomes, and soils), with prognostic soil moisture, snow-cover, and hydrology showed a very realistic simulation of cloud process, incloud water and ice, and cloud-radiative forcing (CRF). The simulated ITCZ showed a realistic time-mean structure and seasonal cycle, while the simulated CRF showed sensitivity to vertical distribution of cloud water which can be easily

  11. Hydro/Engineering Geophysical Parameters and Design Response Spectrum for Sustainable Development in Ras Muhammed National Park, Sinai

    NASA Astrophysics Data System (ADS)

    Khalil, Mohamed H.; Gamal, Mohamed A.

    2016-06-01

    The Egyptian government is preparing a sustainable development master plan for the Ras Muhammed National Park (RMNP), south Sinai. Noteworthy, the scarcity of the freshwater resources and close proximity to the active seismic zones of the Gulf of Aqaba implicate geophysical investigations for the fresh groundwater aquifers and construct a design response spectrum, respectively. Accordingly, 14 VESs, hydro/engineering geophysical analysis, pumping tests, downhole seismic test, a design response spectrum for buildings, and borehole data were carried out in the study area. The unconfined freshwater aquifer was effectively depicted with true resistivities, thickness, and EC ranged from 56 to 135 Ω m, 11 to 112 m, and 1.4 to 7.1 mS/m, respectively. The Northeastern part was characterized by higher aquifer potentiality, where coarser grains size, highest thickness (112 m), high true resistivity (135 Ω m), groundwater flow (0.074 m3/day), tortuosity (1.293-1.312), formation resistivity factor (4.1-4.6), and storativity (0.281-0.276). An increase in pumping rate was accompanied by an increase in well loss, increase in aquifer losses, decrease in well specific capacity, and decrease in well efficiency. Design response spectrum prognosticated the short buildings (<7 floors) in RMNP to be suffering from a high peak horizontal acceleration and shear forces for acceleration between 0.25 and 0.35 g. Therefore, appropriate detailing of shear reinforcement is indispensable to reduce the risk of structural damages at RMNP.

  12. Combined Rational Design and a High Throughput Screening Platform for Identifying Chemical Inhibitors of a Ras-activating Enzyme*

    PubMed Central

    Evelyn, Chris R.; Biesiada, Jacek; Duan, Xin; Tang, Hong; Shang, Xun; Papoian, Ruben; Seibel, William L.; Nelson, Sandra; Meller, Jaroslaw; Zheng, Yi

    2015-01-01

    The Ras family small GTPases regulate multiple cellular processes, including cell growth, survival, movement, and gene expression, and are intimately involved in cancer pathogenesis. Activation of these small GTPases is catalyzed by a special class of enzymes, termed guanine nucleotide exchange factors (GEFs). Herein, we developed a small molecule screening platform for identifying lead hits targeting a Ras GEF enzyme, SOS1. We employed an ensemble structure-based virtual screening approach in combination with a multiple tier high throughput experimental screen utilizing two complementary fluorescent guanine nucleotide exchange assays to identify small molecule inhibitors of GEF catalytic activity toward Ras. From a library of 350,000 compounds, we selected a set of 418 candidate compounds predicted to disrupt the GEF-Ras interaction, of which dual wavelength GDP dissociation and GTP-loading experimental screening identified two chemically distinct small molecule inhibitors. Subsequent biochemical validations indicate that they are capable of dose-dependently inhibiting GEF catalytic activity, binding to SOS1 with micromolar affinity, and disrupting GEF-Ras interaction. Mutagenesis studies in conjunction with structure-activity relationship studies mapped both compounds to different sites in the catalytic pocket, and both inhibited Ras signaling in cells. The unique screening platform established here for targeting Ras GEF enzymes could be broadly useful for identifying lead inhibitors for a variety of small GTPase-activating GEF reactions. PMID:25825487

  13. Combined rational design and a high throughput screening platform for identifying chemical inhibitors of a Ras-activating enzyme.

    PubMed

    Evelyn, Chris R; Biesiada, Jacek; Duan, Xin; Tang, Hong; Shang, Xun; Papoian, Ruben; Seibel, William L; Nelson, Sandra; Meller, Jaroslaw; Zheng, Yi

    2015-05-15

    The Ras family small GTPases regulate multiple cellular processes, including cell growth, survival, movement, and gene expression, and are intimately involved in cancer pathogenesis. Activation of these small GTPases is catalyzed by a special class of enzymes, termed guanine nucleotide exchange factors (GEFs). Herein, we developed a small molecule screening platform for identifying lead hits targeting a Ras GEF enzyme, SOS1. We employed an ensemble structure-based virtual screening approach in combination with a multiple tier high throughput experimental screen utilizing two complementary fluorescent guanine nucleotide exchange assays to identify small molecule inhibitors of GEF catalytic activity toward Ras. From a library of 350,000 compounds, we selected a set of 418 candidate compounds predicted to disrupt the GEF-Ras interaction, of which dual wavelength GDP dissociation and GTP-loading experimental screening identified two chemically distinct small molecule inhibitors. Subsequent biochemical validations indicate that they are capable of dose-dependently inhibiting GEF catalytic activity, binding to SOS1 with micromolar affinity, and disrupting GEF-Ras interaction. Mutagenesis studies in conjunction with structure-activity relationship studies mapped both compounds to different sites in the catalytic pocket, and both inhibited Ras signaling in cells. The unique screening platform established here for targeting Ras GEF enzymes could be broadly useful for identifying lead inhibitors for a variety of small GTPase-activating GEF reactions.

  14. Characterization of a third ras gene, rasB, that is expressed throughout the growth and development of Dictyostelium discoideum.

    PubMed

    Daniel, J; Spiegelman, G B; Weeks, G

    1993-04-01

    Previous reports have indicated that the cellular slime mold Dictyostelium discoideum possesses two ras genes (rasG and rasD) and one rap gene (rap1). All three genes are developmentally regulated, with each showing a different pattern of transcription during the Dictyostelium life cycle. To establish whether there are additional ras or rap genes in Dictyostelium, we used degenerate oligonucleotide primers to the highly conserved GTP-binding domains and both ras- and rap-unique sequences to amplify products from cDNA using the polymerase chain reaction (PCR). No additional rap genes were amplified, but a fragment whose nucleotide sequence predicted a novel ras gene was isolated. Using this PCR product as a probe, a full-length cDNA clone was isolated and sequenced. Its deduced amino acid sequence predicted a 197 amino acid protein that is 71% and 68% identical to RasG and RasD respectively. The new ras gene contains the conserved Ras-specific effector domain, the conserved binding site for the Ras-specific Y13-259 monoclonal antibody, and shows greater sequence similarity to the human H-Ras protein than to any other mammalian Ras protein. In view of this high level of identity to the ras gene subfamily, we have designated this gene rasB. Northern blot analysis has shown that rasB is developmentally regulated with maximum levels of a single 950-bp message detected during vegetative growth and the first 8 h of development.

  15. Integrated Product Design Simulation

    DTIC Science & Technology

    2007-11-02

    scenario barriers application DOME world LABVIEW plugin Computer with I/O card Programmable logic controller Machine tool world Application Manufacturing object module: MOM design context need concept scenario barriers application

  16. About the RAS Initiative

    Cancer.gov

    The RAS Initiative, a "hub and spoke" model, connects researchers to better understand and target the more than 30% of cancers driven by mutations in RAS genes. Includes oversight and contact information.

  17. RAS Initiative - Community Outreach

    Cancer.gov

    Through community and technical collaborations, workshops and symposia, and the distribution of reference reagents, the RAS Initiative seeks to increase the sharing of knowledge and resources essential to defeating cancers caused by mutant RAS genes.

  18. RAS Initiative - Events

    Cancer.gov

    The NCI RAS Initiative has organized multiple events with outside experts to discuss how the latest scientific and technological breakthroughs can be applied to discover vulnerabilities in RAS-driven cancers.

  19. RAS - Screens & Assays

    Cancer.gov

    A primary goal of the RAS Initiative is to develop assays for RAS activity, localization, and signaling and adapt those assays so they can be used for finding new drug candidates. Explore the work leading to highly validated screening protocols.

  20. RAS - Target Identification - Informatics

    Cancer.gov

    The RAS Informatics lab group develops tools to track and analyze “big data” from the RAS Initiative, as well as analyzes data from external projects. By integrating internal and external data, this group helps improve understanding of RAS-driven cancers.

  1. Synthesis, biological, and biophysical studies of DAG-indololactones designed as selective activators of RasGRP.

    PubMed

    Garcia, Lia C; Donadío, Lucia Gandolfi; Mann, Ella; Kolusheva, Sofiya; Kedei, Noemi; Lewin, Nancy E; Hill, Colin S; Kelsey, Jessica S; Yang, Jing; Esch, Timothy E; Santos, Marina; Peach, Megan L; Kelley, James A; Blumberg, Peter M; Jelinek, Raz; Marquez, Victor E; Comin, Maria J

    2014-06-15

    The development of selective agents capable of discriminating between protein kinase C (PKC) isoforms and other diacylglycerol (DAG)-responsive C1 domain-containing proteins represents an important challenge. Recent studies have highlighted the role that Ras guanine nucleotide-releasing protein (RasGRP) isoforms play both in immune responses as well as in the development of prostate cancer and melanoma, suggesting that the discovery of selective ligands could have potential therapeutic value. Thus far, the N-methyl-substituted indololactone 1 is the agonist with the highest reported potency and selectivity for RasGRP relative to PKC. Here we present the synthesis, binding studies, cellular assays and biophysical analysis of interactions with model membranes of a family of regioisomers of 1 (compounds 2-5) that differ in the position of the linkage between the indole ring and the lactone moiety. These structural variations were studied to explore the interaction of the active complex (C1 domain-ligand) with cellular membranes, which is believed to be an important factor for selectivity in the activation of DAG-responsive C1 domain containing signaling proteins. All compounds were potent and selective activators of RasGRP when compared to PKCα with selectivities ranging from 6 to 65 fold. However, the parent compound 1 was appreciably more selective than any of the other isomers. In intact cells, modest differences in the patterns of translocation of the C1 domain targets were observed. Biophysical studies using giant vesicles as model membranes did show substantial differences in terms of molecular interactions impacting lipid organization, dynamics and membrane insertion. However, these differences did not yield correspondingly large changes in patterns of biological response, at least for the parameters examined.

  2. Synthesis, Biological, and Biophysical Studies of DAG-indololactones Designed as Selective Activators of RasGRP

    PubMed Central

    Garcia, Lia C.; Donadío, Lucia Gandolfi; Mann, Ella; Kolusheva, Sofiya; Kedei, Noemi; Lewin, Nancy E.; Hill, Colin S.; Kelsey, Jessica S.; Yang, Jing; Esch, Timothy E.; Santos, Marina; Peach, Megan L.; Kelley, James A.; Blumberg, Peter M.; Jelinek, Raz; Marquez, Victor E.; Comin, Maria J.

    2014-01-01

    The development of selective agents capable of discriminating between protein kinase C (PKC) isoforms and other diacylglycerol (DAG)-responsive C1 domain-containing proteins represents an important challenge. Recent studies have highlighted the role that Ras guanine nucleotide-releasing protein (RasGRP) isoforms play both in immune responses as well as in the development of prostate cancer and melanoma, suggesting that the discovery of selective ligands could have potential therapeutic value. Thus far, the N-methyl-substituted indololactone 1 is the agonist with the highest reported potency and selectivity for RasGRP relative to PKC. Here we present the synthesis, binding studies, cellular assays and biophysical analysis of interactions with model membranes of a family of regioisomers of 1 (compounds 2 to 5) that differ in the position of the linkage between the indole ring and the lactone moiety. These structural variations were studied to explore the interaction of the active complex (C1 domain-ligand) with cellular membranes, which is believed to be an important factor for selectivity in the activation of DAG-responsive C1 domain containing signaling proteins. All compounds were potent and selective activators of RasGRP when compared to PKCα with selectivities ranging from 6 to 65 fold. However, the parent compound 1 was appreciably more selective than any of the other isomers. In intact cells, modest differences in the patterns of translocation of the C1 domain targets were observed. Biophysical studies using giant vesicles as model membranes did show substantial differences in terms of molecular interactions impacting lipid organization, dynamics and membrane insertion. However, these differences did not yield correspondingly large changes in patterns of biological response, at least for the parameters examined. PMID:24794745

  3. Process simulation and design '94

    SciTech Connect

    Not Available

    1994-06-01

    This first-of-a-kind report describes today's process simulation and design technology for specific applications. It includes process names, diagrams, applications, descriptions, objectives, economics, installations, licensors, and a complete list of process submissions. Processes include: alkylation, aromatics extraction, catalytic reforming, cogeneration, dehydration, delayed coking, distillation, energy integration, catalytic cracking, gas sweetening, glycol/methanol injection, hydrocracking, NGL recovery and stabilization, solvent dewaxing, visbreaking. Equipment simulations include: amine plant, ammonia plant, heat exchangers, cooling water network, crude preheat train, crude unit, ethylene furnace, nitrogen rejection unit, refinery, sulfur plant, and VCM furnace. By-product processes include: olefins, polyethylene terephthalate, and styrene.

  4. Spinning Rocket Simulator Turntable Design

    NASA Technical Reports Server (NTRS)

    Miles, Robert W.

    2001-01-01

    Contained herein is the research and data acquired from the Turntable Design portion of the Spinning Rocket Simulator (SRS) project. The SRS Project studies and eliminates the effect of coning on thrust-propelled spacecraft. This design and construction of the turntable adds a structural support for the SRS model and two degrees of freedom. The two degrees of freedom, radial and circumferential, will help develop a simulated thrust force perpendicular to the plane of the spacecraft model while undergoing an unstable coning motion. The Turntable consists of a ten-foot linear track mounted to a sprocket and press-fit to a thrust bearing. A two-inch high column grounded by a Triangular Baseplate supports this bearing and houses the slip rings and pressurized, air-line swivel. The thrust bearing allows the entire system to rotate under the moment applied through the chain-driven sprocket producing a circumferential degree of freedom. The radial degree of freedom is given to the model through the helically threaded linear track. This track allows the Model Support and Counter Balance to simultaneously reposition according to the coning motion of the Model. Two design factors that hinder the linear track are bending and twist due to torsion. A Standard Aluminum "C" channel significantly reduces these two deflections. Safety considerations dictate the design of all the components involved in this project.

  5. Xyce parallel electronic simulator design.

    SciTech Connect

    Thornquist, Heidi K.; Rankin, Eric Lamont; Mei, Ting; Schiek, Richard Louis; Keiter, Eric Richard; Russo, Thomas V.

    2010-09-01

    This document is the Xyce Circuit Simulator developer guide. Xyce has been designed from the 'ground up' to be a SPICE-compatible, distributed memory parallel circuit simulator. While it is in many respects a research code, Xyce is intended to be a production simulator. As such, having software quality engineering (SQE) procedures in place to insure a high level of code quality and robustness are essential. Version control, issue tracking customer support, C++ style guildlines and the Xyce release process are all described. The Xyce Parallel Electronic Simulator has been under development at Sandia since 1999. Historically, Xyce has mostly been funded by ASC, the original focus of Xyce development has primarily been related to circuits for nuclear weapons. However, this has not been the only focus and it is expected that the project will diversify. Like many ASC projects, Xyce is a group development effort, which involves a number of researchers, engineers, scientists, mathmaticians and computer scientists. In addition to diversity of background, it is to be expected on long term projects for there to be a certain amount of staff turnover, as people move on to different projects. As a result, it is very important that the project maintain high software quality standards. The point of this document is to formally document a number of the software quality practices followed by the Xyce team in one place. Also, it is hoped that this document will be a good source of information for new developers.

  6. Simulation of a Wall-Bounded Flow using a Hybrid LES/RAS Approach with Turbulence Recycling

    NASA Technical Reports Server (NTRS)

    Quinlan, Jesse R.; Mcdaniel, James; Baurle, Robert A.

    2012-01-01

    Simulations of a supersonic recessed-cavity flow are performed using a hybrid large-eddy/ Reynolds-averaged simulation approach utilizing an inflow turbulence recycling procedure and hybridized inviscid flux scheme. Calorically perfect air enters the three-dimensional domain at a free stream Mach number of 2.92. Simulations are performed to assess grid sensitivity of the solution, efficacy of the turbulence recycling, and effect of the shock sensor used with the hybridized inviscid flux scheme. Analysis of the turbulent boundary layer upstream of the rearward-facing step for each case indicates excellent agreement with theoretical predictions. Mean velocity and pressure results are compared to Reynolds-averaged simulations and experimental data for each case, and these comparisons indicate good agreement on the finest grid. Simulations are repeated on a coarsened grid, and results indicate strong grid density sensitivity. The effect of turbulence recycling on the solution is illustrated by performing coarse grid simulations with and without inflow turbulence recycling. Two shock sensors, one of Ducros and one of Larsson, are assessed for use with the hybridized inviscid flux reconstruction scheme.

  7. Sensitivity of Cirrus and Mixed-phase Clouds to the Ice Nuclei Spectra in McRAS-AC: Single Column Model Simulations

    NASA Technical Reports Server (NTRS)

    Betancourt, R. Morales; Lee, D.; Oreopoulos, L.; Sud, Y. C.; Barahona, D.; Nenes, A.

    2012-01-01

    The salient features of mixed-phase and ice clouds in a GCM cloud scheme are examined using the ice formation parameterizations of Liu and Penner (LP) and Barahona and Nenes (BN). The performance of LP and BN ice nucleation parameterizations were assessed in the GEOS-5 AGCM using the McRAS-AC cloud microphysics framework in single column mode. Four dimensional assimilated data from the intensive observation period of ARM TWP-ICE campaign was used to drive the fluxes and lateral forcing. Simulation experiments where established to test the impact of each parameterization in the resulting cloud fields. Three commonly used IN spectra were utilized in the BN parameterization to described the availability of IN for heterogeneous ice nucleation. The results show large similarities in the cirrus cloud regime between all the schemes tested, in which ice crystal concentrations were within a factor of 10 regardless of the parameterization used. In mixed-phase clouds there are some persistent differences in cloud particle number concentration and size, as well as in cloud fraction, ice water mixing ratio, and ice water path. Contact freezing in the simulated mixed-phase clouds contributed to transfer liquid to ice efficiently, so that on average, the clouds were fully glaciated at T approximately 260K, irrespective of the ice nucleation parameterization used. Comparison of simulated ice water path to available satellite derived observations were also performed, finding that all the schemes tested with the BN parameterization predicted 20 average values of IWP within plus or minus 15% of the observations.

  8. RAS Ordinary Meeting

    NASA Astrophysics Data System (ADS)

    2014-08-01

    Here are summarized talks from the February and March RAS Ordinary Meetings. The February meeting also enjoyed the Eddington Lecture from Prof. Lisa Kewley (Australian National University) on galaxy evolution in 3D.

  9. Automated Simulation For Analysis And Design

    NASA Technical Reports Server (NTRS)

    Cantwell, E.; Shenk, Tim; Robinson, Peter; Upadhye, R.

    1992-01-01

    Design Assistant Workstation (DAWN) software being developed to facilitate simulation of qualitative and quantitative aspects of behavior of life-support system in spacecraft, chemical-processing plant, heating and cooling system of large building, or any of variety of systems including interacting process streams and processes. Used to analyze alternative design scenarios or specific designs of such systems. Expert system will automate part of design analysis: reason independently by simulating design scenarios and return to designer with overall evaluations and recommendations.

  10. Fully conservative coupling of HEC-1 RAS with MODFLOW to simulate stream-aquifer interactions in a drainage basin 1960

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This work describes the application of a methodology designed to improve the representation of water surface profiles along open drain channels within the framework of regional groundwater modeling. The proposed methodology employs an iterative procedure that combines two public domain computational...

  11. Functional overlap of the dictyostelium RasG, RasD and RasB proteins.

    PubMed

    Khosla, M; Spiegelman, G B; Insall, R; Weeks, G

    2000-04-01

    Disruption of the rasG gene in Dictyostelium discoideum results in several distinct phenotypes: a defect in cytokinesis, reduced motility and reduced growth. Reintroduction of the rasG gene restores all of the properties of the rasG(-) cells to those of the wild type. To determine whether the defects are due to impaired interactions with a single or multiple downstream effectors, we tested the ability of the highly related but non identical Dictyostelium ras genes, rasD and rasB, to rescue the defects. Introduction of the rasD gene under the control of the rasG promoter into rasG null (rasG(-)) cells corrected all phenotypes except the motility defect, suggesting that motility is regulated by a RasG mediated pathway that is different to those regulating growth or cytokinesis. Western blot analysis of RasD protein levels revealed that vegetative rasG(- )cells contained considerably more protein than the parental AX-3 cells, suggesting that RasD protein levels are negatively regulated in vegetative cells by RasG. The level of RasD was enhanced when the rasD gene was introduced under the control of the rasG promoter, and this increase in protein is presumably responsible for the reversal of the growth and cytokinesis defects of the rasG(- )cells. Thus, RasD protein levels are controlled by the level of RasG, but not by the level of RasD. Introduction of the rasB gene under the control of the rasG promoter into rasG(-) cells produced a complex phenotype. The transformants were extremely small and mononucleate and exhibited enhanced motility. However, the growth of these cells was considerably slower than the growth of the rasG(-) cells, suggesting the possibility that high levels of RasB inhibit an essential process. This was confirmed by expressing rasB in wild-type cells; the resulting transformants exhibited severely impaired growth. When RasB protein levels were determined by western blot analysis, it was found that levels were higher in the rasG(- )cells than they

  12. Engineering design and integration simulation utilization manual

    NASA Technical Reports Server (NTRS)

    Hirsch, G. N.

    1976-01-01

    A description of the Engineering Design Integration (EDIN) Simulation System as it exists at Johnson Space Center is provided. A discussion of the EDIN Simulation System capabilities and applications is presented.

  13. The ras superfamily proteins.

    PubMed

    Chardin, P

    1988-07-01

    Several recent discoveries indicate that the ras genes, frequently activated to a transforming potential in some human tumours, belong to a large family that can be divided into three main branches: the first branch represented by the ras, ral and rap genes; the second branch, by the rho genes; and the third branch, by the rab genes. The C-terminal end of the encoded proteins always includes a cystein, which may become fatty-acylated, suggesting a sub-membrane localization. The ras superfamily proteins share four regions of high homology corresponding to the GTP binding site; however, even in these regions, significant differences are found, suggesting that the various proteins may possess slightly different biochemical properties. Recent reports show that some of these proteins play an essential role in the control of physical processes such as cell motility, membrane ruffling, endocytosis and exocytosis. Nevertheless, the characterization of the proteins directly interacting with the ras or ras-related gene-products will be required to precisely understand their function.

  14. Oncogenic K-Ras Binds to an Anionic Membrane in Two Distinct Orientations: A Molecular Dynamics Analysis.

    PubMed

    Prakash, Priyanka; Zhou, Yong; Liang, Hong; Hancock, John F; Gorfe, Alemayehu A

    2016-03-08

    K-Ras is a membrane-associated GTPase that cycles between active and inactive conformational states to regulate a variety of cell signaling pathways. Somatic mutations in K-Ras are linked to 15-20% of all human tumors. K-Ras attaches to the inner leaflet of the plasma membrane via a farnesylated polybasic domain; however, the structural details of the complex remain poorly understood. Based on extensive (7.5 μs total) atomistic molecular dynamics simulations here we show that oncogenic mutant K-Ras interacts with a negatively charged lipid bilayer membrane in multiple orientations. Of these, two highly populated orientations account for ∼54% of the conformers whose catalytic domain directly interacts with the bilayer. In one of these orientation states, membrane binding involves helices 3 and 4 of the catalytic domain in addition to the farnesyl and polybasic motifs. In the other orientation, β-strands 1-3 and helix 2 on the opposite face of the catalytic domain contribute to membrane binding. Flexibility of the linker region was found to be important for the reorientation. The biological significance of these observations was evaluated by initial experiments in cells overexpressing mutant K-Ras as well as by an analysis of Ras-effector complex structures. The results suggest that only one of the two major orientation states is capable of effector binding. We propose that the different modes of membrane binding may be exploited in structure-based drug design efforts for cancer therapy.

  15. In service design by simulations

    SciTech Connect

    Nasr H. Ghoniem

    2004-03-14

    Irradiation of materials by energetic particles (e.g. electrons, ions and neutrons) is associated with very high internal power dissipation, which can drive the underlying nano- and microstructure far from normal equilibrium conditions. One of the most unusual responses in this connection is the ability of the material's nano- and microstructure to self-assemble in well-organized, two- and three-dimensional periodic arrangements. We reviewed and assessed experimental evidence and theoretical models pertaining to the physical understanding of nano- and microstructure self-organization under irradiation conditions. Experimental observations on the formation of self-organized defect clusters, dislocation loops, voids and bubbles were presented and critically assessed. Implantation of metals with energetic helium results in remarkable self-assembled bubble super-lattices with wavelengths (super-lattice parameters) in the range of 5-8 nm. Ion and neutron irradiation produce a wide variety of self-assembled 3-D defect walls and void lattices, with wavelengths that can be tailored in the range of 10's to 100's of nanometers. Theoretical models aimed at explaining these observations were introduced, and a consistent description of many features is outlined. The primary focus of the most recent modeling efforts, which are based on stability theory and concepts of non-linear dynamics, was to determine criteria for the evolution and spatial symmetry of self-organized microstructures. The correspondence between this theoretical framework and experimental observations was also examined, highlighting areas of agreement and pointing out unresolved questions. The main objective of this research was to develop new computational tools for in-service design and performance prediction of advanced fusion material systems by computational simulation. We also need to develop these computational tools to assist in planning and assessment of corresponding radiation experiments. In the

  16. RAS - Screens & Assays - Drug Discovery

    Cancer.gov

    The RAS Drug Discovery group aims to develop assays that will reveal aspects of RAS biology upon which cancer cells depend. Successful assay formats are made available for high-throughput screening programs to yield potentially effective drug compounds.

  17. Differential dynamics of RAS isoforms in GDP- and GTP-bound states.

    PubMed

    Kapoor, Abhijeet; Travesset, Alex

    2015-06-01

    RAS subfamily proteins regulates cell growth promoting signaling processes by cycling between active (GTP-bound) and inactive (GDP-bound) states. Different RAS isoforms, though structurally similar, exhibit functional specificity and are associated with different types of cancers and developmental disorders. Understanding the dynamical differences between the isoforms is crucial for the design of inhibitors that can selectively target a particular malfunctioning isoform. In this study, we provide a comprehensive comparison of the dynamics of all the three RAS isoforms (HRAS, KRAS, and NRAS) using extensive molecular dynamics simulations in both the GDP- (total of 3.06 μs) and GTP-bound (total of 2.4 μs) states. We observed significant differences in the dynamics of the isoforms, which rather interestingly, varied depending on the type of the nucleotide bound and the simulation temperature. Both SwitchI (Residues 25-40) and SwitchII (Residues 59-75) differ significantly in their flexibility in the three isoforms. Furthermore, Principal Component Analysis showed that there are differences in the conformational space sampled by the GTP-bound RAS isoforms. We also identified a previously unreported pocket, which opens transiently during MD simulations, and can be targeted to regulate nucleotide exchange reaction or possibly interfere with membrane localization. Further, we present the first simulation study showing GDP destabilization in the wild-type RAS protein. The destabilization of GDP/GTP occurred only in 1/50 simulations, emphasizing the need of guanine nucleotide exchange factors (GEFs) to accelerate such an extremely unfavorable process. This observation along with the other results presented in this article further support our previously hypothesized mechanism of GEF-assisted nucleotide exchange.

  18. Converging Lens Simulation Design and Image Predictions

    ERIC Educational Resources Information Center

    Bryan, J. A.; Slough, S. W.

    2009-01-01

    While computer technology continues to enhance the teaching and learning of all science disciplines, computer simulations, in particular, have become exceptionally beneficial in physics education. In addition to the manner in which physics instructors integrate computer simulations into their instructional practices, the design of a simulation may…

  19. Shuttle mission simulator hardware conceptual design report

    NASA Technical Reports Server (NTRS)

    Burke, J. F.

    1973-01-01

    The detailed shuttle mission simulator hardware requirements are discussed. The conceptual design methods, or existing technology, whereby those requirements will be fulfilled are described. Information of a general nature on the total design problem plus specific details on how these requirements are to be satisfied are reported. The configuration of the simulator is described and the capabilities for various types of training are identified.

  20. Simulation and Spacecraft Design: Engineering Mars Landings.

    PubMed

    Conway, Erik M

    2015-10-01

    A key issue in history of technology that has received little attention is the use of simulation in engineering design. This article explores the use of both mechanical and numerical simulation in the design of the Mars atmospheric entry phases of the Viking and Mars Pathfinder missions to argue that engineers used both kinds of simulation to develop knowledge of their designs' likely behavior in the poorly known environment of Mars. Each kind of simulation could be used as a warrant of the other's fidelity, in an iterative process of knowledge construction.

  1. Analysis of the diffusion of Ras2 in Saccharomyces cerevisiae using fluorescence recovery after photobleaching

    NASA Astrophysics Data System (ADS)

    Vinnakota, Kalyan C.; Mitchell, David A.; Deschenes, Robert J.; Wakatsuki, Tetsuro; Beard, Daniel A.

    2010-06-01

    Binding, lateral diffusion and exchange are fundamental dynamic processes involved in protein association with cellular membranes. In this study, we developed numerical simulations of lateral diffusion and exchange of fluorophores in membranes with arbitrary bleach geometry and exchange of the membrane-localized fluorophore with the cytosol during fluorescence recovery after photobleaching (FRAP) experiments. The model simulations were used to design FRAP experiments with varying bleach region sizes on plasma membrane-localized wild-type GFP-Ras2 with a dual lipid anchor and mutant GFP-Ras2C318S with a single lipid anchor in live yeast cells to investigate diffusional mobility and the presence of any exchange processes operating in the time scale of our experiments. Model parameters estimated using data from FRAP experiments with a 1 µm × 1 µm bleach region-of-interest (ROI) and a 0.5 µm × 0.5 µm bleach ROI showed that GFP-Ras2, single or dual lipid modified, diffuses as single species with no evidence of exchange with a cytoplasmic pool. This is the first report of Ras2 mobility in the yeast plasma membrane. The methods developed in this study are generally applicable for studying diffusion and exchange of membrane-associated fluorophores using FRAP on commercial confocal laser scanning microscopes.

  2. Haptics for Product Design and Manufacturing Simulation.

    PubMed

    Xia, Pingjun

    2016-01-01

    Product design and manufacturing simulation is a promising research and application area for haptics. By benefiting from its natural human-computer interaction and realistic force/torque feedback, haptics can change the traditional design and manufacturing approaches which are mainly based on physical mock-ups or CAD (Computer Aided Design) modes. This paper provides a detailed and comprehensive survey of haptics for product design and manufacturing simulation in the past 10 years, mainly from 2004-2014, including haptics for product design and shape modelling, haptics for machining simulation, and haptics for virtual assembly and maintenance simulation. The new haptic devices and rendering algorithms involved in this area are introduced, the major research efforts and the typical systems are discussed, and the new ideas and research progresses are investigated. Then, conclusions and future trends are summarized.

  3. Simulator design for advanced ISDN satellite design and experiments

    NASA Technical Reports Server (NTRS)

    Pepin, Gerald R.

    1992-01-01

    This simulation design task completion report documents the simulation techniques associated with the network models of both the Interim Service ISDN (integrated services digital network) Satellite (ISIS) and the Full Service ISDN Satellite (FSIS) architectures. The ISIS network model design represents satellite systems like the Advanced Communication Technology Satellite (ACTS) orbiting switch. The FSIS architecture, the ultimate aim of this element of the Satellite Communications Applications Research (SCAR) program, moves all control and switching functions on-board the next generation ISDN communication satellite. The technical and operational parameters for the advanced ISDN communications satellite design will be obtained from the simulation of ISIS and FSIS engineering software models for their major subsystems. Discrete events simulation experiments will be performed with these models using various traffic scenarios, design parameters and operational procedures. The data from these simulations will be used to determine the engineering parameters for the advanced ISDN communications satellite.

  4. Prosthetic knee design by simulation

    SciTech Connect

    Hollerbach, K; Hollister, A

    1999-07-30

    Although 150,000 total knee replacement surgeries are performed annually in North America, current designs of knee prostheses have mechanical problems that include a limited range of motion, abnormal gait patterns, patellofemoral joint dysfunction, implant loosening or subsidence, and excessive wear. These problems fall into three categories: failure to reproduce normal joint kinematics, which results in altered limb function; bone-implant interface failure; and material failure. Modern computer technology can be used to design, prototype, and test new total knee implants. The design team uses the full range of CAD-CAM to design and produce implant prototypes for mechanical and clinical testing. Closer approximation of natural knee kinematics and kinetics is essential for improved patient function and diminished implant loads. Current knee replacement designs are based on 19th Century theories that the knee moves about a variable axis of rotation. Recent research has shown, however, that knee motion occurs about two fixed, offset axes of rotation. These aces are not perpendicular to the long axes of the bones or to each other, and the axes do not intersect. Bearing surfaces of mechanisms that move about axes of rotation are surfaces of revolution of those axes which advanced CAD technology can produce. Solids with surfaces of revolution for the two axes of rotation for the knee have been made using an HP9000 workstation and Structural Ideas Master Series CAD software at ArthroMotion. The implant's CAD model should closely replicate movements of the normal knee. The knee model will have a range of flexion-extension (FE) from -5 to 120 degrees. Movements include varus, valgus, internal and external rotation, as well as flexion and extension. The patellofemoral joint is aligned perpendicular to the FE axis and replicates the natural joint more closely than those of existing prostheses. The bearing surfaces will be more congruent than current designs and should

  5. Shuttle mission simulator software conceptual design

    NASA Technical Reports Server (NTRS)

    Burke, J. F.

    1973-01-01

    Software conceptual designs (SCD) are presented for meeting the simulator requirements for the shuttle missions. The major areas of the SCD discussed include: malfunction insertion, flight software, applications software, systems software, and computer complex.

  6. Refinery burner simulation design architecture summary.

    SciTech Connect

    Pollock, Guylaine M.; McDonald, Michael James; Halbgewachs, Ronald D.

    2011-10-01

    This report describes the architectural design for a high fidelity simulation of a refinery and refinery burner, including demonstrations of impacts to the refinery if errors occur during the refinery process. The refinery burner model and simulation are a part of the capabilities within the Sandia National Laboratories Virtual Control System Environment (VCSE). Three components comprise the simulation: HMIs developed with commercial SCADA software, a PLC controller, and visualization software. All of these components run on different machines. This design, documented after the simulation development, incorporates aspects not traditionally seen in an architectural design, but that were utilized in this particular demonstration development. Key to the success of this model development and presented in this report are the concepts of the multiple aspects of model design and development that must be considered to capture the necessary model representation fidelity of the physical systems.

  7. Simulation as an Aid to Experimental Design.

    ERIC Educational Resources Information Center

    Frazer, Jack W.; And Others

    1983-01-01

    Discusses simulation program to aid in the design of enzyme kinetic experimentation (includes sample runs). Concentration versus time profiles of any subset or all nine states of reactions can be displayed with/without simulated instrumental noise, allowing the user to estimate the practicality of any proposed experiment given known instrument…

  8. KAPAO Prime: Design and Simulation

    NASA Astrophysics Data System (ADS)

    McGonigle, Lorcan; Choi, P. I.; Severson, S. A.; Spjut, E.

    2013-01-01

    KAPAO (KAPAO A Pomona Adaptive Optics instrument) is a dual-band natural guide star adaptive optics system designed to measure and remove atmospheric aberration over UV-NIR wavelengths from Pomona College’s telescope atop Table Mountain. We present here, the final optical system, KAPAO Prime, designed in Zemax Optical Design Software that uses custom off-axis paraboloid mirrors (OAPs) to manipulate light appropriately for a Shack-Hartman wavefront sensor, deformable mirror, and science cameras. KAPAO Prime is characterized by diffraction limited imaging over the full 81” field of view of our optical camera at f/33 as well as over the smaller field of view of our NIR camera at f/50. In Zemax, tolerances of 1% on OAP focal length and off-axis distance were shown to contribute an additional 4 nm of wavefront error (98% confidence) over the field of view of our optical camera; the contribution from surface irregularity was determined analytically to be 40nm for OAPs specified to λ/10 surface irregularity (632.8nm). Modeling of the temperature deformation of the breadboard in SolidWorks revealed 70 micron contractions along the edges of the board for a decrease of 75°F when applied to OAP positions such displacements from the optimal layout are predicted to contribute an additional 20 nanometers of wavefront error. Flexure modeling of the breadboard due to gravity is on-going. We hope to begin alignment and testing of KAPAO Prime in Q1 2013.

  9. KAPAO Prime: Design and Simulation

    NASA Astrophysics Data System (ADS)

    McGonigle, Lorcan

    2012-11-01

    KAPAO (KAPAO A Pomona Adaptive Optics instrument) is a dual-band natural guide star adaptive optics system designed to measure and remove atmospheric aberration from Pomona College's telescope atop Table Mountain. We present here, the final optical system, referred to as Prime, designed in Zemax Optical Design Software. Prime is characterized by diffraction limited imaging over the full 73'' field of view of our Andor Camera at f/33 as well as for our NIR Xenics camera at f/50. In Zemax, tolerances of 1% on OAP focal length and off-axis distance were shown to contribute an additional 4 nm of wavefront error (98% confidence) over the field of view of the Andor camera; the contribution from surface irregularity was determined analytically to be 40nm for OAPs specified to l/10 surface irregularity. Modeling of the temperature deformation of the breadboard in SolidWorks revealed 70 micron contractions along the edges of the board for a decrease of 75 F; when applied to OAP positions such displacements from the optimal layout are predicted to contribute an additional 20 nanometers of wavefront error. Flexure modeling of the breadboard due to gravity is on-going. We hope to begin alignment and testing of ``Prime'' in Q1 2013.

  10. Simulation, Design Abstraction, and SystemC

    ERIC Educational Resources Information Center

    Harcourt, Ed

    2007-01-01

    SystemC is a system-level design and simulation language based on C++. We've been using SystemC for computer organization and design projects for the past several years. Because SystemC is embedded in C++ it contains the powerful abstraction mechanisms of C++ not found in traditional hardware description languages, such as support for…

  11. CAGE IIIA Distributed Simulation Design Methodology

    DTIC Science & Technology

    2014-05-01

    and Execution Process (FEDEP), Synthetic Environment Development and Exploitation Process (SEDEP), Distributed Simulation Engineering and Execution... Process (DSEEP) and Kweley and Wood [Andreas Tolk et al. (2012)] all assume a central design authority and thus full control of the system of... Process ......................................................................... 6 2.3.2.1 Scenario Design Products

  12. Design and simulation of a gyroklystron amplifier

    SciTech Connect

    Chauhan, M. S. Swati, M. V.; Jain, P. K.

    2015-03-15

    In the present paper, a design methodology of the gyroklystron amplifier has been described and subsequently used for the design of a typically selected 200 kW, Ka-band, four-cavity gyroklystron amplifier. This conceptual device design has been validated through the 3D particle-in-cell (PIC) simulation and nonlinear analysis. Commercially available PIC simulation code “MAGIC” has been used for the electromagnetic study at the different location of the device RF interaction structure for the beam-absent case, i.e., eigenmode study as well as for the electron beam and RF wave interaction behaviour study in the beam present case of the gyroklystron. In addition, a practical problem of misalignment of the RF cavities with drift tubes within the tube has been also investigated and its effect on device performance studied. The analytical and simulation results confirmed the validity of the gyroklystron device design. The PIC simulation results of the present gyroklystron produced a stable RF output power of ∼218 kW for 0% velocity spread at 35 GHz, with ∼45 dB gain, 37% efficiency, and a bandwidth of 0.3% for a 70 kV, 8.2 A gyrating electron beam. The simulated values of RF output power have been found in agreement with the nonlinear analysis results within ∼5%. Further, the PIC simulation has been extended to study a practical problem of misalignment of the cavities axis and drift tube axis of the gyroklystron amplifier and found that the RF output power is more sensitive to misalignments in comparison to the device bandwidth. The present paper, gyroklystron device design, nonlinear analysis, and 3D PIC simulation using commercially available code had been systematically described would be of use to the high-power gyro-amplifier tube designers and research scientists.

  13. Design considerations for healthcare simulation facilities.

    PubMed

    Seropian, Michael; Lavey, Robert

    2010-12-01

    The number of simulation facilities across the United States and internationally is growing rapidly. The capital investment required can be substantive regardless of size. This article focuses on ways to optimize expenditures and maximize utility. Several key factors will play decisive roles in the successful launch of a new simulation facility. Mission/vision, budget, functional need, and space are partners in determining the final design of the simulation facility. Ideally, the budget is based on the functional requirements and desired capacity; but when this is not the case, of course, the owner must prioritize the needs of the new center. The type of space allocated for the facility is also critical and can seriously impact the budget because renovating a space that is fitted for another purpose versus constructing the center in an open shell space can add considerable cost. A well-balanced design team led by a diligent and knowledgeable project manager who can keep the team focused is integral to the success of designing and constructing a new facility. Users should inform themselves about each of the issues that a design team may consider to ensure that the issues are resolved in a way that meets the needs and vision of the program(s). A simulation facility, such as any education facility, should be built around the concepts of the overall mission, vision, and values of the institution(s) and stakeholder(s). For any new educational facility to be a success, the thoughts, ideas, and creativity of the owner, users, and stakeholders must find its way into the ultimate built environment. The experience base of simulation facility design is fragmented and not standardized. Therefore, we live at a time where the risk of ineffective design is higher than one would like given the costs involved. It behooves the owner to set parameters with the planning and design team that they want a balanced, controlled, collaborative, and inclusive design process.

  14. Design of penicillin fermentation process simulation system

    NASA Astrophysics Data System (ADS)

    Qi, Xiaoyu; Yuan, Zhonghu; Qi, Xiaoxuan; Zhang, Wenqi

    2011-10-01

    Real-time monitoring for batch process attracts increasing attention. It can ensure safety and provide products with consistent quality. The design of simulation system of batch process fault diagnosis is of great significance. In this paper, penicillin fermentation, a typical non-linear, dynamic, multi-stage batch production process, is taken as the research object. A visual human-machine interactive simulation software system based on Windows operation system is developed. The simulation system can provide an effective platform for the research of batch process fault diagnosis.

  15. Simulation design for microalgal protein optimization

    PubMed Central

    Imamoglu, Esra

    2015-01-01

    A method for designing the operating parameters (surface light intensity, operating temperature and agitation rate) was proposed for microalgal protein production. Furthermore, quadratic model was established and validated (R2 > 0.90) with experimental data. It was recorded that temperature and agitation rate were slightly interdependent. The microalgal protein performance could be estimated using the simulated experimental setup and procedure developed in this study. The results also showed a holistic approach for opening a new avenue on simulation design for microalgal protein optimization. PMID:26418695

  16. The Process Design Courses at Pennsylvania: Impact of Process Simulators.

    ERIC Educational Resources Information Center

    Seider, Warren D.

    1984-01-01

    Describes the use and impact of process design simulators in process design courses. Discusses topics covered, texts used, computer design simulations, and how they are integrated into the process survey course as well as in plant design projects. (JM)

  17. [Vernier Anode Design and Image Simulation].

    PubMed

    Zhao, Ai-rong; Ni, Qi-liang; Song, Ke-fei

    2015-12-01

    Based-MCP position-sensitive anode photon-counting imaging detector is good at detecting extremely faint light, which includes micro-channel plate (MCP), position-sensitive anode and readout, and the performances of these detectors are mainly decided by the position-sensitive anode. As a charge division anode, Vernier anode using cyclically varying electrode areas which replaces the linearly varying electrodes of wedge-strip anode can get better resolution and greater electrode dynamic range. Simulation and design of the Vernier anode based on Vernier's decode principle are given here. Firstly, we introduce the decode and design principle of Vernier anode with nine electrodes in vector way, and get the design parameters which are the pitch, amplitude and the coarse wavelength of electrode. Secondly, we analyze the effect of every design parameters to the imaging of the detector. We simulate the electron cloud, the Vernier anode and the detector imaging using Labview software and get the relationship between the pitch and the coarse wavelength of the anode. Simultaneously, we get the corresponding electron cloud for the designing parameters. Based on the result of the simulation and the practical machining demand, a nine electrodes Vernier anode was designed and fabricated which has a pitch of 891 µm, insulation width of 25 µm, amplitude of 50 µm, coarse pixel numbers of 5.

  18. Designing Online Scaffolds for Interactive Computer Simulation

    ERIC Educational Resources Information Center

    Chen, Ching-Huei; Wu, I-Chia; Jen, Fen-Lan

    2013-01-01

    The purpose of this study was to examine the effectiveness of online scaffolds in computer simulation to facilitate students' science learning. We first introduced online scaffolds to assist and model students' science learning and to demonstrate how a system embedded with online scaffolds can be designed and implemented to help high school…

  19. Parachute system design, analysis, and simulation tool

    SciTech Connect

    Sundberg, W.D.; McBride, D.D.; Gwinn, K.W.; Waye, D.E.; Hailey, C.E.

    1992-01-01

    For over twenty years designers at Sandia National Laboratories have developed various parachute simulation codes to model deployment, inflation, loading, trajectories, aircraft downwash and line sail. In addition to these codes, material property data bases have been acquired. Recently we have initiated project to integrate these codes and data bases into a single software tool entitled SPARSYS (Sandia PARachute SYstem Simulation). We have constructed a graphical user interface as the driver and framework for SPARSYS. In this paper we present a status report on SPARSYS describing progress in developing and incorporating independent modules, in developing an integrated trajectory package, and in developing a materials data base including high-rate-of-strain data.

  20. Oncogenic K-Ras Binds to an Anionic Membrane in Two Distinct Orientations: A Molecular Dynamics Analysis

    PubMed Central

    Prakash, Priyanka; Zhou, Yong; Liang, Hong; Hancock, John F.; Gorfe, Alemayehu A.

    2016-01-01

    K-Ras is a membrane-associated GTPase that cycles between active and inactive conformational states to regulate a variety of cell signaling pathways. Somatic mutations in K-Ras are linked to 15–20% of all human tumors. K-Ras attaches to the inner leaflet of the plasma membrane via a farnesylated polybasic domain; however, the structural details of the complex remain poorly understood. Based on extensive (7.5 μs total) atomistic molecular dynamics simulations here we show that oncogenic mutant K-Ras interacts with a negatively charged lipid bilayer membrane in multiple orientations. Of these, two highly populated orientations account for ∼54% of the conformers whose catalytic domain directly interacts with the bilayer. In one of these orientation states, membrane binding involves helices 3 and 4 of the catalytic domain in addition to the farnesyl and polybasic motifs. In the other orientation, β-strands 1–3 and helix 2 on the opposite face of the catalytic domain contribute to membrane binding. Flexibility of the linker region was found to be important for the reorientation. The biological significance of these observations was evaluated by initial experiments in cells overexpressing mutant K-Ras as well as by an analysis of Ras-effector complex structures. The results suggest that only one of the two major orientation states is capable of effector binding. We propose that the different modes of membrane binding may be exploited in structure-based drug design efforts for cancer therapy. PMID:26958889

  1. Plasma membrane regulates Ras signaling networks

    PubMed Central

    Chavan, Tanmay Sanjeev; Muratcioglu, Serena; Marszalek, Richard; Jang, Hyunbum; Keskin, Ozlem; Gursoy, Attila; Nussinov, Ruth; Gaponenko, Vadim

    2015-01-01

    Ras GTPases activate more than 20 signaling pathways, regulating such essential cellular functions as proliferation, survival, and migration. How Ras proteins control their signaling diversity is still a mystery. Several pieces of evidence suggest that the plasma membrane plays a critical role. Among these are: (1) selective recruitment of Ras and its effectors to particular localities allowing access to Ras regulators and effectors; (2) specific membrane-induced conformational changes promoting Ras functional diversity; and (3) oligomerization of membrane-anchored Ras to recruit and activate Raf. Taken together, the membrane does not only attract and retain Ras but also is a key regulator of Ras signaling. This can already be gleaned from the large variability in the sequences of Ras membrane targeting domains, suggesting that localization, environment and orientation are important factors in optimizing the function of Ras isoforms. PMID:27054048

  2. Plasma membrane regulates Ras signaling networks.

    PubMed

    Chavan, Tanmay Sanjeev; Muratcioglu, Serena; Marszalek, Richard; Jang, Hyunbum; Keskin, Ozlem; Gursoy, Attila; Nussinov, Ruth; Gaponenko, Vadim

    2015-01-01

    Ras GTPases activate more than 20 signaling pathways, regulating such essential cellular functions as proliferation, survival, and migration. How Ras proteins control their signaling diversity is still a mystery. Several pieces of evidence suggest that the plasma membrane plays a critical role. Among these are: (1) selective recruitment of Ras and its effectors to particular localities allowing access to Ras regulators and effectors; (2) specific membrane-induced conformational changes promoting Ras functional diversity; and (3) oligomerization of membrane-anchored Ras to recruit and activate Raf. Taken together, the membrane does not only attract and retain Ras but also is a key regulator of Ras signaling. This can already be gleaned from the large variability in the sequences of Ras membrane targeting domains, suggesting that localization, environment and orientation are important factors in optimizing the function of Ras isoforms.

  3. Design of a TEM cell EMP simulator

    NASA Astrophysics Data System (ADS)

    Sevat, Pete

    1991-06-01

    Electromagnetic pulse (EMP) simulators are designed to simulate the EMP generated by a nuclear weapon and are used to harden equipment against the effects of EMP. A transverse electromagnetic (TEM) cell is a square or rectangular coaxial transmission line tapered at each end to form a closed cell. The cell is fed at one end with a signal generator, a continuous wave or pulse generator, and terminated at the other end with a resistor equal to the characteristic impedance of the line. An advantage of the TEM cell is that the field is well characterized and reasonably uniform. A small, symmetric, TEM cell EMP simulator is described which is intended for applications such as susceptibility testing of small equipment, calibration of sensors, design and testing of countermeasures, measurement of transfer functions, and research and development. A detailed design is presented for a 50 ohm and 100 ohm TEM cell with an inner volume of 4 m(exp 3) and a test volume of 0.24 m(exp 3). The pulse generator and terminating network are integrated into the cell to form a completely shielded structure. In this way no interference from the inside of the cell to the outside, or vice versa, will occur.

  4. Design and characterization of a cough simulator.

    PubMed

    Zhang, Bo; Zhu, Chao; Ji, Zhiming; Lin, Chao-Hsin

    2017-02-23

    Expiratory droplets from human coughing have always been considered as potential carriers of pathogens, responsible for respiratory infectious disease transmission. To study the transmission of disease by human coughing, a transient repeatable cough simulator has been designed and built. Cough droplets are generated by different mechanisms, such as the breaking of mucus, condensation and high-speed atomization from different depths of the respiratory tract. These mechanisms in coughing produce droplets of different sizes, represented by a bimodal distribution of 'fine' and 'coarse' droplets. A cough simulator is hence designed to generate transient sprays with such bimodal characteristics. It consists of a pressurized gas tank, a nebulizer and an ejector, connected in series, which are controlled by computerized solenoid valves. The bimodal droplet size distribution is characterized for the coarse droplets and fine droplets, by fibrous collection and laser diffraction, respectively. The measured size distributions of coarse and fine droplets are reasonably represented by the Rosin-Rammler and log-normal distributions in probability density function, which leads to a bimodal distribution. To assess the hydrodynamic consequences of coughing including droplet vaporization and polydispersion, a Lagrangian model of droplet trajectories is established, with its ambient flow field predetermined from a computational fluid dynamics simulation.

  5. Analysis of binding site hot spots on the surface of Ras GTPase.

    PubMed

    Buhrman, Greg; O'Connor, Casey; Zerbe, Brandon; Kearney, Bradley M; Napoleon, Raeanne; Kovrigina, Elizaveta A; Vajda, Sandor; Kozakov, Dima; Kovrigin, Evgenii L; Mattos, Carla

    2011-11-04

    We have recently discovered an allosteric switch in Ras, bringing an additional level of complexity to this GTPase whose mutants are involved in nearly 30% of cancers. Upon activation of the allosteric switch, there is a shift in helix 3/loop 7 associated with a disorder to order transition in the active site. Here, we use a combination of multiple solvent crystal structures and computational solvent mapping (FTMap) to determine binding site hot spots in the "off" and "on" allosteric states of the GTP-bound form of H-Ras. Thirteen sites are revealed, expanding possible target sites for ligand binding well beyond the active site. Comparison of FTMaps for the H and K isoforms reveals essentially identical hot spots. Furthermore, using NMR measurements of spin relaxation, we determined that K-Ras exhibits global conformational dynamics very similar to those we previously reported for H-Ras. We thus hypothesize that the global conformational rearrangement serves as a mechanism for allosteric coupling between the effector interface and remote hot spots in all Ras isoforms. At least with respect to the binding sites involving the G domain, H-Ras is an excellent model for K-Ras and probably N-Ras as well. Ras has so far been elusive as a target for drug design. The present work identifies various unexplored hot spots throughout the entire surface of Ras, extending the focus from the disordered active site to well-ordered locations that should be easier to target.

  6. Analysis of Binding Site Hot Spots on the Surface of Ras GTPase

    SciTech Connect

    Buhrman, Greg; O; #8242; Connor, Casey; Zerbe, Brandon; Kearney, Bradley M.; Napoleon, Raeanne; Kovrigina, Elizaveta A.; Vajda, Sandor; Kozakov, Dima; Kovrigin, Evgenii L.; Mattos, Carla

    2012-09-17

    We have recently discovered an allosteric switch in Ras, bringing an additional level of complexity to this GTPase whose mutants are involved in nearly 30% of cancers. Upon activation of the allosteric switch, there is a shift in helix 3/loop 7 associated with a disorder to order transition in the active site. Here, we use a combination of multiple solvent crystal structures and computational solvent mapping (FTMap) to determine binding site hot spots in the 'off' and 'on' allosteric states of the GTP-bound form of H-Ras. Thirteen sites are revealed, expanding possible target sites for ligand binding well beyond the active site. Comparison of FTMaps for the H and K isoforms reveals essentially identical hot spots. Furthermore, using NMR measurements of spin relaxation, we determined that K-Ras exhibits global conformational dynamics very similar to those we previously reported for H-Ras. We thus hypothesize that the global conformational rearrangement serves as a mechanism for allosteric coupling between the effector interface and remote hot spots in all Ras isoforms. At least with respect to the binding sites involving the G domain, H-Ras is an excellent model for K-Ras and probably N-Ras as well. Ras has so far been elusive as a target for drug design. The present work identifies various unexplored hot spots throughout the entire surface of Ras, extending the focus from the disordered active site to well-ordered locations that should be easier to target.

  7. Design and simulation of a neutron facility.

    PubMed

    Studenski, Matthew T; Kearfott, Kimberlee J

    2007-02-01

    State and other regulatory entities require that for any facility housing a particle accelerator the surrounding areas must be restricted to public access unless the dose equivalent rate is less than 0.02 mSv h at 5 cm from any accessible wall surrounding the facility under conditions of maximum radiation output. A Monte Carlo radiation transport simulation code, MCNP5, was used to design a proposed facility to shield two D-T neutron generators and one D-D neutron generator. A number of different designs were simulated, but due to cost and space issues a small concrete cave proved to be the best solution for the shielding problem. With this design, all of the neutron generators could be used and all of the rooms surrounding the neutron facility could be considered unrestricted to public access. To prevent unauthorized access into the restricted area of the neutron facility, light curtains, warning lights, door interlocks, and rope barriers will be built into the facility.

  8. Simulated Data for High Temperature Composite Design

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.; Abumeri, Galib H.

    2006-01-01

    The paper describes an effective formal method that can be used to simulate design properties for composites that is inclusive of all the effects that influence those properties. This effective simulation method is integrated computer codes that include composite micromechanics, composite macromechanics, laminate theory, structural analysis, and multi-factor interaction model. Demonstration of the method includes sample examples for static, thermal, and fracture reliability for a unidirectional metal matrix composite as well as rupture strength and fatigue strength for a high temperature super alloy. Typical results obtained for a unidirectional composite show that the thermal properties are more sensitive to internal local damage, the longitudinal properties degrade slowly with temperature, the transverse and shear properties degrade rapidly with temperature as do rupture strength and fatigue strength for super alloys.

  9. Digital autopilots: Design considerations and simulator evaluations

    NASA Technical Reports Server (NTRS)

    Osder, S.; Neuman, F.; Foster, J.

    1971-01-01

    The development of a digital autopilot program for a transport aircraft and the evaluation of that system's performance on a transport aircraft simulator is discussed. The digital autopilot includes three axis attitude stabilization, automatic throttle control and flight path guidance functions with emphasis on the mode progression from descent into the terminal area through automatic landing. The study effort involved a sequence of tasks starting with the definition of detailed system block diagrams of control laws followed by a flow charting and programming phase and concluding with performance verification using the transport aircraft simulation. The autopilot control laws were programmed in FORTRAN 4 in order to isolate the design process from requirements peculiar to an individual computer.

  10. VOCs monitoring system simulation and design

    NASA Astrophysics Data System (ADS)

    Caldararu, Florin; Vasile, Alexandru; Vatra, Cosmin

    2010-11-01

    The designed and simulated system will be used in the tanning industry, for Volatile Organic Compound (VOC) measurements. In this industry, about 90% of the solvent contained in the emulsions evaporates during its application, giving rise to VOC, which are at the same time hazardous atmospheric pollutants and one of the sources of ground level photochemical ozone formation. It results that a monitoring system is necessary in a leather finishing process, in order to detect hazardous VOC concentration and conducting process in order of VOC concentration diminishing. The paper presents the design of a VOC monitoring system, which includes sensors for VOCs and temperature, the conditioning circuitry for these sensors, the suction system of the gas in the hood, the data acquisition and the computing system and graphic interface. The used sensor in the detection system is a semiconductor sensor, produced by Figaro Engineering Inc., characterized by a short response time, high sensitivity at almost all VOC substances. The design of the conditioning circuitry and data acquisition is done in order to compensate the sensor response variation with temperature and to maintain the low response time of the sensor. The temperature compensation is obtained by using a thermistor circuitry, and the compensation is done within the software design. A Mitsubishi PLC is used to receive the output signals of the circuits including the sensor and of the thermistor, respectively. The acquisition and computing system is done using Mitsubishi ALPHA 2 controller and a graphical terminal, GOT 1000.

  11. Ras proteins have multiple functions in vegetative cells of Dictyostelium.

    PubMed

    Bolourani, Parvin; Spiegelman, George; Weeks, Gerald

    2010-11-01

    During the aggregation of Dictyostelium cells, signaling through RasG is more important in regulating cyclic AMP (cAMP) chemotaxis, whereas signaling through RasC is more important in regulating the cAMP relay. However, RasC is capable of substituting for RasG for chemotaxis, since rasG⁻ cells are only partially deficient in chemotaxis, whereas rasC⁻/rasG⁻ cells are totally incapable of chemotaxis. In this study we have examined the possible functional overlap between RasG and RasC in vegetative cells by comparing the vegetative cell properties of rasG⁻, rasC⁻, and rasC⁻/rasG⁻ cells. In addition, since RasD, a protein not normally found in vegetative cells, is expressed in vegetative rasG⁻ and rasC⁻/rasG⁻ cells and appears to partially compensate for the absence of RasG, we have also examined the possible functional overlap between RasG and RasD by comparing the properties of rasG⁻ and rasC⁻/rasG⁻ cells with those of the mutant cells expressing higher levels of RasD. The results of these two lines of investigation show that RasD is capable of totally substituting for RasG for cytokinesis and growth in suspension, whereas RasC is without effect. In contrast, for chemotaxis to folate, RasC is capable of partially substituting for RasG, but RasD is totally without effect. Finally, neither RasC nor RasD is able to substitute for the role that RasG plays in regulating actin distribution and random motility. These specificity studies therefore delineate three distinct and none-overlapping functions for RasG in vegetative cells.

  12. Calcium activation of Ras mediated by neuronal exchange factor Ras-GRF.

    PubMed

    Farnsworth, C L; Freshney, N W; Rosen, L B; Ghosh, A; Greenberg, M E; Feig, L A

    1995-08-10

    Tyrosine kinase receptors stimulate the Ras signalling pathway by enhancing the activity of the SOS nucleotide-exchange factor. This occurs, at least in part, by the recruitment of an SOS-GRB2 complex to Ras in the plasma membrane. Here we describe a different signalling pathway to Ras that involves activation of the Ras-GRF exchange factor in response to Ca2+ influx. In particular, we show that the ability of Ras-GRF to activate Ras in vivo is markedly enhanced by raised Ca2+ concentrations. Activation is mediated by calmodulin binding to an IQ motif in Ras-GRF, because substitutions in conserved amino acids in this motif prevent both calmodulin binding to Ras-GRF and Ras-GRF activation in vivo. So far, full-length Ras-GRF has been detected only in brain neurons. Our findings implicate Ras-GRF in the regulation of neuronal functions that are influenced by Ca2+ signals.

  13. Aurora kinase A interacts with H-Ras and potentiates Ras-MAPK signaling.

    PubMed

    Umstead, MaKendra; Xiong, Jinglin; Qi, Qi; Du, Yuhong; Fu, Haian

    2017-02-03

    In cancer, upregulated Ras promotes cellular transformation and proliferation in part through activation of oncogenic Ras-MAPK signaling. While directly inhibiting Ras has proven challenging, new insights into Ras regulation through protein-protein interactions may offer unique opportunities for therapeutic intervention. Here we report the identification and validation of Aurora kinase A (Aurora A) as a novel Ras binding protein. We demonstrate that the kinase domain of Aurora A mediates the interaction with the N-terminal domain of H-Ras. Further more, the interaction of Aurora A and H-Ras exists in a protein complex with Raf-1. We show that binding of H-Ras to Raf-1 and subsequent MAPK signaling is enhanced by Aurora A, and requires active H-Ras. Thus, the functional linkage between Aurora A and the H-Ras/Raf-1 protein complex may provide a mechanism for Aurora A's oncogenic activity through direct activation of the Ras/MAPK pathway.

  14. Mechanisms of Membrane Binding of Small GTPase K-Ras4B Farnesylated Hypervariable Region*

    PubMed Central

    Jang, Hyunbum; Abraham, Sherwin J.; Chavan, Tanmay S.; Hitchinson, Ben; Khavrutskii, Lyuba; Tarasova, Nadya I.; Nussinov, Ruth; Gaponenko, Vadim

    2015-01-01

    K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. PMID:25713064

  15. Cardiac remodelling and RAS inhibition

    PubMed Central

    Ferrario, Carlos M.

    2016-01-01

    Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin–angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS. PMID:27105891

  16. Design and simulation of e-calendar system circuits

    NASA Astrophysics Data System (ADS)

    Liu, Li-jun

    2015-02-01

    The digital calendar circuits controlled by 80C52 have been designed based on Proteus simulation software. The whole design process is made of three parts: hardware circuits, software programming and software simulation. Finally, it shows that the circuit design of hardware and software is correct through Proteus software simulation. The method of circuit design is systematic and practical, which will provide certain design ideas and reference value for display circuit in the future.

  17. PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus.

    PubMed

    Jin, Ting; Ding, Qiurong; Huang, Heng; Xu, Daqian; Jiang, Yuhui; Zhou, Ben; Li, Zhenghu; Jiang, Xiaomeng; He, Jing; Liu, Weizhong; Zhang, Yixuan; Pan, Yi; Wang, Zhenzhen; Thomas, Walter G; Chen, Yan

    2012-04-01

    Ras plays a pivotal role in many cellular activities, and its subcellular compartmentalization provides spatial and temporal selectivity. Here we report a mode of spatial regulation of Ras signaling in the Golgi apparatus by two highly homologous proteins PAQR10 and PAQR11 of the progestin and AdipoQ receptors family. PAQR10 and PAQR11 are exclusively localized in the Golgi apparatus. Overexpression of PAQR10/PAQR11 stimulates basal and EGF-induced ERK phosphorylation and increases the expression of ERK target genes in a dose-dependent manner. Overexpression of PAQR10/PAQR11 markedly elevates Golgi localization of HRas, NRas and KRas4A, but not KRas4B. PAQR10 and PAQR11 can also interact with HRas, NRas and KRas4A, but not KRas4B. The increased Ras protein at the Golgi apparatus by overexpression of PAQR10/PAQR11 is in an active state. Consistently, knockdown of PAQR10 and PAQR11 reduces EGF-stimulated ERK phosphorylation and Ras activation at the Golgi apparatus. Intriguingly, PAQR10 and PAQR11 are able to interact with RasGRP1, a guanine nucleotide exchange protein of Ras, and increase Golgi localization of RasGRP1. The C1 domain of RasGRP1 is both necessary and sufficient for the interaction of RasGRP1 with PAQR10/PAQR11. The simulation of ERK phosphorylation by overexpressed PAQR10/PAQR11 is abrogated by downregulation of RasGRP1. Furthermore, differentiation of PC12 cells is significantly enhanced by overexpression of PAQR10/PAQR11. Collectively, this study uncovers a new paradigm of spatial regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQR11.

  18. Drugging the undruggable Ras: mission possible?

    PubMed Central

    Cox, Adrienne D.; Fesik, Stephen W.; Kimmelman, Alec C.; Luo, Ji; Der, Channing J.

    2015-01-01

    Despite more than three decades of intensive effort, no effective pharmacologic inhibitors of the Ras oncoproteins have reached the clinic, prompting the widely held perception that Ras proteins are “undruggable”. However, there is renewed hope that this is not the case. In this review, we summarize the progress and promise of five key directions. First, we focus on the prospects of direct inhibitors of Ras. Second, we revisit the issue of whether blocking Ras membrane association is a viable approach. Third, we assess the status of targeting Ras downstream effector signalling, arguably the most favourable current direction. Fourth, we address whether the search for synthetic lethal interactors of mutant RAS still holds promise. Finally, Ras-mediated changes in cell metabolism have recently been described. Can these changes be exploited for new therapeutic directions? We conclude with perspectives on how additional complexities, not yet fully understood, may impact each of these approaches. PMID:25323927

  19. Lead identification for the K-Ras protein: virtual screening and combinatorial fragment-based approaches

    PubMed Central

    Pathan, Akbar Ali Khan; Panthi, Bhavana; Khan, Zahid; Koppula, Purushotham Reddy; Alanazi, Mohammed Saud; Sachchidanand; Parine, Narasimha Reddy; Chourasia, Mukesh

    2016-01-01

    Objective Kirsten rat sarcoma (K-Ras) protein is a member of Ras family belonging to the small guanosine triphosphatases superfamily. The members of this family share a conserved structure and biochemical properties, acting as binary molecular switches. The guanosine triphosphate-bound active K-Ras interacts with a range of effectors, resulting in the stimulation of downstream signaling pathways regulating cell proliferation, differentiation, and apoptosis. Efforts to target K-Ras have been unsuccessful until now, placing it among high-value molecules against which developing a therapy would have an enormous impact. K-Ras transduces signals when it binds to guanosine triphosphate by directly binding to downstream effector proteins, but in case of guanosine diphosphate-bound conformation, these interactions get disrupted. Methods In the present study, we targeted the nucleotide-binding site in the “on” and “off” state conformations of the K-Ras protein to find out suitable lead compounds. A structure-based virtual screening approach has been used to screen compounds from different databases, followed by a combinatorial fragment-based approach to design the apposite lead for the K-Ras protein. Results Interestingly, the designed compounds exhibit a binding preference for the “off” state over “on” state conformation of K-Ras protein. Moreover, the designed compounds’ interactions are similar to guanosine diphosphate and, thus, could presumably act as a potential lead for K-Ras. The predicted drug-likeness properties of these compounds suggest that these compounds follow the Lipinski’s rule of five and have tolerable absorption, distribution, metabolism, excretion and toxicity values. Conclusion Thus, through the current study, we propose targeting only “off” state conformations as a promising strategy for the design of reversible inhibitors to pharmacologically inhibit distinct conformations of K-Ras protein. PMID:27217775

  20. Simulation Tools Model Icing for Aircraft Design

    NASA Technical Reports Server (NTRS)

    2012-01-01

    Here s a simple science experiment to try: Place an unopened bottle of distilled water in your freezer. After 2-3 hours, if the water is pure enough, you will notice that it has not frozen. Carefully pour the water into a bowl with a piece of ice in it. When it strikes the ice, the water will instantly freeze. One of the most basic and commonly known scientific facts is that water freezes at around 32 F. But this is not always the case. Water lacking any impurities for ice crystals to form around can be supercooled to even lower temperatures without freezing. High in the atmosphere, water droplets can achieve this delicate, supercooled state. When a plane flies through clouds containing these droplets, the water can strike the airframe and, like the supercooled water hitting the ice in the experiment above, freeze instantly. The ice buildup alters the aerodynamics of the plane - reducing lift and increasing drag - affecting its performance and presenting a safety issue if the plane can no longer fly effectively. In certain circumstances, ice can form inside aircraft engines, another potential hazard. NASA has long studied ways of detecting and countering atmospheric icing conditions as part of the Agency s efforts to enhance aviation safety. To do this, the Icing Branch at Glenn Research Center utilizes a number of world-class tools, including the Center s Icing Research Tunnel and the NASA 607 icing research aircraft, a "flying laboratory" for studying icing conditions. The branch has also developed a suite of software programs to help aircraft and icing protection system designers understand the behavior of ice accumulation on various surfaces and in various conditions. One of these innovations is the LEWICE ice accretion simulation software. Initially developed in the 1980s (when Glenn was known as Lewis Research Center), LEWICE has become one of the most widely used tools in icing research and aircraft design and certification. LEWICE has been transformed over

  1. Improving Life Cycle Management Through Simulation and Efficient Design

    DTIC Science & Technology

    2008-09-01

    design, the author uses the orthogonal and nearly orthogonal LH worksheet (Sanchez, 2005) to develop the design points. The worksheet is an Excel ...11 listing each design points. The worksheet is an Excel -based tool developed to ease in the design of large-scale simulation experiments. low...NOLH worksheet design ................................................................22 Figure 5. Two-way input combinations

  2. Telescope simulators for Hubble - An overview of optical designs

    NASA Technical Reports Server (NTRS)

    Davilla, Pam; Wood, H. J.; Atcheson, Paul D.; Saunders, Renee; Sullivan, Joe; Vaughan, Arthur H.; Saisse, Michel

    1993-01-01

    This paper briefly describes optical design of the Hubble Space Telescope (HST) and overviews three optical design simulators for HST which have been proposed for use as verification tools to characterize the performance of second-generation instruments during ground testing. These simulators are: the Refractive Aberrated Simulator developed at Ball Aerospace, the Optical Simulator developed at Laboratoire Astronomie Spatiale, and the Jet Propulsion Laboratory Stimulus. Relative advantages and disadvantages of each optical configuration are discussed.

  3. How to Target Activated Ras Proteins: Direct Inhibition vs. Induced Mislocalization

    PubMed Central

    Brock, Ethan J.; Ji, Kyungmin; Reiners, John J.; Mattingly, Raymond R.

    2016-01-01

    Oncogenic Ras proteins are a driving force in a significant set of human cancers and wild-type, unmutated Ras proteins likely contribute to the malignant phenotype of many more. The overall challenge of targeting activated Ras proteins has great promise to treat cancer, but this goal has yet to be achieved. Significant efforts and resources have been committed to inhibiting Ras, but these energies have so far made little impact in the clinic. Direct attempts to target activated Ras proteins have faced many obstacles, including the fundamental nature of the gain-of-function oncogenic activity being produced by a loss-of-function at the biochemical level. Nevertheless, there has been very promising recent pre-clinical progress. The major strategy that has so far reached the clinic aimed to inhibit activated Ras indirectly through blocking its post-translational modification and inducing its mislocalization. While these efforts to indirectly target Ras through inhibition of farnesyl transferase (FTase) were rationally designed, this strategy suffered from insufficient attention to the distinctions between the isoforms of Ras. This led to subsequent failures in large-scale clinical trials targeting K-Ras driven lung, colon, and pancreatic cancers. Despite these setbacks, efforts to indirectly target activated Ras through inducing its mislocalization have persisted. It is plausible that FTase inhibitors may still have some utility in the clinic, perhaps in combination with statins or other agents. Alternative approaches for inducing mislocalization of Ras through disruption of its palmitoylation cycle or interaction with chaperone proteins are in early stages of development. PMID:26423696

  4. Design and simulation of lithium rechargeable batteries

    SciTech Connect

    Doyle, C.M.

    1995-08-01

    Lithium -based rechargeable batteries that utilize insertion electrodes are being considered for electric-vehicle applications because of their high energy density and inherent reversibility. General mathematical models are developed that apply to a wide range of lithium-based systems, including the recently commercialized lithium-ion cell. The modeling approach is macroscopic, using porous electrode theory to treat the composite insertion electrodes and concentrated solution theory to describe the transport processes in the solution phase. The insertion process itself is treated with a charge-transfer process at the surface obeying Butler-Volmer kinetics, followed by diffusion of the lithium ion into the host structure. These models are used to explore the phenomena that occur inside of lithium cells under conditions of discharge, charge, and during periods of relaxation. Also, in order to understand the phenomena that limit the high-rate discharge of these systems, we focus on the modeling of a particular system with well-characterized material properties and system parameters. The system chosen is a lithium-ion cell produced by Bellcore in Red Bank, NJ, consisting of a lithium-carbon negative electrode, a plasticized polymer electrolyte, and a lithium-manganese-oxide spinel positive electrode. This battery is being marketed for consumer electronic applications. The system is characterized experimentally in terms of its transport and thermodynamic properties, followed by detailed comparisons of simulation results with experimental discharge curves. Next, the optimization of this system for particular applications is explored based on Ragone plots of the specific energy versus average specific power provided by various designs.

  5. Differential expression of the ras gene family in mice.

    PubMed Central

    Leon, J; Guerrero, I; Pellicer, A

    1987-01-01

    We compared the expression of the ras gene family (H-ras, K-ras, and N-ras) in adult mouse tissues and during development. We found substantial variations in expression among different organs and in the amounts of the different transcripts originating from each gene, especially for the N-ras gene. The expression patterns were consistent with the reported preferential tissue activation of ras genes and suggested different cellular functions for each of the ras genes. Images PMID:3600635

  6. Functional significance of the novel H-RAS gene mutation M72I in a patient with medullary thyroid cancer.

    PubMed

    Barollo, S; Pezzani, R; Cristiani, A; Bertazza, L; Rubin, B; Bulfone, A; Pelizzo, M R; Torresan, F; Mantero, F; Pennelli, G; Moro, S; Mian, C

    2013-10-01

    Medullary thyroid cancer (MTC) accounts for around 5-10% of all thyroid cancers. Though usually sporadic, 1 in 4 cases are of genetic origin, with germinal mutations in the RET proto-oncogene in familial forms and somatic mutations both in RET and in the RAS family genes in sporadic ones.This study aimed to characterize a rare H-RAS sequence variant -M72I- in a patient with sporadic MTC, focusing on its functional significance.Mutation analysis was performed for the RET, N-RAS, K-RAS and H-RAS genes by direct sequencing. Western blot analysis was done on 4 thyroid tissues from 1 patient carrying the M72I mutation in H-RAS, 1 with the Q61R mutation in H-RAS, 1 with no RET, H-RAS, K-RAS or N-RAS gene mutations, and 1 normal thyroid, using different antibodies against Erk1/2, phospho-Erk1/2 (Thr202/Tyr204), Akt and phospho-Akt (Ser473). Large-scale molecular dynamics simulations were completed for H-RAS wt and H-RAS M72I.Western blot analysis demonstrated that both MAPK and PI3K/Akt pathways were activated in the MTC patient carrying the M72I variant. In silico results showed conformational changes in H-RAS that could influence its activation by Sos and phosphate binding. Results of molecular dynamics were consistent with Western blot experiments.The M72I mutation may contribute effectively to proliferation and survival signaling throughout the MAPK and PI3K/Akt pathways. This work underscores the importance of studying genetic alterations that may lead to carcinogenesis.

  7. Phobos: Simulation-Driven Design for Exploration

    NASA Technical Reports Server (NTRS)

    Crues, Edwin

    2015-01-01

    Dr. Edwin "Zack" Crues presented an overview of the current use of modeling and simulation technologies by the NASA Exploration Systems Simulations (NExSyS) team in investigating the spacecraft and missions for the human exploration of Mars' moon Phobos.

  8. AVCS Simulator Test Plan and Design Guide

    NASA Technical Reports Server (NTRS)

    Shelden, Stephen

    2001-01-01

    Internal document for communication of AVCS direction and documentation of simulator functionality. Discusses methods for AVCS simulation evaluation of pilot functions, implementation strategy of varying functional representation of pilot tasks (by instantiations of a base AVCS to reasonably approximate the interface of various vehicles -- e.g. Altair, GlobalHawk, etc.).

  9. A knee arthroscopy simulator: design and validation.

    PubMed

    Escoto, Abelardo; Le Ber, Fraser; Trejos, Ana Luisa; Naish, Michael D; Patel, Rajni V; Lebel, Marie-Eve

    2013-01-01

    Many challenges exist when teaching and learning arthroscopic surgery, carrying a high risk of damaging the joint during the learning process. To minimize risk, the use of arthroscopy simulators allows trainees to learn basic skills in a risk-free environment before entering the operating room. A high-fidelity physical knee arthroscopy simulator is proposed to bridge the gap between surgeons and residents. The simulator is composed of modular and replaceable elements and can measure applied forces, instrument position and hand motion, in order to assess performance in real time. A construct validity study was conducted in order to assess the performance improvement of novices after practicing with the simulator. In addition, a face validity study involving expert surgeons indicated that the simulator provides a realistic scenario suitable for teaching basic skills. Future work involves the development of better metrics to assess user performance.

  10. Simulant Basis for the Standard High Solids Vessel Design

    SciTech Connect

    Peterson, Reid A.; Fiskum, Sandra K.; Suffield, Sarah R.; Daniel, Richard C.; Gauglitz, Phillip A.; Wells, Beric E.

    2016-09-01

    This document provides the requirements for a test simulant suitable for demonstrating the mixing requirements for the Single High Solids Vessel Design (SHSVD). This simulant has not been evaluated for other purposes such as gas retention and release or erosion. The objective of this work is to provide an underpinning for the simulant properties based on actual waste characterization.

  11. Some Current Problems in Simulator Design, Testing and Use.

    ERIC Educational Resources Information Center

    Caro, Paul W.

    Concerned with the general problem of the effectiveness of simulator training, this report reflects information developed during the conduct of aircraft simulator training research projects sponsored by the Air Force, Army, Navy, and Coast Guard. Problems are identified related to simulator design, testing, and use, all of which impact upon…

  12. Mechanical design of NASA Ames Research Center vertical motion simulator

    NASA Technical Reports Server (NTRS)

    Engelbert, D. F.; Bakke, A. P.; Chargin, M. K.; Vallotton, W. C.

    1976-01-01

    NASA has designed and is constructing a new flight simulator with large vertical travel. Several aspects of the mechanical design of this Vertical Motion Simulator (VMS) are discussed, including the multiple rack and pinion vertical drive, a pneumatic equilibration system, and the friction-damped rigid link catenaries used as cable supports.

  13. Automated simulation as part of a design workstation

    NASA Technical Reports Server (NTRS)

    Cantwell, Elizabeth; Shenk, T.; Robinson, P.; Upadhye, R.

    1990-01-01

    A development project for a design workstation for advanced life-support systems (called the DAWN Project, for Design Assistant Workstation), incorporating qualitative simulation, required the implementation of a useful qualitative simulation capability and the integration of qualitative and quantitative simulation such that simulation capabilities are maximized without duplication. The reason is that to produce design solutions to a system goal, the behavior of the system in both a steady and perturbed state must be represented. The Qualitative Simulation Tool (QST), on an expert-system-like model building and simulation interface toll called ScratchPad (SP), and on the integration of QST and SP with more conventional, commercially available simulation packages now being applied in the evaluation of life-support system processes and components are discussed.

  14. Evidence-centered design for simulation-based assessment.

    PubMed

    Mislevy, Robert J

    2013-10-01

    Simulations provide opportunities for people to learn and to develop skills for situations that are expensive, time-consuming, or dangerous. Careful design can support their learning by tailoring the features of situations to their levels of skill, allowing repeated attempts, and providing timely feedback. The same environments provide opportunities for assessing people's capabilities to act in these situations. This article describes an assessment design framework that can help projects develop effective simulation-based assessments. It reviews the rationale and terminology of the "evidence-centered" assessment design framework, discusses how it aligns with the principles of simulation design, and illustrates ideas with examples from engineering and medicine. Advice is offered for designing a new simulation-based assessment and for adapting an existing simulation system for assessment purposes.

  15. RAS and Hedgehog--partners in crime.

    PubMed

    Lauth, Matthias

    2011-06-01

    Both RAS and Hedgehog (HH) pathway activation can be found in approximately one third of all cancers. In many cases, this activation occurs in the same tumor types, suggesting a positive impact of a simultaneous activation of RAS and HH on tumor development. This review aims to summarize the current knowledge about the molecular and functional crosstalk of RAS and HH signaling in the development of hyperproliferative disease.

  16. Control design and simulation of systems modeled using ADAMS

    NASA Technical Reports Server (NTRS)

    Sohoni, Vikram N.

    1989-01-01

    A technique for control design and simulation using the ADAMS software and a control design software package is presented. For design of control systems ADAMS generates a minimum realization linear time invariant (LTI), state space representation of multi-body models. This LTI representation can be produced in formats for input to several commercial control design packages. The user can exercise various design strategies in the control design software to arrive at a suitable compensator. The resulting closed loop model can then be simulated using ADAMS. This procedure is illustrated with two examples.

  17. Ras trafficking, localization and compartmentalized signalling.

    PubMed

    Prior, Ian A; Hancock, John F

    2012-04-01

    Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions. Recent work has revealed how differences between the Ras isoforms in their trafficking, localization and protein-membrane orientation enable signalling specificity to be determined. We review the various strategies used to characterize compartmentalized Ras localization and signalling. Localization is an important contextual modifier of signalling networks and insights from the Ras system are of widespread relevance for researchers interested in signalling initiated from membranes.

  18. Ras Regulates Rb via NORE1A.

    PubMed

    Barnoud, Thibaut; Donninger, Howard; Clark, Geoffrey J

    2016-02-05

    Mutations in the Ras oncogene are one of the most frequent events in human cancer. Although Ras regulates numerous growth-promoting pathways to drive transformation, it can paradoxically promote an irreversible cell cycle arrest known as oncogene-induced senescence. Although senescence has clearly been implicated as a major defense mechanism against tumorigenesis, the mechanisms by which Ras can promote such a senescent phenotype remain poorly defined. We have shown recently that the Ras death effector NORE1A plays a critical role in promoting Ras-induced senescence and connects Ras to the regulation of the p53 tumor suppressor. We now show that NORE1A also connects Ras to the regulation of a second major prosenescent tumor suppressor, the retinoblastoma (Rb) protein. We show that Ras induces the formation of a complex between NORE1A and the phosphatase PP1A, promoting the activation of the Rb tumor suppressor by dephosphorylation. Furthermore, suppression of Rb reduces NORE1A senescence activity. These results, together with our previous findings, suggest that NORE1A acts as a critical tumor suppressor node, linking Ras to both the p53 and the Rb pathways to drive senescence.

  19. Design of a Joint Service Multipurpose Arcade Combat Simulator (JMACS)

    DTIC Science & Technology

    1990-01-01

    SC AD-A221 133 Research Product 90-05 OTIC FILE COP’ Design of a Joint Service Multipurpose Arcade Combat Simulator ( JMACS ) DTICELECTE January 1990...Simulator ( JMACS ) 12. PERSONAL AUTHOR(S) Evans, Kenneth L., (ARI); Marshall, Albert H., & Wolff, Ronald S. (Naval Traininz Svstems Center): Broom. John M...Multipurpose Arcade Combat Simulator ( JMACS ) project. The JMACS project was an outgrowth of the Multipurpose Arcade Combat Simulator (MACS), a pateated part

  20. Simulation Packages Expand Aircraft Design Options

    NASA Technical Reports Server (NTRS)

    2013-01-01

    In 2001, NASA released a new approach to computational fluid dynamics that allows users to perform automated analysis on complex vehicle designs. In 2010, Palo Alto, California-based Desktop Aeronautics acquired a license from Ames Research Center to sell the technology. Today, the product assists organizations in the design of subsonic aircraft, space planes, spacecraft, and high speed commercial jets.

  1. The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B

    PubMed Central

    Lu, Shaoyong; Jang, Hyunbum; Nussinov, Ruth; Zhang, Jian

    2016-01-01

    Ras mediates cell proliferation, survival and differentiation. Mutations in K-Ras4B are predominant at residues G12, G13 and Q61. Even though all impair GAP-assisted GTP → GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Here we aim to figure out their mechanisms and differential oncogenicity. In total, we performed 6.4 μs molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4BWT-GTP/GDP) catalytic domain, the K-Ras4BWT-GTP–GAP complex, and the mutants (K-Ras4BG12C/G12D/G12V-GTP/GDP, K-Ras4BG13D-GTP/GDP, K-Ras4BQ61H-GTP/GDP) and their complexes with GAP. In addition, we simulated ‘exchanged’ nucleotide states. These comprehensive simulations reveal that in solution K-Ras4BWT-GTP exists in two, active and inactive, conformations. Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4BG12C/G12D-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. These mechanisms may help elucidate the differential mutational statistics in K-Ras4B-driven cancers. Exchanged nucleotide simulations reveal that the conformational transition is more accessible in the GTP-to-GDP than in the GDP-to-GTP exchange. Importantly, GAP not only donates its R789 arginine finger, but stabilizes the catalytically-competent conformation and pre-organizes catalytic residue Q61; mutations disturb the R789/Q61 organization, impairing GAP-mediated GTP hydrolysis. Together, our simulations help provide a mechanistic explanation of key mutational events in one of the most oncogenic proteins in cancer. PMID:26902995

  2. Design and Test of Advanced Thermal Simulators for an Alkali Metal-Cooled Reactor Simulator

    NASA Technical Reports Server (NTRS)

    Garber, Anne E.; Dickens, Ricky E.

    2011-01-01

    The Early Flight Fission Test Facility (EFF-TF) at NASA Marshall Space Flight Center (MSFC) has as one of its primary missions the development and testing of fission reactor simulators for space applications. A key component in these simulated reactors is the thermal simulator, designed to closely mimic the form and function of a nuclear fuel pin using electric heating. Continuing effort has been made to design simple, robust, inexpensive thermal simulators that closely match the steady-state and transient performance of a nuclear fuel pin. A series of these simulators have been designed, developed, fabricated and tested individually and in a number of simulated reactor systems at the EFF-TF. The purpose of the thermal simulators developed under the Fission Surface Power (FSP) task is to ensure that non-nuclear testing can be performed at sufficiently high fidelity to allow a cost-effective qualification and acceptance strategy to be used. Prototype thermal simulator design is founded on the baseline Fission Surface Power reactor design. Recent efforts have been focused on the design, fabrication and test of a prototype thermal simulator appropriate for use in the Technology Demonstration Unit (TDU). While designing the thermal simulators described in this paper, effort were made to improve the axial power profile matching of the thermal simulators. Simultaneously, a search was conducted for graphite materials with higher resistivities than had been employed in the past. The combination of these two efforts resulted in the creation of thermal simulators with power capacities of 2300-3300 W per unit. Six of these elements were installed in a simulated core and tested in the alkali metal-cooled Fission Surface Power Primary Test Circuit (FSP-PTC) at a variety of liquid metal flow rates and temperatures. This paper documents the design of the thermal simulators, test program, and test results.

  3. Space shuttle visual simulation system design study

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The current and near-future state-of-the-art in visual simulation equipment technology is related to the requirements of the space shuttle visual system. Image source, image sensing, and displays are analyzed on a subsystem basis, and the principal conclusions are used in the formulation of a recommended baseline visual system. Perceptibility and visibility are also analyzed.

  4. Ras-Mediated Deregulation of the Circadian Clock in Cancer

    PubMed Central

    Relógio, Angela; Thomas, Philippe; Medina-Pérez, Paula; Reischl, Silke; Bervoets, Sander; Gloc, Ewa; Riemer, Pamela; Mang-Fatehi, Shila; Maier, Bert; Schäfer, Reinhold; Leser, Ulf; Herzel, Hanspeter; Kramer, Achim; Sers, Christine

    2014-01-01

    Circadian rhythms are essential to the temporal regulation of molecular processes in living systems and as such to life itself. Deregulation of these rhythms leads to failures in biological processes and eventually to the manifestation of pathological phenotypes including cancer. To address the questions as to what are the elicitors of a disrupted clock in cancer, we applied a systems biology approach to correlate experimental, bioinformatics and modelling data from several cell line models for colorectal and skin cancer. We found strong and weak circadian oscillators within the same type of cancer and identified a set of genes, which allows the discrimination between the two oscillator-types. Among those genes are IFNGR2, PITX2, RFWD2, PPARγ, LOXL2, Rab6 and SPARC, all involved in cancer-related pathways. Using a bioinformatics approach, we extended the core-clock network and present its interconnection to the discriminative set of genes. Interestingly, such gene signatures link the clock to oncogenic pathways like the RAS/MAPK pathway. To investigate the potential impact of the RAS/MAPK pathway - a major driver of colorectal carcinogenesis - on the circadian clock, we used a computational model which predicted that perturbation of BMAL1-mediated transcription can generate the circadian phenotypes similar to those observed in metastatic cell lines. Using an inducible RAS expression system, we show that overexpression of RAS disrupts the circadian clock and leads to an increase of the circadian period while RAS inhibition causes a shortening of period length, as predicted by our mathematical simulations. Together, our data demonstrate that perturbations induced by a single oncogene are sufficient to deregulate the mammalian circadian clock. PMID:24875049

  5. Automated simulation as part of a design workstation

    NASA Technical Reports Server (NTRS)

    Cantwell, E.; Shenk, T.; Robinson, P.; Upadhye, R.

    1990-01-01

    A development project for a design workstation for advanced life-support systems incorporating qualitative simulation, required the implementation of a useful qualitative simulation capability and the integration of qualitative and quantitative simulations, such that simulation capabilities are maximized without duplication. The reason is that to produce design solutions to a system goal, the behavior of the system in both a steady and perturbed state must be represented. The paper reports on the Qualitative Simulation Tool (QST), on an expert-system-like model building and simulation interface toll called ScratchPad (SP), and on the integration of QST and SP with more conventional, commercially available simulation packages now being applied in the evaluation of life-support system processes and components.

  6. Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?

    PubMed

    Cox, Adrienne D; Der, Channing J; Philips, Mark R

    2015-04-15

    RAS proteins require membrane association for their biologic activity, making this association a logical target for anti-RAS therapeutics. Lipid modification of RAS proteins by a farnesyl isoprenoid is an obligate step in that association, and is an enzymatic process. Accordingly, farnesyltransferase inhibitors (FTI) were developed as potential anti-RAS drugs. The lack of efficacy of FTIs as anticancer drugs was widely seen as indicating that blocking RAS membrane association was a flawed approach to cancer treatment. However, a deeper understanding of RAS modification and trafficking has revealed that this was an erroneous conclusion. In the presence of FTIs, KRAS and NRAS, which are the RAS isoforms most frequently mutated in cancer, become substrates for alternative modification, can still associate with membranes, and can still function. Thus, FTIs failed not because blocking RAS membrane association is an ineffective approach, but because FTIs failed to accomplish that task. Recent findings regarding RAS isoform trafficking and the regulation of RAS subcellular localization have rekindled interest in efforts to target these processes. In particular, improved understanding of the palmitoylation/depalmitoylation cycle that regulates RAS interaction with the plasma membrane, endomembranes, and cytosol, and of the potential importance of RAS chaperones, have led to new approaches. Efforts to validate and target other enzymatically regulated posttranslational modifications are also ongoing. In this review, we revisit lessons learned, describe the current state of the art, and highlight challenging but promising directions to achieve the goal of disrupting RAS membrane association and subcellular localization for anti-RAS drug development. Clin Cancer Res; 21(8); 1819-27. ©2015 AACR. See all articles in this CCR Focus section, "Targeting RAS-Driven Cancers."

  7. Optimal Living Environments for the Elderly: A Design Simulation Approach.

    ERIC Educational Resources Information Center

    Hoffman, Stephanie B.; And Others

    PLANNED AGE (Planned Alternatives for Gerontological Environments) is a consumer/advocate-oriented design simulation package that provides: (a) a medium for user-planner interaction in the design of living and service environments for the aged; (b) an educational, planning, design, and evaluation tool that can be used by the elderly, their…

  8. Maintenance Training Simulator Design and Acquisition.

    DTIC Science & Technology

    1980-08-01

    specification also permits the specification to be used in novel ways. For example, the ISD model specification can be used as a pre-TRRRM document to...Provide practice with novel variations in content and form of the basic material to be recalled. 11 115 j I CRITERIA ADJUST CONTROL DECISION LOGIC...plate containing the related series end item designation and the applicable system designation therein shall be engraved in neat, well-formed Gothic

  9. Degradation of Activated K-Ras Orthologue via K-Ras-specific Lysine Residues Is Required for Cytokinesis*

    PubMed Central

    Sumita, Kazutaka; Yoshino, Hirofumi; Sasaki, Mika; Majd, Nazanin; Kahoud, Emily Rose; Takahashi, Hidenori; Takeuchi, Koh; Kuroda, Taruho; Lee, Susan; Charest, Pascale G.; Takeda, Kosuke; Asara, John M.; Firtel, Richard A.; Anastasiou, Dimitrios; Sasaki, Atsuo T.

    2014-01-01

    Mammalian cells encode three closely related Ras proteins, H-Ras, N-Ras, and K-Ras. Oncogenic K-Ras mutations frequently occur in human cancers, which lead to dysregulated cell proliferation and genomic instability. However, mechanistic role of the Ras isoform regulation have remained largely unknown. Furthermore, the dynamics and function of negative regulation of GTP-loaded K-Ras have not been fully investigated. Here, we demonstrate RasG, the Dictyostelium orthologue of K-Ras, is targeted for degradation by polyubiquitination. Both ubiquitination and degradation of RasG were strictly associated with RasG activity. High resolution tandem mass spectrometry (LC-MS/MS) analysis indicated that RasG ubiquitination occurs at C-terminal lysines equivalent to lysines found in human K-Ras but not in H-Ras and N-Ras homologues. Substitution of these lysine residues with arginines (4KR-RasG) diminished RasG ubiquitination and increased RasG protein stability. Cells expressing 4KR-RasG failed to undergo proper cytokinesis and resulted in multinucleated cells. Ectopically expressed human K-Ras undergoes polyubiquitin-mediated degradation in Dictyostelium, whereas human H-Ras and a Dictyostelium H-Ras homologue (RasC) are refractory to ubiquitination. Our results indicate the existence of GTP-loaded K-Ras orthologue-specific degradation system in Dictyostelium, and further identification of the responsible E3-ligase may provide a novel therapeutic approach against K-Ras-mutated cancers. PMID:24338482

  10. Novel Methods for Electromagnetic Simulation and Design

    DTIC Science & Technology

    2016-08-03

    average 1 hour per response, including the time for reviewing instructions, searching existing   data sources, gathering and maintaining the data...perfectly conducting half-space, for the simulation of layered and microstructured metamaterials, and for the analysis of time -domain integral...Lorenz-Mie-Debye formalism for the Maxwell equa- tions to the time -domain. We showed that the problem of scattering from a perfectly con- ducting

  11. Physiological Based Simulator Fidelity Design Guidance

    NASA Technical Reports Server (NTRS)

    Schnell, Thomas; Hamel, Nancy; Postnikov, Alex; Hoke, Jaclyn; McLean, Angus L. M. Thom, III

    2012-01-01

    The evolution of the role of flight simulation has reinforced assumptions in aviation that the degree of realism in a simulation system directly correlates to the training benefit, i.e., more fidelity is always better. The construct of fidelity has several dimensions, including physical fidelity, functional fidelity, and cognitive fidelity. Interaction of different fidelity dimensions has an impact on trainee immersion, presence, and transfer of training. This paper discusses research results of a recent study that investigated if physiological-based methods could be used to determine the required level of simulator fidelity. Pilots performed a relatively complex flight task consisting of mission task elements of various levels of difficulty in a fixed base flight simulator and a real fighter jet trainer aircraft. Flight runs were performed using one forward visual channel of 40 deg. field of view for the lowest level of fidelity, 120 deg. field of view for the middle level of fidelity, and unrestricted field of view and full dynamic acceleration in the real airplane. Neuro-cognitive and physiological measures were collected under these conditions using the Cognitive Avionics Tool Set (CATS) and nonlinear closed form models for workload prediction were generated based on these data for the various mission task elements. One finding of the work described herein is that simple heart rate is a relatively good predictor of cognitive workload, even for short tasks with dynamic changes in cognitive loading. Additionally, we found that models that used a wide range of physiological and neuro-cognitive measures can further boost the accuracy of the workload prediction.

  12. JEFF: Air transport system design simulation

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Jeff is a remotely piloted vehicle designed by the Blue Team, a division of AE441, Inc., to fulfill the mission proposed by G-Dome Enterprises: to build a cost efficient aircraft to service Aeroworld with overnight cargo delivery. The design of Jeff was most significantly influenced by the need to minimize costs. This objective was pursued by building fewer large planes as opposed to many small planes. Thus, by building an aircraft with a large payload capacity, G-Dome Enterprises will be able to minimize the large costs and the large number of cycles that are associated with a large fleet. Another factor which had a significant influence on our design was the constraint that our design had to fit into a 2'x2'x5' storage container. This constraint meant that unless we wanted to build foldable wings that Jeff's span would be limited to 10 feet. Since this was not enough lifting surface to suit our needs a canard configuration was chosen to get the needed lifting surface and avoid the structural dilemma of foldable wings. The aircraft is constructed mainly of balsa, with spruce wing and canard spars and a monokote covering. It was designed to support a maximum payload weight of 35 oz. (total aircraft weight of 108 oz.) and withstand a maximum load factor of 2.5.

  13. ras gene Amplification and malignant transformation.

    PubMed Central

    Pulciani, S; Santos, E; Long, L K; Sorrentino, V; Barbacid, M

    1985-01-01

    Morphologic transformation of NIH 3T3 mouse cells occurs upon transfection of these cells with large amounts (greater than or equal to 10 micrograms) of recombinant DNA molecules carrying the normal human H-ras-1 proto-oncogene. We provide experimental evidence indicating that transformation of these NIH 3T3 cells results from the combined effect of multiple copies of the H-ras-1 proto-oncogene rather than from spontaneous mutation of one of the transfected H-ras-1 clones (E. Santos, E.P. Reddy, S. Pulciani, R.J. Feldman, and M. Barbacid, Proc. Natl. Acad. Sci. USA 80:4679-4683, 1983). Levels of H-ras-1 RNA and p21 expression are highly elevated in the NIH 3T3 transformants, and in those cases examined, these levels correlate with the malignant properties of these cells. We have also investigated the presence of amplified ras genes in a variety of human carcinomas. In 75 tumor biopsies, we found amplification of the human K-ras-2 locus in one carcinoma of the lung. These results indicate that ras gene amplification is an alternative pathway by which ras genes may participate in the development of human neoplasia. Images PMID:3915535

  14. Optimizing depuration of salmon in RAS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fish cultured within water recirculating aquaculture systems (RAS) can acquire "earthy" or "musty" off-flavors due to bioaccumulation of the compounds geosmin and 2-methylisoborneol (MIB), respectively, which are produced by certain bacterial species present in RAS biosolids and microbial biofilms. ...

  15. Dynamics of adaptive structures: Design through simulations

    NASA Technical Reports Server (NTRS)

    Park, K. C.; Alexander, S.

    1993-01-01

    The use of a helical bi-morph actuator/sensor concept by mimicking the change of helical waveform in bacterial flagella is perhaps the first application of bacterial motions (living species) to longitudinal deployment of space structures. However, no dynamical considerations were analyzed to explain the waveform change mechanisms. The objective is to review various deployment concepts from the dynamics point of view and introduce the dynamical considerations from the outset as part of design considerations. Specifically, the impact of the incorporation of the combined static mechanisms and dynamic design considerations on the deployment performance during the reconfiguration stage is studied in terms of improved controllability, maneuvering duration, and joint singularity index. It is shown that intermediate configurations during articulations play an important role for improved joint mechanisms design and overall structural deployability.

  16. Where no Ras has gone before: VPS35 steers N-Ras through the cytosol.

    PubMed

    Zhou, Mo; Philips, Mark R

    2017-01-27

    Ras is the best-studied member of the superfamily of small GTPases because of its role in cancer. Ras proteins transmit signals for proliferation, differentiation and survival. Three RAS genes encode 4 isoforms. All Ras isoforms have long been considered membrane bound, a localization required for function. Our recent study revealed that N-Ras differs from all other isoforms in being largely cytosolic even following modification with a prenyl lipid. Endogenous, cytosolic N-Ras chromatographed in both high and low molecular weight pools, a pattern that required prenylation, suggesting prenyl-dependent interaction with other proteins. VPS35, a coat protein of the retromer, was shown to interact with prenylated N-Ras in the cytosol. Silencing VPS35 results in partial N-Ras mislocalization on vesicular and tubulovesicular structures, reduced GTP-loading of Ras proteins, and inhibited proliferation and MAPK signaling in an oncogenic N-Ras-driven tumor cell line. Our data revealed a novel regulator of N-Ras trafficking and signaling.

  17. Modeling and Simulation for Mission Operations Work System Design

    NASA Technical Reports Server (NTRS)

    Sierhuis, Maarten; Clancey, William J.; Seah, Chin; Trimble, Jay P.; Sims, Michael H.

    2003-01-01

    Work System analysis and design is complex and non-deterministic. In this paper we describe Brahms, a multiagent modeling and simulation environment for designing complex interactions in human-machine systems. Brahms was originally conceived as a business process design tool that simulates work practices, including social systems of work. We describe our modeling and simulation method for mission operations work systems design, based on a research case study in which we used Brahms to design mission operations for a proposed discovery mission to the Moon. We then describe the results of an actual method application project-the Brahms Mars Exploration Rover. Space mission operations are similar to operations of traditional organizations; we show that the application of Brahms for space mission operations design is relevant and transferable to other types of business processes in organizations.

  18. Designing a SCADA system simulator for fast breeder reactor

    NASA Astrophysics Data System (ADS)

    Nugraha, E.; Abdullah, A. G.; Hakim, D. L.

    2016-04-01

    SCADA (Supervisory Control and Data Acquisition) system simulator is a Human Machine Interface-based software that is able to visualize the process of a plant. This study describes the results of the process of designing a SCADA system simulator that aims to facilitate the operator in monitoring, controlling, handling the alarm, accessing historical data and historical trend in Nuclear Power Plant (NPP) type Fast Breeder Reactor (FBR). This research used simulation to simulate NPP type FBR Kalpakkam in India. This simulator was developed using Wonderware Intouch software 10 and is equipped with main menu, plant overview, area graphics, control display, set point display, alarm system, real-time trending, historical trending and security system. This simulator can properly simulate the principle of energy flow and energy conversion process on NPP type FBR. This SCADA system simulator can be used as training media for NPP type FBR prospective operators.

  19. Pyrometry simulator (pyrosim) for diagnostic design.

    SciTech Connect

    Dolan, Daniel H., III

    2011-10-01

    Signal estimates are crucial to the design of time-resolved pyrometry measurements. These estimates affect fundamental design decisions, including the optical relay (fiber versus open beam), spectral range (visible or infrared), and amplification needs (possibly at the expense of time resolution). The pyrosim program makes such estimates, allowing the collected power, photon flux, and measured signal to be determined in a broad range of pyrometry measurements. Geometrical collection limits can be applied; sample emissivity, transfer efficiency, and detector sensitivity may also be specified, either as constants or functions of wavelength.

  20. Estimation of Channel-Forming Discharge and Large-Event Geomorphic Response Using HEC-RAS

    NASA Astrophysics Data System (ADS)

    Hamilton, P.; Strom, K.; Hosseiny, S. M. H.

    2015-12-01

    The goal of the present work was to consider the functionality and applicability of HEC-RAS sediment transport simulations in two situations. The first was as a mode for obtaining quick estimates of the effective discharge, one measure of channel-forming discharge, and the second was as a mode to quickly estimate sediment transport and the commensurate potential erosion and deposition during large flood events. Though there are many other sediment transport and morphodynamic models available, e.g., CCHE1D, Nays2DH, we were interested in using HEC-RAS since this is the model of choice for many regulatory bodies, e.g., FEMA, cities, and counties. This makes using the sediment transport capability of HEC-RAS a natural extension of models that already otherwise exist and are well calibrated. In first looking at the utility of these models, we wanted to estimate the effective discharge of streams. Effective discharge is one way of defining the channel-forming discharge for a stream and is therefore an important parameter in natural channel design and restoration efforts. By running this range of floods, one can easily obtain an estimate for recurrence interval most responsible for moving the majority of sediment over a long time period. Results were compared to data collected within our research group on the Brazos River (TX). Effective discharge is an important estimate, particularly in understanding the equilibrium channel condition. Nevertheless, large floods are contemporaneously catastrophic and understanding their potential effects is desirable. Finally, we performed some sensitivity analysis to better understand the underlying assumptions of the various sediment transport model options and how they might affect the outcome of the aforementioned computations.

  1. Simulation in the Service of Design - Asking the Right Questions

    SciTech Connect

    Donn, Michael; Selkowitz, Stephen; Bordass, Bill

    2009-03-01

    This paper proposes an approach to the creation of design tools that address the real information needs of designers in the early stages of design of nonresidential buildings. Traditional simplified design tools are typically too limited to be of much use, even in conceptual design. The proposal is to provide access to the power of detailed simulation tools, at a stage in design when little is known about the final building, but at a stage also when the freedom to explore options is greatest. The proposed approach to tool design has been derived from consultation with design analysis teams as part of the COMFEN tool development. The paper explores how tools like COMFEN have been shaped by this consultation and how requests from these teams for real-world relevance might shape such tools in the future, drawing into the simulation process the lessons from Post Occupancy Evaluation (POE) of buildings.

  2. Ras oncogene and inflammation: partners in crime.

    PubMed

    Sparmann, Anke; Bar-Sagi, Dafna

    2005-06-01

    It is well established that Ras oncogenes facilitate neoplastic conversion by stimulating tumor cell growth, survival and motility. However, current studies have indicated that the role of Ras in malignant transformation extends beyond these cell-intrinsic effects to include the establishment of a pro-tumorigenic host environment. We have recently demonstrated that Ras-induced secretion of the chemokine Interleukin-8 (CXCL-8/IL-8) elicits a local inflammatory reaction that is critical for neo-vascularization and sustained tumor growth. Our data identify a novel mechanism by which the Ras oncogene promotes tumor-host interactions that are essential for cancer progression, and suggest that CXCL-8 could serve as a surrogate marker for in-vivo Ras activity.

  3. X-ray plasma source design simulations

    SciTech Connect

    Cerjan, C.

    1993-07-01

    The optimization of soft x-ray production from a laser-produced plasma for lithographic applications is discussed in the context of recent experiments by R. Kauffman et al. which indicate that a conversion efficiency of 0.01 can be obtained with Sn targets at modest laser intensity. Computer simulations of the experiments delineate the critical phenomena underlying these high conversion efficiencies, especially the role of hydrodynamic expansion and radiative emission. Qualitative features of the experiments are reproduced including the transition from one-dimensional to two-dimensional flow. The quantitative discrepancy is ascribed to incorrect initiation of the ablating plasma and to inadequate atomic transition rate evaluation.

  4. Isolation of two novel ras genes in Dictyostelium discoideum; evidence for a complex, developmentally regulated ras gene subfamily.

    PubMed

    Daniel, J; Bush, J; Cardelli, J; Spiegelman, G B; Weeks, G

    1994-02-01

    In Dictyostelium discoideum, three ras genes (rasD, rasG and rasB) and one ras-related gene (rap1) have been previously isolated and characterized, and the deduced amino acid sequence of their predicted protein products share at least 50% sequence identity with the human H-Ras protein. We have now cloned and characterized two additional members of the ras gene subfamily in Dictyostelium, rasC and rasS. These genes are developmentally regulated and unlike the previously isolated Dictyostelium ras genes, maximum levels of their transcripts were detected during aggregation, suggesting that the encoded proteins have distinct functions during aggregation. The rasC cDNA encodes a 189 amino acid protein that is 65% identical to the Dictyostelium RasD and RasG proteins and 56% identical to the human H-Ras protein. The predicted 194 amino acid gene product encoded by rasS is 60% identical to the Dictyostelium RasD and RasG proteins and 54% identical to the human H-Ras protein. Whereas RasD, RasG, RasB and Rap1 are totally conserved in their putative effector domains relative to H-Ras, RasC and RasS have single amino acid substitutions in their effector domains, consistent with the idea that they have unique functions. In RasC, aspartic acid-38 has been replaced by asparagine (D38N), and in RasS, isoleucine-36 has been replaced by leucine (I36L). In addition, both proteins have several differences in the effector-proximal domain, a domain which is believed to play a role in Ras target activation. In RasC, there is a single conservative amino acid change in the canonical sequence of the binding site for the Ras-specific monoclonal antibody Y13-259, and consequently, RasC is less immunoreactive with the antibody than either of the Dictyostelium RasD or RasG proteins. In contrast, RasS, which has three substitutions in the Y13-259 binding site, does not react with the Y13-259 antibody.

  5. Design of Object-Oriented Distributed Simulation Classes

    NASA Technical Reports Server (NTRS)

    Schoeffler, James D.

    1995-01-01

    Distributed simulation of aircraft engines as part of a computer aided design package being developed by NASA Lewis Research Center for the aircraft industry. The project is called NPSS, an acronym for "Numerical Propulsion Simulation System". NPSS is a flexible object-oriented simulation of aircraft engines requiring high computing speed. It is desirable to run the simulation on a distributed computer system with multiple processors executing portions of the simulation in parallel. The purpose of this research was to investigate object-oriented structures such that individual objects could be distributed. The set of classes used in the simulation must be designed to facilitate parallel computation. Since the portions of the simulation carried out in parallel are not independent of one another, there is the need for communication among the parallel executing processors which in turn implies need for their synchronization. Communication and synchronization can lead to decreased throughput as parallel processors wait for data or synchronization signals from other processors. As a result of this research, the following have been accomplished. The design and implementation of a set of simulation classes which result in a distributed simulation control program have been completed. The design is based upon MIT "Actor" model of a concurrent object and uses "connectors" to structure dynamic connections between simulation components. Connectors may be dynamically created according to the distribution of objects among machines at execution time without any programming changes. Measurements of the basic performance have been carried out with the result that communication overhead of the distributed design is swamped by the computation time of modules unless modules have very short execution times per iteration or time step. An analytical performance model based upon queuing network theory has been designed and implemented. Its application to realistic configurations has not

  6. Design of object-oriented distributed simulation classes

    NASA Technical Reports Server (NTRS)

    Schoeffler, James D. (Principal Investigator)

    1995-01-01

    Distributed simulation of aircraft engines as part of a computer aided design package is being developed by NASA Lewis Research Center for the aircraft industry. The project is called NPSS, an acronym for 'Numerical Propulsion Simulation System'. NPSS is a flexible object-oriented simulation of aircraft engines requiring high computing speed. It is desirable to run the simulation on a distributed computer system with multiple processors executing portions of the simulation in parallel. The purpose of this research was to investigate object-oriented structures such that individual objects could be distributed. The set of classes used in the simulation must be designed to facilitate parallel computation. Since the portions of the simulation carried out in parallel are not independent of one another, there is the need for communication among the parallel executing processors which in turn implies need for their synchronization. Communication and synchronization can lead to decreased throughput as parallel processors wait for data or synchronization signals from other processors. As a result of this research, the following have been accomplished. The design and implementation of a set of simulation classes which result in a distributed simulation control program have been completed. The design is based upon MIT 'Actor' model of a concurrent object and uses 'connectors' to structure dynamic connections between simulation components. Connectors may be dynamically created according to the distribution of objects among machines at execution time without any programming changes. Measurements of the basic performance have been carried out with the result that communication overhead of the distributed design is swamped by the computation time of modules unless modules have very short execution times per iteration or time step. An analytical performance model based upon queuing network theory has been designed and implemented. Its application to realistic configurations has

  7. Agent Based Simulation Design for Aggregation and Disaggregation

    DTIC Science & Technology

    2011-12-01

    Development of a Generic Data-Driven Simulation.‖ In Proceed- ings of the 2010 Winter Simulation Conference, edited by B. Johansson, S. Jain, J. Montoya ...DARPA, Santa Monica, CA. Davis, P. and R. Hillestad. 1993. ―Families of Models that Cross Levels of Resolution: Issues for Design, Calibration and...Issues, and Prin- ciples.‖ RAND N-3400-DARPA, Santa Monica, CA. Department of Defense. 1995. ―Department of Defense Modeling and Simulation Master

  8. Control Design for a Motion Cueing on Driving Simulator

    NASA Astrophysics Data System (ADS)

    de-J. Lozoya-Santos, Jorge; Tudon-Martinez, Juan C.; Salinas, Julio

    2017-01-01

    A Linear Quadratic Regulator (LQR) has been designed to simulate the pitch and roll vehicle dynamics of a platform which is connected to the real time simulation environment of Dynacar. The motion cueing algorithm translates the movement of the simulated vehicle to the platform using three rotary actuators, by satisfying all actuation boundaries. Experimental results illustrate that the LQR motion cueing algorithm performs satisfactory the tracking control at low frequencies, close to the resonance frequencies of the pitch and roll motion.

  9. The Design, Development, and Evaluation of an Evaluative Computer Simulation.

    ERIC Educational Resources Information Center

    Ehrlich, Lisa R.

    This paper discusses evaluation design considerations for a computer based evaluation simulation developed at the University of Iowa College of Medicine in Cardiology to assess the diagnostic skills of primary care physicians and medical students. The simulation developed allows for the assessment of diagnostic skills of physicians in the…

  10. Telescope simulators for Hubble: an overview of optical designs.

    PubMed

    Davila, P; Wood, H J; Atcheson, P D; Saunders, R; Sullivan, J; Vaughan, A H; Saisse, M

    1993-04-01

    Various optical configurations for Hubble Space Telescope simulators have been proposed, and some are being built for use as verification tools to characterize the performance of second-generation instruments during ground testing. We describe the Hubble Space Telescope, present an overview of three optical designs for simulators, and discuss the relative advantages and disadvantages of each configuration.

  11. Design Model for Learner-Centered, Computer-Based Simulations.

    ERIC Educational Resources Information Center

    Hawley, Chandra L.; Duffy, Thomas M.

    This paper presents a model for designing computer-based simulation environments within a constructivist framework for the K-12 school setting. The following primary criteria for the development of simulations are proposed: (1) the problem needs to be authentic; (2) the cognitive demand in learning should be authentic; (3) scaffolding supports a…

  12. Designing Nursing Simulation Clinical Experiences to Promote Critical Inquiry

    ERIC Educational Resources Information Center

    Beattie, Bev; Koroll, Donna; Price, Susan

    2010-01-01

    The use of high fidelity simulation (HFS) learning opportunities in nursing education has received increased attention in the literature. This article describes the design of a systematic framework used to promote critical inquiry and provide meaningful simulation clinical experiences for second year nursing students. Critical inquiry, as defined…

  13. Arrow 227: Air transport system design simulation

    NASA Technical Reports Server (NTRS)

    Bontempi, Michael; Bose, Dave; Brophy, Georgeann; Cashin, Timothy; Kanarios, Michael; Ryan, Steve; Peterson, Timothy

    1992-01-01

    The Arrow 227 is a student-designed commercial transport for use in a overnight package delivery network. The major goal of the concept was to provide the delivery service with the greatest potential return on investment. The design objectives of the Arrow 227 were based on three parameters; production cost, payload weight, and aerodynamic efficiency. Low production cost helps to reduce initial investment. Increased payload weight allows for a decrease in flight cycles and, therefore, less fuel consumption than an aircraft carrying less payload weight and requiring more flight cycles. In addition, fewer flight cycles will allow a fleet to last longer. Finally, increased aerodynamic efficiency in the form of high L/D will decrease fuel consumption.

  14. Membrane-associated Ras dimers are isoform-specific: K-Ras dimers differ from H-Ras dimers.

    PubMed

    Jang, Hyunbum; Muratcioglu, Serena; Gursoy, Attila; Keskin, Ozlem; Nussinov, Ruth

    2016-06-15

    Are the dimer structures of active Ras isoforms similar? This question is significant since Ras can activate its effectors as a monomer; however, as a dimer, it promotes Raf's activation and MAPK (mitogen-activated protein kinase) cell signalling. In the present study, we model possible catalytic domain dimer interfaces of membrane-anchored GTP-bound K-Ras4B and H-Ras, and compare their conformations. The active helical dimers formed by the allosteric lobe are isoform-specific: K-Ras4B-GTP favours the α3 and α4 interface; H-Ras-GTP favours α4 and α5. Both isoforms also populate a stable β-sheet dimer interface formed by the effector lobe; a less stable β-sandwich interface is sustained by salt bridges of the β-sheet side chains. Raf's high-affinity β-sheet interaction is promoted by the active helical interface. Collectively, Ras isoforms' dimer conformations are not uniform; instead, the isoform-specific dimers reflect the favoured interactions of the HVRs (hypervariable regions) with cell membrane microdomains, biasing the effector-binding site orientations, thus isoform binding selectivity.

  15. X-ray plasma source design simulations.

    PubMed

    Cerjan, C

    1993-12-01

    The optimization of soft x-ray production from a laser-produced plasma for lithographic applications is discussed in the context of recent experiments by Kauffman et al. [Appl. Opt. 32, 6897 (1993)], which indicate that a conversion efficiency of 0.01 can be obtained with Sn targets at modest laser intensity. Computer simulations of the experiments delineate the critical phenomena underlying these high conversion efficiencies, especially the role of hydrodynamic expansion and radiative emission. Qualitative features of the experiments are reproduced, including the transition from one-dimensional to two-dimensional flow. The quantitative discrepancy is ascribed to incorrect initiation of the ablating plasma and to inadequate atomic transition rate evaluation.

  16. SINERGIA laparoscopic virtual reality simulator: didactic design and technical development.

    PubMed

    Lamata, Pablo; Gómez, Enrique J; Sánchez-Margallo, Francisco M; López, Oscar; Monserrat, Carlos; García, Verónica; Alberola, Carlos; Florido, Miguel Angel Rodríguez; Ruiz, Juan; Usón, Jesús

    2007-03-01

    VR laparoscopic simulators have demonstrated its validity in recent studies, and research should be directed towards a high training effectiveness and efficacy. In this direction, an insight into simulators' didactic design and technical development is provided, by describing the methodology followed in the building of the SINERGIA simulator. It departs from a clear analysis of training needs driven by a surgical training curriculum. Existing solutions and validation studies are an important reference for the definition of specifications, which are described with a suitable use of simulation technologies. Five new didactic exercises are proposed to train some of the basic laparoscopic skills. Simulator construction has required existing algorithms and the development of a particle-based biomechanical model, called PARSYS, and a collision handling solution based in a multi-point strategy. The resulting VR laparoscopic simulator includes new exercises and enhanced simulation technologies, and is finding a very good acceptance among surgeons.

  17. Absolute Quantification of Endogenous Ras Isoform Abundance

    PubMed Central

    Mageean, Craig J.; Griffiths, John R.; Smith, Duncan L.; Clague, Michael J.; Prior, Ian A.

    2015-01-01

    Ras proteins are important signalling hubs situated near the top of networks controlling cell proliferation, differentiation and survival. Three almost identical isoforms, HRAS, KRAS and NRAS, are ubiquitously expressed yet have differing biological and oncogenic properties. In order to help understand the relative biological contributions of each isoform we have optimised a quantitative proteomics method for accurately measuring Ras isoform protein copy number per cell. The use of isotopic protein standards together with selected reaction monitoring for diagnostic peptides is sensitive, robust and suitable for application to sub-milligram quantities of lysates. We find that in a panel of isogenic SW48 colorectal cancer cells, endogenous Ras proteins are highly abundant with ≥260,000 total Ras protein copies per cell and the rank order of isoform abundance is KRAS>NRAS≥HRAS. A subset of oncogenic KRAS mutants exhibit increased total cellular Ras abundance and altered the ratio of mutant versus wild type KRAS protein. These data and methodology are significant because Ras protein copy number is required to parameterise models of signalling networks and informs interpretation of isoform-specific Ras functional data. PMID:26560143

  18. Advanced Simulation and Computing Co-Design Strategy

    SciTech Connect

    Ang, James A.; Hoang, Thuc T.; Kelly, Suzanne M.; McPherson, Allen; Neely, Rob

    2015-11-01

    This ASC Co-design Strategy lays out the full continuum and components of the co-design process, based on what we have experienced thus far and what we wish to do more in the future to meet the program’s mission of providing high performance computing (HPC) and simulation capabilities for NNSA to carry out its stockpile stewardship responsibility.

  19. Design and Performance Frameworks for Constructing Problem-Solving Simulations

    ERIC Educational Resources Information Center

    Stevens, Rons; Palacio-Cayetano, Joycelin

    2003-01-01

    Rapid advancements in hardware, software, and connectivity are helping to shorten the times needed to develop computer simulations for science education. These advancements, however, have not been accompanied by corresponding theories of how best to design and use these technologies for teaching, learning, and testing. Such design frameworks…

  20. Design Factors for Educationally Effective Animations and Simulations

    ERIC Educational Resources Information Center

    Plass, Jan L.; Homer, Bruce D.; Hayward, Elizabeth O.

    2009-01-01

    This paper reviews research on learning from dynamic visual representations and offers principles for the design of animations and simulations that assure their educational effectiveness. In addition to established principles, new and revised design principle are presented that have been derived from recent research. Our review focuses on the…

  1. Simulations Using a Computer/Videodisc System: Instructional Design Considerations.

    ERIC Educational Resources Information Center

    Ehrlich, Lisa R.

    Instructional design considerations involved in using level four videodisc systems when designing simulations are explored. Discussion of the hardware and software system characteristics notes that computer based training offers the features of text, graphics, color, animation, and highlighting techniques, while a videodisc player offers all of…

  2. Insights from molecular dynamics simulations for computational protein design.

    PubMed

    Childers, Matthew Carter; Daggett, Valerie

    2017-02-01

    A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics. Here, we review how insights into protein dynamics derived from MD simulations have influenced the design of proteins. One of the greatest strengths of MD is its capacity to reveal information beyond what is available in the static structures deposited in the Protein Data Bank. In this regard simulations can be used to directly guide protein design by providing atomistic details of the dynamic molecular interactions contributing to protein stability and function. MD simulations can also be used as a virtual screening tool to rank, select, identify, and assess potential designs. MD is uniquely poised to inform protein design efforts where the application requires realistic models of protein dynamics and atomic level descriptions of the relationship between dynamics and function. Here, we review cases where MD simulations was used to modulate protein stability and protein function by providing information regarding the conformation(s), conformational transitions, interactions, and dynamics that govern stability and function. In addition, we discuss cases where conformations from protein folding/unfolding simulations have been exploited for protein design, yielding novel outcomes that could not be obtained from static structures.

  3. Design by Dragging: An Interface for Creative Forward and Inverse Design with Simulation Ensembles

    PubMed Central

    Coffey, Dane; Lin, Chi-Lun; Erdman, Arthur G.; Keefe, Daniel F.

    2014-01-01

    We present an interface for exploring large design spaces as encountered in simulation-based engineering, design of visual effects, and other tasks that require tuning parameters of computationally-intensive simulations and visually evaluating results. The goal is to enable a style of design with simulations that feels as-direct-as-possible so users can concentrate on creative design tasks. The approach integrates forward design via direct manipulation of simulation inputs (e.g., geometric properties, applied forces) in the same visual space with inverse design via “tugging” and reshaping simulation outputs (e.g., scalar fields from finite element analysis (FEA) or computational fluid dynamics (CFD)). The interface includes algorithms for interpreting the intent of users’ drag operations relative to parameterized models, morphing arbitrary scalar fields output from FEA and CFD simulations, and in-place interactive ensemble visualization. The inverse design strategy can be extended to use multi-touch input in combination with an as-rigid-as-possible shape manipulation to support rich visual queries. The potential of this new design approach is confirmed via two applications: medical device engineering of a vacuum-assisted biopsy device and visual effects design using a physically based flame simulation. PMID:24051845

  4. Metabolic Dependencies in RAS-Driven Cancers.

    PubMed

    Kimmelman, Alec C

    2015-04-15

    The ability to inhibit the RAS oncogene has been the holy grail of oncology because of the critical role of this gene in a multitude of tumor types. In addition, RAS-mutant tumors are among the most aggressive and refractory to treatment. Although directly targeting the RAS oncogene has proven challenging, an alternative approach for treating RAS-driven cancers is to inhibit critical downstream events that are required for tumor maintenance. Indeed, much focus has been put on inhibiting signaling cascades downstream of RAS. Recent studies have shown that oncogenic RAS promotes a metabolic reprogramming of tumor cells, shifting them toward an anabolic metabolism necessary to produce biomass to support unconstrained proliferation. These cancers also use a diverse set of fuel sources to meet their metabolic needs and have even developed a variety of mechanisms to act as metabolic scavengers to obtain necessary metabolic substrates from both extracellular and intracellular sources. Collectively, these adaptations can create "metabolic bottlenecks" whereby tumor cells rely on particular pathways or rate-limiting metabolites. In this regard, inhibiting individual or combinations of these metabolic pathways can attenuate growth in preclinical models. Because these dependencies are tumor selective and downstream of oncogenic RAS, there is the opportunity for therapeutic intervention. Although targeting tumor metabolism is still in the early days of translation to patients, our continued advances in understanding critical metabolic adaptations in RAS-driven cancers, as well as the ability to study this altered metabolism in relevant tumor models, will accelerate the development of new therapeutic approaches. Clin Cancer Res; 21(8); 1828-34. ©2015 AACR. See all articles in this CCR Focus section, "Targeting RAS-Driven Cancers."

  5. Regulation of Ras Exchange Factors and Cellular Localization of Ras Activation by Lipid Messengers in T Cells

    PubMed Central

    Jun, Jesse E.; Rubio, Ignacio; Roose, Jeroen P.

    2013-01-01

    The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs) catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and Son of Sevenless (SOS)-family GEFs. Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood. One large group of biomolecules critically involved in the control of RasGEFs functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR) stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells. PMID:24027568

  6. Evolutionary Design and Simulation of a Tube Crawling Inspection Robot

    NASA Technical Reports Server (NTRS)

    Craft, Michael; Howsman, Tom; ONeil, Daniel; Howell, Joe T. (Technical Monitor)

    2002-01-01

    The Space Robotics Assembly Team Simulation (SpaceRATS) is an expansive concept that will hopefully lead to a space flight demonstration of a robotic team cooperatively assembling a system from its constitutive parts. A primary objective of the SpaceRATS project is to develop a generalized evolutionary design approach for multiple classes of robots. The portion of the overall SpaceRats program associated with the evolutionary design and simulation of an inspection robot's morphology is the subject of this paper. The vast majority of this effort has concentrated on the use and modification of Darwin2K, a robotic design and simulation software package, to analyze the design of a tube crawling robot. This robot is designed for carrying out inspection duties in relatively inaccessible locations within a liquid rocket engine similar to the SSME. A preliminary design of the tube crawler robot was completed, and the mechanical dynamics of the system were simulated. An evolutionary approach to optimizing a few parameters of the system was utilized, resulting in a more optimum design.

  7. Design, simulation, evaluation, and technological verification of arrayed waveguide gratings

    NASA Astrophysics Data System (ADS)

    Seyringer, Dana; Schmid, Patrick; Bielik, Michal; Uherek, Frantisek; Chovan, Jozef; Kuzma, Anton

    2014-07-01

    We present the design, simulation, evaluation, and technological verification of various low-index optical demultiplexers based on arrayed waveguide gratings (AWGs). When designing such optical demultiplexers, a set of input geometrical parameters must be first calculated. They are essential to create AWG layout that will be then simulated using commercial photonics tools. However, these tools do not support or support only partially such a fundamental calculation. Therefore, a new stand-alone tool called AWG-Parameters was developed, which strongly reduces the time needed for the design. From the calculated geometrical parameters, the AWG layouts were created and simulated using three commercial photonic tools: Optiwave, (Ottawa, Ontario, Canada), Apollo Photonics, (Ancaster, Ontario, Canada), and R-Soft, (Pasadena, California). The designs were also technologically verified. The simulated/measured transmission characteristics were evaluated by our newly developed AWG-Analyzer tool. This tool provides calculations of AWG transmission parameters, which are also missing in commercial photonic tools. Additionally, the tool provides clear definitions of calculated transmission parameters together with their textual and graphical representations. Finally, the transmission characteristics and parameters achieved from different photonic tools were compared with each other and discussed in detail. The simulated results were also compared with the measurements. Very good agreement was achieved between theoretical (AWG-Parameters tool), simulated (commercial photonic tools), and fabricated AWG transmission parameters.

  8. Novel aspects of Ras proteins biology: regulation and implications.

    PubMed

    Pérez-Sala, D; Rebollo, A

    1999-08-01

    The importance of Ras proteins as crucial crossroads in cellular signaling pathways has been well established. In spite of the elucidation of the mechanism of RAS activation by growth factors and the delineation of MAP kinase cascades, the overall framework of Ras interactions is far from being complete. Novel regulators of Ras GDP/GTP exchange have been identified that may mediate the activation of Ras in response to changes in intracellular calcium and diacylglycerol. The direct activation of Ras by free radicals such as nitric oxide also suggests potential regulation of Ras function by the cellular redox state. In addition, the array of Ras effectors continues to expand, uncovering links between Ras and other cellular signaling pathways. Ras is emerging as a dual regulator of cellular functions, playing either positive or negative roles in the regulation of proliferation and apoptosis. The signals transmitted by Ras may be modulated by other pathways triggered in parallel, resulting in the final order for proliferation or apoptosis. The diversity of ras-mediated effects may be related in part to differential involvement of Ras homologues in distinct cellular processes. The study of Ras posttranslational modifications has yielded a broad battery of inhibitors that have been envisaged as anti-cancer agents. Although an irreversible modification, Ras isoprenylation appears to be modulated by growth factors and by the activity of the isoprenoid biosynthetic pathway, which may lead to changes in Ras activity.

  9. SPRED1 Interferes with K-ras but Not H-ras Membrane Anchorage and Signaling.

    PubMed

    Siljamäki, Elina; Abankwa, Daniel

    2016-10-15

    The Ras/mitogen-activated protein kinase (MAPK) signaling pathway is tightly controlled by negative feedback regulators, such as the tumor suppressor SPRED1. The SPRED1 gene also carries loss-of-function mutations in the RASopathy Legius syndrome. Growth factor stimulation translocates SPRED1 to the plasma membrane, triggering its inhibitory activity. However, it remains unclear whether SPRED1 there acts at the level of Ras or Raf. We show that pharmacological or galectin-1 (Gal-1)-mediated induction of B- and C-Raf-containing dimers translocates SPRED1 to the plasma membrane. This is facilitated in particular by SPRED1 interaction with B-Raf and, via its N terminus, with Gal-1. The physiological significance of these novel interactions is supported by two Legius syndrome-associated mutations that show diminished binding to both Gal-1 and B-Raf. On the plasma membrane, SPRED1 becomes enriched in acidic membrane domains to specifically perturb membrane organization and extracellular signal-regulated kinase (ERK) signaling of active K-ras4B (here, K-ras) but not H-ras. However, SPRED1 also blocks on the nanoscale the positive effects of Gal-1 on H-ras. Therefore, a combinatorial expression of SPRED1 and Gal-1 potentially regulates specific patterns of K-ras- and H-ras-dependent signaling output. More broadly, our results open up the possibility that related SPRED and Sprouty proteins act in a similar Ras and Raf isoform-specific manner.

  10. SPRED1 Interferes with K-ras but Not H-ras Membrane Anchorage and Signaling

    PubMed Central

    Siljamäki, Elina

    2016-01-01

    The Ras/mitogen-activated protein kinase (MAPK) signaling pathway is tightly controlled by negative feedback regulators, such as the tumor suppressor SPRED1. The SPRED1 gene also carries loss-of-function mutations in the RASopathy Legius syndrome. Growth factor stimulation translocates SPRED1 to the plasma membrane, triggering its inhibitory activity. However, it remains unclear whether SPRED1 there acts at the level of Ras or Raf. We show that pharmacological or galectin-1 (Gal-1)-mediated induction of B- and C-Raf-containing dimers translocates SPRED1 to the plasma membrane. This is facilitated in particular by SPRED1 interaction with B-Raf and, via its N terminus, with Gal-1. The physiological significance of these novel interactions is supported by two Legius syndrome-associated mutations that show diminished binding to both Gal-1 and B-Raf. On the plasma membrane, SPRED1 becomes enriched in acidic membrane domains to specifically perturb membrane organization and extracellular signal-regulated kinase (ERK) signaling of active K-ras4B (here, K-ras) but not H-ras. However, SPRED1 also blocks on the nanoscale the positive effects of Gal-1 on H-ras. Therefore, a combinatorial expression of SPRED1 and Gal-1 potentially regulates specific patterns of K-ras- and H-ras-dependent signaling output. More broadly, our results open up the possibility that related SPRED and Sprouty proteins act in a similar Ras and Raf isoform-specific manner. PMID:27503857

  11. Biologically-inspired hexapod robot design and simulation

    NASA Technical Reports Server (NTRS)

    Espenschied, Kenneth S.; Quinn, Roger D.

    1994-01-01

    The design and construction of a biologically-inspired hexapod robot is presented. A previously developed simulation is modified to include models of the DC drive motors, the motor driver circuits and their transmissions. The application of this simulation to the design and development of the robot is discussed. The mechanisms thought to be responsible for the leg coordination of the walking stick insect were previously applied to control the straight-line locomotion of a robot. We generalized these rules for a robot walking on a plane. This biologically-inspired control strategy is used to control the robot in simulation. Numerical results show that the general body motion and performance of the simulated robot is similar to that of the robot based on our preliminary experimental results.

  12. The higher level of complexity of K-Ras4B activation at the membrane

    PubMed Central

    Jang, Hyunbum; Banerjee, Avik; Chavan, Tanmay S.; Lu, Shaoyong; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

    2016-01-01

    Is nucleotide exchange sufficient to activate K-Ras4B? To signal, oncogenic rat sarcoma (Ras) anchors in the membrane and recruits effectors by exposing its effector lobe. With the use of NMR and molecular dynamics (MD) simulations, we observed that in solution, farnesylated guanosine 5′-diphosphate (GDP)-bound K-Ras4B is predominantly autoinhibited by its hypervariable region (HVR), whereas the GTP-bound state favors an activated, HVR-released state. On the anionic membrane, the catalytic domain adopts multiple orientations, including parallel (∼180°) and perpendicular (∼90°) alignments of the allosteric helices, with respect to the membrane surface direction. In the autoinhibited state, the HVR is sandwiched between the effector lobe and the membrane; in the active state, with membrane-anchored farnesyl and unrestrained HVR, the catalytic domain fluctuates reinlessly, exposing its effector-binding site. Dimerization and clustering can reduce the fluctuations. This achieves preorganized, productive conformations. Notably, we also observe HVR-autoinhibited K-Ras4B-GTP states, with GDP-bound-like orientations of the helices. Thus, we propose that the GDP/GTP exchange may not be sufficient for activation; instead, our results suggest that the GDP/GTP exchange, HVR sequestration, farnesyl insertion, and orientation/localization of the catalytic domain at the membrane conjointly determine the active or inactive state of K-Ras4B. Importantly, K-Ras4B-GTP can exist in active and inactive states; on its own, GTP binding may not compel K-Ras4B activation.—Jang, H., Banerjee, A., Chavan, T. S, Lu, S., Zhang, J., Gaponenko, V., Nussinov, R. The higher level of complexity of K-Ras4B activation at the membrane. PMID:26718888

  13. NAM: The 2004 RAS National Astronomy Meeting

    NASA Astrophysics Data System (ADS)

    Jones, Barrie; Norton, Andrew

    2004-06-01

    This year's RAS National Astronomy Meeting was held at the Open University's Milton Keynes campus from 29 March to 2 April. The event was organized by members of the OU Physics & Astronomy Department and Planetary & Space Science Research Institute. Around 450 people attended the meeting, at which more than 220 talks were presented, along with around 90 posters. Co-chairs of RAS NAM04, Barrie Jones and Andrew Norton, summarize.

  14. Exploiting the bad eating habits of Ras-driven cancers.

    PubMed

    White, Eileen

    2013-10-01

    Oncogenic Ras promotes glucose fermentation and glutamine use to supply central carbon metabolism, but how and why have only emerged recently. Ras-mediated metabolic reprogramming generates building blocks for growth and promotes antioxidant defense. To fuel metabolic pathways, Ras scavenges extracellular proteins and lipids. To bolster metabolism and mitigate stress, Ras activates cellular self-cannibalization and recycling of proteins and organelles by autophagy. Targeting these distinct features of Ras-driven cancers provides novel approaches to cancer therapy.

  15. New tools for the simulation and design of calorimeters

    SciTech Connect

    Womersley, W.J.

    1989-07-10

    Two new approaches to the simulation and design of large hermetic calorimeters are presented. Firstly, the Shower Library scheme used in the fast generation of showers in the Monte Carlo of the calorimeter for the D-Zero experiment at the Fermilab Tevatron is described. Secondly, a tool for the design future calorimeters is described, which can be integrated with a computer aided design system to give engineering designers an immediate idea of the relative physics capabilities of different geometries. 9 refs., 6 figs., 1 tab.

  16. Designing and implementing full immersion simulation as a research tool.

    PubMed

    Munroe, Belinda; Buckley, Thomas; Curtis, Kate; Morris, Richard

    2016-05-01

    Simulation is a valuable research tool used to evaluate the clinical performance of devices, people and systems. The simulated setting may address concerns unique to complex clinical environments such as the Emergency Department, which make the conduct of research challenging. There is limited evidence available to inform the development of simulated clinical scenarios for the purpose of evaluating practice in research studies, with the majority of literature focused on designing simulated clinical scenarios for education and training. Distinct differences exist in scenario design when implemented in education compared with use in clinical research studies. Simulated scenarios used to assess practice in clinical research must not comprise of any purposeful or planned teaching and be developed with a high degree of validity and reliability. A new scenario design template was devised to develop two standardised simulated clinical scenarios for the evaluation of a new assessment framework for emergency nurses. The scenario development and validation processes undertaken are described and provide an evidence-informed guide to scenario development for future clinical research studies.

  17. Simulators of Superconductor Critical Current: Design, Characteristics, and Applications

    PubMed Central

    Goodrich, L. F.; Srivastava, A. N.; Stauffer, T. C.

    1991-01-01

    The superconductor simulator is an electronic circuit that emulates the extremely nonlinear voltage-current characteristic (the basis of a critical-current measurement) of a superconductor along with its other major electrical properties. Three different types of simulators have been constructed: the passive, active, and hybrid simulator. The passive simulator has the fewest circuit components and offers the least amount of versatility, while the active and hybrid simulators offer more versatility and consequently have more components. Design, characteristics, and applications of the superconductor simulator along with a summary of features are presented. These simulators are high precision instruments, and are thus useful for establishing the integrity of part of a superconductor measurement system. They are potentially useful for testing the measurement method and data acquisition and analysis routines. The 50 A simulator provides critical-current precision of 0.1% at a 1 μV signal. This is significantly higher than the precision of a superconducting standard reference material. The superconductor simulator could significantly benefit superconductor measurement applications that require high-precision quality assurance. PMID:28184143

  18. Using simulation to design a central sterilization department.

    PubMed

    Lin, Feng; Lawley, Mark; Spry, Charlie; McCarthy, Kelly; Coyle-Rogers, Patricia G; Yih, Yuehwern

    2008-10-01

    A simulation project was performed to assist with redesign of the surgery department of a large tertiary hospital and to help administrators make the best decisions about relocating, staffing, and equipping the central sterilization department. A simulation model was created to analyze department configurations, staff schedules, equipment capacities, and cart-washing requirements. Performance measures examined include tray turnaround time, surgery-delay rate, and work-in-process levels. The analysis provides significant insight into how the proposed system will perform, allowing planning for expected patient volume increases. This work illustrates how simulation can facilitate the design of a central sterilization department and improve surgical sterilization operations.

  19. Parallel Monte Carlo Simulation for control system design

    NASA Technical Reports Server (NTRS)

    Schubert, Wolfgang M.

    1995-01-01

    The research during the 1993/94 academic year addressed the design of parallel algorithms for stochastic robustness synthesis (SRS). SRS uses Monte Carlo simulation to compute probabilities of system instability and other design-metric violations. The probabilities form a cost function which is used by a genetic algorithm (GA). The GA searches for the stochastic optimal controller. The existing sequential algorithm was analyzed and modified to execute in a distributed environment. For this, parallel approaches to Monte Carlo simulation and genetic algorithms were investigated. Initial empirical results are available for the KSR1.

  20. An Integrated Approach for Entry Mission Design and Flight Simulations

    NASA Technical Reports Server (NTRS)

    Lu, Ping; Rao, Prabhakara

    2004-01-01

    An integrated approach for entry trajectory design, guidance, and simulation is proposed. The key ingredients for this approach are an on-line 3 degree-of-freedom entry trajectory planning algorithm and the entry guidance algorithm that generates the guidance gains automatically. When fully developed, such a tool could enable end-bend entry mission design and simulations in 3DOF and 6DOF mode from de-orbit burn to the TAEM interface and beyond, all in one key stroke. Some preliminary examples of such a capability are presented in this paper that demonstrate the potential of this type of integrated environment.

  1. Staurosporines disrupt phosphatidylserine trafficking and mislocalize Ras proteins.

    PubMed

    Cho, Kwang-jin; Park, Jin-Hee; Piggott, Andrew M; Salim, Angela A; Gorfe, Alemaheyu A; Parton, Robert G; Capon, Robert J; Lacey, Ernest; Hancock, John F

    2012-12-21

    Oncogenic mutant Ras is frequently expressed in human cancers, but no anti-Ras drugs have been developed. Since membrane association is essential for Ras biological activity, we developed a high content assay for inhibitors of Ras plasma membrane localization. We discovered that staurosporine and analogs potently inhibit Ras plasma membrane binding by blocking endosomal recycling of phosphatidylserine, resulting in redistribution of phosphatidylserine from plasma membrane to endomembrane. Staurosporines are more active against K-Ras than H-Ras. K-Ras is displaced to endosomes and undergoes proteasomal-independent degradation, whereas H-Ras redistributes to the Golgi and is not degraded. K-Ras nanoclustering on the plasma membrane is also inhibited. Ras mislocalization does not correlate with protein kinase C inhibition or induction of apoptosis. Staurosporines selectively abrogate K-Ras signaling and proliferation of K-Ras-transformed cells. These results identify staurosporines as novel inhibitors of phosphatidylserine trafficking, yield new insights into the role of phosphatidylserine and electrostatics in Ras plasma membrane targeting, and validate a new target for anti-Ras therapeutics.

  2. A WXW Motif Is Required for the Anticancer Activity of the TAT-RasGAP317–326 Peptide*

    PubMed Central

    Barras, David; Chevalier, Nadja; Zoete, Vincent; Dempsey, Rosemary; Lapouge, Karine; Olayioye, Monilola A.; Michielin, Olivier; Widmann, Christian

    2014-01-01

    TAT-RasGAP317–326, a cell-permeable 10-amino acid-long peptide derived from the N2 fragment of p120 Ras GTPase-activating protein (RasGAP), sensitizes tumor cells to apoptosis induced by various anticancer therapies. This RasGAP-derived peptide, by targeting the deleted in liver cancer-1 (DLC1) tumor suppressor, also hampers cell migration and invasion by promoting cell adherence and by inhibiting cell movement. Here, we systematically investigated the role of each amino acid within the RasGAP317–326 sequence for the anticancer activities of TAT-RasGAP317–326. We report here that the first three amino acids of this sequence, tryptophan, methionine, and tryptophan (WMW), are necessary and sufficient to sensitize cancer cells to cisplatin-induced apoptosis and to reduce cell migration. The WMW motif was found to be critical for the binding of fragment N2 to DLC1. These results define the interaction mode between the active anticancer sequence of RasGAP and DLC1. This knowledge will facilitate the design of small molecules bearing the tumor-sensitizing and antimetastatic activities of TAT-RasGAP317–326. PMID:25008324

  3. A WXW motif is required for the anticancer activity of the TAT-RasGAP317-326 peptide.

    PubMed

    Barras, David; Chevalier, Nadja; Zoete, Vincent; Dempsey, Rosemary; Lapouge, Karine; Olayioye, Monilola A; Michielin, Olivier; Widmann, Christian

    2014-08-22

    TAT-RasGAP317-326, a cell-permeable 10-amino acid-long peptide derived from the N2 fragment of p120 Ras GTPase-activating protein (RasGAP), sensitizes tumor cells to apoptosis induced by various anticancer therapies. This RasGAP-derived peptide, by targeting the deleted in liver cancer-1 (DLC1) tumor suppressor, also hampers cell migration and invasion by promoting cell adherence and by inhibiting cell movement. Here, we systematically investigated the role of each amino acid within the RasGAP317-326 sequence for the anticancer activities of TAT-RasGAP317-326. We report here that the first three amino acids of this sequence, tryptophan, methionine, and tryptophan (WMW), are necessary and sufficient to sensitize cancer cells to cisplatin-induced apoptosis and to reduce cell migration. The WMW motif was found to be critical for the binding of fragment N2 to DLC1. These results define the interaction mode between the active anticancer sequence of RasGAP and DLC1. This knowledge will facilitate the design of small molecules bearing the tumor-sensitizing and antimetastatic activities of TAT-RasGAP317-326.

  4. Binding hotspots on K-ras: consensus ligand binding sites and other reactive regions from probe-based molecular dynamics analysis.

    PubMed

    Prakash, Priyanka; Hancock, John F; Gorfe, Alemayehu A

    2015-05-01

    We have used probe-based molecular dynamics (pMD) simulations to search for interaction hotspots on the surface of the therapeutically highly relevant oncogenic K-Ras G12D. Combining the probe-based query with an ensemble-based pocket identification scheme and an analysis of existing Ras-ligand complexes, we show that (i) pMD is a robust and cost-effective strategy for binding site identification, (ii) all four of the previously reported ligand binding sites are suitable for structure-based ligand design, and (iii) in some cases probe binding and expanded sampling of configurational space enable pocket expansion and increase the likelihood of site identification. Furthermore, by comparing the distribution of hotspots in nonpocket-like regions with known protein- and membrane-interacting interfaces, we propose that pMD has the potential to predict surface patches responsible for protein-biomolecule interactions. These observations have important implications for future drug design efforts and will facilitate the search for potential interfaces responsible for the proposed transient oligomerization or interaction of Ras with other biomolecules in the cellular milieu.

  5. Binding hotspots on K-Ras: consensus ligand binding sites and other reactive regions from probe-based molecular dynamics analysis

    PubMed Central

    Prakash, Priyanka; Hancock, John F.; Gorfe, Alemayehu A.

    2015-01-01

    We have used probe-based molecular dynamics (pMD) simulations to search for interaction hotspots on the surface of the therapeutically highly relevant oncogenic K-Ras G12D. Combining the probe-based query with an ensemble-based pocket identification scheme and an analysis of existing Ras-ligand complexes, we show that (i) pMD is a robust and cost-effective strategy for binding site identification, (ii) all four of the previously reported ligand binding sites are suitable for structure-based ligand design, and (iii) in some cases probe binding and expanded sampling of configurational space enable pocket expansion and increase the likelihood of site identification. Furthermore, by comparing the distribution of hotspots in non-pocket-like regions with known protein- and membrane-interacting interfaces, we propose that pMD has the potential to predict surface patches responsible for protein-biomolecule interactions. These observations have important implications for future drug design efforts and will facilitate the search for potential interfaces responsible for the proposed transient oligomerization or interaction of Ras with other biomolecules in the cellular milieu. PMID:25740554

  6. Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution

    PubMed Central

    Coyle, Scott M; Lim, Wendell A

    2016-01-01

    The Ras-superfamily GTPases are central controllers of cell proliferation and morphology. Ras signaling is mediated by a system of interacting molecules: upstream enzymes (GEF/GAP) regulate Ras’s ability to recruit multiple competing downstream effectors. We developed a multiplexed, multi-turnover assay for measuring the dynamic signaling behavior of in vitro reconstituted H-Ras signaling systems. By including both upstream regulators and downstream effectors, we can systematically map how different network configurations shape the dynamic system response. The concentration and identity of both upstream and downstream signaling components strongly impacted the timing, duration, shape, and amplitude of effector outputs. The distorted output of oncogenic alleles of Ras was highly dependent on the balance of positive (GAP) and negative (GEF) regulators in the system. We found that different effectors interpreted the same inputs with distinct output dynamics, enabling a Ras system to encode multiple unique temporal outputs in response to a single input. We also found that different Ras-to-GEF positive feedback mechanisms could reshape output dynamics in distinct ways, such as signal amplification or overshoot minimization. Mapping of the space of output behaviors accessible to Ras provides a design manual for programming Ras circuits, and reveals how these systems are readily adapted to produce an array of dynamic signaling behaviors. Nonetheless, this versatility comes with a trade-off of fragility, as there exist numerous paths to altered signaling behaviors that could cause disease. DOI: http://dx.doi.org/10.7554/eLife.12435.001 PMID:26765565

  7. Technology, design, simulation, and evaluation for SEP-hardened circuits

    NASA Technical Reports Server (NTRS)

    Adams, J. R.; Allred, D.; Barry, M.; Rudeck, P.; Woodruff, R.; Hoekstra, J.; Gardner, H.

    1991-01-01

    This paper describes the technology, design, simulation, and evaluation for improvement of the Single Event Phenomena (SEP) hardness of gate-array and SRAM cells. Through the use of design and processing techniques, it is possible to achieve an SEP error rate less than 1.0 x 10(exp -10) errors/bit-day for a 9O percent worst-case geosynchronous orbit environment.

  8. Design Optimization and Simulation of Wave Propagation in Metamaterials

    DTIC Science & Technology

    2014-09-24

    AFRL-OSR-VA-TR-2014-0232 Design Optimizations Simulation of Wave Propagation in Metamaterials Robert Freund MASSACHUSETTS INSTITUTE OF TECHNOLOGY...In Metamaterials FA9550-11-1-0141 FA9550-11-1-0141 Freund, Robert Peraire, Jaime Nguyen, Cuong Massachusetts Institute of Technology 77...cannot be achieved with conventional materials. For instance, metamaterials can be designed to bend electromagnetic waves around an object so that

  9. Dataflow Integration and Simulation Techniques for DSP System Design Tools

    DTIC Science & Technology

    2007-01-01

    the Autocoding Toolset. . . . . . . . . . . . . . . 56 5.8 The ported SAR system in Ptolemy II. . . . . . . . . . . . . . . . . . 57 5.9 SAR...simulation results in Ptolemy II and the Autocoding Toolset. . . 57 viii 6.1 DIF-to-C software synthesis framework. . . . . . . . . . . . . . . . . . 61 6.2 A...LabVIEW from National Instruments, and Ptolemy II from U.C. Berkeley, to name a few. In model-based design methodolo- gies, design representations in terms

  10. Design and validation of a simulator for equine joint injections.

    PubMed

    Fox, Victoria; Sinclair, Charlotte; Bolt, David M; Lowe, John; Weller, Renate

    2013-01-01

    Joint injections are commonly used in equine practice for diagnosis and treatment of joint disorders. Performing joint injections is hence an essential skill for equine practitioners. However, opportunities for veterinary students to practice this skill are often scarce in veterinary curricula. The aim of this study was to design and validate an equine joint injection simulator. We hypothesized that the simulator will enhance student ability and confidence in performing joint injections. The simulator was constructed around an equine forelimb skeleton with soft tissues rebuilt using building foam and rubber bands. An electrical circuit including a buzzer, a battery, wire wool in the joints, and a hypodermic needle at the end of the cable was incorporated. If the students placed the needle into the joint correctly, instant auditory feedback was provided by the buzzer. To validate the simulator, 45 veterinary students were allocated to three groups: cadaver limb, textbook, or simulator. Students' ability to perform joint injections was tested and students' opinions were evaluated with a questionnaire. The proportion of students performing a metacarpophalangeal (MCP) joint injection correctly was significantly higher in the cadaver (93%) and simulator (76%) groups compared to the textbook group (50%). There was no significant difference between groups for performing a distal interphalangeal (DIP) joint injection correctly. Students rated the learning experience with the cadaver and simulator group high and with the textbook group low. The joint injection simulator represents an affordable teaching aid that allows students to repeatedly practice this skill in their own time with immediate feedback.

  11. Enhanced avatar design using cognitive map-based simulation.

    PubMed

    Lee, Kun Chang; Moon, Byung Suk

    2007-12-01

    With the advent of the Internet era and the maturation of electronic commerce, strategic avatar design has become an important way of keeping up with market changes and customer tastes. In this study, we propose a new approach to an adaptive avatar design that uses cognitive map (CM) as a what-if simulation vehicle. The main virtue of the new design is its ability to change specific avatar design features with objective consideration of the subsequent effects upon other design features, thereby enhancing user satisfaction. Statistical analyses of focus group interview results with a group of experts majoring in avatars and CM showed that our proposed approach could be used to effectively analyze avatar design in an adaptive and practical manner when the market situation is changing.

  12. Deformation of a Two-domain Lipid Bilayer due to Asymmetric Insertion of Lipid-modified Ras Peptides.

    PubMed

    Li, Zhenlong; Gorfe, Alemayehu A

    2013-12-21

    Ras proteins are attached to the inner leaflet of the plasma membrane via a lipid-modified anchor. Membrane-bound Ras proteins laterally segregate into nanoscale signaling platforms called nanoclusters. It has been shown that the membrane domain preference of Ras nanoclusters varies with the nature of lipidation but their effect on the membrane has not been well understood. To investigate the effect of Ras insertion on membrane structure, we carried out numerous coarse-grained molecular dynamics (CGMD) simulations on a two-domain DPPC/DLiPC/cholesterol lipid bilayer in which different number and type of H-ras peptides were attached on one side. We have shown previously that this lipid mixture forms co-existing liquid-ordered/liquid-disordered (L o /L d ) domains and that different H-ras peptides form clusters that variously accumulate at the L o /L d regions or the boundary between them. Here we show that asymmetric insertion of each of these peptides induces a vertical relative displacement of the domains and deforms the bilayer, with the domain boundary serving as the center of deformation. The extent of the deformation, however, varies with the type and number of lipid modification. This is because the number and type of the Ras lipid tails determines the degree to which the stress caused by asymmetric peptide insertion is relieved by inter-leaflet cholesterol transfer and lipid tilt. In addition, we have characterized the mechanism of bilayer deformation based on the collective effect of the Ras peptides on inter-leaflet surface area, pressure profile and line tension differences. This allowed us to elucidate how Ras lipid modification affects membrane geometry and how a two-domain bilayer adjusts its shape through boundary deformation. The result contributes to a better understanding of Ras signaling platforms and highlights some of the mechanisms by which a multi-domain membrane responds to external perturbation.

  13. Live-cell imaging of endogenous Ras-GTP illustrates predominant Ras activation at the plasma membrane

    PubMed Central

    Augsten, Martin; Pusch, Rico; Biskup, Christoph; Rennert, Knut; Wittig, Ute; Beyer, Katja; Blume, Alfred; Wetzker, Reinhard; Friedrich, Karlheinz; Rubio, Ignacio

    2006-01-01

    Ras-GTP imaging studies using the Ras-binding domain (RBD) of the Ras effector c-Raf as a reporter for overexpressed Ras have produced discrepant results about the possible activation of Ras at the Golgi apparatus. We report that RBD oligomerization provides probes for visualization of endogenous Ras-GTP, obviating Ras overexpression and the side effects derived thereof. RBD oligomerization results in tenacious binding to Ras-GTP and interruption of Ras signalling. Trimeric RBD probes fused to green fluorescent protein report agonist-induced endogenous Ras activation at the plasma membrane (PM) of COS-7, PC12 and Jurkat cells, but do not accumulate at the Golgi. PM illumination is exacerbated by Ras overexpression and its sensitivity to dominant-negative RasS17N and pharmacological manipulations matches Ras-GTP formation assessed biochemically. Our data illustrate that endogenous Golgi-located Ras is not under the control of growth factors and argue for the PM as the predominant site of agonist-induced Ras activation. PMID:16282985

  14. VPS35 binds farnesylated N-Ras in the cytosol to regulate N-Ras trafficking.

    PubMed

    Zhou, Mo; Wiener, Heidi; Su, Wenjuan; Zhou, Yong; Liot, Caroline; Ahearn, Ian; Hancock, John F; Philips, Mark R

    2016-08-15

    Ras guanosine triphosphatases (GTPases) regulate signaling pathways only when associated with cellular membranes through their C-terminal prenylated regions. Ras proteins move between membrane compartments in part via diffusion-limited, fluid phase transfer through the cytosol, suggesting that chaperones sequester the polyisoprene lipid from the aqueous environment. In this study, we analyze the nature of the pool of endogenous Ras proteins found in the cytosol. The majority of the pool consists of farnesylated, but not palmitoylated, N-Ras that is associated with a high molecular weight (HMW) complex. Affinity purification and mass spectrographic identification revealed that among the proteins found in the HMW fraction is VPS35, a latent cytosolic component of the retromer coat. VPS35 bound to N-Ras in a farnesyl-dependent, but neither palmitoyl- nor guanosine triphosphate (GTP)-dependent, fashion. Silencing VPS35 increased N-Ras's association with cytoplasmic vesicles, diminished GTP loading of Ras, and inhibited mitogen-activated protein kinase signaling and growth of N-Ras-dependent melanoma cells.

  15. Computer-Based Simulation for Man-Computer System Design,

    DTIC Science & Technology

    1980-02-01

    simulations to Investigate huwan factors and crew size (2). The experiment design was a three- problem posed by man omputer interactions in proposed ...hesrighat of t the reflected in iess flying ties, fewer Instances of high Lto are carfger The lD haud tlo desilt itr wihthe speed chis,* and hence, reduced

  16. Iterative simulated quenching for designing irregular-spot-array generators.

    PubMed

    Gillet, J N; Sheng, Y

    2000-07-10

    We propose a novel, to our knowledge, algorithm of iterative simulated quenching with temperature rescaling for designing diffractive optical elements, based on an analogy between simulated annealing and statistical thermodynamics. The temperature is iteratively rescaled at the end of each quenching process according to ensemble statistics to bring the system back from a frozen imperfect state with a local minimum of energy to a dynamic state in a Boltzmann heat bath in thermal equilibrium at the rescaled temperature. The new algorithm achieves much lower cost function and reconstruction error and higher diffraction efficiency than conventional simulated annealing with a fast exponential cooling schedule and is easy to program. The algorithm is used to design binary-phase generators of large irregular spot arrays. The diffractive phase elements have trapezoidal apertures of varying heights, which fit ideal arbitrary-shaped apertures better than do trapezoidal apertures of fixed heights.

  17. Stochastic simulation and robust design optimization of integrated photonic filters

    NASA Astrophysics Data System (ADS)

    Weng, Tsui-Wei; Melati, Daniele; Melloni, Andrea; Daniel, Luca

    2017-01-01

    Manufacturing variations are becoming an unavoidable issue in modern fabrication processes; therefore, it is crucial to be able to include stochastic uncertainties in the design phase. In this paper, integrated photonic coupled ring resonator filters are considered as an example of significant interest. The sparsity structure in photonic circuits is exploited to construct a sparse combined generalized polynomial chaos model, which is then used to analyze related statistics and perform robust design optimization. Simulation results show that the optimized circuits are more robust to fabrication process variations and achieve a reduction of 11%-35% in the mean square errors of the 3 dB bandwidth compared to unoptimized nominal designs.

  18. Stochastic simulation and robust design optimization of integrated photonic filters

    NASA Astrophysics Data System (ADS)

    Weng, Tsui-Wei; Melati, Daniele; Melloni, Andrea; Daniel, Luca

    2016-07-01

    Manufacturing variations are becoming an unavoidable issue in modern fabrication processes; therefore, it is crucial to be able to include stochastic uncertainties in the design phase. In this paper, integrated photonic coupled ring resonator filters are considered as an example of significant interest. The sparsity structure in photonic circuits is exploited to construct a sparse combined generalized polynomial chaos model, which is then used to analyze related statistics and perform robust design optimization. Simulation results show that the optimized circuits are more robust to fabrication process variations and achieve a reduction of 11%-35% in the mean square errors of the 3 dB bandwidth compared to unoptimized nominal designs.

  19. PORFLOW Simulations Supporting Saltstone Disposal Unit Design Optimization

    SciTech Connect

    Flach, G. P.; Hang, T.; Taylor, G. A.

    2015-12-10

    SRNL was requested by SRR to perform PORFLOW simulations to support potential cost-saving design modifications to future Saltstone Disposal Units in Z-Area (SRR-CWDA-2015-00120). The design sensitivity cases are defined in a modeling input specification document SRR-CWDA-2015-00133 Rev. 1. A high-level description of PORFLOW modeling and interpretation of results are provided in SRR-CWDA-2015-00169. The present report focuses on underlying technical issues and details of PORFLOW modeling not addressed by the input specification and results interpretation documents. Design checking of PORFLOW modeling is documented in SRNL-L3200-2015-00146.

  20. Design and Simulation of an Anode Stalk Support Insulator

    SciTech Connect

    Wang, L; Houck, T; Westenskow, G

    2005-05-16

    An anode stalk support insulator in a magnetically insulated transmission line was designed and modeled. One of the important design criteria is that within space constraints, the electric field along the insulator surface has to be minimized in order to prevent a surface flashover. In order to further reduce the field on the insulator surface, metal rings between insulator layers were also specially shaped. To facilitate the design process, electric field simulations were performed to determine the maximum field stress on the insulator surfaces and the transmission line chamber.

  1. Study, simulation and design of a 3D clinostat

    NASA Astrophysics Data System (ADS)

    Pavone, Valentina; Guarnieri, Vincenzo; Lobascio, Cesare; Soma, Aurelio; Bosso, Nicola; Lamantea, Matteo Maria

    High cost and limited number of physically executable experiments in space have introduced the need for ground simulation systems that enable preparing experiments to be carried out on board, identifying phenomena associated with the altered gravity conditions, and taking advantage of these conditions, as in Biotechnology. Among systems developed to simulate microgravity, especially for life sciences experiments, different types of clinostats were realized. This work deals with mechanical design of a three-dimensional clinostat and simulation of the dynamic behavior of the system by varying the operating parameters. The design and simulation phase was preceded by a careful analysis of the state of art and by the review of the most recent results, in particular from the major investigators of Life Sciences in Space. The mechanical design is quite innovative by adoption of a structure entirely in aluminum, which allows robustness while reducing the overall weight. The transmission system of motion has been optimized by means of brushless DC micro motors, light and compact, which helped to reduce weight, dimensions, power consumption and increase the reliability and durability of the system. The study of the dynamic behavior using SIMPACK, a multibody simulation software, led to results in line with those found in the most important and recent scientific publications. This model was also appropriately configured to represent any desired operating condition, and for eventual system scalability. It would be interesting to generate simulated hypogravity - e.g.: 0.38-g (Mars) or 0.17-g (Moon). This would allow to investigate how terrestrial life forms can grow in other planetary habitats, or to determine the gravity threshold response of different organisms. At the moment, such a system can only be achieved by centrifuges in real microgravity. We are confident that simulation and associated tests with our 3D clinostat can help adjusting the parameters allowing variable g

  2. Past, Present, and Future of Targeting Ras for Cancer Therapies.

    PubMed

    Tan, Zhi; Zhang, Shuxing

    2016-01-01

    For decades, mutant Ras (mut-Ras) proteins have been identified as drivers of multiple cancers including pancreatic, lung, and colon cancers. However, targeting this oncogene has been challenging and no Ras inhibitors are on the market to date. Lately several candidates targeting the downstream pathways of Ras signaling, including PI3K and Raf, were approved for cancer treatment. However, they do not present promising therapeutic effects on patients harboring Ras mutations. Recently, a variety of compounds have been reported to impair the activity of Ras, and these exciting discoveries reignite the hope for development of novel drugs targeting mut-Ras. In this article, we will review the progress made in this field and the current state-of-the-art technologies to develop Ras inhibitors. Also we will discuss the future direction of targeting Ras.

  3. Cosmic reionization on computers. I. Design and calibration of simulations

    SciTech Connect

    Gnedin, Nickolay Y.

    2014-09-20

    Cosmic Reionization On Computers is a long-term program of numerical simulations of cosmic reionization. Its goal is to model fully self-consistently (albeit not necessarily from the first principles) all relevant physics, from radiative transfer to gas dynamics and star formation, in simulation volumes of up to 100 comoving Mpc, and with spatial resolution approaching 100 pc in physical units. In this method paper, we describe our numerical method, the design of simulations, and the calibration of numerical parameters. Using several sets (ensembles) of simulations in 20 h {sup –1} Mpc and 40 h {sup –1} Mpc boxes with spatial resolution reaching 125 pc at z = 6, we are able to match the observed galaxy UV luminosity functions at all redshifts between 6 and 10, as well as obtain reasonable agreement with the observational measurements of the Gunn-Peterson optical depth at z < 6.

  4. Design of Accelerator Online Simulator Server Using Structured Data

    SciTech Connect

    Shen, Guobao; Chu, Chungming; Wu, Juhao; Kraimer, Martin; /Argonne

    2012-07-06

    Model based control plays an important role for a modern accelerator during beam commissioning, beam study, and even daily operation. With a realistic model, beam behaviour can be predicted and therefore effectively controlled. The approach used by most current high level application environments is to use a built-in simulation engine and feed a realistic model into that simulation engine. Instead of this traditional monolithic structure, a new approach using a client-server architecture is under development. An on-line simulator server is accessed via network accessible structured data. With this approach, a user can easily access multiple simulation codes. This paper describes the design, implementation, and current status of PVData, which defines the structured data, and PVAccess, which provides network access to the structured data.

  5. How Converging Lens Simulation Designs Affect Understanding of Image Formation

    NASA Astrophysics Data System (ADS)

    Bryan, Joel A.

    2006-12-01

    Although computer technology has greatly enhanced the teaching and learning of all science disciplines, computer simulations, in particular, have become exceptionally beneficial to physics education. As with any innovation, computer simulations should be most effective when used as part of guided inquiry or other research-supported instructional methodologies. In addition to the manners in which physics instructors integrate computer simulations into their instructional practices, computer simulations’ designs must also be considered when evaluating their impact on students’ conceptual development and understandings. This presentation describes the effects of the number of rays depicted and their origination points in three converging lens simulations on students’ predictions of the images observed on a screen when portions of the lens or object are covered. A comparison of student predictions under differing levels of instructor guidance is also presented.

  6. Modeling, simulation, and design of SAW grating filters

    NASA Astrophysics Data System (ADS)

    Schwelb, Otto; Adler, E. L.; Slaboszewicz, J. K.

    1990-05-01

    A systematic procedure for modeling, simulating, and designing SAW (surface acoustic wave) grating filters, taking losses into account, is described. Grating structures and IDTs (interdigital transducers) coupling to SAWs are defined by cascadable transmission-matrix building blocks. Driving point and transfer characteristics (immittances) of complex architectures consisting of gratings, transducers, and coupling networks are obtained by chain-multiplying building-block matrices. This modular approach to resonator filter analysis and design combines the elements of lossy filter synthesis with the transmission-matrix description of SAW components. A multipole filter design procedure based on a lumped-element-model approximation of one-pole two-port resonator building blocks is given and the range of validity of this model examined. The software for simulating the performance of SAW grating devices based on this matrix approach is described, and its performance, when linked to the design procedure to form a CAD/CAA (computer-aided design and analysis) multiple-filter design package, is illustrated with a resonator filter design example.

  7. Computational Aerodynamic Simulations of a Spacecraft Cabin Ventilation Fan Design

    NASA Technical Reports Server (NTRS)

    Tweedt, Daniel L.

    2010-01-01

    Quieter working environments for astronauts are needed if future long-duration space exploration missions are to be safe and productive. Ventilation and payload cooling fans are known to be dominant sources of noise, with the International Space Station being a good case in point. To address this issue cost effectively, early attention to fan design, selection, and installation has been recommended, leading to an effort by NASA to examine the potential for small-fan noise reduction by improving fan aerodynamic design. As a preliminary part of that effort, the aerodynamics of a cabin ventilation fan designed by Hamilton Sundstrand has been simulated using computational fluid dynamics codes, and the computed solutions analyzed to quantify various aspects of the fan aerodynamics and performance. Four simulations were performed at the design rotational speed: two at the design flow rate and two at off-design flow rates. Following a brief discussion of the computational codes, various aerodynamic- and performance-related quantities derived from the computed flow fields are presented along with relevant flow field details. The results show that the computed fan performance is in generally good agreement with stated design goals.

  8. Specific repression of mutant K-RAS by 10-23 DNAzyme: Sensitizing cancer cell to anti-cancer therapies

    SciTech Connect

    Yu, S.-H.; Wang, T.-H.; Au, L.-C.

    2009-01-09

    Point mutations of the Ras family are frequently found in human cancers at a prevalence rate of 30%. The most common mutation K-Ras(G12V), required for tumor proliferation, survival, and metastasis due to its constitutively active GTPase activity, has provided an ideal target for cancer therapy. 10-23 DNAzyme, an oligodeoxyribonucleotide-based ribonuclease consisting of a 15-nucleotide catalytical domain flanked by two target-specific complementary arms, has been shown to effectively cleave the target mRNA at purine-pyrimidine dinucleotide. Taking advantage of this specific property, 10-23 DNAzyme was designed to cleave mRNA of K-Ras(G12V)(GGU {yields} GUU) at the GU dinucleotide while left the wild-type (WT) K-Ras mRNA intact. The K-Ras(G12V)-specific 10-23 DNAzyme was able to reduce K-Ras(G12V) at both mRNA and protein levels in SW480 cell carrying homozygous K-Ras(G12V). No effect was observed on the WT K-Ras in HEK cells. Although K-Ras(G12V)-specific DNAzymes alone did not inhibit proliferation of SW480 or HEK cells, pre-treatment of this DNAzyme sensitized the K-Ras(G12V) mutant cells to anti-cancer agents such as doxorubicin and radiation. These results offer a potential of using allele-specific 10-23 DNAzyme in combination with other cancer therapies to achieve better effectiveness on cancer treatment.

  9. Slide track analysis of eight contemporary hip simulator designs.

    PubMed

    Calonius, Olof; Saikko, Vesa

    2002-11-01

    In an earlier paper, the authors presented a new method of computation of slide tracks in the relative motion between femoral head and acetabular cup of total hip prostheses. For the first time, computed tracks were verified experimentally and with an alternative method of computation. Besides being an efficient way to illustrate hip kinematics, the shapes of the slide tracks are known to be of fundamental importance regarding the wear behaviour of prostheses. The verified method was now applied to eight contemporary hip simulator designs. The use of correct motion waveforms and an Euler sequence of rotations in each case was again found to be essential. Considerable differences were found between the simulators. For instance, the shapes of the tracks drawn by the resultant contact force included a circle, ellipse, irregular oval, leaf, twig, and straight line. Computation of tracks correctly for the most widely used hip simulator, known as biaxial, was made possible by the insight that the device is actually three-axial. Slide track patterns have now been computed for virtually all contemporary hip simulators, and both for the heads and for the cups. This comparative analysis forms a valuable basis for studies on the relationship between the type of multidirectional motion and wear. These studies can produce useful information for the design of joint simulators, and improve the understanding of wear phenomena in prosthetic joints.

  10. Design and evaluation of a computer controlled solar collector simulator

    NASA Astrophysics Data System (ADS)

    Kotas, J. F.; Wood, B. D.

    1980-11-01

    A computer-controlled system has been developed to simulate the thermal processes of a flat-plate solar collector. The simulator is based on four water heaters of capacities of 1.5, 2.5, 5.0 and 5.0 kW providing a maximum design output of 14.0 kW which are controlled by a Nova 3 minicomputer, which also monitors temperatures in the fluid stream. Measurements have been obtained of the steady-state operating values and time constants of the individual heaters at different flow rates in order to utilize effectively their thermal outputs. Software was designed to control the heater system so the total thermal output closely approximates that of an actual heater array, utilizing steady-state or dynamic control modes. Simulation of the heat output of a previously tested collector has resulted in simulated values differing from actual output by a maximum of 3% under identical operating conditions, thus indicating that the simulator represents a viable alternative to the testing of a large field of collectors.

  11. Ras Proteins Have Multiple Functions in Vegetative Cells of Dictyostelium ▿

    PubMed Central

    Bolourani, Parvin; Spiegelman, George; Weeks, Gerald

    2010-01-01

    During the aggregation of Dictyostelium cells, signaling through RasG is more important in regulating cyclic AMP (cAMP) chemotaxis, whereas signaling through RasC is more important in regulating the cAMP relay. However, RasC is capable of substituting for RasG for chemotaxis, since rasG− cells are only partially deficient in chemotaxis, whereas rasC−/rasG− cells are totally incapable of chemotaxis. In this study we have examined the possible functional overlap between RasG and RasC in vegetative cells by comparing the vegetative cell properties of rasG−, rasC−, and rasC−/rasG− cells. In addition, since RasD, a protein not normally found in vegetative cells, is expressed in vegetative rasG− and rasC−/rasG− cells and appears to partially compensate for the absence of RasG, we have also examined the possible functional overlap between RasG and RasD by comparing the properties of rasG− and rasC−/rasG− cells with those of the mutant cells expressing higher levels of RasD. The results of these two lines of investigation show that RasD is capable of totally substituting for RasG for cytokinesis and growth in suspension, whereas RasC is without effect. In contrast, for chemotaxis to folate, RasC is capable of partially substituting for RasG, but RasD is totally without effect. Finally, neither RasC nor RasD is able to substitute for the role that RasG plays in regulating actin distribution and random motility. These specificity studies therefore delineate three distinct and none-overlapping functions for RasG in vegetative cells. PMID:20833893

  12. Parachute system design, analysis, and simulation tool. Status report

    SciTech Connect

    Sundberg, W.D.; McBride, D.D.; Gwinn, K.W.; Waye, D.E.; Hailey, C.E.

    1992-12-31

    For over twenty years designers at Sandia National Laboratories have developed various parachute simulation codes to model deployment, inflation, loading, trajectories, aircraft downwash and line sail. In addition to these codes, material property data bases have been acquired. Recently we have initiated project to integrate these codes and data bases into a single software tool entitled SPARSYS (Sandia PARachute SYstem Simulation). We have constructed a graphical user interface as the driver and framework for SPARSYS. In this paper we present a status report on SPARSYS describing progress in developing and incorporating independent modules, in developing an integrated trajectory package, and in developing a materials data base including high-rate-of-strain data.

  13. Simulation-guided DNA probe design for consistently ultraspecific hybridization

    NASA Astrophysics Data System (ADS)

    Wang, Juexiao Sherry; Zhang, David Yu

    2015-07-01

    Hybridization of complementary sequences is one of the central tenets of nucleic acid chemistry; however, the unintended binding of closely related sequences limits the accuracy of hybridization-based approaches to analysing nucleic acids. Thermodynamics-guided probe design and empirical optimization of the reaction conditions have been used to enable the discrimination of single-nucleotide variants, but typically these approaches provide only an approximately 25-fold difference in binding affinity. Here we show that simulations of the binding kinetics are both necessary and sufficient to design nucleic acid probe systems with consistently high specificity as they enable the discovery of an optimal combination of thermodynamic parameters. Simulation-guided probe systems designed against 44 sequences of different target single-nucleotide variants showed between a 200- and 3,000-fold (median 890) higher binding affinity than their corresponding wild-type sequences. As a demonstration of the usefulness of this simulation-guided design approach, we developed probes that, in combination with PCR amplification, detect low concentrations of variant alleles (1%) in human genomic DNA.

  14. A system for designing and simulating particle physics experiments

    NASA Astrophysics Data System (ADS)

    Żelazny, Roman; Strzałkowski, Piotr

    1987-01-01

    In view of the rapid development of experimental facilities and their costs, the systematic design and preparation of particle physics experiments have become crucial. A software system is proposed as an aid for the experimental designer, mainly for experimental geometry analysis and experimental simulation. The following model is adopted: the description of an experiment is formulated in a language (here called XL) and put by its processor in a data base. The language is based on the entity-relationship-attribute approach. The information contained in the data base can be reported and analysed by an analyser (called XA) and modifications can be made at any time. In particular, the Monte Carlo methods can be used in experiment simulation for both physical phenomena in experimental set-up and detection analysis. The general idea of the system is based on the design concept of ISDOS project information systems. The characteristics of the simulation module are similar to those of the CERN Geant system, but some extensions are proposed. The system could be treated as a component of a greater, integrated software environment for the design of particle physics experiments, their monitoring and data processing.

  15. The Design and Implementation of the Swim Integrated Plasma Simulator

    SciTech Connect

    Elwasif, Wael R; Bernholdt, David E; Shet, Aniruddha G; Foley, Samantha S; Bramley, Randall B; Batchelor, Donald B; Berry, Lee A

    2010-01-01

    As computing capabilities have increased, the coupling of computational models has become an increasingly viable and therefore important way of improving the physical fidelity of simulations. Applications currently using some form of multicode or multi-component coupling include climate modeling, rocket simulations, and chemistry. In recent years, the plasma physics community has also begun to pursue integrated multiphysics simulations for space weather and fusion energy applications. Such model coupling generally exposes new issues in the physical, mathematical, and computational aspects of the problem. This paper focuses on the computational aspects of one such effort, detailing the design, and implementation of the Integrated Plasma Simulator (IPS) for the Center for Simulation of Wave Interactions with Magnetohydrodynamics (SWIM). The IPS framework focuses on maximizing flexibility for the creators of loosely-coupled component-based simulations, and provides services for execution coordination, resource management, data management, and inter-component communication. It also serves as a proving ground for a concurrent 'multi-tasking' execution model to improve resource utilization, and application-level fault tolerance. We also briefly describe how the IPS has been applied to several problems of interest to the fusion community.

  16. Aurora kinase A interacts with H-Ras and potentiates Ras-MAPK signaling | Office of Cancer Genomics

    Cancer.gov

    In cancer, upregulated Ras promotes cellular transformation and proliferation in part through activation of oncogenic Ras-MAPK signaling. While directly inhibiting Ras has proven challenging, new insights into Ras regulation through protein-protein interactions may offer unique opportunities for therapeutic intervention. Here we report the identification and validation of Aurora kinase A (Aurora A) as a novel Ras binding protein. We demonstrate that the kinase domain of Aurora A mediates the interaction with the N-terminal domain of H-Ras.

  17. Mold design with simulation for chalcogenide glass precision molding

    NASA Astrophysics Data System (ADS)

    Zhang, Yunlong; Wang, Zhibin; Li, Junqi; Zhang, Feng; Su, Ying; Wang, Zhongqiang

    2016-10-01

    Compare with the manufacturing of the traditional infrared material, such as signal crystal germanium, zinc sulfide, zinc selenide etc, chalcogenide infrared glass is suitable for precision molding for the low soften temperature to have large mass industry production. So the researches of precision glass molding are necessary, especially for the fast development of infrared product. The mold design is one of the key technologies of precision glass molding. In this paper, the mold processing of a sample chalcogenide glass from the technical drawing, mold design, molding to the lens are introduced. From the result of the precision molding, the technology of finite element simulation is a useful way to guiding the mold design. The molded lens by using mold process fit the design requirement.

  18. Reflectance Anisotropy Spectroscopy(RAS) of Si(111)-(3x1)-Ag and Si(111)-c(12x2): Comparison of hybrid density functional theory and experiment

    NASA Astrophysics Data System (ADS)

    Jorgji, Sofia; McGilp, John; Patterson, Charles

    2013-03-01

    The atomic and electronic structures of the Si(111)-(3x1)-Ag surface have been investigated extensively by LEED, STM and electron spectroscopies. The atomic structure is believed to be a honeycomb chain plus channel (HCC) structure in which channels containing Ag atoms are separated by Si in honeycomb chains. Here we compare results of previous reflectance anisotropy spectroscopy (RAS) experiments with hybrid DFT simulations for the HCC structure. Results of RAS simulations are in very good agreement with RAS experiments and indicate that the HCC structure is likely to be correct. Surface state features responsible for the RAS signal are identified and the effect of dimerisation of Ag chains on the RAS spectrum is considered. This work was supported by the Irish HEA under PRTLI-V

  19. On the design of script languages for neural simulation.

    PubMed

    Brette, Romain

    2012-01-01

    In neural network simulators, models are specified according to a language, either specific or based on a general programming language (e.g. Python). There are also ongoing efforts to develop standardized languages, for example NeuroML. When designing these languages, efforts are often focused on expressivity, that is, on maximizing the number of model types than can be described and simulated. I argue that a complementary goal should be to minimize the cognitive effort required on the part of the user to use the language. I try to formalize this notion with the concept of "language entropy", and I propose a few practical guidelines to minimize the entropy of languages for neural simulation.

  20. Programmable multi-node quantum network design and simulation

    NASA Astrophysics Data System (ADS)

    Dasari, Venkat R.; Sadlier, Ronald J.; Prout, Ryan; Williams, Brian P.; Humble, Travis S.

    2016-05-01

    Software-defined networking offers a device-agnostic programmable framework to encode new network functions. Externally centralized control plane intelligence allows programmers to write network applications and to build functional network designs. OpenFlow is a key protocol widely adopted to build programmable networks because of its programmability, flexibility and ability to interconnect heterogeneous network devices. We simulate the functional topology of a multi-node quantum network that uses programmable network principles to manage quantum metadata for protocols such as teleportation, superdense coding, and quantum key distribution. We first show how the OpenFlow protocol can manage the quantum metadata needed to control the quantum channel. We then use numerical simulation to demonstrate robust programmability of a quantum switch via the OpenFlow network controller while executing an application of superdense coding. We describe the software framework implemented to carry out these simulations and we discuss near-term efforts to realize these applications.

  1. Design of 3D simulation engine for oilfield safety training

    NASA Astrophysics Data System (ADS)

    Li, Hua-Ming; Kang, Bao-Sheng

    2015-03-01

    Aiming at the demand for rapid custom development of 3D simulation system for oilfield safety training, this paper designs and implements a 3D simulation engine based on script-driven method, multi-layer structure, pre-defined entity objects and high-level tools such as scene editor, script editor, program loader. A scripting language been defined to control the system's progress, events and operating results. Training teacher can use this engine to edit 3D virtual scenes, set the properties of entity objects, define the logic script of task, and produce a 3D simulation training system without any skills of programming. Through expanding entity class, this engine can be quickly applied to other virtual training areas.

  2. Simulation models and designs for advanced Fischer-Tropsch technology

    SciTech Connect

    Choi, G.N.; Kramer, S.J.; Tam, S.S.

    1995-12-31

    Process designs and economics were developed for three grass-roots indirect Fischer-Tropsch coal liquefaction facilities. A baseline and an alternate upgrading design were developed for a mine-mouth plant located in southern Illinois using Illinois No. 6 coal, and one for a mine-mouth plane located in Wyoming using Power River Basin coal. The alternate design used close-coupled ZSM-5 reactors to upgrade the vapor stream leaving the Fischer-Tropsch reactor. ASPEN process simulation models were developed for all three designs. These results have been reported previously. In this study, the ASPEN process simulation model was enhanced to improve the vapor/liquid equilibrium calculations for the products leaving the slurry bed Fischer-Tropsch reactors. This significantly improved the predictions for the alternate ZSM-5 upgrading design. Another model was developed for the Wyoming coal case using ZSM-5 upgrading of the Fischer-Tropsch reactor vapors. To date, this is the best indirect coal liquefaction case. Sensitivity studies showed that additional cost reductions are possible.

  3. An automated methodology development. [software design for combat simulation

    NASA Technical Reports Server (NTRS)

    Hawley, L. R.

    1985-01-01

    The design methodology employed in testing the applicability of Ada in large-scale combat simulations is described. Ada was considered as a substitute for FORTRAN to lower life cycle costs and ease the program development efforts. An object-oriented approach was taken, which featured definitions of military targets, the capability of manipulating their condition in real-time, and one-to-one correlation between the object states and real world states. The simulation design process was automated by the problem statement language (PSL)/problem statement analyzer (PSA). The PSL/PSA system accessed the problem data base directly to enhance the code efficiency by, e.g., eliminating non-used subroutines, and provided for automated report generation, besides allowing for functional and interface descriptions. The ways in which the methodology satisfied the responsiveness, reliability, transportability, modifiability, timeliness and efficiency goals are discussed.

  4. Simulation Environment for Orion Launch Abort System Control Design Studies

    NASA Technical Reports Server (NTRS)

    McMinn, J. Dana; Jackson, E. Bruce; Christhilf, David M.

    2007-01-01

    The development and use of an interactive environment to perform control system design and analysis of the proposed Crew Exploration Vehicle Launch Abort System is described. The environment, built using a commercial dynamic systems design package, includes use of an open-source configuration control software tool and a collaborative wiki to coordinate between the simulation developers, control law developers and users. A method for switching between multiple candidate control laws and vehicle configurations is described. Aerodynamic models, especially in a development program, change rapidly, so a means for automating the implementation of new aerodynamic models is described.

  5. [NMR radiofrequency microcoil design: usefulness of electromagnetic simulation].

    PubMed

    Armenean, Mircea; Briguet, André; Saint-Jalmes, Hervé

    2002-04-01

    The extraction of the Nuclear Magnetic Resonance (NMR) spectra of samples having smaller and smaller volumes is a real challenge. Either these reductions of volume are dictated by the difficulties of production of sufficiently large samples or by necessities of miniaturisation of the analysing system, in both cases a careful design of the radiofrequency coil, ensuring an optimum reception of the NMR signal, is required. We have also evaluated the usefulness of electromagnetic simulation software for the design and optimisation of these radio-frequency coils, which are more and more used in biology and health research projects.

  6. RAS Symposium Draws Hundreds of Attendees | Poster

    Cancer.gov

    They call themselves “rasologists”: scientists who study the RAS family of genes and the cancers that can arise due to mutations within them. This field of research is at the heart of some sobering numbers. Almost a third of all human cancers, including 95 percent of pancreatic cancers, are driven by mutated RAS genes. The American Cancer Society estimates there were 48,960 new cases of pancreatic cancer in the United States in 2015 and 40,560 deaths from the disease.

  7. Design and simulation of advanced fault tolerant flight control schemes

    NASA Astrophysics Data System (ADS)

    Gururajan, Srikanth

    This research effort describes the design and simulation of a distributed Neural Network (NN) based fault tolerant flight control scheme and the interface of the scheme within a simulation/visualization environment. The goal of the fault tolerant flight control scheme is to recover an aircraft from failures to its sensors or actuators. A commercially available simulation package, Aviator Visual Design Simulator (AVDS), was used for the purpose of simulation and visualization of the aircraft dynamics and the performance of the control schemes. For the purpose of the sensor failure detection, identification and accommodation (SFDIA) task, it is assumed that the pitch, roll and yaw rate gyros onboard are without physical redundancy. The task is accomplished through the use of a Main Neural Network (MNN) and a set of three De-Centralized Neural Networks (DNNs), providing analytical redundancy for the pitch, roll and yaw gyros. The purpose of the MNN is to detect a sensor failure while the purpose of the DNNs is to identify the failed sensor and then to provide failure accommodation. The actuator failure detection, identification and accommodation (AFDIA) scheme also features the MNN, for detection of actuator failures, along with three Neural Network Controllers (NNCs) for providing the compensating control surface deflections to neutralize the failure induced pitching, rolling and yawing moments. All NNs continue to train on-line, in addition to an offline trained baseline network structure, using the Extended Back-Propagation Algorithm (EBPA), with the flight data provided by the AVDS simulation package. The above mentioned adaptive flight control schemes have been traditionally implemented sequentially on a single computer. This research addresses the implementation of these fault tolerant flight control schemes on parallel and distributed computer architectures, using Berkeley Software Distribution (BSD) sockets and Message Passing Interface (MPI) for inter

  8. Design of Battle Simulations for Command and Staff Training

    DTIC Science & Technology

    1988-04-01

    COMMAND AND STAFF TRAINING SECTION 1. INTRODUCTION Simulations designed to train Army commanders and staffs in planning and conducting milit-iry... plan to automate staff training at high echelons. The Army Research Institute (ARI) Field Unit at Fort Leavenworth has been participating in battle...TRAINING~ SCNA OBJECTIVE CONTRL COMANDE PERSONEL & STAFF AI SIMUATIO TACICA MODEL DAT SYSTEM MEASUEMEN & FEDBAC Figue 1.A tpica co ma.’d saff raiing

  9. Terahertz Free Electron Laser: Design, Simulation and Analysis

    DTIC Science & Technology

    2014-12-01

    general principal is that a “pump” light pulse (usually a high peak power laser ) is incident upon a sample and causes an excitation . A certain time...light in free electron lasers , x-ray sources, and THz sources, and neutron production. Niowave also builds radio frequency ( RF ) guns, superconducting...FREE ELECTRON LASER : DESIGN, SIMULATION AND ANALYSIS by Conor M. Pogue December 2014 Dissertation Supervisor William B. Colson THIS PAGE

  10. Design, Fabrication, and Testing of a Hopper Spacecraft Simulator

    NASA Astrophysics Data System (ADS)

    Mucasey, Evan Phillip Krell

    A robust test bed is needed to facilitate future development of guidance, navigation, and control software for future vehicles capable of vertical takeoff and landings. Specifically, this work aims to develop both a hardware and software simulator that can be used for future flight software development for extra-planetary vehicles. To achieve the program requirements of a high thrust to weight ratio with large payload capability, the vehicle is designed to have a novel combination of electric motors and a micro jet engine is used to act as the propulsion elements. The spacecraft simulator underwent several iterations of hardware development using different materials and fabrication methods. The final design used a combination of carbon fiber and fiberglass that was cured under vacuum to serve as the frame of the vehicle which provided a strong, lightweight platform for all flight components and future payloads. The vehicle also uses an open source software development platform, Arduino, to serve as the initial flight computer and has onboard accelerometers, gyroscopes, and magnetometers to sense the vehicles attitude. To prevent instability due to noise, a polynomial kalman filter was designed and this fed the sensed angles and rates into a robust attitude controller which autonomously control the vehicle' s yaw, pitch, and roll angles. In addition to the hardware development of the vehicle itself, both a software simulation and a real time data acquisition interface was written in MATLAB/SIMULINK so that real flight data could be taken and then correlated to the simulation to prove the accuracy of the analytical model. In result, the full scale vehicle was designed and own outside of the lab environment and data showed that the software model accurately predicted the flight dynamics of the vehicle.

  11. Using Theory and Simulation to Design Self-Healing Surfaces

    DTIC Science & Technology

    2007-11-16

    blends, microcapsules Anna C. Balazs University of Pittsburgh Office of Sponsored Programs 3700 O’Hara St Pittsburgh, PA 15260 - REPORT DOCUMENTATION PAGE...novel computational approach (P5) to simulate the rolling motion of fluid-driven, particle-filled microcapsules along heterogeneous, adhesive substrates...established guidelines for designing particle-filled microcapsules that perform a “repair and go” function and could ultimately be used to restore

  12. Design, modelling and simulation aspects of an ankle rehabilitation device

    NASA Astrophysics Data System (ADS)

    Racu, C. M.; Doroftei, I.

    2016-08-01

    Ankle injuries are amongst the most common injuries of the lower limb. Besides initial treatment, rehabilitation of the patients plays a crucial role for future activities and proper functionality of the foot. Traditionally, ankle injuries are rehabilitated via physiotherapy, using simple equipment like elastic bands and rollers, requiring intensive efforts of therapists and patients. Thus, the need of robotic devices emerges. In this paper, the design concept and some modelling and simulation aspects of a novel ankle rehabilitation device are presented.

  13. Simulation in the design of gas pressure control equipment

    NASA Astrophysics Data System (ADS)

    Stoves, D.; Thompson, B.; Graham, P.

    1984-06-01

    To investigate the effects of changes in significant parameters of gas supply network pressure regulating equipment, a regulator model was established. The modeling of a supply network posed particular problems due to the large variation in actual pipework arrangements. Acoustic analysis was used to identify a representative characterization of a network. Use of computer simulation to establish appropriate response criteria and aid the design of a regulator to satisfy these criteria is described.

  14. Design of transient light signal simulator based on FPGA

    NASA Astrophysics Data System (ADS)

    Kang, Jing; Chen, Rong-li; Wang, Hong

    2014-11-01

    A design scheme of transient light signal simulator based on Field Programmable gate Array (FPGA) was proposed in this paper. Based on the characteristics of transient light signals and measured feature points of optical intensity signals, a fitted curve was created in MATLAB. And then the wave data was stored in a programmed memory chip AT29C1024 by using SUPERPRO programmer. The control logic was realized inside one EP3C16 FPGA chip. Data readout, data stream cache and a constant current buck regulator for powering high-brightness LEDs were all controlled by FPGA. A 12-Bit multiplying CMOS digital-to-analog converter (DAC) DAC7545 and an amplifier OPA277 were used to convert digital signals to voltage signals. A voltage-controlled current source constituted by a NPN transistor and an operational amplifier controlled LED array diming to achieve simulation of transient light signal. LM3405A, 1A Constant Current Buck Regulator for Powering LEDs, was used to simulate strong background signal in space. Experimental results showed that the scheme as a transient light signal simulator can satisfy the requests of the design stably.

  15. On the acoustic wedge design and simulation of anechoic chamber

    NASA Astrophysics Data System (ADS)

    Jiang, Changyong; Zhang, Shangyu; Huang, Lixi

    2016-10-01

    This study proposes an alternative to the classic wedge design for anechoic chambers, which is the uniform-then-gradient, flat-wall (UGFW) structure. The working mechanisms of the proposed structure and the traditional wedge are analyzed. It is found that their absorption patterns are different. The parameters of both structures are optimized for achieving minimum absorber depth, under the condition of absorbing 99% of normal incident sound energy. It is found that, the UGFW structure achieves a smaller total depth for the cut-off frequencies ranging from 100 Hz to 250 Hz. This paper also proposes a modification for the complex source image (CSI) model for the empirical simulation of anechoic chambers, originally proposed by Bonfiglio et al. [J. Acoust. Soc. Am. 134 (1), 285-291 (2013)]. The modified CSI model considers the non-locally reactive effect of absorbers at oblique incidence, and the improvement is verified by a full, finite-element simulation of a small chamber. With the modified CSI model, the performance of both decorations with the optimized parameters in a large chamber is simulated. The simulation results are analyzed and checked against the tolerance of 1.5 dB deviation from the inverse square law, stipulated in the ISO standard 3745(2003). In terms of the total decoration depth and anechoic chamber performance, the UGFW structure is better than the classic wedge design.

  16. A mechanism of catalyzed GTP hydrolysis by Ras protein through magnesium ion

    NASA Astrophysics Data System (ADS)

    Lu, Qiang; Nassar, Nicolas; Wang, Jin

    2011-11-01

    The hydrolysis by Ras plays pivotal roles in the activation of signaling pathways that lead to cell growth, proliferation, and differentiation. Despite their significant role in human cancer, the hydrolysis mechanism remains unclear. In the present Letter, we propose a GTP hydrolysis mechanism in which the γ phosphate is cut off primarily by magnesium ion. We studied both normal and mutated Ras and the cause of the malfunction of these mutants, compared the effect of Mg2+ and Mn2+. The simulation results are consistent with the experiments and support the new hydrolysis mechanism. This work will benefit both GTPases and ATPases hydrolysis studies.

  17. 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.

  18. Quantitative Assays for RAS Pathway Proteins and Phosphorylation States

    Cancer.gov

    The NCI CPTAC program is applying its expertise in quantitative proteomics to develop assays for RAS pathway proteins. Targets include key phosphopeptides that should increase our understanding of how the RAS pathway is regulated.

  19. The RAS Problem: Turning Off a Broken Switch

    Cancer.gov

    The RAS gene is commonly mutated in cancer and researchers are working to better understand how to develop drugs that can target the RAS protein, which for many years has been considered to be “undruggable.”

  20. RAS one-equation turbulence model with non-singular eddy-viscosity coefficient

    NASA Astrophysics Data System (ADS)

    Rahman, M. M.; Agarwal, R. K.; Siikonen, T.

    2016-02-01

    A simplified consistency formulation for Pk/ε (production to dissipation ratio) is devised to obtain a non-singular Cμ (coefficient of eddy-viscosity) in the explicit algebraic Reynolds stress model of Gatski and Speziale. The coefficient Cμ depends non-linearly on both rotational/irrotational strains and is used in the framework of an improved RAS (Rahman-Agarwal-Siikonen) one-equation turbulence model to calculate a few well-documented turbulent flows, yielding predictions in good agreement with the direct numerical simulation and experimental data. The strain-dependent Cμ assists the RAS model in constructing the coefficients and functions such as to benefit complex flows with non-equilibrium turbulence. Comparisons with the Spalart-Allmaras one-equation model and the shear stress transport k-ω model demonstrate that Cμ improves the response of RAS model to non-equilibrium effects.

  1. Designing a Distributed Space Systems Simulation in Accordance with the Simulation Interoperability Standards Organization (SISO)

    NASA Technical Reports Server (NTRS)

    Cowen, Benjamin

    2011-01-01

    Simulations are essential for engineering design. These virtual realities provide characteristic data to scientists and engineers in order to understand the details and complications of the desired mission. A standard development simulation package known as Trick is used in developing a source code to model a component (federate in HLA terms). The runtime executive is integrated into an HLA based distributed simulation. TrickHLA is used to extend a Trick simulation for a federation execution, develop a source code for communication between federates, as well as foster data input and output. The project incorporates international cooperation along with team collaboration. Interactions among federates occur throughout the simulation, thereby relying on simulation interoperability. Communication through the semester went on between participants to figure out how to create this data exchange. The NASA intern team is designing a Lunar Rover federate and a Lunar Shuttle federate. The Lunar Rover federate supports transportation across the lunar surface and is essential for fostering interactions with other federates on the lunar surface (Lunar Shuttle, Lunar Base Supply Depot and Mobile ISRU Plant) as well as transporting materials to the desired locations. The Lunar Shuttle federate transports materials to and from lunar orbit. Materials that it takes to the supply depot include fuel and cargo necessary to continue moon-base operations. This project analyzes modeling and simulation technologies as well as simulation interoperability. Each team from participating universities will work on and engineer their own federate(s) to participate in the SISO Spring 2011 Workshop SIW Smackdown in Boston, Massachusetts. This paper will focus on the Lunar Rover federate.

  2. ASPP2 Is a Novel Pan-Ras Nanocluster Scaffold

    PubMed Central

    Posada, Itziar M. D.; Serulla, Marc; Zhou, Yong; Oetken-Lindholm, Christina

    2016-01-01

    Ras-induced senescence mediated through ASPP2 represents a barrier to tumour formation. It is initiated by ASPP2’s interaction with Ras at the plasma membrane, which stimulates the Raf/MEK/ERK signaling cascade. Ras to Raf signalling requires Ras to be organized in nanoscale signalling complexes, called nanocluster. We therefore wanted to investigate whether ASPP2 affects Ras nanoclustering. Here we show that ASPP2 increases the nanoscale clustering of all oncogenic Ras isoforms, H-ras, K-ras and N-ras. Structure-function analysis with ASPP2 truncation mutants suggests that the nanocluster scaffolding activity of ASPP2 converges on its α-helical domain. While ASPP2 increased effector recruitment and stimulated ERK and AKT phosphorylation, it did not increase colony formation of RasG12V transformed NIH/3T3 cells. By contrast, ASPP2 was able to suppress the transformation enhancing ability of the nanocluster scaffold Gal-1, by competing with the specific effect of Gal-1 on H-rasG12V- and K-rasG12V-nanoclustering, thus imposing ASPP2’s ERK and AKT signalling signature. Similarly, ASPP2 robustly induced senescence and strongly abrogated mammosphere formation irrespective of whether it was expressed alone or together with Gal-1, which by itself showed the opposite effect in Ras wt or H-ras mutant breast cancer cells. Our results suggest that Gal-1 and ASPP2 functionally compete in nanocluster for active Ras on the plasma membrane. ASPP2 dominates the biological outcome, thus switching from a Gal-1 supported growth-promoting setting to a senescence inducing and stemness suppressive program in cancer cells. Our results support Ras nanocluster as major integrators of tumour fate decision events. PMID:27437940

  3. Ras1 and Ras2 play antagonistic roles in regulating cellular cAMP level, stationary-phase entry and stress response in Candida albicans.

    PubMed

    Zhu, Yong; Fang, Hao-Ming; Wang, Yan-Ming; Zeng, Gui-Sheng; Zheng, Xin-De; Wang, Yue

    2009-11-01

    The GTPase Ras1 activates the yeast-to-hypha transition in Candida albicans by activating cAMP synthesis. Here, we have characterized Ras2. Ras2 belongs to a group of atypical Ras proteins in some fungal species that share poor identity with other Ras GTPases with many variations in conserved motifs thought to be crucial for Ras-associated activities. We find that recombinant Ras2 is enzymatically as active as Ras1. However, only RAS1 can rescue the lethality of the Saccharomyces cerevisiae ras1 ras2 mutant, suggesting functional divergence of the two genes. ras2Delta is normal in hyphal growth, but deleting RAS2 in the ras1Delta background greatly aggravates the hyphal defect, indicating that Ras2 also has a role in hyphal development. Strikingly, while RAS1 deletion causes a approximately 20-fold decrease in cellular cAMP, further deletion of RAS2 restores it to approximately 30% of the wild-type level. Consistently, while the ras1Delta mutant enters the stationary phase prematurely, the double mutant does so normally. Moreover, ras1Delta cells exhibit increased resistance to H(2)O(2) and higher sensitivity to the heavy metal Co(2+), whereas ras2Delta cells show the opposite phenotypes. Together, our data reveal a novel regulatory mechanism by which two antagonizing Ras GTPases balance each other in regulating multiple cellular processes in C. albicans.

  4. Design and Simulation of the nuSTORM Pion Beamline

    DOE PAGES

    Liu, A.; Neuffer, D.; Bross, A.

    2015-08-15

    The nuSTORM (neutrinos from STORed Muons) proposal presents a detailed design for a neutrino facility based on a muon storage ring, with muon decay in the production straight section of the ring providing well defined neutrino beams. The facility includes a primary high-energy proton beam line, a target station with pion production and collection, and a pion beamline for pion transportation and injection into a muon decay ring. The nuSTORM design uses “stochastic injection”, in which pions are directed by a chicane, referred to as the Orbit Combination Section (OCS), into the production straight section of the storage ring. Pionsmore » that decay within that straight section provide muons within the circulating acceptance of the ring. Furthermore, the design enables injection without kickers or a separate pion decay transport line. The beam line that the pions traverse before being extracted from the decay ring is referred to as the pion beamline. Our paper describes the design and simulation of the pion beamline, and includes full beam dynamics simulations of the system.« less

  5. Design and Simulation of the nuSTORM Pion Beamline

    SciTech Connect

    Liu, A.; Neuffer, D.; Bross, A.

    2015-08-15

    The nuSTORM (neutrinos from STORed Muons) proposal presents a detailed design for a neutrino facility based on a muon storage ring, with muon decay in the production straight section of the ring providing well defined neutrino beams. The facility includes a primary high-energy proton beam line, a target station with pion production and collection, and a pion beamline for pion transportation and injection into a muon decay ring. The nuSTORM design uses “stochastic injection”, in which pions are directed by a chicane, referred to as the Orbit Combination Section (OCS), into the production straight section of the storage ring. Pions that decay within that straight section provide muons within the circulating acceptance of the ring. Furthermore, the design enables injection without kickers or a separate pion decay transport line. The beam line that the pions traverse before being extracted from the decay ring is referred to as the pion beamline. Our paper describes the design and simulation of the pion beamline, and includes full beam dynamics simulations of the system.

  6. Design and Simulation of an Electrothermal Actuator Based Rotational Drive

    NASA Astrophysics Data System (ADS)

    Beeson, Sterling; Dallas, Tim

    2008-10-01

    As a participant in the Micro and Nano Device Engineering (MANDE) Research Experience for Undergraduates program at Texas Tech University, I learned how MEMS devices operate and the limits of their operation. Using specialized AutoCAD-based design software and the ANSYS simulation program, I learned the MEMS fabrication process used at Sandia National Labs, the design limitations of this process, the abilities and drawbacks of micro devices, and finally, I redesigned a MEMS device called the Chevron Torsional Ratcheting Actuator (CTRA). Motion is achieved through electrothermal actuation. The chevron (bent-beam) actuators cause a ratcheting motion on top of a hub-less gear so that as voltage is applied the CTRA spins. The voltage applied needs to be pulsed and the frequency of the pulses determine the angular frequency of the device. The main objective was to design electromechanical structures capable of transforming the electrical signals into mechanical motion without overheating. The design was optimized using finite element analysis in ANSYS allowing multi-physics simulations of our model system.

  7. Design and simulation of the CG1 beamline at HFIR

    NASA Astrophysics Data System (ADS)

    Nagler, S. E.; Lee, W.-T.; Moon, R. M.

    In the near future a super-critical hydrogen cold source will be installed in the HB4 beam tube of the High Flux Isotope Reactor (HFIR), Oak Ridge National Laboratory. The cold source will illuminate four neutron guides. Here we discuss the design and simulation of the guide CG1, dedicated to a new triple axis spectrometer. The conceptual design for the HFIR guides, including CG1, was aided by numerical calculations of neutron trajectories and acceptance diagrams. The CG1 guide consists of a partially trumpeting two-channel bender and a straight guide section. The design was subsequently modeled in detail from source to specimen, utilizing the McStas program. The lessons learned from the McStas simulations resulted in some minor but important changes in the design, and these were also verified using the original method of calculation. The resulting combination of guide and vertically focusing monochromator should deliver a beam with excellent spatial and angular distributions in and out of the scattering plane. The available intensity will enable the construction of a powerful spectrometer for incident energies as large as 20-25 meV.

  8. Design and simulation of silicon photonic schematics and layouts

    NASA Astrophysics Data System (ADS)

    Chrostowski, Lukas; Lu, Zeqin; Flueckiger, Jonas; Wang, Xu; Klein, Jackson; Liu, Amy; Jhoja, Jaspreet; Pond, James

    2016-05-01

    Electronic circuit designers commonly start their design process with a schematic, namely an abstract representation of the physical circuit. In integrated photonics on the other hand, it is common for the design to begin at the physical component level, and create a layout by connecting components with interconnects. In this paper, we discuss how to create a schematic from the physical layout via netlist extraction, which enables circuit simulations. Post-layout extraction can also be used to predict how fabrication variability and non-uniformity will impact circuit performance. This is based on the component position information, compact models that are parameterized for dimensional variations, and manufacturing variability models such as a simulated wafer thickness map. This final step is critical in understanding how real-world silicon photonic circuits will behave. We present an example based on treating the ring resonator as a circuit. A silicon photonics design kit, as described here, is available for download at http://github.com/lukasc-ubc/SiEPIC_EBeam_PDK.

  9. Design and simulation of the nuSTORM facility

    NASA Astrophysics Data System (ADS)

    Liu, Ao

    This thesis provides a full design and simulation of the nuSTORM beam line facility including the pion beam line , the pion and muon orbit combination section, and the muon decay ring. The study also includes the development of numerical optimization methods and their application to the design. At nuSTORM, one proton batch from the Main Injector (MI) is extracted and transported to the target station to bombard a solid target. A magnetic horn is used as the collection device for the secondary particles such as pions and kaons. A pion beam line is designed to transport the secondary particles downstream to the muon decay ring. In order to avoid the use of a fast kicker with a large aperture for the injection, an Orbit Combination Section (OCS) was designed to combine the reference pion orbit with the circulating muon orbit. This fulfills the stochastic injection scheme proposed in the 1980s. It is shown through the simulation that the pion beam line is able to deliver 0.011 muons per proton on target within the acceptance of the ring. In order to improve the circulating muon flux, an optimization of the magnetic collection horn was studied. A Multi-Objective Genetic Algorithm (MOGA), that was modified to integrate Message Passing Interface (MPI) in the process, is applied to the optimization. The number of muons within the ring acceptance from the pion decay is estimated by the pions after the collection horn. This new method was proposed to lower the requirement on the computing resources for the optimization. The study gives a new and better target and horn configuration after a full investigation of the system. The nuSTORM ring is examined with two optics designs. With different features, the two designs are optimized via correcting the nonlinearities with sextupolar field distribution in the ring. A modified MPI-based Simulated Annealing (SA) algorithm was applied to obtain the optimal ring acceptance. The comparison with the GA shows good agreements on the

  10. Design and simulation of the nuSTORM facility

    SciTech Connect

    Liu, Ao

    2015-04-01

    This thesis provides a full design and simulation of the nuSTORM beam line facility including the pion beam line , the pion and muon orbit combination section, and the muon decay ring. The study also includes the development of numerical optimization methods and their application to the design. At nuSTORM, one proton batch from the Main Injector (MI) is extracted and transported to the target station to bombard a solid target. A magnetic horn is used as the collection device for the secondary particles such as pions and kaons. A pion beam line is designed to transport the secondary particles downstream to the muon decay ring. In order to avoid the use of a fast kicker with a large aperture for the injection, an Orbit Combination Section (OCS) was designed to combine the reference pion orbit with the circulating muon orbit. This ful lls the stochastic injection scheme proposed in the 1980s. It is shown through the simulation that the pion beam line is able to deliver 0.011 muons per proton on target within the acceptance of the ring. In order to improve the circulating muon ux, an optimization of the magnetic collection horn was studied. A Multi-Objective Genetic Algorithm (MOGA), that was modi ed to integrate Message Passing Interface (MPI) in the process, is applied to the optimization. The number of muons within the ring acceptance from the pion decay is estimated by the pions after the collection horn. This new method was proposed to lower the requirement on the computing resources for the optimization. The study gives a new and better target and horn con guration after a full investigation of the system. The nuSTORM ring is examined with two optics designs. With di erent features, the two designs are optimized via correcting the nonlinearities with sextupolar eld distribution in the ring. A modi ed MPI-based Simulated Annealing (SA) algorithm was applied to obtain the optimal ring acceptance. The comparison with the GA shows good agreements on the achieved

  11. Ras and Nox: linked signaling networks?

    PubMed Central

    Wu, Ru Feng; Terada, Lance S.

    2009-01-01

    Both Ras and Nox represent ancient gene families which control a broad range of cellular responses. Both families mediate signals governing motility, differentiation, and proliferation, and both inhabit overlapping subcellular microdomains. Yet little is known of the precise functional relationship between these two ubiquitous families. In this review, we examine the interface where these two large fields meet. PMID:19501154

  12. Using simulation to aid trial design: Ring-vaccination trials

    PubMed Central

    Hitchings, Matt David Thomas; Grais, Rebecca Freeman

    2017-01-01

    Background The 2014–6 West African Ebola epidemic highlights the need for rigorous, rapid clinical trial methods for vaccines. A challenge for trial design is making sample size calculations based on incidence within the trial, total vaccine effect, and intracluster correlation, when these parameters are uncertain in the presence of indirect effects of vaccination. Methods and findings We present a stochastic, compartmental model for a ring vaccination trial. After identification of an index case, a ring of contacts is recruited and either vaccinated immediately or after 21 days. The primary outcome of the trial is total vaccine effect, counting cases only from a pre-specified window in which the immediate arm is assumed to be fully protected and the delayed arm is not protected. Simulation results are used to calculate necessary sample size and estimated vaccine effect. Under baseline assumptions about vaccine properties, monthly incidence in unvaccinated rings and trial design, a standard sample-size calculation neglecting dynamic effects estimated that 7,100 participants would be needed to achieve 80% power to detect a difference in attack rate between arms, while incorporating dynamic considerations in the model increased the estimate to 8,900. This approach replaces assumptions about parameters at the ring level with assumptions about disease dynamics and vaccine characteristics at the individual level, so within this framework we were able to describe the sensitivity of the trial power and estimated effect to various parameters. We found that both of these quantities are sensitive to properties of the vaccine, to setting-specific parameters over which investigators have little control, and to parameters that are determined by the study design. Conclusions Incorporating simulation into the trial design process can improve robustness of sample size calculations. For this specific trial design, vaccine effectiveness depends on properties of the ring

  13. Simulation-Based Design of a Rotatory SMA Drive

    NASA Astrophysics Data System (ADS)

    Dilthey, Sascha; Meier, Horst

    2009-08-01

    The design and optimization of a rotatory drive powered by shape memory alloy (SMA) actuators is described in this paper. SMA actuators used in technical applications are parameterized by the use of trial-and-error methods, because there is a lack of computer-aided design tools for this active material. A numerical modeling approach was developed to design and optimize the geometry and the load and heating conditions of SMA actuators in a technical system to achieve a good dynamic and a high reliability. The shape memory effect used in most technical systems is the extrinsic two way effect (2WE). This effect can be simulated with the numerical model which was implemented in MATLAB/SIMULINK. The focus of the model is on the activation behavior of the SMA actuator, which defines its rate of heating and cooling. Different load conditions and various actuator geometries and shapes, e.g. wire or spring actuator, are simulated by the calculation of the energetic balance of the whole system. The numerical model can be used to simulate time variant heating currents in order to obtain an optimal system performance. The model was used to design a rotatory SMA-drive system, which is based on the moving concept of a wave drive gear set. In contrast to the conventional system, which is driven by an electric motor, the SMA drive consists of a strain wave gear and SMA wire actuators that are applied circularly to generate a rotatory movement. Special characteristics of this drive system are a high torque density and a high positioning accuracy.

  14. Superoxide Inhibits Guanine Nucleotide Exchange Factor (GEF) Action on Ras, but not on Rho, through Desensitization of Ras to GEF

    PubMed Central

    2015-01-01

    Ras and Rho GTPases are molecular switches for various vital cellular signaling pathways. Overactivation of these GTPases often causes development of cancer. Guanine nucleotide exchange factors (GEFs) and oxidants function to upregulate these GTPases through facilitation of guanine nucleotide exchange (GNE) of these GTPases. However, the effect of oxidants on GEF functions, or vice versa, has not been known. We show that, via targeting Ras Cys51, an oxidant inhibits the catalytic action of Cdc25—the catalytic domain of RasGEFs—on Ras. However, the enhancement of Ras GNE by an oxidant continues regardless of the presence of Cdc25. Limiting RasGEF action by an oxidant may function to prevent the pathophysiological overactivation of Ras in the presence of both RasGEFs and oxidants. The continuous exposure of Ras to nitric oxide and its derivatives can form S-nitrosated Ras (Ras-SNO). This study also shows that an oxidant not only inhibits the catalytic action of Cdc25 on Ras-SNO but also fails to enhance Ras-SNO GNE. This lack of enhancement then populates the biologically inactive Ras-SNO in cells, which may function to prevent the continued redox signaling of the Ras pathophysiological response. Finally, this study also demonstrates that, unlike the case with RasGEFs, an oxidant does not inhibit the catalytic action of RhoGEF—Vav or Dbs—on Rho GTPases such as Rac1, RhoA, RhoC, and Cdc42. This result explains the results of the previous study in which, despite the presence of an oxidant, the catalytic action of Dbs in cells continued to enhance RhoC GNE. PMID:24422478

  15. Metrology and test requirements for movement of the RAS/HOMS test facility to NASA-GSFC

    NASA Astrophysics Data System (ADS)

    Wenzel, Greg; Redman, Kevin; Eichhorn, William

    2006-06-01

    The Refractive Aberrated Simulator/Hubble Opto-Mechanical Simulator (RAS/HOMS) test facility previously located at Ball Aerospace Division in Boulder (BASD), CO will be relocated to NASA Goddard Space Flight Center (GSFC). This paper will highlight the metrology and test methods used to characterize the facility prior to disassembly as well as assemble and align the facility once it has been moved to GSFC. The HOMS portion of the facility simulates the mechanical latch mechanisms that hold an axial instrument in alignment with the Hubble Space Telescope (HST) optical path. Two sets of three latches must be aligned in position on the HOMS structure to match that of the two axial bays in HST. The RAS portion of the facility is a refractive optical system that simulates the aberrations in HST's optical telescope assembly. Each mount and lens must be properly aligned within the RAS system in order to accurately simulate the aberrations of HST's optical system. The optical axis of the RAS system must be brought into alignment with the optical axis of HOMS system. Photogrammetry, theodolite auto-collimation data, theodolite coordinate data, and laser tracker coordinate data were used to characterize the system prior to disassembly. The same data will be used to bring the RAS/HOMS system as close to the original alignment as possible.

  16. Designing laboratory wind simulations using artificial neural networks

    NASA Astrophysics Data System (ADS)

    Križan, Josip; Gašparac, Goran; Kozmar, Hrvoje; Antonić, Oleg; Grisogono, Branko

    2015-05-01

    While experiments in boundary layer wind tunnels remain to be a major research tool in wind engineering and environmental aerodynamics, designing the modeling hardware required for a proper atmospheric boundary layer (ABL) simulation can be costly and time consuming. Hence, possibilities are sought to speed-up this process and make it more time-efficient. In this study, two artificial neural networks (ANNs) are developed to determine an optimal design of the Counihan hardware, i.e., castellated barrier wall, vortex generators, and surface roughness, in order to simulate the ABL flow developing above urban, suburban, and rural terrains, as previous ANN models were created for one terrain type only. A standard procedure is used in developing those two ANNs in order to further enhance best-practice possibilities rather than to improve existing ANN designing methodology. In total, experimental results obtained using 23 different hardware setups are used when creating ANNs. In those tests, basic barrier height, barrier castellation height, spacing density, and height of surface roughness elements are the parameters that were varied to create satisfactory ABL simulations. The first ANN was used for the estimation of mean wind velocity, turbulent Reynolds stress, turbulence intensity, and length scales, while the second one was used for the estimation of the power spectral density of velocity fluctuations. This extensive set of studied flow and turbulence parameters is unmatched in comparison to the previous relevant studies, as it includes here turbulence intensity and power spectral density of velocity fluctuations in all three directions, as well as the Reynolds stress profiles and turbulence length scales. Modeling results agree well with experiments for all terrain types, particularly in the lower ABL within the height range of the most engineering structures, while exhibiting sensitivity to abrupt changes and data scattering in profiles of wind-tunnel results. The

  17. Design, modeling, simulation and evaluation of a distributed energy system

    NASA Astrophysics Data System (ADS)

    Cultura, Ambrosio B., II

    This dissertation presents the design, modeling, simulation and evaluation of distributed energy resources (DER) consisting of photovoltaics (PV), wind turbines, batteries, a PEM fuel cell and supercapacitors. The distributed energy resources installed at UMass Lowell consist of the following: 2.5kW PV, 44kWhr lead acid batteries and 1500W, 500W & 300W wind turbines, which were installed before year 2000. Recently added to that are the following: 10.56 kW PV array, 2.4 kW wind turbine, 29 kWhr Lead acid batteries, a 1.2 kW PEM fuel cell and 4-140F supercapacitors. Each newly added energy resource has been designed, modeled, simulated and evaluated before its integration into the existing PV/Wind grid-connected system. The Mathematical and Simulink model of each system was derived and validated by comparing the simulated and experimental results. The Simulated results of energy generated from a 10.56kW PV system are in good agreement with the experimental results. A detailed electrical model of a 2.4kW wind turbine system equipped with a permanent magnet generator, diode rectifier, boost converter and inverter is presented. The analysis of the results demonstrates the effectiveness of the constructed simulink model, and can be used to predict the performance of the wind turbine. It was observed that a PEM fuel cell has a very fast response to load changes. Moreover, the model has validated the actual operation of the PEM fuel cell, showing that the simulated results in Matlab Simulink are consistent with the experimental results. The equivalent mathematical equation, derived from an electrical model of the supercapacitor, is used to simulate its voltage response. The model is completely capable of simulating its voltage behavior, and can predict the charge time and discharge time of voltages on the supercapacitor. The bi-directional dc-dc converter was designed in order to connect the 48V battery bank storage to the 24V battery bank storage. This connection was

  18. Monte Carlo Simulation of rainfall hyetographs for analysis and design

    NASA Astrophysics Data System (ADS)

    Kottegoda, N. T.; Natale, L.; Raiteri, E.

    2014-11-01

    Observations of high intensity rainfalls have been recorded at gauging stations in many parts of the world. In some instances the resulting data sets may not be sufficient in their scope and variability for purposes of analysis or design. By directly incorporating statistical properties of hyetographs with respect to the number of events per year, storm duration, peak intensity, cumulative rainfall and rising and falling limbs we develop a fundamentally basic procedure for Monte Carlo Simulation. Rainfall from Pavia and Milano in Lombardia region and from five gauging stations in the Piemonte region of northern Italy are used in this study. Firstly, we compare the hydrologic output from our model with that from other design storm methods for validation. Secondly, depth-duration-frequency curves are obtained from historical data and corresponding functions from simulated data are compared for further validation of the procedure. By adopting this original procedure one can simulate an unlimited range of realistic hydrographs that can be used in risk assessment. The potential for extension to ungauged catchments is shown.

  19. High-Density Plasma Reactors: Simulations for Design

    NASA Technical Reports Server (NTRS)

    Hash, David B.; Meyyappan, Meyya; Arnold, James O. (Technical Monitor)

    1998-01-01

    The development of improved and more efficient plasma reactors is a costly process for the semiconductor industry. Until five years ago, the Industry made most of its advancements through a trial and error approach. More recently, the role of computational modeling in the design process has increased. Both conventional computational fluid dynamics (CFD) techniques like Navier-Stokes solvers as well as particle simulation methods are used to model plasma reactor flowfields. However, since high-density plasma reactors generally operate at low gas pressures on the order of 1 to 10 mTorr, a particle simulation may be necessary because of the failure of CFD techniques to model rarefaction effects. The direct simulation Monte Carlo method is the most widely accepted and employed particle simulation tool and has previously been used to investigate plasma reactor flowfields. A plasma DSMC code is currently under development at NASA Ames Research Center with its foundation as the object-oriented parallel Cornell DSMC code, MONACO. The present investigation is a follow up of a neutral flow investigation of the effects of process parameters as well as reactor design on etch rate and etch rate uniformity. The previous work concentrated on silicon etch of a chlorine flow in a configuration typical of electron cyclotron resonance (ECR) or helical resonator type reactors. The effects of the plasma on the dissociation chemistry were modeled by making assumptions about the electron temperature and number density. The electrons or ions themselves were not simulated.The present work extends these results by simulating the charged species.The electromagnetic fields are calculated such that power deposition is modeled self-consistently. Electron impact reactions are modeled along with mechanisms for charge exchange. An bipolar diffusion assumption is made whereby electrons remain tied to the ions. However, the velocities of tile electrons are allowed to be modified during collisions

  20. Qatargas exporting LNG from Qatar`s new Ras Laffan Port

    SciTech Connect

    1997-02-24

    When the 135,000 cu m LNG carrier Al Zubarah departed Ras Laffan Port in December, Qatar entered a new era of commerce that will both boost the emirate`s economic development and influence energy trade around the world. The event capped more than a decade of planning, design, and construction of Ras Laffan Port--the world`s newest and largest LNG exporting facility. During the 1980s, the focus in Qatar was on exploration and development of North field, which holds the world`s largest reserves of nonassociated natural gas. In the 1990s, efforts concentrated on establishing a direct production and export link between North field, the new multi-billion-dollar Qatar Liquefied Gas Co. (Qatargas) gas liquefaction plant at Ras Laffan, and LNG export facilities at the 8.5 sq km Ras Laffan Port. Markets of the Far East will be first to be served by LNG from Ras Laffan Port. Two 25-year LNG supply contracts have been signed with buyers in Japan and South Korea, and negotiations are under way with potential customers from China, Taiwan, and Thailand. The paper describes the port, its operations, and export projects.

  1. VPS35 binds farnesylated N-Ras in the cytosol to regulate N-Ras trafficking

    PubMed Central

    Wiener, Heidi; Su, Wenjuan; Liot, Caroline; Hancock, John F.

    2016-01-01

    Ras guanosine triphosphatases (GTPases) regulate signaling pathways only when associated with cellular membranes through their C-terminal prenylated regions. Ras proteins move between membrane compartments in part via diffusion-limited, fluid phase transfer through the cytosol, suggesting that chaperones sequester the polyisoprene lipid from the aqueous environment. In this study, we analyze the nature of the pool of endogenous Ras proteins found in the cytosol. The majority of the pool consists of farnesylated, but not palmitoylated, N-Ras that is associated with a high molecular weight (HMW) complex. Affinity purification and mass spectrographic identification revealed that among the proteins found in the HMW fraction is VPS35, a latent cytosolic component of the retromer coat. VPS35 bound to N-Ras in a farnesyl-dependent, but neither palmitoyl- nor guanosine triphosphate (GTP)–dependent, fashion. Silencing VPS35 increased N-Ras’s association with cytoplasmic vesicles, diminished GTP loading of Ras, and inhibited mitogen-activated protein kinase signaling and growth of N-Ras–dependent melanoma cells. PMID:27502489

  2. A sensitive dual-fluorescence reporter system enables positive selection of ras suppressors by suppression of ras-induced apoptosis.

    PubMed

    Dolnikov, Alla; Shen, Sylvie; Millington, Michelle; Passioura, Toby; Pedler, Michelle; Rasko, John Edward Joshua; Symonds, Geoff

    2003-10-01

    We have developed a novel dual-fluorescence reporter system incorporating green (GFP) and red (RFP) fluorescent proteins to monitor expression of the N-ras(m) gene and an N-ras(m) suppressor, respectively. Retroviral vectors were produced in which human N-ras(m) (codon 13 mutation) was coexpressed with GFP, and a ribozyme specifically targeting N-ras(m) was coexpressed with RFP. N-Ras(m) suppression was monitored by measurement of GFP fluorescence in dual-fluorescent (GFP and RFP) cells. We demonstrated that the degree of N-ras(m) suppression was dependent on the ribozyme dose, proportional to red fluorescence, in dual-fluorescent cells. We further showed that ribozyme-mediated N-ras(m)suppression inhibited growth of NIH3T3 and CD34-positive TF-1 cells. In these cultures, ras suppressor activity resulted in the depletion of suppressor-positive cells due to inhibition of cell growth. In contrast, N-ras(m) suppression produced a growth advantage to human leukemic K562 cells, presumably by inhibiting N-ras(m)-induced apoptosis. In K562 cells, ras suppression resulted in the outgrowth of suppressor-positive cells. This provides a platform to identify suppressors of ras that is based on function.

  3. Design, modeling and simulation of MEMS-based silicon Microneedles

    NASA Astrophysics Data System (ADS)

    Amin, F.; Ahmed, S.

    2013-06-01

    The advancement in semiconductor process engineering and nano-scale fabrication technology has made it convenient to transport specific biological fluid into or out of human skin with minimum discomfort. Fluid transdermal delivery systems such as Microneedle arrays are one such emerging and exciting Micro-Electro Mechanical System (MEMS) application which could lead to a total painless fluid delivery into skin with controllability and desirable yield. In this study, we aimed to revisit the problem with modeling, design and simulations carried out for MEMS based silicon hollow out of plane microneedle arrays for biomedical applications particularly for transdermal drug delivery. An approximate 200 μm length of microneedle with 40 μm diameter of lumen has been successfully shown formed by isotropic and anisotropic etching techniques using MEMS Pro design tool. These microneedles are arranged in size of 2 × 4 matrix array with center to center spacing of 750 μm. Furthermore, comparisons for fluid flow characteristics through these microneedle channels have been modeled with and without the contribution of the gravitational forces using mathematical models derived from Bernoulli Equation. Physical Process simulations have also been performed on TCAD SILVACO to optimize the design of these microneedles aligned with the standard Si-Fabrication lines.

  4. Building interactive simulations in a Web page design program.

    PubMed

    Kootsey, J Mailen; Siriphongs, Daniel; McAuley, Grant

    2004-01-01

    A new Web software architecture, NumberLinX (NLX), has been integrated into a commercial Web design program to produce a drag-and-drop environment for building interactive simulations. NLX is a library of reusable objects written in Java, including input, output, calculation, and control objects. The NLX objects were added to the palette of available objects in the Web design program to be selected and dropped on a page. Inserting an object in a Web page is accomplished by adding a template block of HTML code to the page file. HTML parameters in the block must be set to user-supplied values, so the HTML code is generated dynamically, based on user entries in a popup form. Implementing the object inspector for each object permits the user to edit object attributes in a form window. Except for model definition, the combination of the NLX architecture and the Web design program permits construction of interactive simulation pages without writing or inspecting code.

  5. Design of virtual SCADA simulation system for pressurized water reactor

    NASA Astrophysics Data System (ADS)

    Wijaksono, Umar; Abdullah, Ade Gafar; Hakim, Dadang Lukman

    2016-02-01

    The Virtual SCADA system is a software-based Human-Machine Interface that can visualize the process of a plant. This paper described the results of the virtual SCADA system design that aims to recognize the principle of the Nuclear Power Plant type Pressurized Water Reactor. This simulation uses technical data of the Nuclear Power Plant Unit Olkiluoto 3 in Finland. This device was developed using Wonderware Intouch, which is equipped with manual books for each component, animation links, alarm systems, real time and historical trending, and security system. The results showed that in general this device can demonstrate clearly the principles of energy flow and energy conversion processes in Pressurized Water Reactors. This virtual SCADA simulation system can be used as instructional media to recognize the principle of Pressurized Water Reactor.

  6. Design and simulation of uncooled microbolometer using coventorware

    NASA Astrophysics Data System (ADS)

    Arora, Suryansh; Paras, Neha; Gurjar, Anil; Narwal, Rakesh; Prasad, B.; Kumar, Dinesh

    2016-04-01

    Recently, a lot of attention has been paid to infrared imaging using uncooled microbolometer detectors, primarily because of their low cost, and wide military and civilian applications like disaster rescue, night vision, homing and tracking, ecology and weather forecasting, target acquisition, predictive inspection and maintenance, surveillance, remote temperature sensing and medical diagnostic and treatment. The present work demonstrates the design and simulation of uncooled microbolometer detector using Coventorware tool. Geometrical optimization has been done to minimize the pixel size up to 18×18 µm. Simulated values for Different parameters like Thermal conductance, Time constant and change in temperature calculated for the structure are 1.2 × 10-7W/K, 4.44ms and 3.5K.

  7. Design of virtual SCADA simulation system for pressurized water reactor

    SciTech Connect

    Wijaksono, Umar Abdullah, Ade Gafar; Hakim, Dadang Lukman

    2016-02-08

    The Virtual SCADA system is a software-based Human-Machine Interface that can visualize the process of a plant. This paper described the results of the virtual SCADA system design that aims to recognize the principle of the Nuclear Power Plant type Pressurized Water Reactor. This simulation uses technical data of the Nuclear Power Plant Unit Olkiluoto 3 in Finland. This device was developed using Wonderware Intouch, which is equipped with manual books for each component, animation links, alarm systems, real time and historical trending, and security system. The results showed that in general this device can demonstrate clearly the principles of energy flow and energy conversion processes in Pressurized Water Reactors. This virtual SCADA simulation system can be used as instructional media to recognize the principle of Pressurized Water Reactor.

  8. Quantum circuit design for accurate simulation of qudit channels

    NASA Astrophysics Data System (ADS)

    Wang, Dong-Sheng; Sanders, Barry C.

    2015-04-01

    We construct a classical algorithm that designs quantum circuits for algorithmic quantum simulation of arbitrary qudit channels on fault-tolerant quantum computers within a pre-specified error tolerance with respect to diamond-norm distance. The classical algorithm is constructed by decomposing a quantum channel into a convex combination of generalized extreme channels by convex optimization of a set of nonlinear coupled algebraïc equations. The resultant circuit is a randomly chosen generalized extreme channel circuit whose run-time is logarithmic with respect to the error tolerance and quadratic with respect to Hilbert space dimension, which requires only a single ancillary qudit plus classical dits.

  9. Design, simulation and construction of a Wire Chamber electronics

    NASA Astrophysics Data System (ADS)

    Istemihan, Zehra

    2017-02-01

    Tracking charged particles has a wide spectrum of applications in scientific and industrial projects. The Delay Wire Chamber (DWC) is a kind of gaseous detector which is a simpler form of the Multi Wire Proportional Chamber, and was developed by the Beam Instrumentation Group at CERN. It is preferred in accelerator and particle physics experiments because of its ease of use, affordability and durability, and it also provides decent position precision. In this work, we describe the working principles of the readout electronics of a new DWC that is being designed and constructed at our laboratory. Results from the simulation of the circuit and the constructed prototype will be presented.

  10. Numerical simulation in alternating current field measurement inducer design

    NASA Astrophysics Data System (ADS)

    Zhou, Zhixiong; Zheng, Wenpei

    2017-02-01

    The present work develops a numerical simulation model to evaluate the magnetic field perturbation of a twin coil alternating current field measurement (ACFM) inducer passing above a surface-breaking crack for the purpose of enhanced crack detection. Model predictions show good agreement with experimental data, verifying the accuracy of the model. The model includes the influence of various parameters, such as core dimensions and core positions on the perturbed magnetic field above a crack. Optimized design parameters for a twin coil inducer are given according to the analysis results, which provide for a greatly improved detection effect.

  11. 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.

  12. Beam Dynamics Design and Simulation in Ion Linear Accelerators (

    SciTech Connect

    Ostroumov, Peter N.; Asseev, Vladislav N.; Mustapha, and Brahim

    2006-08-01

    Orginally, the ray tracing code TRACK has been developed to fulfill the many special requirements for the Rare Isotope Accelerator Facility known as RIA. Since no available beam-dynamics code met all the necessary requirements, modifications to the code TRACK were introduced to allow end-to-end (from the ion souce to the production target) simulations of the RIA machine, TRACK is a general beam-dynamics code and can be applied for the design, commissioning and operation of modern ion linear accelerators and beam transport systems.

  13. Design analysis tracking and data relay satellite simulation system

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The design and development of the equipment necessary to simulate the S-band multiple access link between user spacecraft, the Tracking and Data Relay Satellite, and a ground control terminal are discussed. The core of the S-band multiple access concept is the use of an Adaptive Ground Implemented Phased Array. The array contains thirty channels and provides the multiplexing and demultiplexing equipment required to demonstrate the ground implemented beam forming feature. The system provided will make it possible to demonstrate the performance of a desired user and ten interfering sources attempting to pass data through the multiple access system.

  14. Computational studies of Ras and PI3K

    NASA Technical Reports Server (NTRS)

    Ren, Lei; Cucinotta, Francis A.

    2004-01-01

    Until recently, experimental techniques in molecular cell biology have been the primary means to investigate biological risk upon space radiation. However, computational modeling provides an alternative theoretical approach, which utilizes various computational tools to simulate proteins, nucleotides, and their interactions. In this study, we are focused on using molecular mechanics (MM) and molecular dynamics (MD) to study the mechanism of protein-protein binding and to estimate the binding free energy between proteins. Ras is a key element in a variety of cell processes, and its activation of phosphoinositide 3-kinase (PI3K) is important for survival of transformed cells. Different computational approaches for this particular study are presented to calculate the solvation energies and binding free energies of H-Ras and PI3K. The goal of this study is to establish computational methods to investigate the roles of different proteins played in the cellular responses to space radiation, including modification of protein function through gene mutation, and to support the studies in molecular cell biology and theoretical kinetics models for our risk assessment project.

  15. Integrated Simulation Design Challenges to Support TPS Repair Operations

    NASA Technical Reports Server (NTRS)

    Quiocho, Leslie J.; Crues, Edwin Z.; Huynh, An; Nguyen, Hung T.; MacLean, John

    2006-01-01

    )ntegrated Shuttle, SRMS, ISS (with active ACS) in the orbital environment, and (5) dual-arm SRMS/SSRMS dynamics topology. Integrated simulation V&V run suites were created and correlated to verification runs from subsystem simulations, in order to establish the validity of the results. This paper discusses the simulation design challenges encountered while developing simulation capabilities to mirror the ORM operations. The paper also describes the incremental build approach that was utilized, starting with the subsystem simulation elements and integration into increasing more complex simulations until the resulting ORM worksite dynamics simulation had been assembled. Furthermore, the paper presents an overall integrated simulation V&V methodology based upon a subsystem level testing, integrated comparisons, and phased checkout.

  16. Evolutionary expansion of the Ras switch regulatory module in eukaryotes

    PubMed Central

    Díez, Diego; Sánchez-Jiménez, Francisca; Ranea, Juan A. G.

    2011-01-01

    Ras proteins control many aspects of eukaryotic cell homeostasis by switching between active (GTP-bound) and inactive (GDP-bound) conformations, a reaction catalyzed by GTPase exchange factors (GEF) and GTPase activating proteins (GAP) regulators, respectively. Here, we show that the complexity, measured as number of genes, of the canonical Ras switch genetic system (including Ras, RasGEF, RasGAP and RapGAP families) from 24 eukaryotic organisms is correlated with their genome size and is inversely correlated to their evolutionary distances from humans. Moreover, different gene subfamilies within the Ras switch have contributed unevenly to the module’s expansion and speciation processes during eukaryote evolution. The Ras system remarkably reduced its genetic expansion after the split of the Euteleostomi clade and presently looks practically crystallized in mammals. Supporting evidence points to gene duplication as the predominant mechanism generating functional diversity in the Ras system, stressing the leading role of gene duplication in the Ras family expansion. Domain fusion and alternative splicing are significant sources of functional diversity in the GAP and GEF families but their contribution is limited in the Ras family. An evolutionary model of the Ras system expansion is proposed suggesting an inherent ‘decision making’ topology with the GEF input signal integrated by a homologous molecular mechanism and bifurcation in GAP signaling propagation. PMID:21447561

  17. SodC modulates ras and PKB signaling in Dictyostelium.

    PubMed

    Castillo, Boris; Kim, Seon-Hee; Sharief, Mujataba; Sun, Tong; Kim, Lou W

    2017-01-01

    We have previously reported that the basal RasG activity is aberrantly high in cells lacking Superoxide dismutase C (SodC). Here we report that other Ras proteins such as RasC and RasD activities are not affected in sodC(-) cells and mutagenesis studies showed that the presence of the Cys(118) in the Ras proteins is essential for the superoxide-mediated activation of Ras proteins in Dictyostelium. In addition to the loss of SodC, lack of extracellular magnesium ions increased the level of intracellular superoxide and active RasG proteins. Aberrantly active Ras proteins in sodC(-) cells persistently localized at the plasma membrane, but those in wild type cells under magnesium deficient medium exhibited intracellular vesicular localization. Interestingly, the aberrantly activated Ras proteins in wild type cells were largely insulated from their normal downstream events such as Phosphatidylinositol-3,4,5-P3 (PIP3) accumulation, Protein Kinase B (PKB) activation, and PKBs substrates phosphorylation. Intriguingly, however, aberrantly activated Ras proteins in sodC(-) cells were still engaged in signaling to their downstream targets, and thus excessive PKBs substrates phosphorylation persisted. In summary, we suggest that SodC and RasG proteins are essential part of a novel inhibitory mechanism that discourages oxidatively stressed cells from chemotaxis and thus inhibits the delivery of potentially damaged genome to the next generation.

  18. Spatial segregation of Ras signaling: new evidence from fission yeast.

    PubMed

    Chang, Eric C; Philips, Mark R

    2006-09-01

    The Ras GTPases act as binary switches for signal transduction pathways that are important for growth regulation and tumorigenesis. Despite the biochemical simplicity of this switch, Ras proteins control multiple pathways, and the functions of the four mammalian Ras proteins are not overlapping. This raises an important question--how does a Ras protein selectively regulate a particular activity? One recently emerging model suggests that a single Ras protein can control different functions by acting in distinct cellular compartments. A critical test of this model is to identify pathways that are selectively controlled by Ras when it is localized to a particular compartment. A recent study has examined Ras signaling in the fission yeast Schizosaccharomyces pombe, which expresses only one Ras protein that controls two separate evolutionarily conserved pathways. This study demonstrates that whereas Ras localized to the plasma membrane selectively regulates a MAP kinase pathway to mediate mating pheromone signaling, Ras localized to the endomembrane activates a Cdc42 pathway to mediate cell polarity and protein trafficking. This study has provided unambiguous evidence for compartmentalized signaling of Ras.

  19. The RAS-Effector Interaction as a Drug Target.

    PubMed

    Keeton, Adam B; Salter, E Alan; Piazza, Gary A

    2017-01-15

    About a third of all human cancers harbor mutations in one of the K-, N-, or HRAS genes that encode an abnormal RAS protein locked in a constitutively activated state to drive malignant transformation and tumor growth. Despite more than three decades of intensive research aimed at the discovery of RAS-directed therapeutics, there are no FDA-approved drugs that are broadly effective against RAS-driven cancers. Although RAS proteins are often said to be "undruggable," there is mounting evidence suggesting it may be feasible to develop direct inhibitors of RAS proteins. Here, we review this evidence with a focus on compounds capable of inhibiting the interaction of RAS proteins with their effectors that transduce the signals of RAS and that drive and sustain malignant transformation and tumor growth. These reports of direct-acting RAS inhibitors provide valuable insight for further discovery and development of clinical candidates for RAS-driven cancers involving mutations in RAS genes or otherwise activated RAS proteins. Cancer Res; 77(2); 221-6. ©2017 AACR.

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

    NASA Astrophysics Data System (ADS)

    Golovkin, Igor; Macfarlane, Joseph; Golovkina, Viktoriya

    2016-10-01

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

  1. A novel solution for LED wall lamp design and simulation

    NASA Astrophysics Data System (ADS)

    Ge, Rui; Hong, Weibin; Li, Kuangqi; Liang, Pengxiang; Zhao, Fuli

    2014-11-01

    The model of the wall washer lamp and the practical illumination application have been established with a new design of the lens to meet the uniform illumination demand for wall washer lamp based on the Lambertian light sources. Our secondary optical design of freeform surface lens to LED wall washer lamp based on the conservation law of energy and Snell's law can improve the lighting effects as a uniform illumination. With the relationship between the surface of the lens and the surface of the target, a great number of discrete points of the freeform profile curve were obtained through the iterative method. After importing the data into our modeling program, the optical entity was obtained. Finally, to verify the feasibility of the algorithm, the model was simulated by specialized software, with both the LED Lambertian point source and LED panel source model.

  2. An Innovative Ski-Boot: Design, Numerical Simulations and Testing

    PubMed Central

    Corazza, Stefano; Cobelli, Claudio

    2005-01-01

    The present work is concerned with the design of an innovative ski-boot. In order to optimize ergonomics and biomechanical behavior of the ski-boot it is important to take into account the orientation of the leg with respect to the ground. The SGS system (Stance Geometry System) developed in this work allows the skier to adjust for posture in the frontal plane by rotating the sole of the boot about the antero-posterior axis (ski-boot is then locked in the desired position before skiing). A simplified model of the effect of ski-boot deformation on skiing behavior is used to evaluate the minimal stiffness the system must have. An experimental analysis on the ski slopes was carried out to provide ski-boot deformations and loading data in different skiing conditions, to be used in numerical simulations. Finite Elements Method (FEM) simulations were performed for optimal design of the joint between ski-boot and sole. The active loads and local ski-boot deformations during small- and large-radius turns were experimentally determined and used to validate a FEM model of the ski-boot. The model was used to optimize the design for maximum stiffness and to demonstrate the efficacy of virtual design supported by proper experimental data. Mean loads up to 164% body weight were measured on the outer ski during turning. The new SGS design system allows the adjustment of lateral stance before using the ski-boot, optimizing the ski-boot stiffness through FEM analysis. Innovative aspects of this work included not only the stance geometry system ski-boot but also the setup of a virtual design environment that was validated by experimental evidence. An entire dataset describing loads during skiing has been obtained. The optimized SGS ski-boot increases intrinsic knee stability due to proper adjustment of lateral stance, guaranteeing appropriate stiffness of the ski-boot system. Key Points Load acting during different phases of active skiing have been investigated in both qualitative

  3. Simulation of Wind Profile Perturbations for Launch Vehicle Design

    NASA Technical Reports Server (NTRS)

    Adelfang, S. I.

    2004-01-01

    Ideally, a statistically representative sample of measured high-resolution wind profiles with wavelengths as small as tens of meters is required in design studies to establish aerodynamic load indicator dispersions and vehicle control system capability. At most potential launch sites, high- resolution wind profiles may not exist. Representative samples of Rawinsonde wind profiles to altitudes of 30 km are more likely to be available from the extensive network of measurement sites established for routine sampling in support of weather observing and forecasting activity. Such a sample, large enough to be statistically representative of relatively large wavelength perturbations, would be inadequate for launch vehicle design assessments because the Rawinsonde system accurately measures wind perturbations with wavelengths no smaller than 2000 m (1000 m altitude increment). The Kennedy Space Center (KSC) Jimsphere wind profiles (150/month and seasonal 2 and 3.5-hr pairs) are the only adequate samples of high resolution profiles approx. 150 to 300 m effective resolution, but over-sampled at 25 m intervals) that have been used extensively for launch vehicle design assessments. Therefore, a simulation process has been developed for enhancement of measured low-resolution Rawinsonde profiles that would be applicable in preliminary launch vehicle design studies at launch sites other than KSC.

  4. Design and Performance Frameworks for Constructing Problem-Solving Simulations

    PubMed Central

    Stevens, Ron; Palacio-Cayetano, Joycelin

    2003-01-01

    Rapid advancements in hardware, software, and connectivity are helping to shorten the times needed to develop computer simulations for science education. These advancements, however, have not been accompanied by corresponding theories of how best to design and use these technologies for teaching, learning, and testing. Such design frameworks ideally would be guided less by the strengths/limitations of the presentation media and more by cognitive analyses detailing the goals of the tasks, the needs and abilities of students, and the resulting decision outcomes needed by different audiences. This article describes a problem-solving environment and associated theoretical framework for investigating how students select and use strategies as they solve complex science problems. A framework is first described for designing on-line problem spaces that highlights issues of content, scale, cognitive complexity, and constraints. While this framework was originally designed for medical education, it has proven robust and has been successfully applied to learning environments from elementary school through medical school. Next, a similar framework is detailed for collecting student performance and progress data that can provide evidence of students' strategic thinking and that could potentially be used to accelerate student progress. Finally, experimental validation data are presented that link strategy selection and use with other metrics of scientific reasoning and student achievement. PMID:14506505

  5. The LHCb Simulation Application, Gauss: Design, Evolution and Experience

    NASA Astrophysics Data System (ADS)

    Clemencic, M.; Corti, G.; Easo, S.; Jones, C. R.; Miglioranzi, S.; Pappagallo, M.; Robbe, P.; LHCb Collaboration

    2011-12-01

    The LHCb simulation application, Gauss, is based on the Gaudi framework and on experiment basic components such as the Event Model and Detector Description. Gauss also depends on external libraries for the generation of the primary events (PYTHIA 6, EvtGen, etc.) and on GEANT4 for particle transport in the experimental setup. The application supports the production of different types of events from minimum bias to B physics signals and particle guns. It is used for purely generator-level studies as well as full simulations. Gauss is used both directly by users and in massive central productions on the grid. The design and implementation of the application and its evolution due to evolving requirements will be described as in the case of the recently adopted Python-based configuration or the possibility of taking into account detectors conditions via a Simulation Conditions database. The challenge of supporting at the same time the flexibililty needed for the different tasks for which it is used, from evaluation of physics reach to background modeling, together with the stability and reliabilty of the code will also be described.

  6. Carotid artery phantom designment and simulation using field II

    NASA Astrophysics Data System (ADS)

    Lin, Yuan; Yang, Xin; Ding, Mingyue

    2013-10-01

    Carotid atherosclerosis is the major cause of ischemic stroke, a leading cause of mortality and disability. Morphology and structure features of carotid plaques are the keys to identify plaques and monitoring the disease. Manually segmentation on the ultrasonic images to get the best-fitted actual size of the carotid plaques based on physicians personal experience, namely "gold standard", is a important step in the study of plaque size. However, it is difficult to qualitatively measure the segmentation error caused by the operator's subjective factors. In order to reduce the subjective factors, and the uncertainty factors of quantification, the experiments in this paper were carried out. In this study, we firstly designed a carotid artery phantom, and then use three different beam-forming algorithms of medical ultrasound to simulate the phantom. Finally obtained plaques areas were analyzed through manual segmentation on simulation images. We could (1) directly evaluate the different beam-forming algorithms for the ultrasound imaging simulation on the effect of carotid artery; (2) also analyze the sensitivity of detection on different size of plaques; (3) indirectly reflect the accuracy of the manual segmentation base on segmentation results the evaluation.

  7. Integrating Multibody Simulation and CFD: toward Complex Multidisciplinary Design Optimization

    NASA Astrophysics Data System (ADS)

    Pieri, Stefano; Poloni, Carlo; Mühlmeier, Martin

    This paper describes the use of integrated multidisciplinary analysis and optimization of a race car model on a predefined circuit. The objective is the definition of the most efficient geometric configuration that can guarantee the lowest lap time. In order to carry out this study it has been necessary to interface the design optimization software modeFRONTIER with the following softwares: CATIA v5, a three dimensional CAD software, used for the definition of the parametric geometry; A.D.A.M.S./Motorsport, a multi-body dynamic simulation software; IcemCFD, a mesh generator, for the automatic generation of the CFD grid; CFX, a Navier-Stokes code, for the fluid-dynamic forces prediction. The process integration gives the possibility to compute, for each geometrical configuration, a set of aerodynamic coefficients that are then used in the multiboby simulation for the computation of the lap time. Finally an automatic optimization procedure is started and the lap-time minimized. The whole process is executed on a Linux cluster running CFD simulations in parallel.

  8. A design of camera simulator for photoelectric image acquisition system

    NASA Astrophysics Data System (ADS)

    Cai, Guanghui; Liu, Wen; Zhang, Xin

    2015-02-01

    In the process of developing the photoelectric image acquisition equipment, it needs to verify the function and performance. In order to make the photoelectric device recall the image data formerly in the process of debugging and testing, a design scheme of the camera simulator is presented. In this system, with FPGA as the control core, the image data is saved in NAND flash trough USB2.0 bus. Due to the access rate of the NAND, flash is too slow to meet the requirement of the sytsem, to fix the problem, the pipeline technique and the High-Band-Buses technique are applied in the design to improve the storage rate. It reads image data out from flash in the control logic of FPGA and output separately from three different interface of Camera Link, LVDS and PAL, which can provide image data for photoelectric image acquisition equipment's debugging and algorithm validation. However, because the standard of PAL image resolution is 720*576, the resolution is different between PAL image and input image, so the image can be output after the resolution conversion. The experimental results demonstrate that the camera simulator outputs three format image sequence correctly, which can be captured and displayed by frame gather. And the three-format image data can meet test requirements of the most equipment, shorten debugging time and improve the test efficiency.

  9. Simulation, design and fabrication of a planar micro thermoelectric generator

    NASA Astrophysics Data System (ADS)

    Pelegrini, S.; Adami, A.; Collini, C.; Conci, P.; Lorenzelli, L.; Pasa, A. A.

    2013-05-01

    This study describes the design, simulation, and micro fabrication of a micro thermoelectric generator (μTEG) based on planar technology using constantan (CuNi) and copper (Cu) thermocouples deposited electrochemically (ECD) on silicon substrate. The present thin film technology can be manufactured into large area and also on flexible substrate with low cost of production and can be used to exploit waste heat from equipments or hot surfaces in general. In the current implementation, the silicon structure has been designed and optimized with analytical models and FE simulations in order to exploit the different thermal conductivity of silicon and air gaps to produce the maximum temperature difference on a planar surface. The results showed that a temperature difference of 10K across the structure creates a temperature difference of 5.3K on the thermocouples, thus providing an efficiency of thermal distribution up to 55%, depending on the heat convection at the surface. Efficiency of module has been experimentally tested under different working condition, showing the dependence of module output on the external heat exchange (natural and forced convection). Maximum generated potential at 6m/s airflow is 5.7V/m2 K and thermoelectric efficiency is 1.9μW K-2 m-2.

  10. Functional requirements for design of the Space Ultrareliable Modular Computer (SUMC) system simulator

    NASA Technical Reports Server (NTRS)

    Curran, R. T.; Hornfeck, W. A.

    1972-01-01

    The functional requirements for the design of an interpretive simulator for the space ultrareliable modular computer (SUMC) are presented. A review of applicable existing computer simulations is included along with constraints on the SUMC simulator functional design. Input requirements, output requirements, and language requirements for the simulator are discussed in terms of a SUMC configuration which may vary according to the application.

  11. Ras Family Small GTPase-mediated Neuroprotective Signaling in Stroke

    PubMed Central

    Shi, Geng-Xian; Andres, Douglas A.; Cai, Weikang

    2012-01-01

    Selective neuronal cell death is one of the major causes of neuronal damage following stroke, and cerebral cells naturally mobilize diverse survival signaling pathways to protect against ischemia. Importantly, therapeutic strategies designed to improve endogenous anti-apoptotic signaling appear to hold great promise in stroke treatment. While a variety of complex mechanisms have been implicated in the pathogenesis of stroke, the overall mechanisms governing the balance between cell survival and death are not well-defined. Ras family small GTPases are activated following ischemic insults, and in turn, serve as intrinsic switches to regulate neuronal survival and regeneration. Their ability to integrate diverse intracellular signal transduction pathways makes them critical regulators and potential therapeutic targets for neuronal recovery after stroke. This article highlights the contribution of Ras family GTPases to neuroprotective signaling cascades, including mitogen-activated protein kinase (MAPK) family protein kinase- and AKT/PKB-dependent signaling pathways as well as the regulation of cAMP response element binding (CREB), Forkhead box O (FoxO) and hypoxia-inducible factor 1(HIF1) transcription factors, in stroke. PMID:21521171

  12. Application of Simulated Annealing and Related Algorithms to TWTA Design

    NASA Technical Reports Server (NTRS)

    Radke, Eric M.

    2004-01-01

    Simulated Annealing (SA) is a stochastic optimization algorithm used to search for global minima in complex design surfaces where exhaustive searches are not computationally feasible. The algorithm is derived by simulating the annealing process, whereby a solid is heated to a liquid state and then cooled slowly to reach thermodynamic equilibrium at each temperature. The idea is that atoms in the solid continually bond and re-bond at various quantum energy levels, and with sufficient cooling time they will rearrange at the minimum energy state to form a perfect crystal. The distribution of energy levels is given by the Boltzmann distribution: as temperature drops, the probability of the presence of high-energy bonds decreases. In searching for an optimal design, local minima and discontinuities are often present in a design surface. SA presents a distinct advantage over other optimization algorithms in its ability to escape from these local minima. Just as high-energy atomic configurations are visited in the actual annealing process in order to eventually reach the minimum energy state, in SA highly non-optimal configurations are visited in order to find otherwise inaccessible global minima. The SA algorithm produces a Markov chain of points in the design space at each temperature, with a monotonically decreasing temperature. A random point is started upon, and the objective function is evaluated at that point. A stochastic perturbation is then made to the parameters of the point to arrive at a proposed new point in the design space, at which the objection function is evaluated as well. If the change in objective function values (Delta)E is negative, the proposed new point is accepted. If (Delta)E is positive, the proposed new point is accepted according to the Metropolis criterion: rho((Delta)f) = exp((-Delta)E/T), where T is the temperature for the current Markov chain. The process then repeats for the remainder of the Markov chain, after which the temperature is

  13. K-ras oncogene mutation in pterygium.

    PubMed

    Ozturk, B T; Yıldırım, M S; Zamani, A; Bozkurt, B

    2017-03-01

    PurposePterygium is claimed to be a benign proliferation triggered by prolonged exposure to ultraviolet radiation. The frequency of K-ras oncogene mutation, which is among the initial mutations in tumorigenesis, is evaluated in this study.Patients and methodsIn this prospective randomized clinical, trial pterygium tissues and normal conjunctiva tissue specimens are obtained from the superotemporal quadrant of patients who underwent primary pterygium excision with autograft transplantation. DNA extraction from tissues was performed using the QIAamp DNA FFPE tissue kit. A PCR reaction was performed to amplify sequences containing codons 12, 13, and 61 of the K-ras gene in DNA. These PCR products then underwent the 'pyrosequencing' procedure for mutations at these codons.ResultsPterygium and normal conjunctival tissue samples of 25 patients (10 females, 15 males) were evaluated in the study. The mean age of the patients was 54.54±13.13 years. Genetic analysis revealed no K-ras mutations in normal conjunctival tissues, whereas pterygium tissues of the same cases demonstrated mutation at codon 12 in one case and mutations at codon 61 in seven cases, which was statistically significant (P<0.05). The point missense mutations at codon 61 were glutamine to arginine (Glu61Arg CAA>CGA) in four cases and glutamine to leucine (Glu61Leu CAA>CTA) in three cases.ConclusionThe significantly higher frequency of codon 61 mutation of the ras oncogene in primary and bilateral pterygium specimens compared with normal conjunctiva supports the tumoral origin of pterygium, and thus set the stage for research into a targeted therapy for pterygium with better outcomes than surgical excision.

  14. Biomimetic design of a brush-like nanopore: simulation studies.

    PubMed

    Pongprayoon, Prapasiri; Beckstein, Oliver; Sansom, Mark S P

    2012-01-12

    Combining a high degree of selectivity and nanoscale dimensions, biological pores are attractive potential components for nanotechnology devices and applications. Biomimetic design will facilitate production of stable synthetic nanopores with defined functionality. Bacterial porins offer a good source of possible templates for such nanopores as they form stable, selective pores in lipid bilayers. Molecular dynamics simulations have been used to design simple model nanopores with permeation free energy profiles that can be made to mimic a template protein, the OprP porin, which forms pores selective for anions. In particular, we explored the effects of varying the nature of pore-lining groups on free energy profiles for phosphate and chloride ions along the pore axis and the total charge of the permeation pathway of the pore. Cationic side chains lining the model nanopore are required to model the local detail of the OprP permeation landscape, whereas the total charge contributes to its magnitude. These studies indicate that a locally accurate biomimetic design has captured the essentials of the structure/function relationship of the parent protein.

  15. Digital signaling and hysteresis characterize Ras activation in lymphoid cells

    PubMed Central

    Das, Jayajit; Ho, Mary; Zikherman, Julie; Govern, Christopher; Yang, Ming; Weiss, Arthur; Chakraborty, Arup K.; Roose, Jeroen P.

    2009-01-01

    Activation of Ras proteins underlies functional decisions in diverse cell types. Two molecules, RasGRP and SOS, catalyze Ras activation in lymphocytes. Binding of active Ras to SOS′ allosteric pocket markedly increases SOS′ activity establishing a positive feedback loop for SOS-mediated Ras activation. Integrating in silico and in vitro studies, we demonstrate that digital signaling in lymphocytes (cells are “on” or “off”) is predicated upon feedback regulation of SOS. SOS′ feedback loop leads to hysteresis in the dose-response curve, which can enable a capacity to sustain Ras activation as stimuli are withdrawn and exhibit “memory” of past encounters with antigen. Ras activation via RasGRP alone is analog (graded increase in amplitude with stimulus). We describe how complementary analog (RasGRP) and digital (SOS) pathways act on Ras to efficiently convert analog input to digital output. Numerous predictions regarding the impact of our findings on lymphocyte function and development are noted. PMID:19167334

  16. Nuclear Ras2-GTP Controls Invasive Growth in Saccharomyces cerevisiae

    PubMed Central

    Broggi, Serena; Martegani, Enzo; Colombo, Sonia

    2013-01-01

    Using an eGFP-RBD3 probe, which specifically binds Ras-GTP, we recently showed that the fluorescent probe was localized to the plasma membrane and to the nucleus in wild type cells growing exponentially on glucose medium, indicating the presence of active Ras in these cellular compartments. To investigate the nuclear function of Ras-GTP, we generated a strain where Ras2 is fused to the nuclear export signal (NES) from the HIV virus, in order to exclude this protein from the nucleus. Our results show that nuclear active Ras2 is required for invasive growth development in haploid yeast, while the expression of the NES-Ras2 protein does not cause growth defects either on fermentable or non-fermentable carbon sources and does not influence protein kinase A (PKA) activity related phenotypes analysed. Moreover, we show that the cAMP/PKA pathway controls invasive growth influencing the localization of active Ras. In particular, we show that PKA activity plays a role in the localization of active Ras and influences the ability of the cells to invade the agar: high PKA activity leads to a predominant nuclear accumulation of active Ras and induces invasive growth, while low PKA activity leads to plasma membrane localization of active Ras and to a defective invasive growth phenotype. PMID:24244466

  17. Design and simulation of a tunable metamaterial absorber

    NASA Astrophysics Data System (ADS)

    Fu, Yanan; Zhao, Guozhong; Li, Yonghua

    2016-11-01

    A photo-excited tunable and broad band metamaterial absorber in the terahertz region is proposed. The metamaterial absorber is composed of three layers like the sandwich, the top layer is a ring metal-semiconductor square split ring and the bottom layer is a metallic ground plane, these two layers are separated by a dielectric spacer, which we choose as the polyimide. The conductivity of the silicon can be tuned actively with the incident pump power. We use the full wave simulation and the equivalent circuit parameter to analysis this absorber, and interpreted the phenomena showed when the conductivity of the silicon filled in the gap of ring is changed by the electric field. The proposed equivalent circuit parameter can save more time to design this kind of absorber in need. The proposed photo-excited tunable metamaterial absorber can also be used as terahertz modulators and switches.

  18. Colossal Tooling Design: 3D Simulation for Ergonomic Analysis

    NASA Technical Reports Server (NTRS)

    Hunter, Steve L.; Dischinger, Charles; Thomas, Robert E.; Babai, Majid

    2003-01-01

    The application of high-level 3D simulation software to the design phase of colossal mandrel tooling for composite aerospace fuel tanks was accomplished to discover and resolve safety and human engineering problems. The analyses were conducted to determine safety, ergonomic and human engineering aspects of the disassembly process of the fuel tank composite shell mandrel. Three-dimensional graphics high-level software, incorporating various ergonomic analysis algorithms, was utilized to determine if the process was within safety and health boundaries for the workers carrying out these tasks. In addition, the graphical software was extremely helpful in the identification of material handling equipment and devices for the mandrel tooling assembly/disassembly process.

  19. Simulation Assisted Risk Assessment Applied to Launch Vehicle Conceptual Design

    NASA Technical Reports Server (NTRS)

    Mathias, Donovan L.; Go, Susie; Gee, Ken; Lawrence, Scott

    2008-01-01

    A simulation-based risk assessment approach is presented and is applied to the analysis of abort during the ascent phase of a space exploration mission. The approach utilizes groupings of launch vehicle failures, referred to as failure bins, which are mapped to corresponding failure environments. Physical models are used to characterize the failure environments in terms of the risk due to blast overpressure, resulting debris field, and the thermal radiation due to a fireball. The resulting risk to the crew is dynamically modeled by combining the likelihood of each failure, the severity of the failure environments as a function of initiator and time of the failure, the robustness of the crew module, and the warning time available due to early detection. The approach is shown to support the launch vehicle design process by characterizing the risk drivers and identifying regions where failure detection would significantly reduce the risk to the crew.

  20. The design and simulation test of wireless antenna protection network

    NASA Astrophysics Data System (ADS)

    Chen, Zipeng; Dai, Yawen; Li, Peng; Li, Zhuoqiu

    2013-03-01

    In this paper, a wireless antenna protection program has been designed. In the program, the TVS diode was used as the first lever for protection, and the π-type high pass filtering network as the second lever. As a result, the program not only has the traditional function of ESD protection, which can avoid the high voltage damage to the internal circuit, but also achieves the purpose of load matching, ensuring the signal source not to distort. The ADS simulation software was used to test the ability of this program for filtering and impedance matching, which proved the feasibility of this program. The wireless antenna protection network has been practically used, and its' performance of anti-electromagnetic interference has been validated.

  1. K-Ras, H-Ras, N-Ras and B-Raf mutation and expression analysis in Wilms tumors: association with tumor growth.

    PubMed

    Dalpa, Efterpi; Gourvas, Victor; Soulitzis, Nikolaos; Spandidos, Demetrios A

    2017-01-01

    Nephroblastoma (Wilms tumor) is a kidney neoplasia, predominately occurring at very young age, resulting from the malignant transformation of renal stem cells. The Ras proto-oncogenes and B-Raf are members of an intracellular cascade pathway, which regulates cell growth and differentiation, and ultimately cancer development. Our objective was to determine the mutation rate and to measure the mRNA levels of the three Ras genes and of B-Raf in formalin-fixed paraffin-embedded tissue samples from 32 patients with nephroblastoma and 10 controls. No mutations were detected in the four studied genes among our Wilms tumors cases, while Ras and B-Raf expression was higher in malignant samples versus controls. Statistical analysis revealed a positive correlation of K-Ras (p < 0.001) and B-Raf (p = 0.006) with tumor size, a negative correlation of K-Ras (p = 0.041) and H-Ras (p = 0.033) with the percentage of tissue necrosis, and an association of N-Ras (p = 0.047) and B-Raf (p = 0.044) with tissue histology. From the above, we deduce that although Ras and B-Raf mutations are rare events in Wilms tumors, their expression pattern suggests that they play an important role in the development and progression of this malignancy.

  2. Radiosensitization of EGFR/HER2 positive pancreatic cancer is mediated by inhibition of Akt independent of Ras mutational status

    PubMed Central

    Kimple, Randall J.; Vaseva, Angelina V.; Cox, Adrienne D.; Baerman, Kathryn M.; Calvo, Benjamin F.; Tepper, Joel E.; Shields, Janiel M.; Sartor, Carolyn I.

    2009-01-01

    Purpose Epidermal growth factor receptor family members (e.g., EGFR, HER2, HER3, and HER4) are commonly overexpressed in pancreatic cancer. We investigated the effects of inhibition of EGFR/HER2 signaling on pancreatic cancer to elucidate the role(s) of EGFR/HER2 in radiosensitization and to provide evidence in support of further clinical investigations. Experimental Design Expression of EGFR family members in pancreatic cancer lines was assessed by qRT-PCR. Cell growth inhibition was determined by MTS assay. The effects of inhibition of EGFR family receptors and downstream signaling pathways on in vitro radiosensitivity were evaluated using clonogenic assays. Growth delay was used to evaluate the effects of nelfinavir on in vivo tumor radiosensitivity. Results Lapatinib inhibited cell growth in four pancreatic cancer cell lines, but radiosensitized only wild-type K-ras-expressing T3M4 cells. Akt activation was blocked in a wild-type K-ras cell line, whereas constitutive phosphorylation of Akt and ERK was seen in lines expressing mutant K-ras. Overexpression of constitutively-active K-ras(G12V) abrogated lapatinib-mediated inhibition of both Akt phosphorylation and radiosensitization. Inhibition of MEK/ERK signaling with U0126 had no effect on radiosensitization, whereas inhibition of activated Akt with LY294002 (enhancement ratio 1.2–1.8) or nelfinavir (enhancement ratio 1.2–1.4) radiosensitized cells regardless of K-ras mutation status. Oral nelfinavir administration to mice bearing mutant K-ras-containing Capan-2 xenografts resulted in a greater than additive increase in radiation-mediated tumor growth delay (synergy assessment ratio of 1.5). Conclusions Inhibition of EGFR/HER2 enhances radiosensitivity in wild-type K-ras pancreatic cancer. Nelfinavir, and other PI3K/Akt inhibitors, are effective pancreatic radiosensitizers regardless of K-ras mutation status. PMID:20103665

  3. Combining docking and molecular dynamic simulations in drug design.

    PubMed

    Alonso, Hernán; Bliznyuk, Andrey A; Gready, Jill E

    2006-09-01

    A rational approach is needed to maximize the chances of finding new drugs, and to exploit the opportunities of potential new drug targets emerging from genomic and proteomic initiatives, and from the large libraries of small compounds now readily available through combinatorial chemistry. Despite a shaky early history, computer-aided drug design techniques can now be effective in reducing costs and speeding up drug discovery. This happy outcome results from development of more accurate and reliable algorithms, use of more thoughtfully planned strategies to apply them, and greatly increased computer power to allow studies with the necessary reliability to be performed. Our review focuses on applications and protocols, with the main emphasis on critical analysis of recent studies where docking calculations and molecular dynamics (MD) simulations were combined to dock small molecules into protein receptors. We highlight successes to demonstrate what is possible now, but also point out drawbacks and future directions. The review is structured to lead the reader from the simpler to more compute-intensive methods. Thus, while inexpensive and fast docking algorithms can be used to scan large compound libraries and reduce their size, more accurate but expensive MD simulations can be applied when a few selected ligand candidates remain. MD simulations can be used: during the preparation of the protein receptor before docking, to optimize its structure and account for protein flexibility; for the refinement of docked complexes, to include solvent effects and account for induced fit; to calculate binding free energies, to provide an accurate ranking of the potential ligands; and in the latest developments, during the docking process itself to find the binding site and correctly dock the ligand a priori.

  4. Designing Crop Simulation Web Service with Service Oriented Architecture Principle

    NASA Astrophysics Data System (ADS)

    Chinnachodteeranun, R.; Hung, N. D.; Honda, K.

    2015-12-01

    Crop simulation models are efficient tools for simulating crop growth processes and yield. Running crop models requires data from various sources as well as time-consuming data processing, such as data quality checking and data formatting, before those data can be inputted to the model. It makes the use of crop modeling limited only to crop modelers. We aim to make running crop models convenient for various users so that the utilization of crop models will be expanded, which will directly improve agricultural applications. As the first step, we had developed a prototype that runs DSSAT on Web called as Tomorrow's Rice (v. 1). It predicts rice yields based on a planting date, rice's variety and soil characteristics using DSSAT crop model. A user only needs to select a planting location on the Web GUI then the system queried historical weather data from available sources and expected yield is returned. Currently, we are working on weather data connection via Sensor Observation Service (SOS) interface defined by Open Geospatial Consortium (OGC). Weather data can be automatically connected to a weather generator for generating weather scenarios for running the crop model. In order to expand these services further, we are designing a web service framework consisting of layers of web services to support compositions and executions for running crop simulations. This framework allows a third party application to call and cascade each service as it needs for data preparation and running DSSAT model using a dynamic web service mechanism. The framework has a module to manage data format conversion, which means users do not need to spend their time curating the data inputs. Dynamic linking of data sources and services are implemented using the Service Component Architecture (SCA). This agriculture web service platform demonstrates interoperability of weather data using SOS interface, convenient connections between weather data sources and weather generator, and connecting

  5. Constraining continuous rainfall simulations for derived design flood estimation

    NASA Astrophysics Data System (ADS)

    Woldemeskel, F. M.; Sharma, A.; Mehrotra, R.; Westra, S.

    2016-11-01

    Stochastic rainfall generation is important for a range of hydrologic and water resources applications. Stochastic rainfall can be generated using a number of models; however, preserving relevant attributes of the observed rainfall-including rainfall occurrence, variability and the magnitude of extremes-continues to be difficult. This paper develops an approach to constrain stochastically generated rainfall with an aim of preserving the intensity-durationfrequency (IFD) relationships of the observed data. Two main steps are involved. First, the generated annual maximum rainfall is corrected recursively by matching the generated intensity-frequency relationships to the target (observed) relationships. Second, the remaining (non-annual maximum) rainfall is rescaled such that the mass balance of the generated rain before and after scaling is maintained. The recursive correction is performed at selected storm durations to minimise the dependence between annual maximum values of higher and lower durations for the same year. This ensures that the resulting sequences remain true to the observed rainfall as well as represent the design extremes that may have been developed separately and are needed for compliance reasons. The method is tested on simulated 6 min rainfall series across five Australian stations with different climatic characteristics. The results suggest that the annual maximum and the IFD relationships are well reproduced after constraining the simulated rainfall. While our presentation focusses on the representation of design rainfall attributes (IFDs), the proposed approach can also be easily extended to constrain other attributes of the generated rainfall, providing an effective platform for post-processing of stochastic rainfall generators.

  6. Simulation for optimal design of hand-held surgical robots.

    PubMed

    Zahraee, Ali Hassan; Szewczyk, Jerome; Morel, Guillaume

    2009-01-01

    Hand-held surgical robots are manipulators with dexterous effectors to be used by surgeons in minimally invasive surgery and especially in laparoscopy. Mechanical manipulators for laparoscopy have appeared on the markets in recent years with various interfaces and dexterities. 2 examples are RealHand and Laparo-Angle. The question of which interface and control mode is the best has not been answered yet. Also, the effector kinematics has not been studied much. We have made a simulator to study the robot's interface, control mode and kinematics to design a hand-held surgical robot for laparoscopic surgery. We asked test subjects to use the simulator and try to make sutures in a virtual environment. Users opinion is that a joystick as interface is easier to use, compared to a jointed interface translating hand's orientation to that of the effector. It appears that a 6 DOF effector coupled to the shaft is necessary and dexterous enough to make sutures in different angles.

  7. The role of Gln61 and Glu63 of Ras GTPases in their activation by NF1 and Ras GAP.

    PubMed Central

    Nur-E-Kamal, M S; Maruta, H

    1992-01-01

    Two distinct GAPs of 120 and 235 kDa called GAP1 and NF1 serve as attenuators of Ras, a member of GTP-dependent signal transducers, by stimulating its intrinsic guanosine triphosphatase (GTPase) activity. The GAP1 (also called Ras GAP) is highly specific for Ras and does not stimulate the intrinsic GTPase activity of Rap1 or Rho. Using GAP1C, the C-terminal GTPase activating domain (residues 720-1044) of bovine GAP1, we have shown previously that the GAP1 specificity is determined by the Ras domain (residues 61-65) where Gln61 plays the primary role. The corresponding domain (residues 1175-1531) of human NF1 (called NF1C), which shares only 26% sequence identity with the GAP1C, also activates Ras GTPases. In this article, we demonstrate that the NF1C, like the GAP1C, is highly specific for Ras and does not activate either Rap1 or Rho GTPases. Furthermore, using a series of chimeric Ras/Rap1 and mutated Ras GTPases, we show that Gln at position 61 of the GTPases primarily determines that NF1C as well as GAP1C activates Ras GTPases, but not Rap1 GTPases, and Glu at position 63 of the GTPases is required for maximizing the sensitivity of Ras GTPases to both NF1C and GAP1C. Interestingly, replacement of Glu63 of c-HaRas by Lys reduces its intrinsic GTPase activity and abolishes the GTPase activation by both NF1C and GAP1C. Thus, the potentiation of oncogenicity by Lys63 mutation of c-HaRas appears primarily to be due to the loss of its sensitivity to the two major Ras signal attenuators (NF1 and GAP1). PMID:1362901

  8. CDK4 coexpression with Ras generates malignant human epidermal tumorigenesis.

    PubMed

    Lazarov, Mirella; Kubo, Yoshiaki; Cai, Ti; Dajee, Maya; Tarutani, Masahito; Lin, Qun; Fang, Min; Tao, Shiying; Green, Cheryl L; Khavari, Paul A

    2002-10-01

    Ras acts with other proteins to induce neoplasia. By itself, however, strong Ras signaling can suppress proliferation of normal cells. In primary epidermal cells, we found that oncogenic Ras transiently decreases cyclin-dependent kinase (CDK) 4 expression in association with cell cycle arrest in G1 phase. CDK4 co-expression circumvents Ras growth suppression and induces invasive human neoplasia resembling squamous cell carcinoma. Tumorigenesis is dependent on CDK4 kinase function, with cyclin D1 required but not sufficient for this process. In facilitating escape from G1 growth restraints, Ras and CDK4 alter the composition of cyclin D and cyclin E complexes and promote resistance to growth inhibition by INK4 cyclin-dependent kinase inhibitors. These data identify a new role for oncogenic Ras in CDK4 regulation and highlight the functional importance of CDK4 suppression in preventing uncontrolled growth.

  9. Lipid-Sorting Specificity Encoded in K-Ras Membrane Anchor Regulates Signal Output.

    PubMed

    Zhou, Yong; Prakash, Priyanka; Liang, Hong; Cho, Kwang-Jin; Gorfe, Alemayehu A; Hancock, John F

    2017-01-12

    K-Ras is targeted to the plasma membrane by a C-terminal membrane anchor that comprises a farnesyl-cysteine-methyl-ester and a polybasic domain. We used quantitative spatial imaging and atomistic molecular dynamics simulations to examine molecular details of K-Ras plasma membrane binding. We found that the K-Ras anchor binds selected plasma membrane anionic lipids with defined head groups and lipid side chains. The precise amino acid sequence and prenyl group define a combinatorial code for lipid binding that extends beyond simple electrostatics; within this code lysine and arginine residues are non-equivalent and prenyl chain length modifies nascent polybasic domain lipid preferences. The code is realized by distinct dynamic tertiary structures of the anchor on the plasma membrane that govern amino acid side-chain-lipid interactions. An important consequence of this specificity is the ability of such anchors when aggregated to sort subsets of phospholipids into nanoclusters with defined lipid compositions that determine K-Ras signaling output.

  10. Design and simulations of CAEP THz FEL resonator

    NASA Astrophysics Data System (ADS)

    Dou, Yuhuan; Shu, Xiaojian; Deng, Derong; Yang, Xingfan; Li, Ming

    2015-02-01

    A high power China Academy of Engineering Physics(CAEP) THz free electron laser (FEL) is designed and optimized in a radiation frequency range of 1~3 THz and average output power of about 10 W. The main work focuses on the optimization of different schemes through physical analysis. The wiggler peak field strength and electron beam energy have been selected with eleven frequencies ranging from 1 THz to 3 THz. It is found that the values of the gain and output power of the cavity are largest at 2.6 THz. So we can test the facility at this frequency. While the value of the output power is less than the design goal at the lower frequency region of about 1.0 THz due to the serious slippage between the electron bunch and radiation pulse. To increase the output power at the lower frequency region, the scheme of elliptical hole-coupling optical resonator is proposed to solve this problem. The simulation results show that the elliptical hole-coupling output is effective and applicable for the THz FEL and the output power can be increased by more than 30%.

  11. Dimerize RACK1 upon transformation with oncogenic ras

    SciTech Connect

    Chu, L.-Y.; Chen, Y.-H.; Chuang, N.-N. . E-mail: zonnc@sinica.edu.tw

    2005-05-06

    From our previous studies, we learned that syndecan-2/p120-GAP complex provided docking site for Src to prosecute tyrosine kinase activity upon transformation with oncogenic ras. And, RACK1 protein was reactive with syndecan-2 to keep Src inactivated, but not when Ras was overexpressed. In the present study, we characterized the reaction between RACK1 protein and Ras. RACK1 was isolated from BALB/3T3 cells transfected with plasmids pcDNA3.1-[S-ras(Q{sub 61}K)] of shrimp Penaeus japonicus and RACK1 was revealed to react with GTP-K{sub B}-Ras(Q{sub 61}K), not GDP-K{sub B}-Ras(Q{sub 61}K). This selective interaction between RACK1 and GTP-K{sub B}-Ras(Q{sub 61}K) was further confirmed with RACK1 of human placenta and mouse RACK1-encoded fusion protein. We found that RACK1 was dimerized upon reaction with GTP-K{sub B}-Ras(Q{sub 61}K), as well as with 14-3-3{beta} and geranylgeranyl pyrophosphate, as revealed by phosphorylation with Src tyrosine kinase. We reported the complex of RACK1/GTP-K{sub B}-Ras(Q{sub 61}K) reacted selectively with p120-GAP. This interaction was sufficient to dissemble RACK1 into monomers, a preferred form to compete for the binding of syndecan-2. These data indicate that the reaction of GTP-K{sub B}-Ras(Q{sub 61}K) with RACK1 in dimers may operate a mechanism to deplete RACK1 from reaction with syndecan-2 upon transformation by oncogenic ras and the RACK1/GTP-Ras complex may provide a route to react with p120-GAP and recycle monomeric RACK1 to syndecan-2.

  12. Tornado missile simulation and design methodology. Volume 1: simulation methodology, design applications, and TORMIS computer code. Final report

    SciTech Connect

    Twisdale, L.A.; Dunn, W.L.

    1981-08-01

    A probabilistic methodology has been developed to predict the probabilities of tornado-propelled missiles impacting and damaging nuclear power plant structures. Mathematical models of each event in the tornado missile hazard have been developed and sequenced to form an integrated, time-history simulation methodology. The models are data based where feasible. The data include documented records of tornado occurrence, field observations of missile transport, results of wind tunnel experiments, and missile impact tests. Probabilistic Monte Carlo techniques are used to estimate the risk probabilities. The methodology has been encoded in the TORMIS computer code to facilitate numerical analysis and plant-specific tornado missile probability assessments. Sensitivity analyses have been performed on both the individual models and the integrated methodology, and risk has been assessed for a hypothetical nuclear power plant design case study.

  13. Latest Advances Towards Ras Inhibition: A Medicinal Chemistry Perspective.

    PubMed

    Sautier, Brice; Nising, Carl F; Wortmann, Lars

    2016-12-23

    Owing to their high occurrence rate across many human cancers and their lack of druggability so far, mutant forms of the signaling protein Ras are currently among the most attractive (and elusive) oncology targets. This strong appeal explains the sustained effort in the field, and the ensuing progress has rekindled optimism regarding the discovery of Ras inhibitors. In this Minireview, we discuss the most recent advances towards irreversible inhibitors, and highlight approaches to inhibitors of Ras-effector interactions that have been overshadowed by the current focus on direct Ras inhibition. At the same time, we provide a critical assessment from a medicinal chemistry perspective.

  14. Activation of ras oncogenes preceding the onset of neoplasia

    SciTech Connect

    Kumar, R.; Barbacid, M. ); Sukumar, S. )

    1990-06-01

    The identification of ras oncogenes in human and animal cancers including precancerous lesions indicates that these genes participate in the early stages of neoplastic development. Yet, these observations do not define the timing of ras oncogene activation in the multistep process of carcinogenesis. To ascertain the timing of ras oncogene activation, an animal model system was devised that involves the induction of mammary carcinomas in rats exposed at birth to the carcinogen nitrosomethylurea. High-resolution restriction fragment length polymorphism analysis of polymerase chain reaction-amplified ras sequences revealed the presence of both H-ras and K-ras oncogenes in normal mammary glands 2 weeks after carcinogen treatment and at least 2 months before the onset of neoplasia. These ras oncogenes can remain latent within the mammary gland until exposure to estrogens, demonstrating that activation of ras oncogenes can precede the onset of neoplasia and suggesting that normal physiological proliferative processes such as estrogen-induced mammary gland development may lead to neoplasia if the targeted cells harbor latent ras oncogenes.

  15. Variational data assimilation system "INM RAS - Black Sea"

    NASA Astrophysics Data System (ADS)

    Parmuzin, Eugene; Agoshkov, Valery; Assovskiy, Maksim; Giniatulin, Sergey; Zakharova, Natalia; Kuimov, Grigory; Fomin, Vladimir

    2013-04-01

    Development of Informational-Computational Systems (ICS) for Data Assimilation Procedures is one of multidisciplinary problems. To study and solve these problems one needs to apply modern results from different disciplines and recent developments in: mathematical modeling; theory of adjoint equations and optimal control; inverse problems; numerical methods theory; numerical algebra and scientific computing. The problems discussed above are studied in the Institute of Numerical Mathematics of the Russian Academy of Science (INM RAS) in ICS for Personal Computers (PC). Special problems and questions arise while effective ICS versions for PC are being developed. These problems and questions can be solved with applying modern methods of numerical mathematics and by solving "parallelism problem" using OpenMP technology and special linear algebra packages. In this work the results on the ICS development for PC-ICS "INM RAS - Black Sea" are presented. In the work the following problems and questions are discussed: practical problems that can be studied by ICS; parallelism problems and their solutions with applying of OpenMP technology and the linear algebra packages used in ICS "INM - Black Sea"; Interface of ICS. The results of ICS "INM RAS - Black Sea" testing are presented. Efficiency of technologies and methods applied are discussed. The work was supported by RFBR, grants No. 13-01-00753, 13-05-00715 and by The Ministry of education and science of Russian Federation, project 8291, project 11.519.11.1005 References: [1] V.I. Agoshkov, M.V. Assovskii, S.A. Lebedev, Numerical simulation of Black Sea hydrothermodynamics taking into account tide-forming forces. Russ. J. Numer. Anal. Math. Modelling (2012) 27, No.1, 5-31 [2] E.I. Parmuzin, V.I. Agoshkov, Numerical solution of the variational assimilation problem for sea surface temperature in the model of the Black Sea dynamics. Russ. J. Numer. Anal. Math. Modelling (2012) 27, No.1, 69-94 [3] V.B. Zalesny, N.A. Diansky, V

  16. Design and simulation of a hybrid dielectric waveguide

    NASA Astrophysics Data System (ADS)

    Aryal, Krishna Prasad

    Waveguides, in general are used as a means to route photons. Traditional dielectric waveguides, composed of a high index core surrounded by a low index cladding, produce maximum field intensities far from dielectric interfaces. This thesis presents the design of a plasmonic enhanced waveguide, which relocates the maximum optical field intensity from the center of the waveguide to an interfacial region defined by a dielectric and a negative index material. This is accomplished through the use of a metal film, positioned on top of a traditional ridge waveguide in those places where one wishes to excite a plasmon mode as opposed to the more traditional dielectric mode. Plasmon modes have their highest field intensity at the interface located between the metal and the dielectric. In this thesis, the waveguide dimensions of a hybrid dielectric waveguide are determined with the intent of producing single mode operation for a ridge waveguide with and without metal on top. A commercial Eigen mode solver (MODE Lumerical) is used to obtain all field profiles, waveguide effective index and waveguide loss. Multiple simulations were used to design a waveguide, which supports a single plasmonic mode when the metal film is in place and a single dielectric mode when the metal film is absent. Such a waveguide is expected to find use in the field of integrated quantum optics where quantum dots, defined by near surface confining potentials, require high interfacial fields for maximum dot/field interactions. Further, based on the final waveguide design height of ( 5microm ) and width of ( 7.9microm ), an effective index of ( 3.687 ) results when operated in the plasmon mode and (3.619) when operated in dielectric mode. This change in refractive index suggests such hybrid dielectric/plasmon waveguides can be used for the design of Bragg reflectors leading to plasmonic cavities, which, when coupled to the proposed near surface located quantum dots, can be used for the production and

  17. The IAA RAS Correlator First Results

    NASA Technical Reports Server (NTRS)

    Surkis, Igor; Melnikov, Alexey; Shantyr, Violet; Zimovsky, Vladimir

    2010-01-01

    In 2009 the national Russian VLBI observations were processed by the new correlator ARC (Astrometric Radiointerferometric Correlator). The ARC is a VSI-H correlator and equipped with Mark 5B playback terminals. During 2009 ARC was used to process a series of VLBI sessions, observed on stations Svetloe, Zelenchukskaya, and Badary. NGS files were formed, and EOP parameters were obtained by IAA RAS Analysis Center. The accuracies of the pole coordinates and UT1-UTC were 1-2 mas and 0.07-0.1 ms, respectively.

  18. Metrology target design simulations for accurate and robust scatterometry overlay measurements

    NASA Astrophysics Data System (ADS)

    Ben-Dov, Guy; Tarshish-Shapir, Inna; Gready, David; Ghinovker, Mark; Adel, Mike; Herzel, Eitan; Oh, Soonho; Choi, DongSub; Han, Sang Hyun; El Kodadi, Mohamed; Hwang, Chan; Lee, Jeongjin; Lee, Seung Yoon; Lee, Kuntack

    2016-03-01

    Overlay metrology target design is an essential step prior to performing overlay measurements. This step is done through the optimization of target parameters for a given process stack. A simulation tool is therefore used to improve measurement performances. This work shows how our Metrology Target Design (MTD) simulator helps significantly in the target design process. We show the role of film and Optical CD measurements in improving significantly the fidelity of the simulations. We demonstrate that for various target design parameters we are capable of predicting measured performance metrics by simulations and correctly rank various designs performances.

  19. Use of computational fluid dynamics simulations for design of a pretreatment screw conveyor reactor.

    PubMed

    Berson, R Eric; Hanley, Thomas R

    2005-01-01

    Computational fluid dynamics simulations were employed to compare performance of various designs of a pretreatment screw conveyor reactor. The reactor consisted of a vertical screw used to create cross flow between the upward conveying solids and the downward flow of acid. Simulations were performed with the original screw design and a modified design in which the upper flights of the screw were removed. Results of the simulations show visually that the modified design provided favorable plug flow behavior within the reactor. Pressure drop across the length of the reactor without the upper screws in place was predicted by the simulations to be 5 vs 40 kPa for the original design.

  20. Interactive Graphics Simulator: Design, Development, and Effectiveness/Cost Evaluation. Final Report.

    ERIC Educational Resources Information Center

    Pieper, William J.; And Others

    This study was initiated to design, develop, implement, and evaluate a videodisc-based simulator system, the Interactive Graphics Simulator (IGS) for 6883 Converter Flight Control Test Station training at Lowry Air Force Base, Colorado. The simulator provided a means for performing task analysis online, developing simulations from the task…

  1. Effects of Thinking Style on Design Strategies: Using Bridge Construction Simulation Programs

    ERIC Educational Resources Information Center

    Sun, Chuen-Tsai; Wang, Dai-Yi; Chang, Yu-Yeh

    2013-01-01

    Computer simulation users can freely control operational factors and simulation results, repeat processes, make changes, and learn from simulation environment feedback. The focus of this paper is on simulation-based design tools and their effects on student learning processes in a group of 101 Taiwanese senior high school students. Participants…

  2. Purpose and Learning Benefits of Simulations: A Design and Development Perspective.

    ERIC Educational Resources Information Center

    Goosen, Kenneth R.; Jensen, Ron; Wells, Robert

    2001-01-01

    Considers the role of the simulation designer in the development of business enterprise simulations used in collegiate business education. Topics include the designer's knowledge domain; conflicting business administration theories in accounting, finance, economics, marketing, production, and income tax; and other designer issues. (LRW)

  3. Society News: Why become a Fellow of the Society? The 2010 RAS Fellowships; Using the RAS Library; Think grants! New Fellows

    NASA Astrophysics Data System (ADS)

    2011-04-01

    There are many arguments for joining the Society - supporting the RAS in lobbying, funding research and holding meetings, for example - but don't forget that benefits also come to individual Fellows. The RAS is pleased to announce the award of three RAS Fellowships in addition to the RAS Sir Norman Lockyer Fellowship.

  4. Gas-grain simulation experiment module conceptual design and gas-grain simulation facility breadboard development

    NASA Technical Reports Server (NTRS)

    Zamel, James M.; Petach, Michael; Gat, Nahum; Kropp, Jack; Luong, Christina; Wolff, Michael

    1993-01-01

    This report delineates the Option portion of the Phase A Gas-Grain Simulation Facility study. The conceptual design of a Gas-Grain Simulation Experiment Module (GGSEM) for Space Shuttle Middeck is discussed. In addition, a laboratory breadboard was developed during this study to develop a key function for the GGSEM and the GGSF, specifically, a solid particle cloud generating device. The breadboard design and test results are discussed and recommendations for further studies are included. The GGSEM is intended to fly on board a low earth orbit (LEO), manned platform. It will be used to perform a subset of the experiments planned for the GGSF for Space Station Freedom, as it can partially accommodate a number of the science experiments. The outcome of the experiments performed will provide an increased understanding of the operational requirements for the GGSF. The GGSEM will also act as a platform to accomplish technology development and proof-of-principle experiments for GGSF hardware, and to verify concepts and designs of hardware for GGSF. The GGSEM will allow assembled subsystems to be tested to verify facility level operation. The technology development that can be accommodated by the GGSEM includes: GGSF sample generation techniques, GGSF on-line diagnostics techniques, sample collection techniques, performance of various types of sensors for environmental monitoring, and some off-line diagnostics. Advantages and disadvantages of several LEO platforms available for GGSEM applications are identified and discussed. Several of the anticipated GGSF experiments require the deagglomeration and dispensing of dry solid particles into an experiment chamber. During the GGSF Phase A study, various techniques and devices available for the solid particle aerosol generator were reviewed. As a result of this review, solid particle deagglomeration and dispensing were identified as key undeveloped technologies in the GGSF design. A laboratory breadboard version of a solid

  5. Serine214 of Ras2p plays a role in the feedback regulation of the Ras-cAMP pathway in the yeast Saccharomyces cerevisiae.

    PubMed

    Xiaojia, Bai; Jian, Dong

    2010-06-03

    In the yeast Saccharomyces cerevisiae, Ras proteins are essential for the Ras-cAMP signaling pathway. A serine to alanine substitution at position 214 in the yeast Ras2p resulted in enhanced sensitivity to heat shock, reduced levels of storage glycogen and enhanced both basal cAMP level and glucose-induced cAMP signal. Further work showed that Ras2(Ala214)p had a higher GTP-binding capability than wild type Ras2p. These results suggested that serine 214 of Ras2p plays a role in the feedback regulation of the Ras-cAMP pathway.

  6. Geostatistical simulation of rock quality designation (RQD) to support facilities design at Yucca Mountain, Nevada

    SciTech Connect

    Cromer, M.V.; Zelinski, W.P.

    1996-12-31

    The conceptual design of the proposed Yucca Mountain nuclear waste repository facility includes shafts and ramps as access to the repository horizon, located 200 to 400 m below ground surface. Geostatistical simulation techniques are being employed to produce numerical models of selected material properties (rock characteristics) in their proper spatial positions. These numerical models will be used to evaluate behavior of various engineered features, the effects of construction and operating practices, and the waste-isolation performance of the overall repository system. The work presented here represents the first attempt to evaluate the spatial character of the rock strength index known as rock quality designation (RQD). Although it is likely that RQD reflects an intrinsic component of the rock matrix, this component becomes difficult to resolve given the frequency and orientation of data made available from vertical core records. The constraints of the two-dimensional study along the axis of an exploratory drift allow bounds to be placed upon the resulting interpretations, while the use of an indicator transformation allows focus to be placed on specific details that may be of interest to design engineers. The analytical process and subsequent development of material property models is anticipated to become one of the principal means of summarizing, integrating, and reconciling the diverse suite of earth-science data acquired through site characterization and of recasting the data in formats specifically designed for use in further modeling of various physical processes.

  7. Rapidly Re-Configurable Flight Simulator Tools for Crew Vehicle Integration Research and Design

    NASA Technical Reports Server (NTRS)

    Schutte, Paul C.; Trujillo, Anna; Pritchett, Amy R.

    2000-01-01

    While simulation is a valuable research and design tool, the time and difficulty required to create new simulations (or re-use existing simulations) often limits their application. This report describes the design of the software architecture for the Reconfigurable Flight Simulator (RFS), which provides a robust simulation framework that allows the simulator to fulfill multiple research and development goals. The core of the architecture provides the interface standards for simulation components, registers and initializes components, and handles the communication between simulation components. The simulation components are each a pre-compiled library 'plug-in' module. This modularity allows independent development and sharing of individual simulation components. Additional interfaces can be provided through the use of Object Data/Method Extensions (OD/ME). RFS provides a programmable run-time environment for real-time access and manipulation, and has networking capabilities using the High Level Architecture (HLA).

  8. Rapidly Re-Configurable Flight Simulator Tools for Crew Vehicle Integration Research and Design

    NASA Technical Reports Server (NTRS)

    Pritchett, Amy R.

    2002-01-01

    While simulation is a valuable research and design tool, the time and difficulty required to create new simulations (or re-use existing simulations) often limits their application. This report describes the design of the software architecture for the Reconfigurable Flight Simulator (RFS), which provides a robust simulation framework that allows the simulator to fulfill multiple research and development goals. The core of the architecture provides the interface standards for simulation components, registers and initializes components, and handles the communication between simulation components. The simulation components are each a pre-compiled library 'plugin' module. This modularity allows independent development and sharing of individual simulation components. Additional interfaces can be provided through the use of Object Data/Method Extensions (OD/ME). RFS provides a programmable run-time environment for real-time access and manipulation, and has networking capabilities using the High Level Architecture (HLA).

  9. Improving the Aircraft Design Process Using Web-Based Modeling and Simulation

    NASA Technical Reports Server (NTRS)

    Reed, John A.; Follen, Gregory J.; Afjeh, Abdollah A.; Follen, Gregory J. (Technical Monitor)

    2000-01-01

    Designing and developing new aircraft systems is time-consuming and expensive. Computational simulation is a promising means for reducing design cycle times, but requires a flexible software environment capable of integrating advanced multidisciplinary and multifidelity analysis methods, dynamically managing data across heterogeneous computing platforms, and distributing computationally complex tasks. Web-based simulation, with its emphasis on collaborative composition of simulation models, distributed heterogeneous execution, and dynamic multimedia documentation, has the potential to meet these requirements. This paper outlines the current aircraft design process, highlighting its problems and complexities, and presents our vision of an aircraft design process using Web-based modeling and simulation.

  10. Improving the Aircraft Design Process Using Web-based Modeling and Simulation

    NASA Technical Reports Server (NTRS)

    Reed, John A.; Follen, Gregory J.; Afjeh, Abdollah A.

    2003-01-01

    Designing and developing new aircraft systems is time-consuming and expensive. Computational simulation is a promising means for reducing design cycle times, but requires a flexible software environment capable of integrating advanced multidisciplinary and muitifidelity analysis methods, dynamically managing data across heterogeneous computing platforms, and distributing computationally complex tasks. Web-based simulation, with its emphasis on collaborative composition of simulation models, distributed heterogeneous execution, and dynamic multimedia documentation, has the potential to meet these requirements. This paper outlines the current aircraft design process, highlighting its problems and complexities, and presents our vision of an aircraft design process using Web-based modeling and simulation.

  11. The neurotensin gene is a downstream target for Ras activation.

    PubMed Central

    Evers, B M; Zhou, Z; Celano, P; Li, J

    1995-01-01

    Ras regulates novel patterns of gene expression and the differentiation of various eukaryotic cell types. Stable transfection of Ha-ras into the human colon cancer line CaCo2 results in the morphologic differentiation to a small bowel phenotype. The purpose of our study was to determine whether the Ras regulatory pathway plays a role in the expression of the neurotensin gene (NT/N), a terminally differentiated endocrine product specifically localized in the gastrointestinal tract to the adult small bowel. We found that CaCo2-ras cells, but not parental CaCo2, express high levels of the human NT/N gene and, moreover, that this increase in gene expression is regulated at the level of transcription. Transfection experiments using NT/N-CAT mutation constructs identify the proximal 200 bp of NT/N flanking sequence as sufficient for maximal Ras-mediated NT/N reporter gene induction. Furthermore, a proximal AP-1/CRE motif is crucial for this Ras-mediated NT/N activation. Wild-type Ha-ras induces NT/N gene expression, albeit at lower levels than activated Ras; a dominant-negative Raf blocks this NT/N induction, suggesting that Raf lies down-stream of Ras in this pathway. In addition, postconfluent cultures of CaCo2 cells, which are differentiated to a small bowel phenotype, express the NT/N gene by 6 d after reaching confluency; this increase of NT/N expression is associated with concomitant increases of cellular p21ras protein. We conclude that Ras (both wild-type and activated) enhances expression of the NT/N gene in the gut-derived CaCo2 cell line, suggesting an important role for the Ras signaling pathway in NT/N gene transcription. Our results underscore the possibility that tissue-specific genes (such as NT/N) expressed in distinct subpopulations of the gut may be subject to Ras regulation. Finally, we speculate that the NT/N gene and the CaCo2 and CaCo2-ras cell systems will provide unique models to further define the cellular mechanisms leading to mammalian

  12. Computational and biochemical characterization of two partially overlapping interfaces and multiple weak-affinity K-Ras dimers

    PubMed Central

    Prakash, Priyanka; Sayyed-Ahmad, Abdallah; Cho, Kwang-Jin; Dolino, Drew M.; Chen, Wei; Li, Hongyang; Grant, Barry J.; Hancock, John F.; Gorfe, Alemayehu A.

    2017-01-01

    Recent studies found that membrane-bound K-Ras dimers are important for biological function. However, the structure and thermodynamic stability of these complexes remained unknown because they are hard to probe by conventional approaches. Combining data from a wide range of computational and experimental approaches, here we describe the structure, dynamics, energetics and mechanism of assembly of multiple K-Ras dimers. Utilizing a range of techniques for the detection of reactive surfaces, protein-protein docking and molecular simulations, we found that two largely polar and partially overlapping surfaces underlie the formation of multiple K-Ras dimers. For validation we used mutagenesis, electron microscopy and biochemical assays under non-denaturing conditions. We show that partial disruption of a predicted interface through charge reversal mutation of apposed residues reduces oligomerization while introduction of cysteines at these positions enhanced dimerization likely through the formation of an intermolecular disulfide bond. Free energy calculations indicated that K-Ras dimerization involves direct but weak protein-protein interactions in solution, consistent with the notion that dimerization is facilitated by membrane binding. Taken together, our atomically detailed analyses provide unique mechanistic insights into K-Ras dimer formation and membrane organization as well as the conformational fluctuations and equilibrium thermodynamics underlying these processes. PMID:28067274

  13. Comparison of the Effects of RAS vs. Kain-Fritsch Convective Schemes on Katrina Forecasts with GEOS-5

    NASA Technical Reports Server (NTRS)

    Miller, Timothy L.; Cohen, Charles; Paxton, Jessica; Robertson, F. R. (Pete)

    2009-01-01

    Global forecasts were made with the 0.25-degree latitude version of GEOS-5, with the RAS scheme and with the Kain-Fritsch scheme. Examination was made of the Katrina (2005) hurricane simulation. Replacement of the RAS convective scheme with the K-F scheme results in a much more vigorous Katrina, closer to reality. Still, the result is not as vigorous as reality. In terms of wind maximum, the gap was closed by 50%. The result seems to be due to the RAS scheme drying out the boundary layer, thus hampering the grid-scale secondary circulation and attending cyclone development. The RAS case never developed a full warm core, whereas the K-F case did. Not shown here: The K-F scheme also resulted in a more vigorous storm than when GEOS-5 is run with no convective parameterization. Also not shown: An experiment in which the RAS firing level was moved up by 3 model levels resulted in a stronger, warm-core storm, though not as strong as the K-F case. Effects on storm track were noticed, but not studied.

  14. Computational and biochemical characterization of two partially overlapping interfaces and multiple weak-affinity K-Ras dimers

    NASA Astrophysics Data System (ADS)

    Prakash, Priyanka; Sayyed-Ahmad, Abdallah; Cho, Kwang-Jin; Dolino, Drew M.; Chen, Wei; Li, Hongyang; Grant, Barry J.; Hancock, John F.; Gorfe, Alemayehu A.

    2017-01-01

    Recent studies found that membrane-bound K-Ras dimers are important for biological function. However, the structure and thermodynamic stability of these complexes remained unknown because they are hard to probe by conventional approaches. Combining data from a wide range of computational and experimental approaches, here we describe the structure, dynamics, energetics and mechanism of assembly of multiple K-Ras dimers. Utilizing a range of techniques for the detection of reactive surfaces, protein-protein docking and molecular simulations, we found that two largely polar and partially overlapping surfaces underlie the formation of multiple K-Ras dimers. For validation we used mutagenesis, electron microscopy and biochemical assays under non-denaturing conditions. We show that partial disruption of a predicted interface through charge reversal mutation of apposed residues reduces oligomerization while introduction of cysteines at these positions enhanced dimerization likely through the formation of an intermolecular disulfide bond. Free energy calculations indicated that K-Ras dimerization involves direct but weak protein-protein interactions in solution, consistent with the notion that dimerization is facilitated by membrane binding. Taken together, our atomically detailed analyses provide unique mechanistic insights into K-Ras dimer formation and membrane organization as well as the conformational fluctuations and equilibrium thermodynamics underlying these processes.

  15. Endogenous K-ras signaling in erythroid differentiation.

    PubMed

    Zhang, Jing; Lodish, Harvey F

    2007-08-15

    K-ras is one of the most frequently mutated genes in virtually all types of human cancers. Using mouse fetal liver erythroid progenitors as a model system, we studied the role of endogenous K-ras signaling in erythroid differentiation. When oncogenic K-ras is expressed from its endogenous promoter, it hyperactivates cytokine-dependent signaling pathways and results in a partial block in erythroid differentiation. In erythroid progenitors deficient in K-ras, cytokine-dependent Akt activation is greatly reduced, leading to delays in erythroid differentiation. Thus, both loss- and gain-of-Kras functions affect erythroid differentiation through modulation of cytokine signaling. These results support the notion that in human cancer patients oncogenic Ras signaling might be controlled by antagonizing essential cytokines.

  16. Modeling and Simulation for Design of Suspended MEMS

    DTIC Science & Technology

    2003-05-21

    simulating systems with complicated electronics is limited. Exporting reduced-order models to aHDLs enables co-simulation with transistor-level...circuit-level behavioral simulation, the models are implemented in analog hardware description languages ( aHDLs ) or directly in element matrices, both...end of module The physical equations could be implemented in the aHDLs in multiple alternative ways. It has been noticed that the language

  17. Ras activation and symmetry breaking during Dictyostelium chemotaxis.

    PubMed

    Kortholt, Arjan; Keizer-Gunnink, Ineke; Kataria, Rama; Van Haastert, Peter J M

    2013-10-01

    Central to chemotaxis is the molecular mechanism by which a shallow spatial gradient of chemoattractant induces symmetry breaking of activated signaling molecules. Previously, we have used Dictyostelium mutants to investigate the minimal requirements for chemotaxis, and identified a basal signaling module providing activation of Ras and F-actin at the leading edge. Here, we show that Ras activation after application of a pipette releasing the chemoattractant cAMP has three phases, each depending on specific guanine-nucleotide-exchange factors (GEFs). Initially a transient activation of Ras occurs at the entire cell boundary, which is proportional to the local cAMP concentrations and therefore slightly stronger at the front than in the rear of the cell. This transient Ras activation is present in gα2 (gpbB)-null cells but not in gβ (gpbA)-null cells, suggesting that Gβγ mediates the initial activation of Ras. The second phase is symmetry breaking: Ras is activated only at the side of the cell closest to the pipette. Symmetry breaking absolutely requires Gα2 and Gβγ, but not the cytoskeleton or four cAMP-induced signaling pathways, those dependent on phosphatidylinositol (3,4,5)-triphosphate [PtdIns(3,4,5)P3], cGMP, TorC2 and PLA2. As cells move in the gradient, the crescent of activated Ras in the front half of the cell becomes confined to a small area at the utmost front of the cell. Confinement of Ras activation leads to cell polarization, and depends on cGMP formation, myosin and F-actin. The experiments show that activation, symmetry breaking and confinement of Ras during Dictyostelium chemotaxis uses different G-protein subunits and a multitude of Ras GEFs and GTPase-activating proteins (GAPs).

  18. Regulation of collagen I gene expression by ras.

    PubMed Central

    Slack, J L; Parker, M I; Robinson, V R; Bornstein, P

    1992-01-01

    Although transformation of rodent fibroblasts can lead to dramatic changes in expression of extracellular matrix genes, the molecular basis and physiological significance of these changes remain poorly understood. In this study, we have investigated the mechanism(s) by which ras affects expression of the genes encoding type I collagen. Levels of both alpha 1(I) and alpha 2(I) collagen mRNAs were markedly reduced in Rat 1 fibroblasts overexpressing either the N-rasLys-61 or the Ha-rasVal-12 oncogene. In fibroblasts conditionally transformed with N-rasLys-61, alpha 1(I) transcript levels began to decline within 8 h of ras induction and reached 1 to 5% of control levels after 96 h. In contrast, overexpression of normal ras p21 had no effect on alpha 1(I) or alpha 2(I) mRNA levels. Nuclear run-on experiments demonstrated that the transcription rates of both the alpha 1(I) and alpha 2(I) genes were significantly reduced in ras-transformed cells compared with those in parental cells. In addition, the alpha 1(I) transcript was less stable in transformed cells. Chimeric plasmids containing up to 3.6 kb of alpha 1(I) 5'-flanking DNA and up to 2.3 kb of the 3'-flanking region were expressed at equivalent levels in both normal and ras-transformed fibroblasts. However, a cosmid clone containing the entire mouse alpha 1(I) gene, including 3.7 kb of 5'- and 4 kb of 3'-flanking DNA, was expressed at reduced levels in fibroblasts overexpressing oncogenic ras. We conclude that oncogenic ras regulates the type I collagen genes at both transcriptional and posttranscriptional levels and that this effect, at least for the alpha 1(I) gene, may be mediated by sequences located either within the body of the gene itself or in the distal 3'-flanking region. Images PMID:1406656

  19. Characterization of c-Ki-ras and N-ras oncogenes in aflatoxin B1-induced rat liver tumors.

    PubMed Central

    McMahon, G; Davis, E F; Huber, L J; Kim, Y; Wogan, G N

    1990-01-01

    c-Ki-ras and N-ras oncogenes have been characterized in aflatoxin B1-induced hepatocellular carcinomas. Detection of different protooncogene and oncogene sequences and estimation of their frequency distribution were accomplished by polymerase chain reaction, cloning, and plaque screening methods. Two c-Ki-ras oncogene sequences were identified in DNA from liver tumors that contained nucleotide changes absent in DNA from livers of untreated control rats. Sequence changes involving G.C to T.A or G.C to A.T nucleotide substitutions in codon 12 were scored in three of eight tumor-bearing animals. Distributions of c-Ki-ras sequences in tumors and normal liver DNA indicated that the observed nucleotide changes were consistent with those expected to result from direct mutagenesis of the germ-line protooncogene by aflatoxin B1. N-ras oncogene sequences were identified in DNA from two of eight tumors. Three N-ras gene regions were identified, one of which was shown to be associated with an oncogene containing a putative activating amino acid residing at codon 13. All three N-ras sequences, including the region detected in N-ras oncogenes, were present at similar frequencies in DNA samples from control livers as well as liver tumors. The presence of a potential germ-line oncogene may be related to the sensitivity of the Fischer rat strain to liver carcinogenesis by aflatoxin B1 and other chemical carcinogens. Images PMID:2105496

  20. Flexible Space-Filling Designs for Complex System Simulations

    DTIC Science & Technology

    2013-06-01

    effects are possible (Myers et al., 2009). Some of the popular space-filling designs include the sphere-packing, uniform, and maximum entropy designs...design points as uniformly as possible throughout the design space (Fang, 1980). The maximum entropy designs maximize the information contained in...possible random permutations of 1,…,n in which all n! permutations are equally likely. , for j = 1,…,k, are continuous and invertible distribution

  1. Quadruple wild-type (WT) GIST: defining the subset of GIST that lacks abnormalities of KIT, PDGFRA, SDH, or RAS signaling pathways.

    PubMed

    Pantaleo, Maria A; Nannini, Margherita; Corless, Christopher L; Heinrich, Michael C

    2015-01-01

    A subset of GISTs lack mutations in the KIT/PDGFRA or RAS pathways and yet retain an intact succinate dehydrogensase (SDH) complex. We propose that these KIT/PDGFRA/SDH/RAS-P WT GIST tumors be designated as quadruple wild-type (WT) GIST. Further molecular and clinicophatological characterization of quadruple WT GIST will help to determine their prognosis as well as assist in the optimization of medical management, including clinical test of novel therapies.

  2. Ras Laffan helium recovery unit 2

    NASA Astrophysics Data System (ADS)

    Fauve, Eric Arnaud; Grabié, Veronique; Grillot, David; Delcayre, Franck; Deschildre, Cindy

    2012-06-01

    In May 2010, Air Liquide was awarded a contract for the Engineering Procurement and Construction (Turnkey EPC) for a second helium recovery unit [RLH II] dedicated to the Ras Laffan refinery in Qatar. This unit will come in addition to the one [RLH I] delivered and commissioned by Air Liquide in 2005. It will increase the helium production of Qatar from 10% to 28% of worldwide production. RLH I and RLH II use Air Liquide Advanced Technologies helium liquefiers. With a production of 8 tons of liquid helium per day, the RLH I liquefier is the world largest, but not for long. Thanks to the newly developed turbine TC7, Air Liquide was able to propose for RLH II a single liquefier able to produce over 20 tons per day of liquid helium without liquid nitrogen pre-cooling. This liquefier using 6 Air Liquide turbines (TC series) will set a new record in the world of helium liquefaction.

  3. RasGRF1 Regulates the Hypothalamic-Pituitary-Adrenal Axis Specifically in Early-Adolescent Female Mice

    PubMed Central

    Uzturk, Belkis Gizem; Jin, Shan-xue; Rubin, Beverly; Bartolome, Christopher; Feig, Larry A.

    2015-01-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the induction and prolongation of a variety of psychiatric disorders. As such, much effort has been made to understand the molecular mechanisms involved in its control. However, the vast majority of the studies on the HPA axis have used adult animals, and among these the majority has used males. Here we show that in knockout mice lacking the guanine nucleotide exchange factor, RasGRF1, habituation to 30 minutes a day of restraint stress is markedly accelerated, such that these mice do not display elevated corticosterone levels or enhanced locomotion after 7 days of stress exposure, like WT mice do. Strikingly, this phenotype is present in early-adolescent female RasGRF1 knockout mice, but not in their early-adolescent male, mid-adolescent female, adult female or adult male counterparts. Moreover, not only is there a clear response to restraint stress in early-adolescent female RasGRF1 knockout mice, their response after 1, 3, and 5 exposures is magnified ~3-fold compared to WT mice. These findings imply that distinct mechanisms exist to regulate the HPA axis in early-adolescent females that involves RasGRF1. A full understanding of how RasGRF1 controls the HPA axis response to stress may be required to design effective strategies to combat stress-associated psychiatric disorders initiated in young females. PMID:26246084

  4. Research and Methods for Simulation Design: State of the Art

    DTIC Science & Technology

    1990-09-01

    designers. Designers may use this review to identify methods to aid the training-device design process and individuals who manage research programs...maximum training effectiveness at a given cost. The methods should apply to the concept-formulation phase’of the training-device development process ...design process . Finally, individuals who manage research programs may use this information to set priorities for future research efforts. viii RESEARCH

  5. Design Team Approach Simulates Real-World Engineering

    ERIC Educational Resources Information Center

    Portz, Stephen

    2006-01-01

    Creating activities that model engineering design as it appears in industry provides great experience for technology students. Design in general creates an element with special regard to its form and function. Engineering design involves doing that, and going beyond to produce an efficient product that addresses its intended purpose. In this…

  6. Integrated design and simulation for millimeter-wave antenna systems

    NASA Technical Reports Server (NTRS)

    Cwik, T.; Katz, D. S.; Villegas, F. J.

    2000-01-01

    In this paper the development and application of MODTool (Millimeter-wave Optics Design), a design tool that efficiently integrates existing millimeter-wave optics design software with a solid body modeler and thermal/structural analysis packages, will be discussed.

  7. The Design of an ITS-Based Business Simulation: A New Epistemology for Learning.

    ERIC Educational Resources Information Center

    Gold, Steven C.

    1998-01-01

    Discusses the design and use of intelligent tutoring systems (ITS) for computerized business simulations. Reviews the use of ITS as an instructional technology; presents a model for ITS-based business simulations; examines the user interface and link between the ITS and simulation; and recommends expert-consultant diagnostic testing, and…

  8. Challenges in Integrating a Complex Systems Computer Simulation in Class: An Educational Design Research

    ERIC Educational Resources Information Center

    Loke, Swee-Kin; Al-Sallami, Hesham S.; Wright, Daniel F. B.; McDonald, Jenny; Jadhav, Sheetal; Duffull, Stephen B.

    2012-01-01

    Complex systems are typically difficult for students to understand and computer simulations offer a promising way forward. However, integrating such simulations into conventional classes presents numerous challenges. Framed within an educational design research, we studied the use of an in-house built simulation of the coagulation network in four…

  9. Design and simulation of latent heat storage units

    SciTech Connect

    Shamsundar, N.; Stein, E.; Rooz, E.; Bascaran, E.; Lee, T.C. )

    1992-04-01

    This report presents the results of two years of research and development on passive latent heat storage systems. Analytical models have been developed and extended, and a computer code for simulating the performance of a latent heat storage has been developed. The code is intended to be merged into a larger solar energy system simulation code and used for making realistic system studies. Simulation studies using a code which has a flexible and accurate routine for handling the storage subsystem should lead to the development of better systems than those in which storage is added on after the rest of the system has already been selected and optimized.

  10. Design and simulation of latent heat storage units. Final report

    SciTech Connect

    Shamsundar, N.; Stein, E.; Rooz, E.; Bascaran, E.; Lee, T.C.

    1992-04-01

    This report presents the results of two years of research and development on passive latent heat storage systems. Analytical models have been developed and extended, and a computer code for simulating the performance of a latent heat storage has been developed. The code is intended to be merged into a larger solar energy system simulation code and used for making realistic system studies. Simulation studies using a code which has a flexible and accurate routine for handling the storage subsystem should lead to the development of better systems than those in which storage is added on after the rest of the system has already been selected and optimized.

  11. Data Systems Dynamic Simulation - A total system for data system design assessments and trade studies

    NASA Technical Reports Server (NTRS)

    Hooper, J. W.; Rowe, D. W.

    1978-01-01

    Data Systems Dynamic Simulation is a simulation system designed to reduce cost and time and increase the confidence and comprehensiveness of Data Systems Simulation. It is designed to simulate large data processing and communications systems from end-to-end or by subsystem. Those features relevant to system timing, control, sizing, personnel support activities, cost and external influences are modeled. Emphasis is placed on ease of use, comprehensive system performance measures, and extensive post simulation analysis capability. The system has been used to support trade studies of the NASA data system needs in the 1985 to 1990 time frame.

  12. A method motion simulator design based on modeling characteristics of the human operator

    NASA Technical Reports Server (NTRS)

    Repperger, D. W.; Junker, A. M.

    1978-01-01

    A design criteria is obtained to compare two simulators and evaluate their equivalence or credibility. In the subsequent analysis the comparison of two simulators can be considered as the same problem as the comparison of a real world situation and a simulation's representation of this real world situation. The design criteria developed involves modeling of the human operator and defining simple parameters to describe his behavior in the simulator and in the real world situation. In the process of obtaining human operator parameters to define characteristics to evaluate simulators, measures are also obtained on these human operator characteristics which can be used to describe the human as an information processor and controller. First, a study is conducted on the simulator design problem in such a manner that this modeling approach can be used to develop a criteria for the comparison of two simulators.

  13. Analysis of Ras/ERK Compartmentalization by Subcellular Fractionation.

    PubMed

    Agudo-Ibañez, Lorena; Crespo, Piero; Casar, Berta

    2017-01-01

    A vast number of stimuli use the Ras/Raf/MEK/ERK signaling cascade to transmit signals from their cognate receptors, in order to regulate multiple cellular functions, including key processes such as proliferation, cell cycle progression, differentiation, and survival. The duration, intensity and specificity of the responses are, in part, controlled by the compartmentalization/subcellular localization of the signaling intermediaries. Ras proteins are found in different plasma membrane microdomains and endomembranes. At these localizations, Ras is subject to site-specific regulatory mechanisms, distinctively engaging effector pathways and switching-on diverse genetic programs to generate a multitude of biological responses. The Ras effector pathway leading to ERKs activation is also subject to space-related regulatory processes. About half of ERK1/2 substrates are found in the nucleus and function mainly as transcription factors. The other half resides in the cytosol and other cellular organelles. Such subcellular distribution enhances the complexity of the Ras/ERK cascade and constitutes an essential mechanism to endow variability to its signals, which enables their participation in the regulation of a broad variety of functions. Thus, analyzing the subcellular compartmentalization of the members of the Ras/ERK cascade constitutes an important factor to be taken into account when studying specific biological responses evoked by Ras/ERK signals. Herein, we describe methods for such purpose.

  14. KSR: a MAPK scaffold of the Ras pathway?

    PubMed

    Morrison, D K

    2001-05-01

    Kinase Suppressor of Ras (KSR) is an intriguing component of the Ras pathway that was first identified by genetic studies performed in Drosophila melanogaster and Caenorhabditis elegans. In both organisms, inactivating mutations in KSR suppress the phenotypic effects induced by activated Ras. These findings together with the fact that KSR contains many structural features characteristic of a protein kinase led to early speculation that KSR is a kinase functioning upstream of the Ras pathway component Raf-1 or in a parallel Ras-dependent pathway. However, in the six years since its discovery, KSR has been found to lack several key properties of known protein kinases, which has cast doubt on whether KSR is indeed a functional enzyme. A major breakthrough in our understanding of the role of KSR in signal transduction has come from recent findings that KSR interacts with several components of the MAP kinase cascade, including Raf-1, MEK1/2 and ERK1/2. The model now emerging is that KSR acts as a scaffolding protein that coordinates the assembly of a membrane-localized, multiprotein MAP kinase complex, a vital step in Ras-mediated signal transduction. Thus, while Kinase Suppressor of Ras may be its name, phosphorylation may not be its game.

  15. Inhibition of SHP2-mediated dephosphorylation of Ras suppresses oncogenesis

    PubMed Central

    Bunda, Severa; Burrell, Kelly; Heir, Pardeep; Zeng, Lifan; Alamsahebpour, Amir; Kano, Yoshihito; Raught, Brian; Zhang, Zhong-Yin; Zadeh, Gelareh; Ohh, Michael

    2015-01-01

    Ras is phosphorylated on a conserved tyrosine at position 32 within the switch I region via Src kinase. This phosphorylation inhibits the binding of effector Raf while promoting the engagement of GTPase-activating protein (GAP) and GTP hydrolysis. Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling. In comparison to normal astrocytes, SHP2 activity is elevated in astrocytes isolated from glioblastoma multiforme (GBM)-prone H-Ras(12V) knock-in mice as well as in glioma cell lines and patient-derived GBM specimens exhibiting hyperactive Ras. Pharmacologic inhibition of SHP2 activity attenuates cell proliferation, soft-agar colony formation and orthotopic GBM growth in NOD/SCID mice and decelerates the progression of low-grade astrocytoma to GBM in a spontaneous transgenic glioma mouse model. These results identify SHP2 as a direct activator of Ras and a potential therapeutic target for cancers driven by a previously ‘undruggable' oncogenic or hyperactive Ras. PMID:26617336

  16. Inhibition of SHP2-mediated dephosphorylation of Ras suppresses oncogenesis.

    PubMed

    Bunda, Severa; Burrell, Kelly; Heir, Pardeep; Zeng, Lifan; Alamsahebpour, Amir; Kano, Yoshihito; Raught, Brian; Zhang, Zhong-Yin; Zadeh, Gelareh; Ohh, Michael

    2015-11-30

    Ras is phosphorylated on a conserved tyrosine at position 32 within the switch I region via Src kinase. This phosphorylation inhibits the binding of effector Raf while promoting the engagement of GTPase-activating protein (GAP) and GTP hydrolysis. Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling. In comparison to normal astrocytes, SHP2 activity is elevated in astrocytes isolated from glioblastoma multiforme (GBM)-prone H-Ras(12V) knock-in mice as well as in glioma cell lines and patient-derived GBM specimens exhibiting hyperactive Ras. Pharmacologic inhibition of SHP2 activity attenuates cell proliferation, soft-agar colony formation and orthotopic GBM growth in NOD/SCID mice and decelerates the progression of low-grade astrocytoma to GBM in a spontaneous transgenic glioma mouse model. These results identify SHP2 as a direct activator of Ras and a potential therapeutic target for cancers driven by a previously 'undruggable' oncogenic or hyperactive Ras.

  17. Analysis of Ras-induced overproliferation in Drosophila hemocytes.

    PubMed Central

    Asha, H; Nagy, Istvan; Kovacs, Gabor; Stetson, Daniel; Ando, Istvan; Dearolf, Charles R

    2003-01-01

    We use the Drosophila melanogaster larval hematopoietic system as an in vivo model for the genetic and functional genomic analysis of oncogenic cell overproliferation. Ras regulates cell proliferation and differentiation in multicellular eukaryotes. To further elucidate the role of activated Ras in cell overproliferation, we generated a collagen promoter-Gal4 strain to overexpress Ras(V12) in Drosophila hemocytes. Activated Ras causes a dramatic increase in the number of circulating larval hemocytes (blood cells), which is caused by cellular overproliferation. This phenotype is mediated by the Raf/MAPK pathway. The mutant hemocytes retain the ability to phagocytose bacteria as well as to differentiate into lamellocytes. Microarray analysis of hemocytes overexpressing Ras(V12) vs. Ras(+) identified 279 transcripts that are differentially expressed threefold or more in hemocytes expressing activated Ras. This work demonstrates that it will be feasible to combine genetic and functional genomic approaches in the Drosophila hematopoietic system to systematically identify oncogene-specific downstream targets. PMID:12586708

  18. ras activation in human tumors and in animal model systems.

    PubMed Central

    Corominas, M; Sloan, S R; Leon, J; Kamino, H; Newcomb, E W; Pellicer, A

    1991-01-01

    Environmental agents such as radiation and chemicals are known to cause genetic damage. Alterations in a limited set of cellular genes called proto-oncogenes lead to unregulated proliferation and differentiation. We have studied the role of the ras gene family in carcinogenesis using two different animal models. In one case, thymic lymphomas were induced in mice by either gamma or neutron radiation, and in the other, keratoacanthomas were induced in rabbit skin with dimethylbezanthracene. Human keratoacanthomas similar to the ones induced in rabbits were also analyzed. We found that different types of radiation such as gamma rays and neutrons, induced different point mutations in ras genes. A novel K-ras mutation in codon 146 has been found in thymic lymphomas induced by neutrons. Keratoacanthomas induced in rabbit skin by dimethylbenzanthracene show a high frequency of H-ras-activated genes carrying a mutation in codon 61. The same is observed in human keratoacanthomas, although mutations are in both the 12th and the 61st codons of the H-ras gene. H-ras activation is less frequent in human squamous cell carcinomas than in keratoacanthomas, suggesting that ras genes could play a role in vivo in differentiation as well as in proliferation. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. PMID:1773791

  19. Regulation of Ras signaling and function by plasma membrane microdomains.

    PubMed

    Goldfinger, Lawrence E; Michael, James V

    2017-02-07

    Together H-, N- and KRAS mutations are major contributors to ~30% of all human cancers. Thus, Ras inhibition remains an important anti-cancer strategy. The molecular mechanisms of isotypic Ras oncogenesis are still not completely understood. Monopharmacological therapeutics have not been successful in the clinic. These disappointing outcomes have led to attempts to target elements downstream of Ras, mainly targeting either the Phosphatidylinositol 3-Kinase (PI3K) or Mitogen-Activated Protein Kinase (MAPK) pathways. While several such approaches are moderately effective, recent efforts have focused on preclinical evaluation of combination therapies to improve efficacies. This review will detail current understanding of the contributions of plasma membrane microdomain targeting of Ras to mitogenic and tumorigenic signaling and tumor progression. Moreover, this review will outline novel approaches to target Ras in cancers, including targeting schemes for new drug development, as well as putative re-purposing of drugs in current use to take advantage of blunting Ras signaling by interfering with Ras plasma membrane microdomain targeting and retention.

  20. Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells.

    PubMed

    Cengel, Keith A; Voong, K Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B; Stanbridge, Eric; Kao, Gary D; McKenna, W Gillies; Bernhard, Eric J

    2007-04-01

    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor alpha was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers.

  1. Oncogenic K-Ras Signals through Epidermal Growth Factor Receptor and Wild-Type H-Ras to Promote Radiation Survival in Pancreatic and Colorectal Carcinoma Cells1

    PubMed Central

    Cengel, Keith A.; Voong, K. Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B.; Stanbridge, Eric; Kao, Gary D.; McKenna, W. Gillies; Bernhard, Eric J.

    2007-01-01

    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor α was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers. PMID:17460778

  2. Early Design Choices: Capture, Model, Integrate, Analyze, Simulate

    NASA Technical Reports Server (NTRS)

    Malin, Jane T.

    2004-01-01

    I. Designs are constructed incrementally to meet requirements and solve problems: a) Requirements types: objectives, scenarios, constraints, ilities. etc. b) Problem/issue types: risk/safety, cost/difficulty, interaction, conflict, etc. II. Capture requirements, problems and solutions: a) Collect design and analysis products and make them accessible for integration and analysis; b) Link changes in design requirements, problems and solutions; and c) Harvest design data for design models and choice structures. III. System designs are constructed by multiple groups designing interacting subsystems a) Diverse problems, choice criteria, analysis methods and point solutions. IV. Support integration and global analysis of repercussions: a) System implications of point solutions; b) Broad analysis of interactions beyond totals of mass, cost, etc.

  3. The F-92 RELIANT: Air transport system design simulation

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The design proposal of a semester long design project by group 'F' for AE 441 is addressed. In formulating this design, the driving philosophy was not just to fulfill the mission requirements (discussed in chapter two), but to do so in a creative manner - this explains the unconventional aircraft design, named the F-92 RELIANT. Although unconventional, and perhaps more expensive to produce, the design has distinct advantages which could only be attained through such a creative design. Major components of the F-92 Reliant include: (1) unobstructed cargo bay, 1024 cu. in. capability; (2) loading ramp; (3) dual wing configuration; and (4) polyhedral wing configuration. These design components either originated or evolved to create an aircraft that would most effectively meet the goals of cargo transportation in AeroWorld at minimum cost.

  4. Conceptual Design of Simulation Models in an Early Development Phase of Lunar Spacecraft Simulator Using SMP2 Standard

    NASA Astrophysics Data System (ADS)

    Lee, Hoon Hee; Koo, Cheol Hea; Moon, Sung Tae; Han, Sang Hyuck; Ju, Gwang Hyeok

    2013-08-01

    The conceptual study for Korean lunar orbiter/lander prototype has been performed in Korea Aerospace Research Institute (KARI). Across diverse space programs around European countries, a variety of simulation application has been developed using SMP2 (Simulation Modelling Platform) standard related to portability and reuse of simulation models by various model users. KARI has not only first-hand experience of a development of SMP compatible simulation environment but also an ongoing study to apply the SMP2 development process of simulation model to a simulator development project for lunar missions. KARI has tried to extend the coverage of the development domain based on SMP2 standard across the whole simulation model life-cycle from software design to its validation through a lunar exploration project. Figure. 1 shows a snapshot from a visualization tool for the simulation of lunar lander motion. In reality, a demonstrator prototype on the right-hand side of image was made and tested in 2012. In an early phase of simulator development prior to a kick-off start in the near future, targeted hardware to be modelled has been investigated and indentified at the end of 2012. The architectural breakdown of the lunar simulator at system level was performed and the architecture with a hierarchical tree of models from the system to parts at lower level has been established. Finally, SMP Documents such as Catalogue, Assembly, Schedule and so on were converted using a XML(eXtensible Mark-up Language) converter. To obtain benefits of the suggested approaches and design mechanisms in SMP2 standard as far as possible, the object-oriented and component-based design concepts were strictly chosen throughout a whole model development process.

  5. Targeted Genomic Disruption of H-ras and N-ras, Individually or in Combination, Reveals the Dispensability of Both Loci for Mouse Growth and Development

    PubMed Central

    Esteban, Luis M.; Vicario-Abejón, Carlos; Fernández-Salguero, Pedro; Fernández-Medarde, Alberto; Swaminathan, Nalini; Yienger, Kate; Lopez, Eva; Malumbres, Marcos; McKay, Ron; Ward, Jerrold M.; Pellicer, Angel; Santos, Eugenio

    2001-01-01

    Mammalian cells harbor three highly homologous and widely expressed members of the ras family (H-ras, N-ras, and K-ras), but it remains unclear whether they play specific or overlapping cellular roles. To gain insight into such functional roles, here we generated and analyzed H-ras null mutant mice, which were then also bred with N-ras knockout animals to ascertain the viability and properties of potential double null mutations in both loci. Mating among heterozygous H-ras+/− mice produced H-ras−/− offspring with a normal Mendelian pattern of inheritance, indicating that the loss of H-ras did not interfere with embryonic and fetal viability in the uterus. Homozygous mutant H-ras−/− mice reached sexual maturity at the same age as their littermates, and both males and females were fertile. Characterization of lymphocyte subsets in the spleen and thymus showed no significant differences between wild-type and H-ras−/− mice. Analysis of neuronal markers in the brains of knockout and wild-type H-ras mice showed that disruption of this locus did not impair or alter neuronal development. Breeding between our H-ras mutant animals and previously available N-ras null mutants gave rise to viable double knockout (H-ras−/−/N-ras−/−) offspring expressing only K-ras genes which grew normally, were fertile, and did not show any obvious phenotype. Interestingly, however, lower-than-expected numbers of adult, double knockout animals were consistently obtained in Mendelian crosses between heterozygous N-ras/H-ras mice. Our results indicate that, as for N-ras, H-ras gene function is dispensable for normal mouse development, growth, fertility, and neuronal development. Additionally, of the three ras genes, K-ras appears to be not only essential but also sufficient for normal mouse development. PMID:11238881

  6. Canonical RTK-Ras-ERK signaling and related alternative pathways

    PubMed Central

    Sundaram, Meera V.

    2013-01-01

    Receptor Tyrosine Kinase (RTK)-Ras-Extracellular signal-regulated kinase (ERK) signaling pathways control many aspects of C. elegans development and behavior. Studies in C. elegans helped elucidate the basic framework of the RTK-Ras-ERK pathway and continue to provide insights into its complex regulation, its biological roles, how it elicits cell-type appropriate responses, and how it interacts with other signaling pathways to do so. C. elegans studies have also revealed biological contexts in which alternative RTK- or Ras-dependent pathways are used instead of the canonical pathway. PMID:23908058

  7. PGA1-induced apoptosis involves specific activation of H-Ras and N-Ras in cellular endomembranes

    PubMed Central

    Anta, B; Pérez-Rodríguez, A; Castro, J; García- Domínguez, C A; Ibiza, S; Martínez, N; Durá, L M; Hernández, S; Gragera, T; Peña-Jiménez, D; Yunta, M; Zarich, N; Crespo, P; Serrador, J M; Santos, E; Muñoz, A; Oliva, J L; Rojas-Cabañeros, J M

    2016-01-01

    The cyclopentenone prostaglandin A1 (PGA1) is an inducer of cell death in cancer cells. However, the mechanism that initiates this cytotoxic response remains elusive. Here we report that PGA1 triggers apoptosis by a process that entails the specific activation of H- and N-Ras isoforms, leading to caspase activation. Cells without H- and N-Ras did not undergo apoptosis upon PGA1 treatment; in these cells, the cellular demise was rescued by overexpression of either H-Ras or N-Ras. Consistently, the mutant H-Ras-C118S, defective for binding PGA1, did not produce cell death. Molecular analysis revealed a key role for the RAF-MEK-ERK signaling pathway in the apoptotic process through the induction of calpain activity and caspase-12 cleavage. We propose that PGA1 evokes a specific physiological cell death program, through H- and N-Ras, but not K-Ras, activation at endomembranes. Our results highlight a novel mechanism that may be of potential interest for tumor treatment. PMID:27468687

  8. PGA1-induced apoptosis involves specific activation of H-Ras and N-Ras in cellular endomembranes.

    PubMed

    Anta, B; Pérez-Rodríguez, A; Castro, J; García-Domínguez, C A; Ibiza, S; Martínez, N; Durá, L M; Hernández, S; Gragera, T; Peña-Jiménez, D; Yunta, M; Zarich, N; Crespo, P; Serrador, J M; Santos, E; Muñoz, A; Oliva, J L; Rojas-Cabañeros, J M

    2016-07-28

    The cyclopentenone prostaglandin A1 (PGA1) is an inducer of cell death in cancer cells. However, the mechanism that initiates this cytotoxic response remains elusive. Here we report that PGA1 triggers apoptosis by a process that entails the specific activation of H- and N-Ras isoforms, leading to caspase activation. Cells without H- and N-Ras did not undergo apoptosis upon PGA1 treatment; in these cells, the cellular demise was rescued by overexpression of either H-Ras or N-Ras. Consistently, the mutant H-Ras-C118S, defective for binding PGA1, did not produce cell death. Molecular analysis revealed a key role for the RAF-MEK-ERK signaling pathway in the apoptotic process through the induction of calpain activity and caspase-12 cleavage. We propose that PGA1 evokes a specific physiological cell death program, through H- and N-Ras, but not K-Ras, activation at endomembranes. Our results highlight a novel mechanism that may be of potential interest for tumor treatment.

  9. Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy

    PubMed Central

    Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S.; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.

    2015-01-01

    The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012

  10. Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy.

    PubMed

    Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J; Lipskaia, Larissa; Chemaly, Elie R

    2015-11-01

    The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy.

  11. High-Alpha Research Vehicle (HARV) longitudinal controller: Design, analyses, and simulation resultss

    NASA Technical Reports Server (NTRS)

    Ostroff, Aaron J.; Hoffler, Keith D.; Proffitt, Melissa S.; Brown, Philip W.; Phillips, Michael R.; Rivers, Robert A.; Messina, Michael D.; Carzoo, Susan W.; Bacon, Barton J.; Foster, John F.

    1994-01-01

    This paper describes the design, analysis, and nonlinear simulation results (batch and piloted) for a longitudinal controller which is scheduled to be flight-tested on the High-Alpha Research Vehicle (HARV). The HARV is an F-18 airplane modified for and equipped with multi-axis thrust vectoring. The paper includes a description of the facilities, a detailed review of the feedback controller design, linear analysis results of the feedback controller, a description of the feed-forward controller design, nonlinear batch simulation results, and piloted simulation results. Batch simulation results include maximum pitch stick agility responses, angle of attack alpha captures, and alpha regulation for full lateral stick rolls at several alpha's. Piloted simulation results include task descriptions for several types of maneuvers, task guidelines, the corresponding Cooper-Harper ratings from three test pilots, and some pilot comments. The ratings show that desirable criteria are achieved for almost all of the piloted simulation tasks.

  12. Overexpression of wild-type p21Ras plays a prominent role in colorectal cancer

    PubMed Central

    Bai, Shuang; Feng, Qiang; Pan, Xin-Yan; Zou, Hong; Chen, Hao-Bin; Wang, Peng; Zhou, Xin-Liang; Hong, Yan-Ling; Song, Shu-Ling; Yang, Ju-Lun

    2017-01-01

    Colorectal cancer (CRC) is the most common gastrointestinal type of cancer. The overexpression of Ras proteins, particularly p21Ras, are involved in the development of CRC. However, the subtypes of the p21Ras proteins that are overexpressed and the mutation status remain unknown restricting the development of therapeutic antibodies targeting p21Ras proteins. The present study aimed to investigate the mutation status of ras genes associated with Ras proteins that are overexpressed in CRC and explore whether or not wild-type p21Ras could be a target for CRC therapy. p21Ras expression was examined immunohistochemically in normal colorectal epithelium, benign lesions and malignant colorectal tumor tissues by monoclonal antibody (Mab) KGH-R1 which is able to react with three types of p21Ras proteins: H-p21Ras, N-p21Ras and K-p21Ras. Then, the expression levels of p21Ras subtypes were determined in CRC by a specific Mab for each p21Ras subtype. Mutation status of ras genes in p21Ras-overexpressing CRC was detected by DNA sequencing. There was rare p21Ras expression in normal colorectal epithelium but a high level of p21Ras expression in CRC, with a significant increase from normal colorectal epithelium to inflammatory polyps, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and invasive colorectal adenocarcinoma, respectively. Overexpression of K-p21Ras was found in all CRC tissues tested, overexpression of N-p21Ras was found in 85.7% of the CRC tissues, while H-p21Ras expression was not found in any CRC tissue. DNA sequencing showed that there were no K-ras mutations in 60% of the K-p21Ras-overexpressing CRC, while 40% of the CRC tissues harbored K-ras mutations. N-ras mutations were not found in any N-p21Ras-overexpressing CRC. Our findings indicate that overexpression of wild-type p21Ras may play a prominent role in the development of CRC in addition to ras mutations and could be a promising target for CRC therapy. PMID:28259994

  13. ras mutations and expression in head and neck squamous cell carcinomas.

    PubMed

    Yarbrough, W G; Shores, C; Witsell, D L; Weissler, M C; Fidler, M E; Gilmer, T M

    1994-11-01

    Mutational activation and overexpression of the family of ras proto-oncogenes have been associated with many human tumors. The role of mutations of H-ras, K-ras, and N-ras, as well as expression of the respective protein products (p21s) in normal mucosa, dysplastic mucosa, and squamous cell carcinomas (SCCs) of the head and neck has not been fully described. In our study, 51 tumors (40 paraffin embedded and 11 fresh frozen) were examined to determine if mutational activation of ras is an important molecular event in head and neck SCC. Analyses of codons 12, 13, and 61 of H-ras, K-ras, and N-ras revealed no mutations, suggesting that mutational activation of ras is not important in the majority of head and neck SCCs. Immunocytochemistry (ICC) was used to define the expression of H-ras, K-ras, and N-ras in normal mucosa, dysplastic mucosa, and SCC of the head and neck and to determine if expression of ras family members correlated with early or late events in the development of SCC. Expression of p21N-ras in nine samples of histologically normal head and neck mucosa revealed moderate staining in the basal proliferative layers with progressively less staining as cells matured. The most superficial layers of normal mucosa failed to express p21N-ras. A low level of p21H-ras was expressed in all layers of normal mucosa while K-ras was not expressed. ICC of SCC tumor sections revealed cytoplasmic expression of N-ras in nine of nine tumors, H-ras in five of nine tumors, and K-ras in one of nine tumors. Expression of H-ras, K-ras, and N-ras in head and neck SCC was not related to histologic differentiation or TNM staging; however, p21N-ras was overexpressed in seven of nine tumors. Furthermore, the pattern of N-ras expression in dysplastic lesions revealed expression in all layers of the mucosa in contrast to normal mucosa, which expresses p21N-ras primarily in the basal proliferative layer. The change in p21N-ras expression pattern in dysplastic mucosa and its

  14. Aiding Design of Wave Energy Converters via Computational Simulations

    NASA Astrophysics Data System (ADS)

    Jebeli Aqdam, Hejar; Ahmadi, Babak; Raessi, Mehdi; Tootkaboni, Mazdak

    2015-11-01

    With the increasing interest in renewable energy sources, wave energy converters will continue to gain attention as a viable alternative to current electricity production methods. It is therefore crucial to develop computational tools for the design and analysis of wave energy converters. A successful design requires balance between the design performance and cost. Here an analytical solution is used for the approximate analysis of interactions between a flap-type wave energy converter (WEC) and waves. The method is verified using other flow solvers and experimental test cases. Then the model is used in conjunction with a powerful heuristic optimization engine, Charged System Search (CSS) to explore the WEC design space. CSS is inspired by charged particles behavior. It searches the design space by considering candidate answers as charged particles and moving them based on the Coulomb's laws of electrostatics and Newton's laws of motion to find the global optimum. Finally the impacts of changes in different design parameters on the power takeout of the superior WEC designs are investigated. National Science Foundation, CBET-1236462.

  15. Knowledge-Driven Design of Virtual Patient Simulations

    ERIC Educational Resources Information Center

    Vergara, Victor; Caudell, Thomas; Goldsmith, Timothy; Panaiotis; Alverson, Dale

    2009-01-01

    Virtual worlds provide unique opportunities for instructors to promote, study, and evaluate student learning and comprehension. In this article, Victor Vergara, Thomas Caudell, Timothy Goldsmith, Panaiotis, and Dale Alverson explore the advantages of using virtual reality environments to create simulations for medical students. Virtual simulations…

  16. Designing Better Scaffolding in Teaching Complex Systems with Graphical Simulations

    ERIC Educational Resources Information Center

    Li, Na

    2013-01-01

    Complex systems are an important topic in science education today, but they are usually difficult for secondary-level students to learn. Although graphic simulations have many advantages in teaching complex systems, scaffolding is a critical factor for effective learning. This dissertation study was conducted around two complementary research…

  17. Detectors for the superconducting super collider, design concepts, and simulation

    SciTech Connect

    Gabriel, T.A.

    1989-06-01

    The physics of compensation calorimetry is reviewed in the light of the needs of the Superconducting Super Collider (SSC) detectors. The four major detector types: liquid argon, scintillator, room temperature liquids, and silicon, are analyzed with respect to some of their strengths and weaknesses. Finally, general comments are presented which reflect the reliability of simulation code systems.

  18. Case Studies in Computer Adaptive Test Design through Simulation.

    ERIC Educational Resources Information Center

    Eignor, Daniel R.; And Others

    The extensive computer simulation work done in developing the computer adaptive versions of the Graduate Record Examinations (GRE) Board General Test and the College Board Admissions Testing Program (ATP) Scholastic Aptitude Test (SAT) is described in this report. Both the GRE General and SAT computer adaptive tests (CATs), which are fixed length…

  19. Designing Simulations for Athletic Training Students through Interprofessional Teaching Collaboration

    ERIC Educational Resources Information Center

    Tivener, Kristin Ann; Gloe, Donna Sue

    2015-01-01

    Context: While multidisciplinary team approaches to education and practice have been promoted for decades, literature on collaborative efforts in athletic training and nursing remains sparse. Objective: The goal of this article is to provide an example of an interprofessional teaching collaboration in which a simulation scenario was developed…

  20. Rap1 overexpression reveals that activated RasD induces separable defects during Dictyostelium development.

    PubMed

    Louis, S A; Weeks, G; Spiegelman, G B

    1997-10-15

    One of the Dictyostelium ras genes, rasD, is expressed preferentially in prestalk cells at the slug stage of development and overexpression of this gene containing a G12T activating mutation causes the formation of aberrant multitipped aggregates that are blocked from further development (Reymond et al., 1986, Nature, 323, 340-343). The ability of the Dictyostelium rap1 gene to suppress this abnormal developmental phenotype was investigated. The rap1 gene and G12V activated and G10V negative mutant forms of the rap1 gene were independently linked to the rasD promoter and each construct used to transform M1, a Dictyostelium cell line expressing RasD[G12T]. Transformants of M1 that expressed Rap1 or Rap1[G12V] protein still formed multitipped aggregates, but most tips were able to complete development and form fruiting bodies. Cell lines showing this modified phenotype were designated ME (multitipped escape). The rap1[G10V] construct did not modify the M1 phenotype. These data suggest that overexpression of RasD[G12T] has two effects, the formation of a multitipped aggregate and a block in subsequent differentiation and that the expression of Rap1 or Rap1[G12V] reverses only the latter. Differentiation of ME cells in low density monolayers showed the identical low level of stalk and spore cell formation seen for M1 cells under the same conditions. Thus the cell autonomous defect in monolayer differentiation induced in the M1 strain was not corrected in the ME strain. Cell type-specific gene expression during the development of M1 cells is dramatically altered: prestalk cell-specific gene expression is greatly enhanced, whereas prespore-specific gene expression is almost suppressed (Louis et al., 1997, Mol. Biol. Cell, 8, 303-312). During the development of ME cells, ecmA mRNA levels were restored to those seen for Ax3, and tagB mRNA levels were also markedly reduced, although not to Ax3 levels. cotC expression in ME cells was enhanced severalfold relative to M1

  1. The C-terminus of H-Ras as a target for the covalent binding of reactive compounds modulating Ras-dependent pathways.

    PubMed

    Oeste, Clara L; Díez-Dacal, Beatriz; Bray, Francesca; García de Lacoba, Mario; de la Torre, Beatriz G; Andreu, David; Ruiz-Sánchez, Antonio J; Pérez-Inestrosa, Ezequiel; García-Domínguez, Carlota A; Rojas, José M; Pérez-Sala, Dolores

    2011-01-06

    Ras proteins are crucial players in differentiation and oncogenesis and constitute important drug targets. The localization and activity of Ras proteins are highly dependent on posttranslational modifications at their C-termini. In addition to an isoprenylated cysteine, H-Ras, but not other Ras proteins, possesses two cysteine residues (C181 and C184) in the C-terminal hypervariable domain that act as palmitoylation sites in cells. Cyclopentenone prostaglandins (cyPG) are reactive lipidic mediators that covalently bind to H-Ras and activate H-Ras dependent pathways. Dienone cyPG, such as 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) and Δ(12)-PGJ(2) selectively bind to the H-Ras hypervariable domain. Here we show that these cyPG bind simultaneously C181 and C184 of H-Ras, thus potentially altering the conformational tendencies of the hypervariable domain. Based on these results, we have explored the capacity of several bifunctional cysteine reactive small molecules to bind to the hypervariable domain of H-Ras proteins. Interestingly, phenylarsine oxide (PAO), a widely used tyrosine phosphatase inhibitor, and dibromobimane, a cross-linking agent used for cysteine mapping, effectively bind H-Ras hypervariable domain. The interaction of PAO with H-Ras takes place in vitro and in cells and blocks modification of H-Ras by 15d-PGJ(2). Moreover, PAO treatment selectively alters H-Ras membrane partition and the pattern of H-Ras activation in cells, from the plasma membrane to endomembranes. These results identify H-Ras as a novel target for PAO. More importantly, these observations reveal that small molecules or reactive intermediates interacting with spatially vicinal cysteines induce intramolecular cross-linking of H-Ras C-terminus potentially contributing to the modulation of Ras-dependent pathways.

  2. Computational Modeling Reveals that Signaling Lipids Modulate the Orientation of K-Ras4A at the Membrane Reflecting Protein Topology.

    PubMed

    Li, Zhen-Lu; Buck, Matthias

    2017-04-04

    The structural, dynamical, and functional characterization of the small GTPase K-Ras has become a research area of intense focus due to its high occurrence in human cancers. Ras proteins are only fully functional when they interact with the plasma membrane. Here we present all-atom molecular dynamics simulations (totaling 5.8 μs) to investigate the K-Ras4A protein at membranes that contain anionic lipids (phosphatidyl serine or phosphatidylinositol bisphosphate). We find that similarly to the homologous and highly studied K-Ras4B, K-Ras4A prefers a few distinct orientations at the membrane. Remarkably, the protein surface charge and certain lipids can strongly modulate the orientation preference. In a novel analysis, we reveal that the electrostatic interaction (attraction but also repulsion) between the protein's charged residues and anionic lipids determines the K-Ras4A orientation, but that this is also influenced by the topology of the protein, reflecting the geometry of its surfaces.

  3. Identification and expression analysis of ras gene in silkworm, Bombyx mori.

    PubMed

    Ogura, Takehiko; Tan, Anjiang; Tsubota, Takuya; Nakakura, Takayo; Shiotsuki, Takahiro

    2009-11-25

    Ras proteins play important roles in development especially for cell proliferation and differentiation in various organisms. However, their functions in the most insect species are still not clear. We identified three ras cDNAs from the silk worm, Bombyx mori. These sequences corresponded to three Ras of Drosophila melanogaster, but not to three mammalian Ras (H-Ras, K-Ras, N-Ras). Subsequently, the expression profiles of ras were investigated by quantitative real-time PCR using whole body of individuals from the embryonic to adult stages, and various tissues of 4th and 5th instar larvae. Each of three Bombyx ras showed different expression patterns. We also showed membrane localization of their products. These results indicate that the three Bombyx Ras are functional and have different roles.

  4. High Altitude Venus Operations Concept Trajectory Design, Modeling and Simulation

    NASA Technical Reports Server (NTRS)

    Lugo, Rafael A.; Ozoroski, Thomas A.; Van Norman, John W.; Arney, Dale C.; Dec, John A.; Jones, Christopher A.; Zumwalt, Carlie H.

    2015-01-01

    A trajectory design and analysis that describes aerocapture, entry, descent, and inflation of manned and unmanned High Altitude Venus Operation Concept (HAVOC) lighter-than-air missions is presented. Mission motivation, concept of operations, and notional entry vehicle designs are presented. The initial trajectory design space is analyzed and discussed before investigating specific trajectories that are deemed representative of a feasible Venus mission. Under the project assumptions, while the high-mass crewed mission will require further research into aerodynamic decelerator technology, it was determined that the unmanned robotic mission is feasible using current technology.

  5. A Spreadsheet Simulation Tool for Terrestrial and Planetary Balloon Design

    NASA Technical Reports Server (NTRS)

    Raquea, Steven M.

    1999-01-01

    During the early stages of new balloon design and development, it is necessary to conduct many trade studies. These trade studies are required to determine the design space, and aid significantly in determining overall feasibility. Numerous point designs then need to be generated as details of payloads, materials, mission, and manufacturing are determined. To accomplish these numerous designs, transient models are both unnecessary and time intensive. A steady state model that uses appropriate design inputs to generate system-level descriptive parameters can be very flexible and fast. Just such a steady state model has been developed and has been used during both the MABS 2001 Mars balloon study and the Ultra Long Duration Balloon Project. Using Microsoft Excel's built-in iteration routine, a model was built. Separate sheets were used for performance, structural design, materials, and thermal analysis as well as input and output sheets. As can be seen from figure 1, the model takes basic performance requirements, weight estimates, design parameters, and environmental conditions and generates a system level balloon design. Figure 2 shows a sample output of the model. By changing the inputs and a few of the equations in the model, balloons on earth or other planets can be modeled. There are currently several variations of the model for terrestrial and Mars balloons, as well there are versions of the model that perform crude material design based on strength and weight requirements. To perform trade studies, the Visual Basic language built into Excel was used to create an automated matrix of designs. This trade study module allows a three dimensional trade surface to be generated by using a series of values for any two design variables. Once the fixed and variable inputs are defined, the model automatically steps through the input matrix and fills a spreadsheet with the resulting point designs. The proposed paper will describe the model in detail, including current

  6. A virtual simulator designed for collision prevention in proton therapy

    SciTech Connect

    Jung, Hyunuk; Kum, Oyeon; Han, Youngyih Park, Hee Chul; Kim, Jin Sung; Choi, Doo Ho

    2015-10-15

    Purpose: In proton therapy, collisions between the patient and nozzle potentially occur because of the large nozzle structure and efforts to minimize the air gap. Thus, software was developed to predict such collisions between the nozzle and patient using treatment virtual simulation. Methods: Three-dimensional (3D) modeling of a gantry inner-floor, nozzle, and robotic-couch was performed using SolidWorks based on the manufacturer’s machine data. To obtain patient body information, a 3D-scanner was utilized right before CT scanning. Using the acquired images, a 3D-image of the patient’s body contour was reconstructed. The accuracy of the image was confirmed against the CT image of a humanoid phantom. The machine components and the virtual patient were combined on the treatment-room coordinate system, resulting in a virtual simulator. The simulator simulated the motion of its components such as rotation and translation of the gantry, nozzle, and couch in real scale. A collision, if any, was examined both in static and dynamic modes. The static mode assessed collisions only at fixed positions of the machine’s components, while the dynamic mode operated any time a component was in motion. A collision was identified if any voxels of two components, e.g., the nozzle and the patient or couch, overlapped when calculating volume locations. The event and collision point were visualized, and collision volumes were reported. Results: All components were successfully assembled, and the motions were accurately controlled. The 3D-shape of the phantom agreed with CT images within a deviation of 2 mm. Collision situations were simulated within minutes, and the results were displayed and reported. Conclusions: The developed software will be useful in improving patient safety and clinical efficiency of proton therapy.

  7. Chaperone-mediated specificity in Ras and Rap signaling.

    PubMed

    Azoulay-Alfaguter, Inbar; Strazza, Marianne; Mor, Adam

    2015-01-01

    Ras and Rap proteins are closely related small guanosine triphosphatase (GTPases) that share similar effector-binding domains but operate in a very different signaling networks; Ras has a dominant role in cell proliferation, while Rap mediates cell adhesion. Ras and Rap proteins are regulated by several shared processes such as post-translational modification, phosphorylation, activation by guanine exchange factors and inhibition by GTPase-activating proteins. Sub-cellular localization and trafficking of these proteins to and from the plasma membrane are additional important regulatory features that impact small GTPases function. Despite its importance, the trafficking mechanisms of Ras and Rap proteins are not completely understood. Chaperone proteins play a critical role in trafficking of GTPases and will be the focus of the discussion in this work. We will review several aspects of chaperone biology focusing on specificity toward particular members of the small GTPase family. Understanding this specificity should provide key insights into drug development targeting individual small GTPases.

  8. Women and the RAS: 100 years of Fellowship

    NASA Astrophysics Data System (ADS)

    Bailey, Mandy

    2016-02-01

    In January 1916, the RAS elected its first women Fellows. Mandy Bailey looks back at the social and scientific circumstances of this step towards equality, introducing a year of articles celebrating the centenary.

  9. Simulations of Inducers at Low-flow Off-design Conditions

    NASA Technical Reports Server (NTRS)

    Hosangadi, Ashvin; Ahuja, Vineet; Ungewitter, Ronald J.

    2005-01-01

    Background on thermal effects on cavitation and numerical framework. Validation of numerical model for cryogens in CRUNCH CFD(R). Comparison with subscale test data hord (1973). Simulations of liquid hydrogen inducer at various flow coefficients. 120% of design, Design, and 80% of Design flow rate. Detailed comparison of flow profiles. Sensitivity of backflow to turbulent viscosity noted. Conclusion.

  10. Design evolution of a telerobotic servicer through neutral buoyancy simulation

    NASA Technical Reports Server (NTRS)

    Akin, David L.; Howard, Russell D.; Smith, Jennifer A.; Graves, Joseph

    1992-01-01

    This paper briefly recounts the history of telerobotic vehicles in the Space Systems Laboratory. Based on this overview, the design of two vehicles are examined in depth, and directly compared. The Beam Assembly Teleoperator was the first true telerobot designed be the Space Systems Laboratory, and has been used extensively for six years. Ranger is the newest telerobot of the SSL, and is currently under development for operational testing in the summer of 1992. The primary focus of this paper is to compare and contrast the design details of these two telerobots, and to examine in some detail the evolution of design knowledge on some telerobots gained over the years of neutral buoyancy testing in the SSL.

  11. A framework-based approach to designing simulation-augmented surgical education and training programs.

    PubMed

    Cristancho, Sayra M; Moussa, Fuad; Dubrowski, Adam

    2011-09-01

    The goal of simulation-based medical education and training is to help trainees acquire and refine the technical and cognitive skills necessary to perform clinical procedures. When designers incorporate simulation into programs, their efforts should be in line with training needs, rather than technology. Designers of simulation-augmented surgical training programs, however, face particular problems related to identifying a framework that guides the curricular design activity to fulfill the particular requirements of such training programs. These problems include the lack of (1) an objective identification of training needs, (2) a systematic design methodology to match training objectives with simulation resources, (3) structured assessments of performance, and (4) a research-centered view to evaluate and validate systematically the educational effectiveness of the program. In this report, we present a process called "Aim - FineTune - FollowThrough" to enable the connection of the identified problems to solutions, using frameworks from psychology, motor learning, education and experimental design.

  12. Clinical simulation as a boundary object in design of health IT-systems.

    PubMed

    Rasmussen, Stine Loft; Jensen, Sanne; Lyng, Karen Marie

    2013-01-01

    Healthcare organizations are very complex, holding numerous stakeholders with various approaches and goals towards the design of health IT-systems. Some of these differences may be approached by applying the concept of boundary objects in a participatory IT-design process. Traditionally clinical simulation provides the opportunity to evaluate the design and the usage of clinical IT-systems without endangering the patients and interrupting clinical work. In this paper we present how clinical simulation additionally holds the potential to function as a boundary object in the design process. The case points out that clinical simulation provides an opportunity for discussions and mutual learning among the various stakeholders involved in design of standardized electronic clinical documentation templates. The paper presents and discusses the use of clinical simulation in the translation, transfer and transformation of knowledge between various stakeholders in a large healthcare organization.

  13. Design of the IPIRG-2 simulated seismic forcing function

    SciTech Connect

    Olson, R.; Scott, P.; Wilkowski, G.

    1996-02-01

    A series of pipe system experiments was conducted in IPIRG-2 that used a realistic seismic forcing function. Because the seismic forcing function was more complex than the single-frequency increasing-amplitude sinusoidal forcing function used in the IPIRG-1 pipe system experiments, considerable effort went into designing the function. This report documents the design process for the seismic forcing function used in the IPIRG-2 pipe system experiments.

  14. Simulation and design of high precision unit processes via numerical methods

    NASA Astrophysics Data System (ADS)

    Stafford, Roger

    1988-08-01

    SDRC has developed new computer codes specifically tailored for precise and fist simulations of manufacturing processes. Critical aspects of unit processes involve nonlinear transient heat transfer coupled with slow creeping flow. Finite element methods are chosen. Numerical algorithms are adopted which are specifically suited to the problem. Key elements of these simulations are outlined. SDRC has integrated unit process simulations with CAD/CAM design systems, analysis graphics systems, automated inspection, and data base. An example will illustrate data flow, simulation results, and how engineers are using these tools to design new processes for large complex parts.

  15. Targeting N-RAS as a Therapeutic Approach for Melanoma

    DTIC Science & Technology

    2013-10-01

    with activation of N-RAS would make a significant impact on the way melanoma is treated. 15. SUBJECT TERMS Prostate cancer ; Ras; small molecule...describe the development of new specific PKCδ inhibitory molecules, and then show the results of the testing of these compounds on prostate cancer ...using recombinant PKC isozymes, prior to comparative testing on prostate cancer cell lines. 10 Table 1: Summary PKCδ and PKCα inhibitory

  16. Genetic and Molecular Analysis of Suppressors of Ras Mutations

    DTIC Science & Technology

    1999-10-01

    mediated signal transduction pathway during C. elegans vulval development. Mutations in sur-8 were identified as suppressors of an activated let-60...positively regulates an RTK-Ras-MAP kinase signaling cascade during Caenorhabditis elegans vulval induction. Although reduction of sur-6 PP2A-B function...Protein Phosphatase 2A (PP2A) and also positively regulates an RTK-Ras-MAP kinase signaling cascade during Caenorhabditis elegans vulval induction

  17. Ras Homolog Enriched in Brain (Rheb) Enhances Apoptotic Signaling*

    PubMed Central

    Karassek, Sascha; Berghaus, Carsten; Schwarten, Melanie; Goemans, Christoph G.; Ohse, Nadine; Kock, Gerd; Jockers, Katharina; Neumann, Sebastian; Gottfried, Sebastian; Herrmann, Christian; Heumann, Rolf; Stoll, Raphael

    2010-01-01

    Rheb is a homolog of Ras GTPase that regulates cell growth, proliferation, and regeneration via mammalian target of rapamycin (mTOR). Because of the well established potential of activated Ras to promote survival, we sought to investigate the ability of Rheb signaling to phenocopy Ras. We found that overexpression of lipid-anchored Rheb enhanced the apoptotic effects induced by UV light, TNFα, or tunicamycin in an mTOR complex 1 (mTORC1)-dependent manner. Knocking down endogenous Rheb or applying rapamycin led to partial protection, identifying Rheb as a mediator of cell death. Ras and c-Raf kinase opposed the apoptotic effects induced by UV light or TNFα but did not prevent Rheb-mediated apoptosis. To gain structural insight into the signaling mechanisms, we determined the structure of Rheb-GDP by NMR. The complex adopts the typical canonical fold of RasGTPases and displays the characteristic GDP-dependent picosecond to nanosecond backbone dynamics of the switch I and switch II regions. NMR revealed Ras effector-like binding of activated Rheb to the c-Raf-Ras-binding domain (RBD), but the affinity was 1000-fold lower than the Ras/RBD interaction, suggesting a lack of functional interaction. shRNA-mediated knockdown of apoptosis signal-regulating kinase 1 (ASK-1) strongly reduced UV or TNFα-induced apoptosis and suppressed enhancement by Rheb overexpression. In conclusion, Rheb-mTOR activation not only promotes normal cell growth but also enhances apoptosis in response to diverse toxic stimuli via an ASK-1-mediated mechanism. Pharmacological regulation of the Rheb/mTORC1 pathway using rapamycin should take the presence of cellular stress into consideration, as this may have clinical implications. PMID:20685651

  18. High Sensitivity MEMS Strain Sensor: Design and Simulation

    PubMed Central

    Mohammed, Ahmed A. S.; Moussa, Walied A.; Lou, Edmond

    2008-01-01

    In this article, we report on the new design of a miniaturized strain microsensor. The proposed sensor utilizes the piezoresistive properties of doped single crystal silicon. Employing the Micro Electro Mechanical Systems (MEMS) technology, high sensor sensitivities and resolutions have been achieved. The current sensor design employs different levels of signal amplifications. These amplifications include geometric, material and electronic levels. The sensor and the electronic circuits can be integrated on a single chip, and packaged as a small functional unit. The sensor converts input strain to resistance change, which can be transformed to bridge imbalance voltage. An analog output that demonstrates high sensitivity (0.03mV/με), high absolute resolution (1με) and low power consumption (100μA) with a maximum range of ±4000με has been reported. These performance characteristics have been achieved with high signal stability over a wide temperature range (±50°C), which introduces the proposed MEMS strain sensor as a strong candidate for wireless strain sensing applications under harsh environmental conditions. Moreover, this sensor has been designed, verified and can be easily modified to measure other values such as force, torque…etc. In this work, the sensor design is achieved using Finite Element Method (FEM) with the application of the piezoresistivity theory. This design process and the microfabrication process flow to prototype the design have been presented. PMID:27879841

  19. Advanced Information Technology in Simulation Based Life Cycle Design

    NASA Technical Reports Server (NTRS)

    Renaud, John E.

    2003-01-01

    In this research a Collaborative Optimization (CO) approach for multidisciplinary systems design is used to develop a decision based design framework for non-deterministic optimization. To date CO strategies have been developed for use in application to deterministic systems design problems. In this research the decision based design (DBD) framework proposed by Hazelrigg is modified for use in a collaborative optimization framework. The Hazelrigg framework as originally proposed provides a single level optimization strategy that combines engineering decisions with business decisions in a single level optimization. By transforming this framework for use in collaborative optimization one can decompose the business and engineering decision making processes. In the new multilevel framework of Decision Based Collaborative Optimization (DBCO) the business decisions are made at the system level. These business decisions result in a set of engineering performance targets that disciplinary engineering design teams seek to satisfy as part of subspace optimizations. The Decision Based Collaborative Optimization framework more accurately models the existing relationship between business and engineering in multidisciplinary systems design.

  20. Constraining Particle Variation in Lunar Regolith for Simulant Design

    NASA Technical Reports Server (NTRS)

    Schrader, Christian M.; Rickman, Doug; Stoeser, Douglas; Hoelzer, Hans

    2008-01-01

    Simulants are used by the lunar engineering community to develop and test technologies for In Situ Resource Utilization (ISRU), excavation and drilling, and for mitigation of hazards to machinery and human health. Working with the United States Geological Survey (USGS), other NASA centers, private industry and academia, Marshall Space Flight Center (MSFC) is leading NASA s lunar regolith simulant program. There are two main efforts: simulant production and simulant evaluation. This work requires a highly detailed understanding of regolith particle type, size, and shape distribution, and of bulk density. The project has developed Figure of Merit (FoM) algorithms to quantitatively compare these characteristics between two materials. The FoM can be used to compare two lunar regolith samples, regolith to simulant, or two parcels of simulant. In work presented here, we use the FoM algorithm to examine the variance of particle type in Apollo 16 highlands regolith core and surface samples. For this analysis we have used internally consistent particle type data for the 90-150 m fraction of Apollo core 64001/64002 from station 4, core 60009/60010 from station 10, and surface samples from various Apollo 16 stations. We calculate mean modal compositions for each core and for the group of surface samples and quantitatively compare samples of each group to its mean as a measurement of within-group variance; we also calculate an FoM for every sample against the mean composition of 64001/64002. This gives variation with depth at two locations and between Apollo 16 stations. Of the tested groups, core 60009/60010 has the highest internal variance with an average FoM score of 0.76 and core 64001/64002 has the lowest with an average FoM of 0.92. The surface samples have a low but intermediate internal variance with an average FoM of 0.79. FoM s calculated against the 64001/64002 mean reference composition range from 0.79-0.97 for 64001/64002, from 0.41-0.91 for 60009/60010, and from

  1. Comparative Roles of Overexpressed and Mutated H- and K-ras in Mammary Carcinogenesis.

    DTIC Science & Technology

    1996-08-01

    initiated tumors ) using the mismatch amplification mutation assay ( MAMA ) developed by Cha et al (5). Our initial studies indicated that there was...fold more potent at inducing mammary tumors than the activated K-ras gene. Yet, the K-ras oncogene was still effective at mammary carcinoma induction...transgenic rats harboring a H-ras gene (HrHr transgenics) or K-ras gene (HrKr transgenics) controlled by H-ras gene regulatory elements. Mammary tumor

  2. Simulation And Design Of A Reflection Magnet For The EAST Neutral Beam System

    SciTech Connect

    Zhen Liangli; Dong Huchun

    2011-09-26

    The simulation and design of a reflection magnet to be installed in the Experimental Advanced Superconducting Tokamak (EAST) neutral beam injection system are reported. A parametric design and simulation for the reflection magnet was carried out. For a deuterium beam with 42 cm as the bending radius, the intensity of reflection magnet field is about 1376 Gs at the energy of 80 keV. In order to determine position of the ion dump and the surface power load, a particle simulation with Monte Carlo was developed to study ion trajectories. In addition, the louver design is introduced.

  3. Simulations and design of microfabricated interdigitated electrodes for use in a gold nanoparticle enhanced biosensor.

    PubMed

    Hermansen, Peter; MacKay, Scott; Wishart, David; Jie Chen

    2016-08-01

    Microfabricated interdigitated electrode chips have been designed for use in a unique gold-nanoparticle based biosensor system. The use of these electrodes will allow for simple, accurate, inexpensive, and portable biosensing, with potential applications in diagnostics, medical research, and environmental testing. To determine the optimal design for these electrodes, finite element analysis simulations were carried out using COMSOL Multiphysics software. The results of these simulations determined some of the optimal design parameters for microfabricating interdigitated electrodes as well as predicting the effects of different electrode materials. Finally, based on the results of these simulations two different kinds of interdigitated electrode chips were made using photolithography.

  4. Basic architecture and design of store simulation construction set

    SciTech Connect

    Sehgal, A.; Volz, R.

    1999-02-01

    Regular practice these days has been to build a simulation prototype of an actual entity needing to be built prior to building an actual physical model. Computer simulation and modeling techniques aid greatly in this practice. In a critical system such as a fissile material storage system, various issues such as safety, security, and automation of handling processes can be assessed through virtual environments, thereby creating a safe atmosphere for research versus hands-on experimentation and possible worker exposures. By utilizing the approaches presented in this study, the concepts can be applied for rapid virtual prototyping of other systems, as this type of system is not limited to the storage of nuclear materials.

  5. Quantification of spatiotemporal patterns of Ras isoform expression during development

    PubMed Central

    Newlaczyl, Anna U.; Coulson, Judy M.; Prior, Ian A.

    2017-01-01

    Ras proteins are important signalling hubs frequently dysregulated in cancer and in a group of developmental disorders called Rasopathies. Three Ras genes encode four proteins that differentially contribute to these phenotypes. Using quantitative real-time PCR (qRT-PCR) we have measured the gene expression profiles of each of the Ras isoforms in a panel of mouse tissues derived from a full developmental time course spanning embryogenesis through to adulthood. In most tissues and developmental stages we observe a relative contribution of KRas4B > > NRas ≥ KRas4A > HRas to total Ras expression with KRas4B typically representing 60–99% of all Ras transcripts. KRas4A is the most dynamically regulated Ras isoform with significant up-regulation of expression observed pre-term in stomach, intestine, kidney and heart. The expression patterns assist interpretation of the essential role of KRas in development and the preponderance of KRas mutations in cancer. PMID:28117393

  6. Ras and Rap signaling in synaptic plasticity and mental disorders.

    PubMed

    Stornetta, Ruth L; Zhu, J Julius

    2011-02-01

    The Ras family GTPases (Ras, Rap1, and Rap2) and their downstream mitogen-activated protein kinases (ERK, JNK, and p38MAPK) and PI3K signaling cascades control various physiological processes. In neuronal cells, recent studies have shown that these parallel cascades signal distinct forms of AMPA-sensitive glutamate receptor trafficking during experience-dependent synaptic plasticity and adaptive behavior. Interestingly, both hypo- and hyperactivation of Ras/ Rap signaling impair the capacity of synaptic plasticity, underscoring the importance of a "happy-medium" dynamic regulation of the signaling. Moreover, accumulating reports have linked various genetic defects that either up- or down-regulate Ras/Rap signaling with several mental disorders associated with learning disability (e.g., Alzheimer's disease, Angelman syndrome, autism, cardio-facio-cutaneous syndrome, Coffin-Lowry syndrome, Costello syndrome, Cowden and Bannayan-Riley-Ruvalcaba syndromes, fragile X syndrome, neurofibromatosis type 1, Noonan syndrome, schizophrenia, tuberous sclerosis, and X-linked mental retardation), highlighting the necessity of happy-medium dynamic regulation of Ras/Rap signaling in learning behavior. Thus, the recent advances in understanding of neuronal Ras/Rap signaling provide a useful guide for developing novel treatments for mental diseases.

  7. Cooperative loss of RAS feedback regulation drives myeloid leukemognesis

    PubMed Central

    Zhao, Zhen; Chen, Chi-Chao; Rillahan, Cory D.; Shen, Ronglai; Kitzing, Thomas; McNerney, Megan E.; Diaz-Flores, Ernesto; Zuber, Johannes; Shannon, Kevin; Le Beau, Michelle M.; Spector, Mona S.; Kogan, Scott C.; Lowe, Scott W.

    2015-01-01

    RAS network activation is common in human cancers and, in acute myeloid leukemia (AML), achieved mainly through gain-of-function mutations in KRAS, NRAS, or the FLT3 receptor tyrosine kinase1. In mice, we show that premalignant myeloid cells harboring a KrasG12D allele retain low Ras signaling owing to a negative feedback involving Spry4 that prevents transformation. In humans, SPRY4 is located on chromosome 5q, a region affected by large heterozygous deletion that are associated with an aggressive disease in which gain-of-function RAS pathway mutations are rare. These 5q deletions often co-occur with chromosome 17 alterations involving deletion of NF1 - another RAS negative regulator - and TP53. Accordingly, combined suppression of Spry4, Nf1 and Trp53 produces high Ras signaling and drives AML in mice. Therefore, SPRY4 is a 5q tumor suppressor whose disruption contributes to a lethal AML subtype that appears to acquire RAS pathway activation through loss of negative regulators. PMID:25822087

  8. PRG3 induces Ras-dependent oncogenic cooperation in gliomas

    PubMed Central

    Yakubov, Eduard; Chen, Daishi; Broggini, Thomas; Sehm, Tina; Majernik, Gökce Hatipoglu; Hock, Stefan W.; Schwarz, Marc; Engelhorn, Tobias; Doerfler, Arnd; Buchfelder, Michael; Eyupoglu, Ilker Y.; Savaskan, Nicolai E.

    2016-01-01

    Malignant gliomas are one of the most devastating cancers in humans. One characteristic hallmark of malignant gliomas is their cellular heterogeneity with frequent genetic lesions and disturbed gene expression levels conferring selective growth advantage. Here, we report on the neuronal-associated growth promoting gene PRG3 executing oncogenic cooperation in gliomas. We have identified perturbed PRG3 levels in human malignant brain tumors displaying either elevated or down-regulated PRG3 levels compared to non-transformed specimens. Further, imbalanced PRG3 levels in gliomas foster Ras-driven oncogenic amplification with increased proliferation and cell migration although angiogenesis was unaffected. Hence, PRG3 interacts with RasGEF1 (RasGRF1/CDC25), undergoes Ras-induced challenges, whereas deletion of the C-terminal domain of PRG3 (PRG3ΔCT) inhibits Ras. Moreover PRG3 silencing makes gliomas resistant to Ras inhibition. In vivo disequilibrated PRG3 gliomas show aggravated proliferation, invasion, and deteriorate clinical outcome. Thus, our data show that the interference with PRG3 homeostasis amplifies oncogenic properties and foster the malignancy potential in gliomas. PMID:27058420

  9. [Mouse models of K-ras-initiated oncogenesis].

    PubMed

    Barrière, C; Marjou, F El; Louvard, D; Robine, S

    2009-12-01

    Activating mutations of the oncogene K-ras are found in one third of all human cancers. Much of our knowledge on K-ras signal transduction and its influence on tumor initiation and progression come from in vitro studies with cell lines. However, mouse models of human cancer allow a much more faithful recapitulation of the human disease, and the in vivo perspective is crucial for our understanding of neoplasia. In recent years, several new murine models for K-ras-induced tumorigenesis have been described. They allow new insights into the specific role that oncogenic K-ras proteins play in different solid tumors, and they permit the molecular dissection of the pathways that are initiated by somatic mutations in subsets of cells. Key advances have been made by the use of tissue-specific and inducible control of expression, which is achieved by the Cre/loxP technology or the tetracycline system. From these sophisticated models, a common picture emerges: the effects of K-ras on tumor initiation depend strongly on the cellular context, and different tissues vary in their susceptibility to K-ras transformation.

  10. Ras, Raf, and MAP kinase in melanoma.

    PubMed

    Solus, Jason F; Kraft, Stefan

    2013-07-01

    A growing understanding of the biology and molecular mechanisms of melanoma has led to the identification of a number of driver mutations for this aggressive tumor. The most common mutations affect signaling of the Ras/Raf/MAPK (mitogen-activated protein kinase) pathway. This review will focus on mutations in genes encoding proteins that play a role in the MAPK pathway and that have been implicated in melanoma biology, such as BRAF, NRAS, and MEK (MAPK kinase), and detail the current understanding of their role in melanoma progression from a molecular biology perspective. Furthermore, this review will also consider some additional mutations in genes such as KIT, GNAQ, and GNA11, which can be seen in certain subtypes of melanoma and whose gene products interact with the MAPK pathway. In addition, the association of these molecular changes with clinical and classical histopathologic characteristics of melanoma will be outlined and their role in diagnosis of melanocytic lesions discussed. Finally, a basic overview of the current targeted therapy landscape, as far as relevant to the pathologist, will be provided.

  11. Design Notebook for Naval Air Defense Simulation (NADS). Revision.

    DTIC Science & Technology

    1986-10-09

    from sources outside the game ; and definition of other "rules of the game " which have been left to the discretion of the model user. The second...sources outside the game ; and equipment failures.** Transactions generated to simulate events of these types are based on the input scenario...Salvo Fighter 316 Enroute to Station 117 Deferred Launch Order 3.7 Go On Cap 318 CV Aircraft Status Report 319 Enroute to CAP 320 BINGO (Return to Base

  12. Annotated Bibliography of Vessel Simulation Studies Used in Channel Design.

    DTIC Science & Technology

    1986-07-01

    No. 24-8012-01. Kings Point, NY: National Maritime Research Center. The Nueces County Navigation District No. I proposes to widen and deepen the...Simulation Evaluation of Proposed Port Arun LNG Terminal Expansion . CAORP Report No. 75-7808-01. Kings Point, NY: National Maritime Research Center...transportation flow patterns, economic conditiohs and trends, navigation conditions, soil and bathymetric conditions, hydrographic and meteorological

  13. Design and Implementation of the Interactive Communications Simulator (ICS).

    DTIC Science & Technology

    1981-04-01

    graphics and includes a Digital Equip- ment Corporation (DEC) PDP-11/40 acting as host to a Floating Point Systems, Inc., AP-120B floating-point array...ability to configure and execute a simulation program independent of the actual baud rate. This facilitates user inter- action with the comunications ...34Characterization of Randomly Time-Variant Linear Channels", IEEE Trans. Comun . Syst.;Vol. CS-i, pp. 360-393, Dec. 1963. 6. R. S. Kennedy, Fading Dispersive

  14. Hermes CX-7: Air transport system design simulation

    NASA Technical Reports Server (NTRS)

    Amer, Brian; Barter, John; Colucci, Jay; Foley, Caryn; Kockler, James; Rapp, David; Zeiger, Matthew

    1992-01-01

    The Hermes CX-7 has been designed to service the overnight parcel package delivery needs of the cities of Aeroworld as determined in the G-Dome Enterprises market survey. The design optimization centers on the prime goal of servicing the needs of these cities as efficiently and profitably as possible. The greatest factors which affect the design of an aircraft for the mission outlined in the Request for Proposal are cost, construction feasibility and effectiveness of the design. Other influencing factors are given by the constraints of the market, including a maximum takeoff and landing distance of 60 feet, storage capability in a container of size 5 ft. x 3 ft. x 2 ft., cargo packages of 2 inch and 4 inch cubes, and ability to turn with a radius no larger than 60 feet. Safety considerations such as flying at or below Mach one (30 ft/s) and controllability and maintainability of the aircraft must also be designed into the aircraft. Another influential factor is the efficiency of the aircraft which involves optimizations and tradeoffs of such factors as weight, lifting surface sizing, structural redundancy, and material costs.

  15. Yeast screens for inhibitors of Ras-Raf interaction and characterization of MCP inhibitors of Ras-Raf interaction.

    PubMed

    Khazak, Vladimir; Kato-Stankiewicz, Juran; Tamanoi, Fuyu; Golemis, Erica A

    2006-01-01

    Because of the central role of Ras in cancer cell signaling, there has been considerable interest in developing small molecule inhibitors of the Ras signaling pathways as potential chemotherapeutic agents. This chapter describes the use of a two-hybrid approach to identify the MCP compounds, small molecules that disrupt the interaction between Ras and its effector Raf. We first outline the reagent development and selection/counter selection methods required to successfully apply a two-hybrid approach to isolation of MCP compounds. Separately, we describe the collateral benefits of this screening approach in yielding novel antifungal compounds. We then discuss secondary physiological validation approaches to confirm the MCP compounds specifically target Ras-Raf signaling. Finally, we develop a decision tree for subsequent preclinical characterization and optimization of this class of pathway-targeted reagent.

  16. Continuous Coaxial Nozzle Design for LMD based on Numerical Simulation

    NASA Astrophysics Data System (ADS)

    Arrizubieta, J. I.; Tabernero, I.; Ruiz, J. Exequiel; Lamikiz, A.; Martinez, S.; Ukar, E.

    The LMD technology is becoming one of the most important emerging manufacturing technologies in the modern industry, due to its benefits when building-up geometries, repairing damaged parts or the creation of coatings to improve material properties and behaviour. One of the most relevant parameters in LMD process is the efficiency of the trapped powder into the melt pool, since metallic material powders use to be very expensive. With the aim of improving the ratio between the trapped powder in the deposited area and the total injected powder, the work presents a new methodology for continuous coaxial nozzle design for the LMD process based on a complete CFD model. The numerical model can predict particle flow, speed, powder concentration, etc. and design can be optimized using this input data. The model has been validated and then, it has been used for the design of two different nozzles: one discrete and one continuous coaxial nozzle.

  17. Architectural design and simulation of a virtual memory

    NASA Technical Reports Server (NTRS)

    Kwok, G.; Chu, Y.

    1971-01-01

    Virtual memory is an imaginary main memory with a very large capacity which the programmer has at his disposal. It greatly contributes to the solution of the dynamic storage allocation problem. The architectural design of a virtual memory is presented which implements by hardware the idea of queuing and scheduling the page requests to a paging drum in such a way that the access of the paging drum is increased many times. With the design, an increase of up to 16 times in page transfer rate is achievable when the virtual memory is heavily loaded. This in turn makes feasible a great increase in the system throughput.

  18. Design and validation of inert homemade explosive simulants for X-ray-based inspection systems

    NASA Astrophysics Data System (ADS)

    Faust, Anthony A.; Nacson, Sabatino; Koffler, Bruce; Bourbeau, Éric; Gagne, Louis; Laing, Robin; Anderson, C. J.

    2014-05-01

    Transport Canada (TC), the Canadian Armed Forces, and other public security agencies have an interest in the assessment of the potential utility of advanced explosives detection technologies to aid in the detection and interdiction of commercial grade, military grade, and homemade or improvised explosives (HME or IE). The availability of suitable, non-hazardous, non-toxic, explosive simulants is of concern when assessing the potential utility of such detection systems. Lack of simulants limits the training opportunities, and ultimately the detection probability, of security personnel using these systems. While simulants for commercial and military grade explosives are available for a wide variety of detection technologies, the design and production of materials to simulate improvised explosives has not kept pace with this emerging threat. Funded by TC and the Canadian Safety and Security Program, Defence Research and Development Canada (DRDC), Visiontec Systems, and Optosecurity engaged in an effort to develop inert, non-toxic Xray interrogation simulants for IE materials such as ammonium nitrate, potassium chlorate, and triacetone triperoxide. These simulants were designed to mimic key X-ray interrogation-relevant material properties of real improvised explosives, principally their bulk density and effective atomic number. Different forms of the simulants were produced and tested, simulating the different explosive threat formulations that could be encountered by front line security workers. These simulants comply with safety and stability requirements, and as best as possible match form and homogeneity. This paper outlines the research program, simulant design, and validation.

  19. Association of yeast adenylyl cyclase with cyclase-associated protein CAP forms a second Ras-binding site which mediates its Ras-dependent activation.

    PubMed

    Shima, F; Okada, T; Kido, M; Sen, H; Tanaka, Y; Tamada, M; Hu, C D; Yamawaki-Kataoka, Y; Kariya, K; Kataoka, T

    2000-01-01

    Posttranslational modification, in particular farnesylation, of Ras is crucial for activation of Saccharomyces cerevisiae adenylyl cyclase (CYR1). Based on the previous observation that association of CYR1 with cyclase-associated protein (CAP) is essential for its activation by posttranslationally modified Ras, we postulated that the associated CAP might contribute to the formation of a Ras-binding site of CYR1, which mediates CYR1 activation, other than the primary Ras-binding site, the leucine-rich repeat domain. Here, we observed a posttranslational modification-dependent association of Ras with a complex between CAP and CYR1 C-terminal region. When CAP mutants defective in Ras signaling but retaining the CYR1-binding activity were isolated by screening of a pool of randomly mutagenized CAP, CYR1 complexed with two of the obtained three mutants failed to be activated efficiently by modified Ras and exhibited a severely impaired ability to bind Ras, providing a genetic evidence for the importance of the physical association with Ras at the second Ras-binding site. On the other hand, CYR1, complexed with the other CAP mutant, failed to be activated by Ras but exhibited a greatly enhanced binding to Ras. Conversely, a Ras mutant E31K, which exhibits a greatly enhanced binding to the CYR1-CAP complex, failed to activate CYR1 efficiently. Thus, the strength of interaction at the second Ras-binding site appears to be a critical determinant of CYR1 regulation by Ras: too-weak and too-strong interactions are both detrimental to CYR1 activation. These results, taken together with those obtained with mammalian Raf, suggest the importance of the second Ras-binding site in effector regulation.

  20. Characterization of c-Ki-ras and N-ras oncogenes in aflatoxin B sub 1 -induced rat liver tumors

    SciTech Connect

    McMahon, G.; Davis, E.F.; Huber, L.J.; Kim, Youngsoo; Wogan, G.N. )

    1990-02-01

    c-Ki-ras and N-ras oncogenes have been characterized in aflatoxin B{sub 1}-induced hepatocellular carcinomas. Detection of different protooncogene and oncogene sequences and estimation of their frequency distribution were accomplished by polymerase chain reaction, cloning, and plaque screening methods. Two c-Ki-ras oncogene sequences were identified in DNA from liver tumors that contained nucleotide changes absent in DNA from livers of untreated control rats. Sequence changes involving G{center dot}C to T{center dot}A or G{center dot}C to A{center dot}T nucleotide substitutions in codon 12 were scored in three of eight tumor-bearing animals. Distributions of c-Ki-ras sequences in tumors and normal liver DNA indicated that the observed nucleotide changes were consistent with those expected to result from direct mutagenesis of the germ-line protooncogene by aflatoxin B{sub 1}. N-ras oncogene sequences were identified in DNA from two of eight tumors. Three N-ras gene regions were identified, one of which was shown to be associated with an oncogene containing a putative activating amino acid residing at codon 13. All three N-ras sequences, including the region detected in N-ras oncogenes, were present at similar frequencies in DNA samples from control livers as well as liver tumors. The presence of a potential germ-line oncogene may be related to the sensitivity of the Fischer rat strain to liver carcinogenesis by aflatoxin B{sub 1} and other chemical carcinogens.

  1. LiteVis: Integrated Visualization for Simulation-Based Decision Support in Lighting Design.

    PubMed

    Sorger, Johannes; Ortner, Thomas; Luksch, Christian; Schwärzler, Michael; Gröller, Eduard; Piringer, Harald

    2016-01-01

    State-of-the-art lighting design is based on physically accurate lighting simulations of scenes such as offices. The simulation results support lighting designers in the creation of lighting configurations, which must meet contradicting customer objectives regarding quality and price while conforming to industry standards. However, current tools for lighting design impede rapid feedback cycles. On the one side, they decouple analysis and simulation specification. On the other side, they lack capabilities for a detailed comparison of multiple configurations. The primary contribution of this paper is a design study of LiteVis, a system for efficient decision support in lighting design. LiteVis tightly integrates global illumination-based lighting simulation, a spatial representation of the scene, and non-spatial visualizations of parameters and result indicators. This enables an efficient iterative cycle of simulation parametrization and analysis. Specifically, a novel visualization supports decision making by ranking simulated lighting configurations with regard to a weight-based prioritization of objectives that considers both spatial and non-spatial characteristics. In the spatial domain, novel concepts support a detailed comparison of illumination scenarios. We demonstrate LiteVis using a real-world use case and report qualitative feedback of lighting designers. This feedback indicates that LiteVis successfully supports lighting designers to achieve key tasks more efficiently and with greater certainty.

  2. Click-Chemistry Based High Throughput Screening Platform for Modulators of Ras Palmitoylation

    PubMed Central

    Ganesan, Lakshmi; Shieh, Peyton; Bertozzi, Carolyn R.; Levental, Ilya

    2017-01-01

    Palmitoylation is a widespread, reversible lipid modification that has been implicated in regulating a variety of cellular processes. Approximately one thousand proteins are annotated as being palmitoylated, and for some of these, including several oncogenes of the Ras and Src families, palmitoylation is indispensable for protein function. Despite this wealth of disease-relevant targets, there are currently few effective pharmacological tools to interfere with protein palmitoylation. One reason for this lack of development is the dearth of assays to efficiently screen for small molecular inhibitors of palmitoylation. To address this shortcoming, we have developed a robust, high-throughput compatible, click chemistry-based approach to identify small molecules that interfere with the palmitoylation of Ras, a high value therapeutic target that is mutated in up to a third of human cancers. This assay design shows excellent performance in 384-well format and is sensitive to known, non-specific palmitoylation inhibitors. Further, we demonstrate an ideal counter-screening strategy, which relies on a target peptide from an unrelated protein, the Src-family kinase Fyn. The screening approach described here provides an integrated platform to identify specific modulators of palmitoylated proteins, demonstrated here for Ras and Fyn, but potentially applicable to pharmaceutical targets involved in a variety of human diseases. PMID:28112226

  3. Design, development and testing of an ambient lighting simulator for external illumination of a transport simulator cockpit

    NASA Technical Reports Server (NTRS)

    Batson, Vernon M.; Gupton, Lawrence E.

    1990-01-01

    Researchers at the NASA-Langley Research Center several years ago began to examine concepts for a facility which could simulate the full range of lighting conditions encountered in flight. The purpose of this facility was to evaluate advanced technology display devices in a cockpit environment. The Aircraft Cockpit Ambient Lighting Simulation System (ACALSS) has been developed to meet that need. The ACALSS surrounds a wide-body part-task simulator cockpit, the Advanced Display Evaluation Cockpit, and interfaces with a VAX 11/780 computer, which is used to host both a math model of a modern transport aircraft and a solar motion model (which animates a servoed sun simulator). Several concepts were evaluated and an efficient design using an ellipsoid reflector and Fresnel luminaires was selected for implementation.

  4. Advanced Simulation Technology to Design Etching Process on CMOS Devices

    NASA Astrophysics Data System (ADS)

    Kuboi, Nobuyuki

    2015-09-01

    Prediction and control of plasma-induced damage is needed to mass-produce high performance CMOS devices. In particular, side-wall (SW) etching with low damage is a key process for the next generation of MOSFETs and FinFETs. To predict and control the damage, we have developed a SiN etching simulation technique for CHxFy/Ar/O2 plasma processes using a three-dimensional (3D) voxel model. This model includes new concepts for the gas transportation in the pattern, detailed surface reactions on the SiN reactive layer divided into several thin slabs and C-F polymer layer dependent on the H/N ratio, and use of ``smart voxels''. We successfully predicted the etching properties such as the etch rate, polymer layer thickness, and selectivity for Si, SiO2, and SiN films along with process variations and demonstrated the 3D damage distribution time-dependently during SW etching on MOSFETs and FinFETs. We confirmed that a large amount of Si damage was caused in the source/drain region with the passage of time in spite of the existing SiO2 layer of 15 nm in the over etch step and the Si fin having been directly damaged by a large amount of high energy H during the removal step of the parasitic fin spacer leading to Si fin damage to a depth of 14 to 18 nm. By analyzing the results of these simulations and our previous simulations, we found that it is important to carefully control the dose of high energy H, incident energy of H, polymer layer thickness, and over-etch time considering the effects of the pattern structure, chamber-wall condition, and wafer open area ratio. In collaboration with Masanaga Fukasawa and Tetsuya Tatsumi, Sony Corporation. We thank Mr. T. Shigetoshi and Mr. T. Kinoshita of Sony Corporation for their assistance with the experiments.

  5. Simulation and simplified design studies of photovoltaic systems

    SciTech Connect

    Evans, D.L.; Facinelli, W.A.; Koehler, L.P.

    1980-09-01

    Results of TRNSYS simulations of photovoltaic systems with electrical storage are described. Studies of the sensitivity of system performance, in terms of the fraction of the electrical load supplied by the solar energy system, to variables such as array size, battery size, location, time of year, and load shape are reported. An accurate simplified method for predicting array output of max-power photovoltaic systems is presented. A second simplified method, which estimates the overall performance of max-power systems, is developed. Finally, a preliminary technique for predicting clamped-voltage system performance is discussed.

  6. Regulation of an H-ras-related transcript by parathyroid hormone in rat osteosarcoma cells

    NASA Technical Reports Server (NTRS)

    Scott, D. K.; Weaver, W. R.; Clohisy, J. C.; Brakenhoff, K. D.; Kahn, A. J.; Partridge, N. C.

    1992-01-01

    The rat osteosarcoma cell line UMR 106-01 is a commonly used model system for the study of osteoblast function. However, it also expresses a phenotype characteristic of transformed cells. To test whether the latter could be accounted for by aberrant oncogene expression, we probed Northern blots of UMR and other osteoblastic cells with a panel of oncogene probes. These blots, when probed with a cDNA specific for v-H-ras, revealed a 7.0-kilobase (kb) H-ras-related transcript (designated HRRT) in UMR 106-01 cells that was not expressed in other osteoblastic cells. Osteoblast-enriched calvarial cells expressed the typical 1.1-kb H-ras mRNA, which was absent in UMR cells. Additionally, Western blots of lysates of UMR cells documented the presence of three proteins immunologically related to H-rasp21. To determine whether HRRT represented a recombinant retrovirus product, Northern blots were probed with a cDNA specific for the highly conserved gag-pol region of Moloney murine leukemia virus. These blots showed parallel cross-reactivity with an apparently identical transcript of 7.0 kb. The 7.0-kb transcripts detected by both v-H-ras and gag-pol probes declined to the same extent after treatment with concentrations of PTH known to inhibit proliferation of these cells. PTH regulated the abundance of HRRT in a time- and dose-dependent manner, with greatest repression of the transcript after 8 h of treatment with 10(-8) M PTH. The decrease in HRRT could not be completely accounted for by changes in transcriptional activity, as determined by nuclear run-on assays.(ABSTRACT TRUNCATED AT 250 WORDS).

  7. Design and implementation of interactive strap-down inertial navigation simulation system for UAV

    NASA Astrophysics Data System (ADS)

    Cheng, Chuan-qi; Cheng, Xiang; Hao, Xiang-yang; Zhao, Man-dan

    2016-01-01

    Strap-down inertial navigation system (SINS) is widely used in military field, to facilitate the study of SINS algorithms and various coupled navigation algorithms, a simulation system of SINS is designed. Based on modular design, with good portability and expansibility, the system consists of four independent modules: analysis module of motion state, trajectory simulator, IMU simulation module and SINS calculation module. With graphical interface, the system can control every motion state of the trajectory, which is convenient to generate various trajectories efficiently. Using rotation vector attitude algorithm to process simulation data, experiment results show that the attitude, velocity and position error is consistent with the theoretical value, which verifies the rationality of the simulation model and the availability of the simulation system.

  8. The Numerical Propulsion System Simulation: A Multidisciplinary Design System for Aerospace Vehicles

    NASA Technical Reports Server (NTRS)

    Lytle, John K.

    1999-01-01

    Advances in computational technology and in physics-based modeling are making large scale, detailed simulations of complex systems possible within the design environment. For example, the integration of computing, communications, and aerodynamics has reduced the time required to analyze ma or propulsion system components from days and weeks to minutes and hours. This breakthrough has enabled the detailed simulation of major propulsion system components to become a routine part of design process and to provide the designer with critical information about the components early in the design process. This paper describes the development of the Numerical Propulsion System Simulation (NPSS), a multidisciplinary system of analysis tools that is focussed on extending the simulation capability from components to the full system. This will provide the product developer with a "virtual wind tunnel" that will reduce the number of hardware builds and tests required during the development of advanced aerospace propulsion systems.

  9. Design and simulation of satellite attitude control system based on Simulink and VR

    NASA Astrophysics Data System (ADS)

    Zhang, Yang; Gan, Qingbo; Kang, Jingshu

    2016-01-01

    In order to research satellite attitude control system design and visual simulation, the simulation framework of satellite dynamics and attitude control using Simulink were established. The design of satellite earth-oriented control system based on quaternion feedback was completed. The 3D scene based on VR was created and models in the scene were driven by simulation data of Simulink. By coordinate transformation. successful observing the scene in inertial coordinate system, orbit coordinate system and body coordinate system. The result shows that application of simulation method of Simulink combined with VR in the design of satellite attitude control system field, has the advantages of high confidence level, hard real-time property, multi-perspective and multi-coordinate system observing the scene, and improves the comprehensibility and accuracy of the design.

  10. SKA weak lensing- II. Simulated performance and survey design considerations

    NASA Astrophysics Data System (ADS)

    Bonaldi, Anna; Harrison, Ian; Camera, Stefano; Brown, Michael L.

    2016-12-01

    We construct a pipeline for simulating weak lensing cosmology surveys with the Square Kilometre Array (SKA), taking as inputs telescope sensitivity curves; correlated source flux, size and redshift distributions; a simple ionospheric model; source redshift and ellipticity measurement errors. We then use this simulation pipeline to optimize a 2-yr weak lensing survey performed with the first deployment of the SKA (SKA1). Our assessments are based on the total signal to noise of the recovered shear power spectra, a metric that we find to correlate very well with a standard dark energy figure of merit. We first consider the choice of frequency band, trading off increases in number counts at lower frequencies against poorer resolution; our analysis strongly prefers the higher frequency Band 2 (950-1760 MHz) channel of the SKA-MID telescope to the lower frequency Band 1 (350-1050 MHz). Best results would be obtained by allowing the centre of Band 2 to shift towards lower frequency, around 1.1 GHz. We then move on to consider survey size, finding that an area of 5000 deg2 is optimal for most SKA1 instrumental configurations. Finally, we forecast the performance of a weak lensing survey with the second deployment of the SKA. The increased survey size (3π steradian) and sensitivity improves both the signal to noise and the dark energy metrics by two orders of magnitude.

  11. Unified Simulation and Analysis Framework for Deep Space Navigation Design

    NASA Technical Reports Server (NTRS)

    Anzalone, Evan; Chuang, Jason; Olsen, Carrie

    2013-01-01

    As the technology that enables advanced deep space autonomous navigation continues to develop and the requirements for such capability continues to grow, there is a clear need for a modular expandable simulation framework. This tool's purpose is to address multiple measurement and information sources in order to capture system capability. This is needed to analyze the capability of competing navigation systems as well as to develop system requirements, in order to determine its effect on the sizing of the integrated vehicle. The development for such a framework is built upon Model-Based Systems Engineering techniques to capture the architecture of the navigation system and possible state measurements and observations to feed into the simulation implementation structure. These models also allow a common environment for the capture of an increasingly complex operational architecture, involving multiple spacecraft, ground stations, and communication networks. In order to address these architectural developments, a framework of agent-based modules is implemented to capture the independent operations of individual spacecraft as well as the network interactions amongst spacecraft. This paper describes the development of this framework, and the modeling processes used to capture a deep space navigation system. Additionally, a sample implementation describing a concept of network-based navigation utilizing digitally transmitted data packets is described in detail. This developed package shows the capability of the modeling framework, including its modularity, analysis capabilities, and its unification back to the overall system requirements and definition.

  12. Designing and Implementing Nervous System Simulations on LEGO Robots

    PubMed Central

    Blustein, Daniel; Rosenthal, Nikolai; Ayers, Joseph

    2013-01-01

    We present a method to use the commercially available LEGO Mindstorms NXT robotics platform to test systems level neuroscience hypotheses. The first step of the method is to develop a nervous system simulation of specific reflexive behaviors of an appropriate model organism; here we use the American Lobster. Exteroceptive reflexes mediated by decussating (crossing) neural connections can explain an animal's taxis towards or away from a stimulus as described by Braitenberg and are particularly well suited for investigation using the NXT platform.1 The nervous system simulation is programmed using LabVIEW software on the LEGO Mindstorms platform. Once the nervous system is tuned properly, behavioral experiments are run on the robot and on the animal under identical environmental conditions. By controlling the sensory milieu experienced by the specimens, differences in behavioral outputs can be observed. These differences may point to specific deficiencies in the nervous system model and serve to inform the iteration of the model for the particular behavior under study. This method allows for the experimental manipulation of electronic nervous systems and serves as a way to explore neuroscience hypotheses specifically regarding the neurophysiological basis of simple innate reflexive behaviors. The LEGO Mindstorms NXT kit provides an affordable and efficient platform on which to test preliminary biomimetic robot control schemes. The approach is also well suited for the high school classroom to serve as the foundation for a hands-on inquiry-based biorobotics curriculum. PMID:23728477

  13. Sphericity estimation bias for repeated measures designs in simulation studies.

    PubMed

    Bono, Roser; Arnau, Jaume; Blanca, María J; Alarcón, Rafael

    2016-12-01

    In this study, we explored the accuracy of sphericity estimation and analyzed how the sphericity of covariance matrices may be affected when the latter are derived from simulated data. We analyzed the consequences that normal and nonnormal data generated from an unstructured population covariance matrix-with low (ε = .57) and high (ε = .75) sphericity-can have on the sphericity of the matrix that is fitted to these data. To this end, data were generated for four types of distributions (normal, slightly skewed, moderately skewed, and severely skewed or log-normal), four sample sizes (very small, small, medium, and large), and four values of the within-subjects factor (K = 4, 6, 8, and 10). Normal data were generated using the Cholesky decomposition of the correlation matrix, whereas the Vale-Maurelli method was used to generate nonnormal data. The results indicate the extent to which sphericity is altered by recalculating the covariance matrix on the basis of simulated data. We concluded that bias is greater with spherical covariance matrices, nonnormal distributions, and small sample sizes, and that it increases in line with the value of K. An interaction was also observed between sample size and K: With very small samples, the observed bias was greater as the value of K increased.

  14. Simple Simulations: A Guide to the Design and Use of Simulation/Games in Teaching Political Science. Instructional Resource Monograph No. 3.

    ERIC Educational Resources Information Center

    Walcott, Charles; Walcott, Anne

    Designed to improve undergraduate political science instruction, this monograph provides a guide to the design and use of simulations and games in the political science classroom. The book is divided into five chapters that stress the legitimate need and use of simulations and games. Chapter one outlines the background of simulations and games and…

  15. Designing a Virtual Olympic Games Framework by Using Simulation in Web 2.0 Technologies

    ERIC Educational Resources Information Center

    Stoilescu, Dorian

    2013-01-01

    Instructional simulation had major difficulties in the past for offering limited possibilities in practice and learning. This article proposes a link between instructional simulation and Web 2.0 technologies. More exactly, I present the design of the Virtual Olympic Games Framework (VOGF), as a significant demonstration of how interactivity in…

  16. Computer simulation and optimal designing of energy-saving technologies of the induction heating of metals

    NASA Astrophysics Data System (ADS)

    Demidovich, V. B.

    2012-12-01

    Advanced energy-saving technologies of induction heating of metals are discussed. The importance of the joint simulation of electromagnetic and temperature fields on induction heating is demonstrated. The package of specialized programs for simulating not only induction heating devices, but also technologies that employ industrial heating has been developed. An intimate connection between optimal design and control of induction heaters is shown.

  17. Design and Application of Interactive Simulations in Problem-Solving in University-Level Physics Education

    ERIC Educational Resources Information Center

    Ceberio, Mikel; Almudí, José Manuel; Franco, Ángel

    2016-01-01

    In recent years, interactive computer simulations have been progressively integrated in the teaching of the sciences and have contributed significant improvements in the teaching-learning process. Practicing problem-solving is a key factor in science and engineering education. The aim of this study was to design simulation-based problem-solving…

  18. Design, testing, and simulation of microscale gas chromatography columns

    SciTech Connect

    Hudson, M.L.; Kottenstette, R.; Matzke, C.M.; Frye-Mason, G.C.; Shollenberger, K.A.; Adkins, D.R.; Wong, C.C.

    1998-08-01

    A microscale gas chromatography column is one component in a microscale chemistry laboratory for detecting chemical agents. Several columns were fabricated using the Bosch etch process which allows deep, high aspect ratio channels of rectangular cross-section. A design tool, based on analytical models, was developed to evaluate the effects of operating conditions and column specifications on separation resolution and time. The effects of slip flow, channel configuration, and cross-sectional shape were included to evaluate the differences between conventional round, straight columns and the microscale rectangular, spiral columns. Experimental data were obtained and compared with the predicted flowrates and theoretical number of plates. The design tool was then employed to select more optimum channel dimensions and operating conditions for high resolution separations.

  19. Design of an Indoor Sonic Boom Simulator at NASA Langley Research Center

    NASA Technical Reports Server (NTRS)

    Klos, Jacob; Sullivan, Brenda M.; Shepherd, Kevin P.

    2008-01-01

    Construction of a simulator to recreate the soundscape inside residential buildings exposed to sonic booms is scheduled to start during the summer of 2008 at NASA Langley Research Center. The new facility should be complete by the end of the year. The design of the simulator allows independent control of several factors that create the indoor soundscape. Variables that will be isolated include such factors as boom duration, overpressure, rise time, spectral shape, level of rattle, level of squeak, source of rattle and squeak, level of vibration and source of vibration. Test subjects inside the simulator will be asked to judge the simulated soundscape, which will represent realistic indoor boom exposure. Ultimately, this simulator will be used to develop a functional relationship between human response and the sound characteristics creating the indoor soundscape. A conceptual design has been developed by NASA personnel, and is currently being vetted through small-scale risk reduction tests that are being performed in-house. The purpose of this document is to introduce the conceptual design, identify how the indoor response will be simulated, briefly outline some of the risk reduction tests that have been completed to vet the design, and discuss the impact of these tests on the simulator design.

  20. Rainwater catchment system design using simulated future climate data

    NASA Astrophysics Data System (ADS)

    Wallace, Corey D.; Bailey, Ryan T.; Arabi, Mazdak

    2015-10-01

    Rainwater harvesting techniques are used worldwide to augment potable water supply, provide water for small-scale irrigation practices, increase rainwater-use efficiency for sustained crop growth in arid and semi-arid regions, decrease urban stormwater flow volumes, and in general to relieve dependency on urban water resources cycles. A number of methods have been established in recent years to estimate reliability of rainwater catchment systems (RWCS) and thereby properly size the components (roof catchment area, storage tank size) of the system for a given climatic region. These methods typically use historical or stochastically-generated rainfall patterns to quantify system performance and optimally size the system, with the latter accounting for possible rainfall scenarios based on statistical relationships of historical rainfall patterns. To design RWCS systems that can sustainably meet water demand under future climate conditions, this paper introduces a method that employs climatic data from general circulation models (GCMs) to develop a suite of catchment area vs. storage size design curves that capture uncertainty in future climate scenarios. Monthly rainfall data for the 2010-2050 time period is statistically downscaled to daily values using a Markov chain algorithm, with results used only from GCMs that yield rainfall patterns that are statistically consistent with historical rainfall patterns. The process is demonstrated through application to two climatic regions of the Federated States of Micronesia (FSM) in the western Pacific, wherein the majority of the population relies on rainwater harvesting for potable water supply. Through the use of design curves, communities can provide household RWCS that achieve a certain degree of storage reliability. The method described herein can be applied generally to any geographic region. It can be used to first, assess the future performance of existing household systems; and second, to design or modify systems

  1. Design and Simulation of Electron Gun for a Multibeam Klystron

    NASA Astrophysics Data System (ADS)

    Nehra, A. K.; Gupta, R. K.; Sharma, S. M.; Panda, P. C.; Choyal, Y.; Sharma, R. K.

    2012-11-01

    This paper represents the design of multi-beam (sixty-beam) electron gun and focusing system for high power, compact klystron. The beam voltage is 4 kV with a total beam current of 513 (8.55 × 60) mA which is equally divided among sixty-beam. Each beam has a perveance of 0.033 μP making a total gun perveance of 2.02 μP corresponding to a total beam power of more than 2 kW. The cathode radius is7 mm and individual emitter radius is 0.2 mm having current density 6.7 A/cm2. The design has been accomplished using OPERA 3D code. All beamlets have individual anode as well as BFE and a common focusing system. Potential difference between cathode and anode is 4 kV. A magnetic field of 1200 Gauss is applied along the beam axis. A major challenge for the development of multi-beam klystron is design and technology for the focusing of off-axis beamlets because off-axis beams are at various azimuths.

  2. Nanosatellite optical downlink experiment: design, simulation, and prototyping

    NASA Astrophysics Data System (ADS)

    Clements, Emily; Aniceto, Raichelle; Barnes, Derek; Caplan, David; Clark, James; Portillo, Iñigo del; Haughwout, Christian; Khatsenko, Maxim; Kingsbury, Ryan; Lee, Myron; Morgan, Rachel; Twichell, Jonathan; Riesing, Kathleen; Yoon, Hyosang; Ziegler, Caleb; Cahoy, Kerri

    2016-11-01

    The nanosatellite optical downlink experiment (NODE) implements a free-space optical communications (lasercom) capability on a CubeSat platform that can support low earth orbit (LEO) to ground downlink rates>10 Mbps. A primary goal of NODE is to leverage commercially available technologies to provide a scalable and cost-effective alternative to radio-frequency-based communications. The NODE transmitter uses a 200-mW 1550-nm master-oscillator power-amplifier design using power-efficient M-ary pulse position modulation. To facilitate pointing the 0.12-deg downlink beam, NODE augments spacecraft body pointing with a microelectromechanical fast steering mirror (FSM) and uses an 850-nm uplink beacon to an onboard CCD camera. The 30-cm aperture ground telescope uses an infrared camera and FSM for tracking to an avalanche photodiode detector-based receiver. Here, we describe our approach to transition prototype transmitter and receiver designs to a full end-to-end CubeSat-scale system. This includes link budget refinement, drive electronics miniaturization, packaging reduction, improvements to pointing and attitude estimation, implementation of modulation, coding, and interleaving, and ground station receiver design. We capture trades and technology development needs and outline plans for integrated system ground testing.

  3. Optimal seat suspension design based on minimum "simulated subjective response".

    PubMed

    Wan, Y; Schimmels, J M

    1997-11-01

    This work addresses a method for improving vertical whole body vibration isolation through optimal seat suspension design. The primary thrusts of this investigation are: (1) the development of a simple model that captures the essential dynamics of a seated human exposed to vertical vibration, (2) the selection and evaluation of several standards for assessing human sensitivity to vertical vibration, and (3) the determination of the seat suspension parameters that minimize these standards to yield optimal vibration isolation. Results show that the optimal seat and cushion damping coefficients depend very much on the selection of the vibration sensitivity standard and on the lower bound of the stiffnesses used in the constrained optimization procedure. In all cases, however, the optimal seat damping obtained here is significantly larger (by than a factor of 10) than that obtained using existing seat suspension design methods or from previous optimal suspension studies. This research also indicates that the existing means of assessing vibration in suspension design (ISO 7096) requires modification.

  4. Simulation verification techniques study: Simulation self test hardware design and techniques report

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The final results are presented of the hardware verification task. The basic objectives of the various subtasks are reviewed along with the ground rules under which the overall task was conducted and which impacted the approach taken in deriving techniques for hardware self test. The results of the first subtask and the definition of simulation hardware are presented. The hardware definition is based primarily on a brief review of the simulator configurations anticipated for the shuttle training program. The results of the survey of current self test techniques are presented. The data sources that were considered in the search for current techniques are reviewed, and results of the survey are presented in terms of the specific types of tests that are of interest for training simulator applications. Specifically, these types of tests are readiness tests, fault isolation tests and incipient fault detection techniques. The most applicable techniques were structured into software flows that are then referenced in discussions of techniques for specific subsystems.

  5. Neutron micro-beam design simulation by Monte Carlo

    NASA Astrophysics Data System (ADS)

    Pazirandeh, Ali; Taheri, Ali

    2007-09-01

    Over the last two decades neutron micro-beam has increasingly been developing in view of various applications in molecular activation analysis, micro-radiography in space and aviation and in radiation induced bystander effects in bio-cells. In this paper the structure and simulation of a neutron micro-beam is presented. The collimator for micro-beam is made of a polyethylene cylinder with a small hole along the centerline of the cylinder. The hole is filled with very thin needles in triangular or rectangular arrangement. The neutron source was reactor neutrons or a spontaneous Cf-252 neutron source falling on the top side of the collimator. The outgoing thermal and epithermal neutron fluxes were calculated.

  6. Cost performance satellite design using queueing theory. [via digital simulation

    NASA Technical Reports Server (NTRS)

    Hein, G. F.

    1975-01-01

    A modified Poisson arrival, infinite server queuing model is used to determine the effects of limiting the number of broadcast channels (C) of a direct broadcast satellite used for public service purposes (remote health care, education, etc.). The model is based on the reproductive property of the Poisson distribution. A difference equation has been developed to describe the change in the Poisson parameter. When all initially delayed arrivals reenter the system a (C plus 1) order polynomial must be solved to determine the effective value of the Poisson parameter. When less than 100% of the arrivals reenter the system the effective value must be determined by solving a transcendental equation. The model was used to determine the minimum number of channels required for a disaster warning satellite without degradation in performance. Results predicted by the queuing model were compared with the results of digital simulation.

  7. Surgical simulation using virtual reality technology: design, implementation, and implications.

    PubMed

    Merril, J R; Preminger, G M; Babayan, R; Roy, R T; Merril, G L

    1994-01-01

    Atremendous demand exists for enhancing the way by which physicians learn new invasive procedures. Appropriate education in new medical and surgical procedures is often outpaced by the desire of physicians to incorporate a procedure in their practice. Computerized surgical simulations have the potential for improving surgical morbidy and mortality. Studies have shown that, for a wide range of diagnostic and therapeutic procedures, doctors doing their first few to several dozen cases are much more likely to make a greater number of errors. This phenomenon has been referred to as 'the learning curve'. Adequate proctoring of learners by experienced surgeons is cumbersome, as there are few surgeons experienced to proctor their colleagues. It is difficult for physicians, particularly those in rural areas, to travel to larger medical centers for training. The requirement also places a burden on experts who could become overwhelmed with proctoring requests, in addition to leaving their clinical responsibilities.

  8. Simulating Water Markets to Help Design Water Rights Regimes

    NASA Astrophysics Data System (ADS)

    Harou, J. J.; Erfani, T.; Huskova, I.; Binions, O.

    2012-12-01

    In many catchments in England no further licenses are available from the Environmental regulator that provides them. The possibility of trading water between license holders has been recognized as a potentially effective and economically efficient strategy to mitigate increasing scarcity. Although trading licenses has been possible since several years, it very rarely happens (roughly 50 trades in 8 years). Several barriers to trade exist including lack of sufficient and prolonged scarcity, license-holder unwillingness to risk future renewal, likelihood license will be downgraded during a trade, duration of time required for approving a trade, etc. Regulators seek to make policy changes so that their inability to grant new licenses will not harm the local and national economy. What policy changes will most cost-effectively increase trading and allow it to effectively reduce the economic cost of scarcity events? A screening tool that could help evaluate problems and advantages of different regulatory solutions, and that could serve to test, assuming transaction costs can be quantified, their effect on trading under specific conditions would be useful. We propose such a water market simulator that predicts economically efficient pair-wise trade (between willing buyers and sellers) and represents the interaction of trades with natural hydrological flows, engineered infrastructure and a particular regulatory regime. The model emulates license-holders' willingness to engage in short-term trade transactions. In their initial form different 'agents' (license holders) are represented using an economic benefit function of water use which is supplemented by rules to represent behavioral or other characteristics of realistic system behavior. A case study based on the river Ouse basin (UK) is made to test the model. The model simulates the catchment weekly over several years considering reservoirs and pair-wise specific transaction costs. Several regulatory policies are tested

  9. The Significance of Ras Activity in Pancreatic Cancer Initiation

    PubMed Central

    Logsdon, Craig D.; Lu, Weiqin

    2016-01-01

    The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Rasmt alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Rasmt. Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Rasmt is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Rasmt activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Rasmt. Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Rasmt activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease. PMID:26929740

  10. Design of a high-speed digital processing element for parallel simulation

    NASA Technical Reports Server (NTRS)

    Milner, E. J.; Cwynar, D. S.

    1983-01-01

    A prototype of a custom designed computer to be used as a processing element in a multiprocessor based jet engine simulator is described. The purpose of the custom design was to give the computer the speed and versatility required to simulate a jet engine in real time. Real time simulations are needed for closed loop testing of digital electronic engine controls. The prototype computer has a microcycle time of 133 nanoseconds. This speed was achieved by: prefetching the next instruction while the current one is executing, transporting data using high speed data busses, and using state of the art components such as a very large scale integration (VLSI) multiplier. Included are discussions of processing element requirements, design philosophy, the architecture of the custom designed processing element, the comprehensive instruction set, the diagnostic support software, and the development status of the custom design.

  11. Approximate simulation model for analysis and optimization in engineering system design

    NASA Technical Reports Server (NTRS)

    Sobieszczanski-Sobieski, Jaroslaw

    1989-01-01

    Computational support of the engineering design process routinely requires mathematical models of behavior to inform designers of the system response to external stimuli. However, designers also need to know the effect of the changes in design variable values on the system behavior. For large engineering systems, the conventional way of evaluating these effects by repetitive simulation of behavior for perturbed variables is impractical because of excessive cost and inadequate accuracy. An alternative is described based on recently developed system sensitivity analysis that is combined with extrapolation to form a model of design. This design model is complementary to the model of behavior and capable of direct simulation of the effects of design variable changes.

  12. Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis?

    PubMed

    Repasky, Gretchen A; Chenette, Emily J; Der, Channing J

    2004-11-01

    Ras proteins function as signal transducers and are mutationally activated in many human cancers. In 1993, Raf was identified as a key downstream effector of Ras signaling, and it was believed then that the primary function of Ras was simply to facilitate Raf activation. However, the subsequent discovery of other proteins that are effectors of Ras function suggested that oncogenic activities of Ras are mediated by both Raf-dependent and Raf-independent signaling. Further complexity arose with the identification of Ras effectors with putative tumor suppressor, rather than oncogenic, functions. However, the recent identification of B-raf mutations in human cancers has renewed the debate regarding whether Raf activation alone promotes Ras-mediated oncogenesis. In this article, we summarize the current knowledge of the contribution of Ras effectors in Ras-mediated oncogenesis.

  13. Analyzing and designing object-oriented missile simulations with concurrency

    NASA Astrophysics Data System (ADS)

    Randorf, Jeffrey Allen

    2000-11-01

    A software object model for the six degree-of-freedom missile modeling domain is presented. As a precursor, a domain analysis of the missile modeling domain was started, based on the Feature-Oriented Domain Analysis (FODA) technique described by the Software Engineering Institute (SEI). It was subsequently determined the FODA methodology is functionally equivalent to the Object Modeling Technique. The analysis used legacy software documentation and code from the ENDOSIM, KDEC, and TFrames 6-DOF modeling tools, including other technical literature. The SEI Object Connection Architecture (OCA) was the template for designing the object model. Three variants of the OCA were considered---a reference structure, a recursive structure, and a reference structure with augmentation for flight vehicle modeling. The reference OCA design option was chosen for maintaining simplicity while not compromising the expressive power of the OMT model. The missile architecture was then analyzed for potential areas of concurrent computing. It was shown how protected objects could be used for data passing between OCA object managers, allowing concurrent access without changing the OCA reference design intent or structure. The implementation language was the 1995 release of Ada. OCA software components were shown how to be expressed as Ada child packages. While acceleration of several low level and other high operations level are possible on proper hardware, there was a 33% degradation of 4th order Runge-Kutta integrator performance of two simultaneous ordinary differential equations using Ada tasking on a single processor machine. The Defense Department's High Level Architecture was introduced and explained in context with the OCA. It was shown the HLA and OCA were not mutually exclusive architectures, but complimentary. HLA was shown as an interoperability solution, with the OCA as an architectural vehicle for software reuse. Further directions for implementing a 6-DOF missile modeling

  14. Improved Space Charge Modeling for Simulation and Design of Photoinjectors

    SciTech Connect

    Robert H. Jackson, Thuc Bui, John Verboncoeur

    2010-04-19

    Photoinjectors in advanced high-energy accelerators reduce beam energy spreads and enhance undulator photon fluxes. Photoinjector design is difficult because of the substantial differences in time and spatial scales. This Phase I program explored an innovative technique, the local Taylor polynomial (LTP) formulation, for improving finite difference analysis of photoinjectors. This included improved weighting techniques, systematic formula for high order interpolation and electric field computation, and improved handling of space charge. The Phase I program demonstrated that the approach was powerful, accurate, and efficient. It handles space charge gradients better than currently available technology.

  15. Flow simulation and shape optimization for aircraft design

    NASA Astrophysics Data System (ADS)

    Kroll, Norbert; Gauger, Nicolas R.; Brezillon, Joel; Dwight, Richard; Fazzolari, Antonio; Vollmer, Daniel; Becker, Klaus; Barnewitz, Holger; Schulz, Volker; Hazra, Subhendu

    2007-06-01

    Within the framework of the German aerospace research program, the CFD project MEGADESIGN was initiated. The main goal of the project is the development of efficient numerical methods for shape design and optimization. In order to meet the requirements of industrial implementations a co-operative effort has been set up which involves the German aircraft industry, the DLR, several universities and some small enterprises specialized in numerical optimization. This paper outlines the planned activities within MEGADESIGN, the status at the beginning of the project and it presents some early results achieved in the project.

  16. Signal Integration by Lipid-Mediated Spatial Cross Talk between Ras Nanoclusters

    PubMed Central

    Zhou, Yong; Liang, Hong; Rodkey, Travis; Ariotti, Nicholas; Parton, Robert G.

    2014-01-01

    Lipid-anchored Ras GTPases form transient, spatially segregated nanoclusters on the plasma membrane that are essential for high-fidelity signal transmission. The lipid composition of Ras nanoclusters, however, has not previously been investigated. High-resolution spatial mapping shows that different Ras nanoclusters have distinct lipid compositions, indicating that Ras proteins engage in isoform-selective lipid sorting and accounting for different signal outputs from different Ras isoforms. Phosphatidylserine is a common constituent of all Ras nanoclusters but is only an obligate structural component of K-Ras nanoclusters. Segregation of K-Ras and H-Ras into spatially and compositionally distinct lipid assemblies is exquisitely sensitive to plasma membrane phosphatidylserine levels. Phosphatidylserine spatial organization is also modified by Ras nanocluster formation. In consequence, Ras nanoclusters engage in remote lipid-mediated communication, whereby activated H-Ras disrupts the assembly and operation of spatially segregated K-Ras nanoclusters. Computational modeling and experimentation reveal that complex effects of caveolin and cortical actin on Ras nanoclustering are similarly mediated through regulation of phosphatidylserine spatiotemporal dynamics. We conclude that phosphatidylserine maintains the lateral segregation of diverse lipid-based assemblies on the plasma membrane and that lateral connectivity between spatially remote lipid assemblies offers important previously unexplored opportunities for signal integration and signal processing. PMID:24366544

  17. Differentiated functions of Ras1 and Ras2 proteins in regulating the germination, growth, conidiation, multi-stress tolerance and virulence of Beauveria bassiana.

    PubMed

    Xie, Xue-Qin; Guan, Yi; Ying, Sheng-Hua; Feng, Ming-Guang

    2013-02-01

    Ras1 and Ras2 are two distinct Ras GTPases in Beauveria bassiana, an entomopathogenic fungus whose biocontrol potential against insect pests depends largely on virulence and multi-stress tolerance. The functions of both proteins were characterized for the first time by constructing dominant-active (GTP-bound) Ras1(G19V) and dominant-negative (GDP-bound) Ras1(D126A) and integrating them and normal Ras1 into wild type and ΔRas2 for a series of phenotypic and transcriptional analyses. The resultant mutants showed gradient changes of multiple phenotypes but little difference in conidial thermotolerance. Expression of Ras1(D126A) caused vigorous hyphal growth, severely defective conidiation, and increased tolerances to oxidation, cell wall disturbance, fungicide and UV-A/UV-B irradiations, but affected slightly germination, osmosensitivity and virulence. These phenotypes were antagonistically altered by mRas1(G19V) expressed in either wild type or ΔRas2, which was severely defective in conidial germination and hyphal growth and displayed intermediate changes in other mentioned phenotypes between paired mutants expressing Ras1(G19V) or Ras1(D126A) in wild type and ΔRas2. Their growth, UV tolerance or virulence was significantly correlated with cellular response to oxidation or cell wall disturbance. Transcriptional changes of 35 downstream effector genes involved in conidiation and multi-stress responses also related to most of the phenotypic changes among the mutants. Our findings highlight that Ras1 and Ras2 regulate differentially or antagonistically the germination, growth, conidiation, multi-stress tolerance and virulence of B. bassiana, thereby exerting profound effects on the fungal biocontrol potential.

  18. The role of simulation in the design of a neural network chip

    NASA Technical Reports Server (NTRS)

    Desai, Utpal; Roppel, Thaddeus A.; Padgett, Mary L.

    1993-01-01

    An iterative, simulation-based design procedure for a neural network chip is introduced. For this design procedure, the goal is to produce a chip layout for a neural network in which the weights are determined by transistor gate width-to-length ratios. In a given iteration, the current layout is simulated using the circuit simulator SPICE, and layout adjustments are made based on conventional gradient-decent methods. After the iteration converges, the chip is fabricated. Monte Carlo analysis is used to predict the effect of statistical fabrication process variations on the overall performance of the neural network chip.

  19. A Novel Simulation Technician Laboratory Design: Results of a Survey-Based Study

    PubMed Central

    Hughes, Patrick G; Friedl, Ed; Ortiz Figueroa, Fabiana; Cepeda Brito, Jose R; Frey, Jennifer; Birmingham, Lauren E; Atkinson, Steven Scott

    2016-01-01

    Objective  The purpose of this study was to elicit feedback from simulation technicians prior to developing the first simulation technician-specific simulation laboratory in Akron, OH. Background Simulation technicians serve a vital role in simulation centers within hospitals/health centers around the world. The first simulation technician degree program in the US has been approved in Akron, OH. To satisfy the requirements of this program and to meet the needs of this special audience of learners, a customized simulation lab is essential.  Method A web-based survey was circulated to simulation technicians prior to completion of the lab for the new program. The survey consisted of questions aimed at identifying structural and functional design elements of a novel simulation center for the training of simulation technicians. Quantitative methods were utilized to analyze data. Results Over 90% of technicians (n=65) think that a lab designed explicitly for the training of technicians is novel and beneficial. Approximately 75% of respondents think that the space provided appropriate audiovisual (AV) infrastructure and space to evaluate the ability of technicians to be independent. The respondents think that the lab needed more storage space, visualization space for a large number of students, and more space in the technical/repair area. Conclusions  A space designed for the training of simulation technicians was considered to be beneficial. This laboratory requires distinct space for technical repair, adequate bench space for the maintenance and repair of simulators, an appropriate AV infrastructure, and space to evaluate the ability of technicians to be independent. PMID:27096134

  20. Simulation/optimization modeling for robust pumping strategy design.

    PubMed

    Kalwij, Ineke M; Peralta, Richard C

    2006-01-01

    A new simulation/optimization modeling approach is presented for addressing uncertain knowledge of aquifer parameters. The Robustness Enhancing Optimizer (REO) couples genetic algorithm and tabu search as optimizers and incorporates aquifer parameter sensitivity analysis to guide multiple-realization optimization. The REO maximizes strategy robustness for a pumping strategy that is optimal for a primary objective function (OF), such as cost. The more robust a strategy, the more likely it is to achieve management goals in the field, even if the physical system differs from the model. The REO is applied to trinitrotoluene and Royal Demolition Explosive plumes at Umatilla Chemical Depot in Oregon to develop robust least cost strategies. The REO efficiently develops robust pumping strategies while maintaining the optimal value of the primary OF-differing from the common situation in which a primary OF value degrades as strategy reliability increases. The REO is especially valuable where data to develop realistic probability density functions (PDFs) or statistically derived realizations are unavailable. Because they require much less field data, REO-developed strategies might not achieve as high a mathematical reliability as strategies developed using many realizations based upon real aquifer parameter PDFs. REO-developed strategies might or might not yield a better OF value in the field.

  1. DSC: software tool for simulation-based design of control strategies applied to wastewater treatment plants.

    PubMed

    Ruano, M V; Ribes, J; Seco, A; Ferrer, J

    2011-01-01

    This paper presents a computer tool called DSC (Simulation based Controllers Design) that enables an easy design of control systems and strategies applied to wastewater treatment plants. Although the control systems are developed and evaluated by simulation, this tool aims to facilitate the direct implementation of the designed control system to the PC of the full-scale WWTP (wastewater treatment plants). The designed control system can be programmed in a dedicated control application and can be connected to either the simulation software or the SCADA of the plant. To this end, the developed DSC incorporates an OPC server (OLE for process control) which facilitates an open-standard communication protocol for different industrial process applications. The potential capabilities of the DSC tool are illustrated through the example of a full-scale application. An aeration control system applied to a nutrient removing WWTP was designed, tuned and evaluated with the DSC tool before its implementation in the full scale plant. The control parameters obtained by simulation were suitable for the full scale plant with only few modifications to improve the control performance. With the DSC tool, the control systems performance can be easily evaluated by simulation. Once developed and tuned by simulation, the control systems can be directly applied to the full-scale WWTP.

  2. A Simulation-Based LED Design Project in Photonics Instruction Based on Industry-University Collaboration

    ERIC Educational Resources Information Center

    Chang, S. -H.; Chen, M. -L.; Kuo, Y. -K.; Shen, Y. -C.

    2011-01-01

    In response to the growing industrial demand for light-emitting diode (LED) design professionals, based on industry-university collaboration in Taiwan, this paper develops a novel instructional approach: a simulation-based learning course with peer assessment to develop students' professional skills in LED design as required by industry as well as…

  3. Fractal Simulations of African Design in Pre-College Computing Education

    ERIC Educational Resources Information Center

    Eglash, Ron; Krishnamoorthy, Mukkai; Sanchez, Jason; Woodbridge, Andrew

    2011-01-01

    This article describes the use of fractal simulations of African design in a high school computing class. Fractal patterns--repetitions of shape at multiple scales--are a common feature in many aspects of African design. In African architecture we often see circular houses grouped in circular complexes, or rectangular houses in rectangular…

  4. Assessing the Effectiveness of a Computer Simulation for Teaching Ecological Experimental Design

    ERIC Educational Resources Information Center

    Stafford, Richard; Goodenough, Anne E.; Davies, Mark S.

    2010-01-01

    Designing manipulative ecological experiments is a complex and time-consuming process that is problematic to teach in traditional undergraduate classes. This study investigates the effectiveness of using a computer simulation--the Virtual Rocky Shore (VRS)--to facilitate rapid, student-centred learning of experimental design. We gave a series of…

  5. A Framework for the Design of Computer-Assisted Simulation Training for Complex Police Situations

    ERIC Educational Resources Information Center

    Söderström, Tor; Åström, Jan; Anderson, Greg; Bowles, Ron

    2014-01-01

    Purpose: The purpose of this paper is to report progress concerning the design of a computer-assisted simulation training (CAST) platform for developing decision-making skills in police students. The overarching aim is to outline a theoretical framework for the design of CAST to facilitate police students' development of search techniques in…

  6. Using R to Simulate Permutation Distributions for Some Elementary Experimental Designs

    ERIC Educational Resources Information Center

    Eudey, T. Lynn; Kerr, Joshua D.; Trumbo, Bruce E.

    2010-01-01

    Null distributions of permutation tests for two-sample, paired, and block designs are simulated using the R statistical programming language. For each design and type of data, permutation tests are compared with standard normal-theory and nonparametric tests. These examples (often using real data) provide for classroom discussion use of metrics…

  7. The Interior Design Simulator. Courseware Evaluation for Vocational and Technical Education.

    ERIC Educational Resources Information Center

    Worts, Nancy; And Others

    This courseware evaluation rates the Interior Design Simulator program developed by Orange Juice Software Systems. (This program--not contained in this document--allows the user to design a room of any shape with maximum dimensions of 14 x 26 feet.) Part A describes the program in terms of subject area (furniture arrangement) and hardware…

  8. Design, simulation, fabrication, and characterization of MEMS vibration energy harvesters

    NASA Astrophysics Data System (ADS)

    Oxaal, John

    Energy harvesting from ambient sources has been a longtime goal for microsystem engineers. The energy available from ambient sources is substantial and could be used to power wireless micro devices, making them fully autonomous. Self-powered wireless sensors could have many applications in for autonomous monitoring of residential, commercial, industrial, geological, or biological environments. Ambient vibrations are of particular interest for energy harvesting as they are ubiquitous and have ample kinetic energy. In this work a MEMS device for vibration energy harvesting using a variable capacitor structure is presented. The nonlinear electromechanical dynamics of a gap-closing type structure is experimentally studied. Important experimental considerations such as the importance of reducing off-axis vibration during testing, characterization methods, dust contamination, and the effect of grounding on parasitic capacitance are discussed. A comprehensive physics based model is developed and validated with two different microfabricated devices. To achieve maximal power, devices with high aspect ratio electrodes and a novel two-level stopper system are designed and fabricated. The maximum achieved power from the MEMS device when driven by sinusoidal vibrations was 3.38 muW. Vibrations from HVAC air ducts, which have a primary frequency of 65 Hz and amplitude of 155 mgrms, are targeted as the vibration source and devices are designed for maximal power harvesting potential at those conditions. Harvesting from the air ducts, the devices reached 118 nW of power. When normalized to the operating conditions, the best figure of merit of the devices tested was an order of magnitude above state-of-the-art of the devices (1.24E-6).

  9. Interim Service ISDN Satellite (ISIS) simulator development for advanced satellite designs and experiments

    NASA Technical Reports Server (NTRS)

    Pepin, Gerard R.

    1992-01-01

    The simulation development associated with the network models of both the Interim Service Integrated Services Digital Network (ISDN) Satellite (ISIS) and the Full Service ISDN Satellite (FSIS) architectures is documented. The ISIS Network Model design represents satellite systems like the Advanced Communications Technology Satellite (ACTS) orbiting switch. The FSIS architecture, the ultimate aim of this element of the Satellite Communications Applications Research (SCAR) Program, moves all control and switching functions on-board the next generation ISDN communications satellite. The technical and operational parameters for the advanced ISDN communications satellite design will be obtained from the simulation of ISIS and FSIS engineering software models for their major subsystems. Discrete event simulation experiments will be performed with these models using various traffic scenarios, design parameters, and operational procedures. The data from these simulations will be used to determine the engineering parameters for the advanced ISDN communications satellite.

  10. The simulative calculation and optimum design for FOA, the purge gas sweeping system

    NASA Astrophysics Data System (ADS)

    Wang, Liquan; Jing, Yukun; Feng, Bing; Li, Fuquan; Xiang, Yong; Han, Wei; Wang, Fang

    2016-01-01

    This paper first studies the structure effect law in order to design a reasonable option in theory for the Final Optics Assembly(FOA)' harmonic converter module, involved in the design of the fluid theory, including the basic equations of fluid motion, the form of fluid motion and fluid movement in the small hole. Optimizing the structure need to be applied to the simulation software, which requires the Fluent simulation principle. Then, combined with theoretical knowledge to design the overall structure of the multiplier module, It will apply the simulation software to optimize structural parameters of the board and use control system to realize it for verifying the law obtained by simulation under various conditions whether consistent with the law in actual work of the sweeping system.

  11. Design data package and operating procedures for MSFC solar simulator test facility

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Design and operational data for the solar simulator test facility are reviewed. The primary goal of the facility is to evaluate the performance capacibility and worst case failure modes of collectors, which utilize either air or liquid transport media. The facility simulates environmental parameters such as solar radiation intensity, solar spectrum, collimation, uniformity, and solar attitude. The facility also simulates wind conditions of velocity and direction, solar system conditions imposed on the collector, collector fluid inlet temperature, and geometric factors of collector tilt and azimuth angles. Testing the simulator provides collector efficiency data, collector time constant, incident angle modifier data, and stagnation temperature values.

  12. An optimal control approach to the design of moving flight simulators

    NASA Technical Reports Server (NTRS)

    Sivan, R.; Ish-Shalom, J.; Huang, J.-K.

    1982-01-01

    An abstract flight simulator design problem is formulated in the form of an optimal control problem, which is solved for the linear-quadratic-Gaussian special case using a mathematical model of the vestibular organs. The optimization criterion used is the mean-square difference between the physiological outputs of the vestibular organs of the pilot in the aircraft and the pilot in the simulator. The dynamical equations are linearized, and the output signal is modeled as a random process with rational power spectral density. The method described yields the optimal structure of the simulator's motion generator, or 'washout filter'. A two-degree-of-freedom flight simulator design, including single output simulations, is presented.

  13. Pleiotrophin mediates hematopoietic regeneration via activation of RAS.

    PubMed

    Himburg, Heather A; Yan, Xiao; Doan, Phuong L; Quarmyne, Mamle; Micewicz, Eva; McBride, William; Chao, Nelson J; Slamon, Dennis J; Chute, John P

    2014-11-01

    Hematopoietic stem cells (HSCs) are highly susceptible to ionizing radiation-mediated death via induction of ROS, DNA double-strand breaks, and apoptotic pathways. The development of therapeutics capable of mitigating ionizing radiation-induced hematopoietic toxicity could benefit both victims of acute radiation sickness and patients undergoing hematopoietic cell transplantation. Unfortunately, therapies capable of accelerating hematopoietic reconstitution following lethal radiation exposure have remained elusive. Here, we found that systemic administration of pleiotrophin (PTN), a protein that is secreted by BM-derived endothelial cells, substantially increased the survival of mice following radiation exposure and after myeloablative BM transplantation. In both models, PTN increased survival by accelerating the recovery of BM hematopoietic stem and progenitor cells in vivo. PTN treatment promoted HSC regeneration via activation of the RAS pathway in mice that expressed protein tyrosine phosphatase receptor-zeta (PTPRZ), whereas PTN treatment did not induce RAS signaling in PTPRZ-deficient mice, suggesting that PTN-mediated activation of RAS was dependent upon signaling through PTPRZ. PTN strongly inhibited HSC cycling following irradiation, whereas RAS inhibition abrogated PTN-mediated induction of HSC quiescence, blocked PTN-mediated recovery of hematopoietic stem and progenitor cells, and abolished PTN-mediated survival of irradiated mice. These studies demonstrate the therapeutic potential of PTN to improve survival after myeloablation and suggest that PTN-mediated hematopoietic regeneration occurs in a RAS-dependent manner.

  14. Ras regulation of DNA-methylation and cancer

    SciTech Connect

    Patra, Samir Kumar

    2008-04-01

    Genome wide hypomethylation and regional hypermethylation of cancer cells and tissues remain a paradox, though it has received a convincing confirmation that epigenetic switching systems, including DNA-methylation represent a fundamental regulatory mechanism that has an impact on genome maintenance and gene transcription. Methylated cytosine residues of vertebrate DNA are transmitted by clonal inheritance through the strong preference of DNA methyltransferase, DNMT1, for hemimethylated-DNA. Maintenance of methylation patterns is necessary for normal development of mice, and aberrant methylation patterns are associated with many human tumours. DNMT1 interacts with many proteins during cell cycle progression, including PCNA, p53, EZH2 and HP1. Ras family of GTPases promotes cell proliferation by its oncogenic nature, which transmits signals by multiple pathways in both lipid raft dependent and independent fashion. DNA-methylation-mediated repression of DNA-repair protein O6-methylguanine DNA methyltransferase (MGMT) gene and increased rate of K-Ras mutation at codon for amino acids 12 and 13 have been correlated with a secondary role for Ras-effector homologues (RASSFs) in tumourigenesis. Lines of evidence suggest that DNA-methylation associated repression of tumour suppressors and apoptotic genes and ceaseless proliferation of tumour cells are regulated in part by Ras-signaling. Control of Ras GTPase signaling might reduce the aberrant methylation and accordingly may reduce the risk of cancer development.

  15. Pleiotrophin mediates hematopoietic regeneration via activation of RAS

    PubMed Central

    Himburg, Heather A.; Yan, Xiao; Doan, Phuong L.; Quarmyne, Mamle; Micewicz, Eva; McBride, William; Chao, Nelson J.; Slamon, Dennis J.; Chute, John P.

    2014-01-01

    Hematopoietic stem cells (HSCs) are highly susceptible to ionizing radiation–mediated death via induction of ROS, DNA double-strand breaks, and apoptotic pathways. The development of therapeutics capable of mitigating ionizing radiation–induced hematopoietic toxicity could benefit both victims of acute radiation sickness and patients undergoing hematopoietic cell transplantation. Unfortunately, therapies capable of accelerating hematopoietic reconstitution following lethal radiation exposure have remained elusive. Here, we found that systemic administration of pleiotrophin (PTN), a protein that is secreted by BM-derived endothelial cells, substantially increased the survival of mice following radiation exposure and after myeloablative BM transplantation. In both models, PTN increased survival by accelerating the recovery of BM hematopoietic stem and progenitor cells in vivo. PTN treatment promoted HSC regeneration via activation of the RAS pathway in mice that expressed protein tyrosine phosphatase receptor-zeta (PTPRZ), whereas PTN treatment did not induce RAS signaling in PTPRZ-deficient mice, suggesting that PTN-mediated activation of RAS was dependent upon signaling through PTPRZ. PTN strongly inhibited HSC cycling following irradiation, whereas RAS inhibition abrogated PTN-mediated induction of HSC quiescence, blocked PTN-mediated recovery of hematopoietic stem and progenitor cells, and abolished PTN-mediated survival of irradiated mice. These studies demonstrate the therapeutic potential of PTN to improve survival after myeloablation and suggest that PTN-mediated hematopoietic regeneration occurs in a RAS-dependent manner. PMID:25250571

  16. Backtracking RAS mutations in high hyperdiploid childhood acute lymphoblastic leukemia.

    PubMed

    Wiemels, Joseph L; Kang, Michelle; Chang, Jeffrey S; Zheng, Lily; Kouyoumji, Carina; Zhang, Luoping; Smith, Martyn T; Scelo, Ghislaine; Metayer, Catherine; Buffler, Patricia; Wiencke, John K

    2010-10-15

    High hyperdiploidy is the single largest subtype of childhood acute lymphoblastic leukemia (ALL) and is defined by the presence of 51-68 chromosomes in a karyotype. The 5 or more extra chromosomes characterizing this subtype are known to occur in a single mitotic event, prenatally. We screened for RAS mutations among 517 acute childhood leukemias (including 437 lymphocytic, of which 393 were B-cell subtypes) and found mutations in 30% of high hyperdiploids compared to only 10% of leukemias of other subtypes (P<0.0001). We assessed whether KRAS mutations occurred before birth using a PCR-restriction enzyme-mediated Taqman quantitative PCR reaction, and found no evidence for prenatal KRAS mutations in 14 patients tested. While RAS mutations were previously associated with prior chemical exposures in childhood and adult leukemias, in this study RAS-mutated cases were not significantly associated with parental smoking when compared to study controls. IGH rearrangements were backtracked in three RAS-positive patients (which were negative for KRAS mutation at birth) and found to be evident before birth, confirming a prenatal origin for the leukemia clone. We posit a natural history for hyperdiploid leukemia in which prenatal mitotic catastrophe is followed by a postnatal RAS mutation to produce the leukemic cell phenotype.

  17. Spred is a Sprouty-related suppressor of Ras signalling.

    PubMed

    Wakioka, T; Sasaki, A; Kato, R; Shouda, T; Matsumoto, A; Miyoshi, K; Tsuneoka, M; Komiya, S; Baron, R; Yoshimura, A

    2001-08-09

    Cellular proliferation, and differentiation of cells in response to extracellular signals, are controlled by the signal transduction pathway of Ras, Raf and MAP (mitogen-activated protein) kinase. The mechanisms that regulate this pathway are not well known. Here we describe two structurally similar tyrosine kinase substrates, Spred-1 and Spred-2. These two proteins contain a cysteine-rich domain related to Sprouty (the SPR domain) at the carboxy terminus. In Drosophila, Sprouty inhibits the signalling by receptors of fibroblast growth factor (FGF) and epidermal growth factor (EGF) by suppressing the MAP kinase pathway. Like Sprouty, Spred inhibited growth-factor-mediated activation of MAP kinase. The Ras-MAP kinase pathway is essential in the differentiation of neuronal cells and myocytes. Expression of a dominant negative form of Spred and Spred-antibody microinjection revealed that endogenous Spred regulates differentiation in these types of cells. Spred constitutively associated with Ras but did not prevent activation of Ras or membrane translocation of Raf. Instead, Spred inhibited the activation of MAP kinase by suppressing phosphorylation and activation of Raf. Spred may represent a class of proteins that modulate Ras-Raf interaction and MAP kinase signalling.

  18. Modeling, simulation, and concept design for hybrid-electric medium-size military trucks

    NASA Astrophysics Data System (ADS)

    Rizzoni, Giorgio; Josephson, John R.; Soliman, Ahmed; Hubert, Christopher; Cantemir, Codrin-Gruie; Dembski, Nicholas; Pisu, Pierluigi; Mikesell, David; Serrao, Lorenzo; Russell, James; Carroll, Mark

    2005-05-01

    A large scale design space exploration can provide valuable insight into vehicle design tradeoffs being considered for the U.S. Army"s FMTV (Family of Medium Tactical Vehicles). Through a grant from TACOM (Tank-automotive and Armaments Command), researchers have generated detailed road, surface, and grade conditions representative of the performance criteria of this medium-sized truck and constructed a virtual powertrain simulator for both conventional and hybrid variants. The simulator incorporates the latest technology among vehicle design options, including scalable ultracapacitor and NiMH battery packs as well as a variety of generator and traction motor configurations. An energy management control strategy has also been developed to provide efficiency and performance. A design space exploration for the family of vehicles involves running a large number of simulations with systematically varied vehicle design parameters, where each variant is paced through several different mission profiles and multiple attributes of performance are measured. The resulting designs are filtered to remove dominated designs, exposing the multi-criterial surface of optimality (Pareto optimal designs), and revealing the design tradeoffs as they impact vehicle performance and economy. The results are not yet definitive because ride and drivability measures were not included, and work is not finished on fine-tuning the modeled dynamics of some powertrain components. However, the work so far completed demonstrates the effectiveness of the approach to design space exploration, and the results to date suggest the powertrain configuration best suited to the FMTV mission.

  19. CLARREO shortwave observing system simulation experiments of the twenty-first century: Simulator design and implementation

    SciTech Connect

    Feldman, D.R.; Algieri, C.A.; Ong, J.R.; Collins, W.D.

    2011-04-01

    Projected changes in the Earth system will likely be manifested in changes in reflected solar radiation. This paper introduces an operational Observational System Simulation Experiment (OSSE) to calculate the signals of future climate forcings and feedbacks in top-of-atmosphere reflectance spectra. The OSSE combines simulations from the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report for the NCAR Community Climate System Model (CCSM) with the MODTRAN radiative transfer code to calculate reflectance spectra for simulations of current and future climatic conditions over the 21st century. The OSSE produces narrowband reflectances and broadband fluxes, the latter of which have been extensively validated against archived CCSM results. The shortwave reflectance spectra contain atmospheric features including signals from water vapor, liquid and ice clouds, and aerosols. The spectra are also strongly influenced by the surface bidirectional reflectance properties of predicted snow and sea ice and the climatological seasonal cycles of vegetation. By comparing and contrasting simulated reflectance spectra based on emissions scenarios with increasing projected and fixed present-day greenhouse gas and aerosol concentrations, we find that prescribed forcings from increases in anthropogenic sulfate and carbonaceous aerosols are detectable and are spatially confined to lower latitudes. Also, changes in the intertropical convergence zone and poleward shifts in the subsidence zones and the storm tracks are all detectable along with large changes in snow cover and sea ice fraction. These findings suggest that the proposed NASA Climate Absolute Radiance and Refractivity Observatory (CLARREO) mission to measure shortwave reflectance spectra may help elucidate climate forcings, responses, and feedbacks.

  20. MEMS 3-DoF gyroscope design, modeling and simulation through equivalent circuit lumped parameter model

    NASA Astrophysics Data System (ADS)

    Mian, Muhammad Umer; Dennis, John Ojur; Khir, M. H. Md.; Riaz, Kashif; Iqbal, Abid; Bazaz, Shafaat A.; Tang, T. B.

    2015-07-01

    Pre-fabrication, behavioural and performance analysis with computer aided design (CAD) tools is a common and fabrication cost effective practice. In light of this we present a simulation methodology for a dual-mass oscillator based 3 Degree of Freedom (3-DoF) MEMS gyroscope. 3-DoF Gyroscope is modeled through lumped parameter models using equivalent circuit elements. These equivalent circuits consist of elementary components which are counterpart of their respective mechanical components, used to design and fabricate 3-DoF MEMS gyroscope. Complete designing of equivalent circuit model, mathematical modeling and simulation are being presented in this paper. Behaviors of the equivalent lumped models derived for the proposed device design are simulated in MEMSPRO T-SPICE software. Simulations are carried out with the design specifications following design rules of the MetalMUMPS fabrication process. Drive mass resonant frequencies simulated by this technique are 1.59 kHz and 2.05 kHz respectively, which are close to the resonant frequencies found by the analytical formulation of the gyroscope. The lumped equivalent circuit modeling technique proved to be a time efficient modeling technique for the analysis of complex MEMS devices like 3-DoF gyroscopes. The technique proves to be an alternative approach to the complex and time consuming couple field analysis Finite Element Analysis (FEA) previously used.

  1. Computer Simulator for OTEC System Design : Pump Control of Flow Rate

    NASA Astrophysics Data System (ADS)

    Nakamura, Masatoshi; Ikegami, Yasuyuki; Uehara, Haruo

    The purpose of ocean thermal energy conversion (OTEC) is to extract power from temperature differences existing in the oceans. The OTEC system design mainly comprises an OTEC plant design and an OTEC control design. The main purpose of this paper is to demonstrate the importance of a computer simulator for the OTEC system design. The computer simulator, constructed by a computer with A/D and D/A converters, produces analogue input and output signals which are equivalent to those of an actual OTEC plant. By using the computer simulator of an OTEC plant, we can estimate properties of any OTEC plant easily, economically and safely. The computer simulator also plays an important role in detecting difficulties in designing the OTEC controller. We furthermore described the procedure for designing the OTEC controller as follows: (i) statement of the control objective, (ii) modeling of the controlled object, (iii) application of control theory to the model, (iv) characterization of the detector and the input signal part, and (v) construction of the controller. We constructed the computer simulator and the controller for pump flow rate as part of the OTEC plant. We then obtained satisfactory control performance for flow rate control of experiments.

  2. MEMS 3-DoF gyroscope design, modeling and simulation through equivalent circuit lumped parameter model

    SciTech Connect

    Mian, Muhammad Umer Khir, M. H. Md.; Tang, T. B.; Dennis, John Ojur; Riaz, Kashif; Iqbal, Abid; Bazaz, Shafaat A.

    2015-07-22

    Pre-fabrication, behavioural and performance analysis with computer aided design (CAD) tools is a common and fabrication cost effective practice. In light of this we present a simulation methodology for a dual-mass oscillator based 3 Degree of Freedom (3-DoF) MEMS gyroscope. 3-DoF Gyroscope is modeled through lumped parameter models using equivalent circuit elements. These equivalent circuits consist of elementary components which are counterpart of their respective mechanical components, used to design and fabricate 3-DoF MEMS gyroscope. Complete designing of equivalent circuit model, mathematical modeling and simulation are being presented in this paper. Behaviors of the equivalent lumped models derived for the proposed device design are simulated in MEMSPRO T-SPICE software. Simulations are carried out with the design specifications following design rules of the MetalMUMPS fabrication process. Drive mass resonant frequencies simulated by this technique are 1.59 kHz and 2.05 kHz respectively, which are close to the resonant frequencies found by the analytical formulation of the gyroscope. The lumped equivalent circuit modeling technique proved to be a time efficient modeling technique for the analysis of complex MEMS devices like 3-DoF gyroscopes. The technique proves to be an alternative approach to the complex and time consuming couple field analysis Finite Element Analysis (FEA) previously used.

  3. Developing a workstation-based, real-time simulation for rapid handling qualities evaluations during design

    NASA Technical Reports Server (NTRS)

    Anderson, Frederick; Biezad, Daniel J.

    1994-01-01

    This paper describes the Rapid Aircraft DynamIcs AssessmeNt (RADIAN) project - an integration of the Aircraft SYNThesis (ACSTNT) design code with the USAD DATCOM code that estimates stability derivatives. Both of these codes are available to universities. These programs are then linked to flight simulation and flight controller synthesis tools and resulting design is evaluated on a graphics workstation. The entire process reduces the preliminary design time by an order of magnitude and provides an initial handling qualities evaluation of the design coupled to a control law. The integrated design process is applicable to both conventional aircraft taken from current textbooks and to unconventional designs emphasizing agility and propulsive control of attitude. The interactive and concurrent nature of the design process has been well received by industry and by design engineers at NASA. The process is being implemented into the design curriculum and is being used by students who view it as a significant advance over prior methods.

  4. Simulation Results for the New NSTX HHFW Antenna Straps Design by Using Microwave Studio

    SciTech Connect

    Kung, C C; Brunkhorst, C; Greenough, N; Fredd, E; Castano, A; Miller, D; D'Amico, G; Yager, R; Hosea, J; Wilson, J R; Ryan, P

    2009-05-26

    Experimental results have shown that the high harmonic fast wave (HHFW) at 30 MHz can provide substantial plasma heating and current drive for the NSTX spherical tokamak operation. However, the present antenna strap design rarely achieves the design goal of delivering the full transmitter capability of 6 MW to the plasma. In order to deliver more power to the plasma, a new antenna strap design and the associated coaxial line feeds are being constructed. This new antenna strap design features two feedthroughs to replace the old single feed-through design. In the design process, CST Microwave Studio has been used to simulate the entire new antenna strap structure including the enclosure and the Faraday shield. In this paper, the antenna strap model and the simulation results will be discussed in detail. The test results from the new antenna straps with their associated resonant loops will be presented as well.

  5. Design and simulation of a cable-pulley-based transmission for artificial ankle joints

    NASA Astrophysics Data System (ADS)

    Liu, Huaxin; Ceccarelli, Marco; Huang, Qiang

    2016-06-01

    In this paper, a mechanical transmission based on cable pulley is proposed for human-like actuation in the artificial ankle joints of human-scale. The anatomy articular characteristics of the human ankle is discussed for proper biomimetic inspiration in designing an accurate, efficient, and robust motion control of artificial ankle joint devices. The design procedure is presented through the inclusion of conceptual considerations and design details for an interactive solution of the transmission system. A mechanical design is elaborated for the ankle joint angular with pitch motion. A multi-body dynamic simulation model is elaborated accordingly and evaluated numerically in the ADAMS environment. Results of the numerical simulations are discussed to evaluate the dynamic performance of the proposed design solution and to investigate the feasibility of the proposed design in future applications for humanoid robots.

  6. Acoustic Analysis and Design of the E-STA MSA Simulator

    NASA Technical Reports Server (NTRS)

    Bittinger, Samantha A.

    2016-01-01

    The Orion European Service Module Structural Test Article (E-STA) Acoustic Test was completed in May 2016 to verify that the European Service Module (ESM) can withstand qualification acoustic environments. The test article required an aft closeout to simulate the Multi-Purpose Crew Vehicle (MPCV) Stage Adapter (MSA) cavity, however, the flight MSA design was too cost-prohibitive to build. NASA Glenn Research Center (GRC) had 6 months to design an MSA Simulator that could recreate the qualification prediction MSA cavity sound pressure level to within a reasonable tolerance. This paper summarizes the design and analysis process to arrive at a design for the MSA Simulator, and then compares its performance to the final prediction models created prior to test.

  7. Design study to simulate the development of a commercial transportation system

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Seven teams of senior-level Aerospace Engineering undergraduates were given a Request for Proposals (RFP) for a design concept of a remotely piloted vehicle (RPV). The RPV designs were intended to simulate commercial transport aircraft within the model of 'Aeroworld.' The Aeroworld model was developed so that the RPV designs would be subject to many of the engineering problems and tradeoffs that dominate real-world commercial air transport designs, such as profitability, fuel efficiency, range vs. payload capabilities, and ease of production and maintenance. As part of the proposal, each team was required to construct a prototype and validate its design with a flight demonstration.

  8. Optimal design and uncertainty quantification in blood flow simulations for congenital heart disease

    NASA Astrophysics Data System (ADS)

    Marsden, Alison

    2009-11-01

    Recent work has demonstrated substantial progress in capabilities for patient-specific cardiovascular flow simulations. Recent advances include increasingly complex geometries, physiological flow conditions, and fluid structure interaction. However inputs to these simulations, including medical image data, catheter-derived pressures and material properties, can have significant uncertainties associated with them. For simulations to predict clinically useful and reliable output information, it is necessary to quantify the effects of input uncertainties on outputs of interest. In addition, blood flow simulation tools can now be efficiently coupled to shape optimization algorithms for surgery design applications, and these tools should incorporate uncertainty information. We present a unified framework to systematically and efficient account for uncertainties in simulations using adaptive stochastic collocation. In addition, we present a framework for derivative-free optimization of cardiovascular geometries, and layer these tools to perform optimization under uncertainty. These methods are demonstrated using simulations and surgery optimization to improve hemodynamics in pediatric cardiology applications.

  9. Designing GUIs for low vision by simulating reduced visual acuity: reduced resolution versus shrinking.

    PubMed

    Sandnes, Frode Eika

    2015-01-01

    The visual uniqueness of information carrying icon and text elements has received little attention in the HCI research literature. The information carrying elements of graphical designs must be visually unique in order to be visually recognizable. This is increasingly important with the diversity of form factors and types of information displays. This paper explores two simple strategies for testing visual designs by simulating low visual acuity, namely by reducing the resolution and by shrinking. Two case studies demonstrate that low vision simulation by shrinking is more effective than reducing the resolution. Moreover, the case studies show how the low vision simulation can help identify design aspects that need attention. Design shrinking is not a substitute for user testing on actual user groups, but meant as a tool for early screening of designs and an aid for designers to help understand the effects of their design. The method can also be used as a tool for communicating design problems and justifying design decisions to stakeholders of a project through presentations and reports.

  10. Hepatitis B virus HBx protein activates Ras-GTP complex formation and establishes a Ras, Raf, MAP kinase signaling cascade.

    PubMed Central

    Benn, J; Schneider, R J

    1994-01-01

    Hepatitis B virus produces a small (154-amino acid) transcriptional transactivating protein, HBx, which is required for viral infection and has been implicated in virus-mediated liver oncogenesis. However, the molecular mechanism for HBx activity and its possible influence on cell proliferation have remained obscure. A number of studies suggest that HBx may stimulate transcription by indirectly activating transcription factors, possibly by influencing cell signaling pathways. We now present biochemical evidence that HBx activates Ras and rapidly induces a cytoplasmic signaling cascade linking Ras, Raf, and mitogen-activated protein kinase (MAP kinase), leading to transcriptional transactivation. HBx strongly elevates levels of GTP-bound Ras, activated and phosphorylated Raf, and tyrosine-phosphorylated and activated MAP kinase. Transactivation of transcription factor AP-1 by HBx is blocked by inhibition of Ras or Raf activities but not by inhibition of Ca(2+)- and diacylglycerol-dependent protein kinase C. HBx was also found to stimulate DNA synthesis in serum-starved cells. The hepatitis B virus HBx protein therefore stimulates Ras-GTP complex formation and promotes downstream signaling through Raf and MAP kinases, and may influence cell proliferation. Images PMID:7937954

  11. Galectin-1 dimers can scaffold Raf-effectors to increase H-ras nanoclustering

    PubMed Central

    Blaževitš, Olga; Mideksa, Yonatan G.; Šolman, Maja; Ligabue, Alessio; Ariotti, Nicholas; Nakhaeizadeh, Hossein; Fansa, Eyad K.; Papageorgiou, Anastassios C.; Wittinghofer, Alfred; Ahmadian, Mohammad R.; Abankwa, Daniel

    2016-01-01

    Galectin-1 (Gal-1) dimers crosslink carbohydrates on cell surface receptors. Carbohydrate-derived inhibitors have been developed for cancer treatment. Intracellularly, Gal-1 was suggested to interact with the farnesylated C-terminus of Ras thus specifically stabilizing GTP-H-ras nanoscale signalling hubs in the membrane, termed nanoclusters. The latter activity may present an alternative mechanism for how overexpressed Gal-1 stimulates tumourigenesis. Here we revise the current model for the interaction of Gal-1 with H-ras. We show that it indirectly forms a complex with GTP-H-ras via a high-affinity interaction with the Ras binding domain (RBD) of Ras effectors. A computationally generated model of the Gal-1/C-Raf-RBD complex is validated by mutational analysis. Both cellular FRET as well as proximity ligation assay experiments confirm interaction of Gal-1 with Raf proteins in mammalian cells. Consistently, interference with H-rasG12V-effector interactions basically abolishes H-ras nanoclustering. In addition, an intact dimer interface of Gal-1 is required for it to positively regulate H-rasG12V nanoclustering, but negatively K-rasG12V nanoclustering. Our findings suggest stacked dimers of H-ras, Raf and Gal-1 as building blocks of GTP-H-ras-nanocluster at high Gal-1 levels. Based on our results the Gal-1/effector interface represents a potential drug target site in diseases with aberrant Ras signalling. PMID:27087647

  12. Design for dependability: A simulation-based approach. Ph.D. Thesis, 1993

    NASA Technical Reports Server (NTRS)

    Goswami, Kumar K.

    1994-01-01

    This research addresses issues in simulation-based system level dependability analysis of fault-tolerant computer systems. The issues and difficulties of providing a general simulation-based approach for system level analysis are discussed and a methodology that address and tackle these issues is presented. The proposed methodology is designed to permit the study of a wide variety of architectures under various fault conditions. It permits detailed functional modeling of architectural features such as sparing policies, repair schemes, routing algorithms as well as other fault-tolerant mechanisms, and it allows the execution of actual application software. One key benefit of this approach is that the behavior of a system under faults does not have to be pre-defined as it is normally done. Instead, a system can be simulated in detail and injected with faults to determine its failure modes. The thesis describes how object-oriented design is used to incorporate this methodology into a general purpose design and fault injection package called DEPEND. A software model is presented that uses abstractions of application programs to study the behavior and effect of software on hardware faults in the early design stage when actual code is not available. Finally, an acceleration technique that combines hierarchical simulation, time acceleration algorithms and hybrid simulation to reduce simulation time is introduced.

  13. Use of crop simulation modelling to aid ideotype design of future cereal cultivars.

    PubMed

    Rötter, R P; Tao, F; Höhn, J G; Palosuo, T

    2015-06-01

    A major challenge of the 21st century is to achieve food supply security under a changing climate and roughly a doubling in food demand by 2050 compared to present, the majority of which needs to be met by the cereals wheat, rice, maize, and barley. Future harvests are expected to be especially threatened through increased frequency and severity of extreme events, such as heat waves and drought, that pose particular challenges to plant breeders and crop scientists. Process-based crop models developed for simulating interactions between genotype, environment, and management are widely applied to assess impacts of environmental change on crop yield potentials, phenology, water use, etc. During the last decades, crop simulation has become important for supporting plant breeding, in particular in designing ideotypes, i.e. 'model plants', for different crops and cultivation environments. In this review we (i) examine the main limitations of crop simulation modelling for supporting ideotype breeding, (ii) describe developments in cultivar traits in response to climate variations, and (iii) present examples of how crop simulation has supported evaluation and design of cereal cultivars for future conditions. An early success story for rice demonstrates the potential of crop simulation modelling for ideotype breeding. Combining conventional crop simulation with new breeding methods and genetic modelling holds promise to accelerate delivery of future cereal cultivars for different environments. Robustness of model-aided ideotype design can further be enhanced through continued improvements of simulation models to better capture effects of extremes and the use of multi-model ensembles.

  14. Performance-based landfill design: development of a design component selection matrix using GIS and system simulation models

    NASA Astrophysics Data System (ADS)

    Tarhan, Başak; Ünlü, Kahraman

    2005-11-01

    Designing environmentally safe and economically feasible landfills can be a challenging task due to complex interactions that need to be taken into account between landfill size, waste and site characteristics. The main focus of this study is, by interfacing the geographic information systems (GIS) with system simulation models (SSM), to develop a methodology and a landfill design component selection matrix that can enable the determination of landfill design components providing the desired performance with minimal design details. In this paper, the conceptual framework and applications of the developed methodology demonstrating the selection of landfill design components that are suitable for the existing site conditions are presented. The conceptual model defines design variables, performance criteria and design components of a landfill. GIS and SSM are used to handle the site-specific data and to evaluate the landfill performance, respectively. Results indicate that the landfills having the same design characteristics show different performance under different site conditions; therefore, a landfill design that is technically and economically feasible should be selected on the basis of performance.

  15. Design, Test, Redesign: Simulation in Technology, Engineering, and Design Education Classrooms

    ERIC Educational Resources Information Center

    Swinson, Ronnie; Clark, Aaron C.; Ernst, Jeremy V.; Sutton, Kevin

    2016-01-01

    Today's engineers, designers, and technologists are often thrust into the role of problem solver, from the initial design phase of a product or process all the way to final development. Many engineers in manufacturing environments are tasked with solving problems and continuously improving processes to enhance company profitability, efficiency,…

  16. Optimal design of TIR prism for the infrared target simulator based on DMD

    NASA Astrophysics Data System (ADS)

    Liu, Fang; Sun, Dan; Gao, Jiaobo; Zheng, Yawei; Hu, Yu; Zhang, Fang; Wang, Xicheng

    2016-10-01

    Overall structure of the infrared target simulator system and the principle of DMD are introduced. When DMD is on "open" state, all of the incidence light can rip into the pupil of the projection system. In addition, when it is on "close" state or "flat" state, all of the incident light can't rip into the pupil of the projection system. Based on this principle, with a specific infrared target simulator, TIR prism with BaF2 as material is designed. And then, this design is improved by ZnSe material instead of BaF2. ZnSe transmission rate is very well in the range of 0.6 microns to 14 microns and the infrared target simulator in this project requires 3 to 5 microns and 8 to 14 microns wavelength. This material is hard and easy to be processed. The design idea and design process are introduced in details in this paper and angle parameters are obtained. To improve light utilization and image quality in infrared target simulator system, two types of thin film on TIR prism different surfaces are designed. One is high transmittance with incidence angle of 0° and 24° - the other is 55°. Finally, this scheme is simulated and optimized by Tracepro software. Approving results were acquired.

  17. Analyzing the influence of median cross-section design on highway safety using vehicle dynamics simulations.

    PubMed

    Stine, Jason S; Hamblin, Bridget C; Brennan, Sean N; Donnell, Eric T

    2010-11-01

    Although vehicle dynamics simulations have long been used in vehicle design and crash reconstruction, their use for highway design is rare. This paper investigates the safety of highway medians through iterative simulations of off-road median encroachments. The commercially available software CarSim was used to simulate over one hundred thousand encroachments, representing the entire passenger vehicle fleet and a wide range of encroachment angles, departure speeds, steering inputs, and braking inputs. Each individual simulation output was then weighted using data from previous studies to reflect the probability of each specific accident scenario occurring in a real-life median encroachment. Results of this analysis illustrate the relative influence of median cross-section geometry on the resulting accident outcomes. The simulations indicate that the overall safety of a highway median depends on the occurrence of both vehicle rollover and median crossover events, and the cross-section shape, slope, and width are all shown to greatly affect each of these incidents. An evaluation of the simulation results was conducted with vehicle trajectories from previous experimental crash tests. Further assessment of the aggregate simulation results to actual crash data was achieved through comparison with several databases of crash statistics. Both efforts showed a strong agreement between the simulations and the real-life crash data.

  18. The Tumor Suppressor DiRas3 Forms a Complex with H-Ras and C-RAF Proteins and Regulates Localization, Dimerization, and Kinase Activity of C-RAF*

    PubMed Central

    Baljuls, Angela; Beck, Matthias; Oenel, Ayla; Robubi, Armin; Kroschewski, Ruth; Hekman, Mirko; Rudel, Thomas; Rapp, Ulf R.

    2012-01-01

    The maternally imprinted Ras-related tumor suppressor gene DiRas3 is lost or down-regulated in more than 60% of ovarian and breast cancers. The anti-tumorigenic effect of DiRas3 is achieved through several mechanisms, including inhibition of cell proliferation, motility, and invasion, as well as induction of apoptosis and autophagy. Re-expression of DiRas3 in cancer cells interferes with the signaling through Ras/MAPK and PI3K. Despite intensive research, the mode of interference of DiRas3 with the Ras/RAF/MEK/ERK signal transduction is still a matter of speculation. In this study, we show that DiRas3 associates with the H-Ras oncogene and that activation of H-Ras enforces this interaction. Furthermore, while associated with DiRas3, H-Ras is able to bind to its effector protein C-RAF. The resulting multimeric complex consisting of DiRas3, C-RAF, and active H-Ras is more stable than the two protein complexes H-Ras·C-RAF or H-Ras·DiRas3, respectively. The consequence of this complex formation is a DiRas3-mediated recruitment and anchorage of C-RAF to components of the membrane skeleton, suppression of C-RAF/B-RAF heterodimerization, and inhibition of C-RAF kinase activity. PMID:22605333

  19. High resolution simulations of ignition capsule designs for the National Ignition Facility

    SciTech Connect

    Clark, D S; Haan, S W; Cook, A W; Edwards, M J; Hammel, B A; Koning, J M; Marinak, M M

    2011-02-17

    Ignition capsule designs for the National Ignition Facility (NIF) [G. H. Miller, E. I. Moses, and C. R. Wuest, Opt. Eng. 443, 2841 (2004)] have continued to evolve in light of improved physical data inputs, improving simulation techniques, and - most recently - experimental data from a growing number of NIF sub-ignition experiments. This paper summarizes a number of recent changes to the cryogenic capsule design and some of our latest techniques in simulating its performance. Specifically, recent experimental results indicated harder x-ray drive spectra in NIF hohlraums than were predicted and used in previous capsule optimization studies. To accommodate this harder drive spectrum, a series of high-resolution 2-D simulations, resolving Legendre mode numbers as high as two thousand, were run and the germanium dopant concentration and ablator shell thicknesses re-optimized accordingly. Simultaneously, the possibility of cooperative or nonlinear interaction between neighboring ablator surface defects has motivated a series of fully 3-D simulations run with the massively parallel HYDRA code. These last simulations include perturbations seeded on all capsule interfaces and can use actual measured shell surfaces as initial conditions. 3-D simulations resolving Legendre modes up to two hundred on large capsule sectors have run through ignition and burn, and higher resolution simulations resolving as high as mode twelve hundred have been run to benchmark high-resolution 2-D runs. Finally, highly resolved 3-D simulations have also been run of the jet-type perturbation caused by the fill tube fitted to the capsule. These 3-D simulations compare well with the more typical 2-D simulations used in assessing the fill tube's impact on ignition. Coupled with the latest experimental inputs from NIF, our improving simulation capability yields a fuller and more accurate picture of NIF ignition capsule performance.

  20. IB: a Monte Carlo Simulation Tool for Neutron Scattering Instrument Design under Parallel Virtual Machine

    SciTech Connect

    Zhao, Jinkui

    2011-01-01

    IB is a Monte Carlo simulation tool for aiding neutron scattering instrument designs. It is written in C++ and implemented under Parallel Virtual Machine. The program has a few basic components, or modules, that can be used to build a virtual neutron scattering instrument. More complex components, such as neutron guides and multichannel beam benders, can be constructed using the grouping technique unique to IB. Users can specify a collection of modules as a group. For example, a neutron guide can be constructed by grouping four neutron mirrors together that make up the four sides of the guide. IB s simulation engine ensures that neutrons entering a group will be properly operated upon by all members of the group. For simulations that require higher computer speed, the program can be run in parallel mode under the PVM architecture. Initially, the program was written for designing instruments on pulsed neutron sources, it has since been used to simulate reactor based instruments as well.

  1. Role of Computational Simulations in Heart Valve Dynamics and Design of Valvular Prostheses

    PubMed Central

    Chandran, Krishnan B.

    2010-01-01

    Computational simulations are playing an increasingly important role in enhancing our understanding of the normal human physiological function, etiology of diseased states, surgical and interventional planning, and in the design and evaluation of artificial implants. Researchers are taking advantage of computational simulations to speed up the initial design of implantable devices before a prototype is developed and hence able to reduce animal experimentation for the functional evaluation of the devices under development. A review of the reported studies to date relevant to the simulation of the native and prosthetic heart valve dynamics is the subject of the present paper. Potential future directions toward multi-scale simulation studies for our further understanding of the physiology and pathophysiology of heart valve dynamics and valvular implants are also discussed. PMID:20606715

  2. Quasi-optimum design of a six degree of freedom moving base simulator control system

    NASA Technical Reports Server (NTRS)

    Friedland, B.; Ling, C.; Hutton, M. F.

    1973-01-01

    The design of a washout control system for a moving base simulator is treated by a quasi-optimum control technique. The broad objective of the design is to reproduce the sensed motion of a six degree of freedom simulator as accurately as possible without causing the simulator excursions to exceed specified limits. A performance criterion is established that weights magnitude and direction errors in specific force and in angular velocity and attempts to maintain the excursion within set limits by penalizing excessive excursions. A FORTRAN routine for relizing the washout law was developed and typical time histories using the washout routine were simulated for a range of parameters in the penalty- and weighting-functions. These time histories and the listing of the routine are included in the report.

  3. Multidisciplinary Simulation of Graphite-Composite and Cermet Fuel Elements for NTP Point of Departure Designs

    NASA Technical Reports Server (NTRS)

    Stewart, Mark E.; Schnitzler, Bruce G.

    2015-01-01

    This paper compares the expected performance of two Nuclear Thermal Propulsion fuel types. High fidelity, fluid/thermal/structural + neutronic simulations help predict the performance of graphite-composite and cermet fuel types from point of departure engine designs from the Nuclear Thermal Propulsion project. Materials and nuclear reactivity issues are reviewed for each fuel type. Thermal/structural simulations predict thermal stresses in the fuel and thermal expansion mis-match stresses in the coatings. Fluid/thermal/structural/neutronic simulations provide predictions for full fuel elements. Although NTP engines will utilize many existing chemical engine components and technologies, nuclear fuel elements are a less developed engine component and introduce design uncertainty. Consequently, these fuel element simulations provide important insights into NTP engine performance.

  4. Design optimization of pixel sensors using device simulations for the phase-II CMS tracker upgrade

    NASA Astrophysics Data System (ADS)

    Jain, G.; Bhardwaj, A.; Dalal, R.; Eber, R.; Eichorn, T.; Fernandez, M.; Lalwani, K.; Messineo, A.; Palomo, F. R.; Peltola, T.; Printz, M.; Ranjan, K.; Villa, I.; Hidalgo, S.

    2016-07-01

    In order to address the problems caused by the harsh radiation environment during the high luminosity phase of the LHC (HL-LHC), all silicon tracking detectors (pixels and strips) in the CMS experiment will undergo an upgrade. And so to develop radiation hard pixel sensors, simulations have been performed using the 2D TCAD device simulator, SILVACO, to obtain design parameters. The effect of various design parameters like pixel size, pixel depth, implant width, metal overhang, p-stop concentration, p-stop depth and bulk doping density on the leakage current and critical electric field are studied for both non-irradiated as well as irradiated pixel sensors. These 2D simulation results of planar pixels are useful for providing insight into the behaviour of non-irradiated and irradiated silicon pixel sensors and further work on 3D simulation is underway.

  5. Designing Scenarios for Controller-in-the-Loop Air Traffic Simulations

    NASA Technical Reports Server (NTRS)

    Kupfer, Michael; Mercer, Joey S.; Cabrall, Christopher; Callantine, Todd

    2013-01-01

    Well prepared traffic scenarios contribute greatly to the success of controller-in-the-loop simulations. This paper describes each stage in the design process of realistic scenarios based on real-world traffic, to be used in the Airspace Operations Laboratory for simulations within the Air Traffic Management Technology Demonstration 1 effort. The steps from the initial analysis of real-world traffic, to the editing of individual aircraft records in the scenario file, until the final testing of the scenarios before the simulation conduct, are all described. The iterative nature of the design process and the various efforts necessary to reach the required fidelity, as well as the applied design strategies, challenges, and tools used during this process are also discussed.

  6. Novel peptides from the RAS-p21 and p53 proteins for the treatment of cancer.

    PubMed

    Bowne, Wilbur B; Michl, Josef; Bluth, Martin H; Zenilman, Michael E; Pincus, Matthew R

    2007-01-01

    We have employed a novel computer-based molecular modeling method to design peptides from the ras-p21 and p53 proteins that block proliferation of cancer cells. The rationale of our approach is to identify peptide domains from each protein that alter conformation in response to oncogenic amino acid substitutions in their polypeptide chain. We accomplish this by first generating and comparing low energy average structures for oncogenic and wild-type proteins using conformational energy calculations. Peptides are then synthesized corresponding to these domains. These domains are then linked to a trans-membrane-penetrating sequence (called penetratin) and tested against cancer and untransformed cell lines. Remarkably, we have found that two ras-p21 peptides, 35-47 and 96-110, called PNC-7 and PNC-2, respectively, can induce phenotypic reversion of ras-transformed TUC-3 pancreatic cancer cells and ras-transformed HT1080 human fibrosarcoma cells to their untransformed phenotypes. Moreover, both peptides were found to be cytotoxic to ras-transformed human MIA-PaCa-2 pancreatic carcinoma cells and human U-251 astrocytoma cells. Importantly, these peptides have no effect on the growth of their normal cellular counterparts. We have also synthesized peptides from the p53 protein corresponding to its hdm-2-binding domain sequences (residues 12-26), also linked to the penetratin sequence. Surprisingly, we have found that these peptides induce 100 percent tumor cell necrosis, not apoptosis, in 13 different human cancer cell lines but have no effect on normal pancreatic acinar cells, breast epithelial cells, and human stem cells. Moreover, these peptides are cytotoxic to TUC-3 pancreatic tumor cells in nude mice plus eradicate these tumor cells when administered at sites near these tumors. These novel peptides appear to hold much promise as new, non-toxic anti-cancer agents.

  7. Modeling and Simulation of Reliability & Maintainability Parameters for Reusable Launch Vehicles using Design of Experiments

    NASA Technical Reports Server (NTRS)

    Unal, Resit; Morris, W. Douglas; White, Nancy H.; Lepsch, Roger A.

    2004-01-01

    This paper describes the development of a methodology for estimating reliability and maintainability distribution parameters for a reusable launch vehicle. A disciplinary analysis code and experimental designs are used to construct approximation models for performance characteristics. These models are then used in a simulation study to estimate performance characteristic distributions efficiently. The effectiveness and limitations of the developed methodology for launch vehicle operations simulations are also discussed.

  8. Toward Technological Application of Non-Newtonian Fluids & Complex Materials/Modeling, Simulation, & Design of Experiments

    DTIC Science & Technology

    2007-11-02

    34Therrmanechanical Equations Governing a Material with Prescribed Temperature-Dependent Density, with Applications to Nonisothernal Plane Poiseuille Flow ", D...1-0431 Materials/Modeling, Simulation , & Design of Experiments 6. AUTHORS M. Gregory Forest & Stephen E. Bechtel 7. PERFORMING ORGANIZATION NAME(S...made significant progress in each of these general areas. We produced high resolution models and codes that simulate molten fiber manufacturing

  9. Rasputin, the Drosophila homologue of the RasGAP SH3 binding protein, functions in ras- and Rho-mediated signaling.

    PubMed

    Pazman, C; Mayes, C A; Fanto, M; Haynes, S R; Mlodzik, M

    2000-04-01

    The small GTPase Ras plays an important role in many cellular signaling processes. Ras activity is negatively regulated by GTPase activating proteins (GAPs). It has been proposed that RasGAP may also function as an effector of Ras activity. We have identified and characterized the Drosophila homologue of the RasGAP-binding protein G3BP encoded by rasputin (rin). rin mutants are viable and display defects in photoreceptor recruitment and ommatidial polarity in the eye. Mutations in rin/G3BP genetically interact with components of the Ras signaling pathway that function at the level of Ras and above, but not with Raf/MAPK pathway components. These interactions suggest that Rin is required as an effector in Ras signaling during eye development, supporting an effector role for RasGAP. The ommatidial polarity phenotypes of rin are similar to those of RhoA and the polarity genes, e.g. fz and dsh. Although rin/G3BP interacts genetically with RhoA, affecting both photoreceptor differentiation and polarity, it does not interact with the gain-of-function genotypes of fz and dsh. These data suggest that Rin is not a general component of polarity generation, but serves a function specific to Ras and RhoA signaling pathways.

  10. Exploring the interactions of the RAS family in the human protein network and their potential implications in RAS-directed therapies

    PubMed Central

    Bueno, Anibal; Morilla, Ian; Diez, Diego; Moya-Garcia, Aurelio A.; Lozano, José; Ranea, Juan A.G.

    2016-01-01

    RAS proteins are the founding members of the RAS superfamily of GTPases. They are involved in key signaling pathways regulating essential cellular functions such as cell growth and differentiation. As a result, their deregulation by inactivating mutations often results in aberrant cell proliferation and cancer. With the exception of the relatively well-known KRAS, HRAS and NRAS proteins, little is known about how the interactions of the other RAS human paralogs affect cancer evolution and response to treatment. In this study we performed a comprehensive analysis of the relationship between the phylogeny of RAS proteins and their location in the protein interaction network. This analysis was integrated with the structural analysis of conserved positions in available 3D structures of RAS complexes. Our results show that many RAS proteins with divergent sequences are found close together in the human interactome. We found specific conserved amino acid positions in this group that map to the binding sites of RAS with many of their signaling effectors, suggesting that these pairs could share interacting partners. These results underscore the potential relevance of cross-talking in the RAS signaling network, which should be taken into account when considering the inhibitory activity of drugs targeting specific RAS oncoproteins. This study broadens our understanding of the human RAS signaling network and stresses the importance of considering its potential cross-talk in future therapies. PMID:27713118

  11. A RasGAP SH3 Peptide Aptamer Inhibits RasGAP-Aurora Interaction and Induces Caspase-Independent Tumor Cell Death

    PubMed Central

    Bickle, Marc; Corneloup, Claudine; Barthelaix, Audrey; Lepelletier, Yves; Mercier, Perrine; Schapira, Matthieu; Samson, Jérôme; Mathieu, Anne-Laure; Hugo, Nicolas; Moncorgé, Olivier; Mikaelian, Ivan; Dufour, Sylvie; Garbay, Christiane; Colas, Pierre

    2008-01-01

    The Ras GTPase-activating protein RasGAP catalyzes the conversion of active GTP-bound Ras into inactive GDP-bound Ras. However, RasGAP also acts as a positive effector of Ras and exerts an anti-apoptotic activity that is independent of its GAP function and that involves its SH3 (Src homology) domain. We used a combinatorial peptide aptamer approach to select a collection of RasGAP SH3 specific ligands. We mapped the peptide aptamer binding sites by performing yeast two-hybrid mating assays against a panel of RasGAP SH3 mutants. We examined the biological activity of a peptide aptamer targeting a pocket delineated by residues D295/7, L313 and W317. This aptamer shows a caspase-independent cytotoxic activity on tumor cell lines. It disrupts the interaction between RasGAP and Aurora B kinase. This work identifies the above-mentioned pocket as an interesting therapeutic target to pursue and points its cognate peptide aptamer as a promising guide to discover RasGAP small-molecule drug candidates. PMID:18682833

  12. A large scale software system for simulation and design optimization of mechanical systems

    NASA Technical Reports Server (NTRS)

    Dopker, Bernhard; Haug, Edward J.

    1989-01-01

    The concept of an advanced integrated, networked simulation and design system is outlined. Such an advanced system can be developed utilizing existing codes without compromising the integrity and functionality of the system. An example has been used to demonstrate the applicability of the concept of the integrated system outlined here. The development of an integrated system can be done incrementally. Initial capabilities can be developed and implemented without having a detailed design of the global system. Only a conceptual global system must exist. For a fully integrated, user friendly design system, further research is needed in the areas of engineering data bases, distributed data bases, and advanced user interface design.

  13. Design of flexible manufacturing systems with reuse in a KB simulation environment

    SciTech Connect

    Kovacs, G.L.; Kopacsi, S.; Kmecs, I.

    1996-12-31

    In this paper object-oriented design and the reuse of FMS components in new applications using a hybrid simulation and scheduling system (SSS) will be introduced. The goal of this research is to provide methods and tools to build up FMS simulation models easily, fast and reliable. Simulation is one of the most effective tools for assisting in the design of FMS. SSS has been implemented as a combination of a traditional simulation language (SIMAN/Cinema) and an intelligent expert environment (G2). The application of the real-time, intelligent G2 environment points to one of our recent R&D goal, to intelligent, real-time control of FMS. Reuse in SIMAN/Cinema and in G2 will be analyzed separately and together in general, and in the context of FMS to get acceptable solutions, to build up new simulation models fast and reliable reusing elements of previous, different other models. The design methodology used for model development is based on the object-oriented Rational Rose CASE tool and on use-case design of the OOSE methodology.

  14. Simulation study to determine the impact of different design features on design efficiency in discrete choice experiments

    PubMed Central

    Vanniyasingam, Thuva; Cunningham, Charles E; Foster, Gary; Thabane, Lehana

    2016-01-01

    Objectives Discrete choice experiments (DCEs) are routinely used to elicit patient preferences to improve health outcomes and healthcare services. While many fractional factorial designs can be created, some are more statistically optimal than others. The objective of this simulation study was to investigate how varying the number of (1) attributes, (2) levels within attributes, (3) alternatives and (4) choice tasks per survey will improve or compromise the statistical efficiency of an experimental design. Design and methods A total of 3204 DCE designs were created to assess how relative design efficiency (d-efficiency) is influenced by varying the number of choice tasks (2–20), alternatives (2–5), attributes (2–20) and attribute levels (2–5) of a design. Choice tasks were created by randomly allocating attribute and attribute level combinations into alternatives. Outcome Relative d-efficiency was used to measure the optimality of each DCE design. Results DCE design complexity influenced statistical efficiency. Across all designs, relative d-efficiency decreased as the number of attributes and attribute levels increased. It increased for designs with more alternatives. Lastly, relative d-efficiency converges as the number of choice tasks increases, where convergence may not be at 100% statistical optimality. Conclusions Achieving 100% d-efficiency is heavily dependent on the number of attributes, attribute levels, choice tasks and alternatives. Further exploration of overlaps and block sizes are needed. This study's results are widely applicable for researchers interested in creating optimal DCE designs to elicit individual preferences on health services, programmes, policies and products. PMID:27436671

  15. The design and implementation of a multi-waveform radar echo simulator.

    PubMed

    Quan, Yinghui; Gao, Xiaoxiao; Li, Yachao; Xing, Mengdao

    2015-10-01

    Radar simulator is an effective tool for performance assessment of radar systems by accurately reproducing echo signals from complicated environment. This paper presents a design of fast multi-waveform radar echo generation based on deconvolution method. First, scene information is retrieved from outfield data based on improved conjugate gradient algorithm. Then, the new radar echoes are generated through convolution of new transmitted signal and restored scene information. A fast and area-efficient field programmable gate array realization is provided to meet the real-time requirement of radar echo simulation. Finally, a series of experiments are performed to evaluate the effectiveness of proposed radar simulation instrument.

  16. SOI Hall cells design selection using three-dimensional physical simulations

    NASA Astrophysics Data System (ADS)

    Paun, Maria-Alexandra; Udrea, Florin

    2014-12-01

    The main characteristics of Hall Effect Sensors, based on “silicon-on-insulator” (SOI) structure in the ideal design features, are evaluated by performing three-dimensional physical simulations. A particular Hall shape reproducing an XFAB SOI XI10 integration process is analyzed in details. In order to assess the performance of the considered Hall cell, the Hall voltage, absolute sensitivity and input resistance were extracted through simulations. Electrostatic potential distribution and Hall mobility were also produced through simulations for the considered SOI Hall Basic cell. A comparison between the performance of the same Hall cell manufactured in regular bulk and SOI CMOS technology respectively is given.

  17. Consensus Standardization of Slurry Simulant Development Process to Reduce Design Risk Within the DOE Complex

    SciTech Connect

    Smith, Gary L.; Enderlin, Carl W.; Wells, Beric E.; Kurath, Dean E.; Denslow, Kayte M.

    2014-06-30

    A critical responsibility of DOE’s Office of Environmental Management is the design, construction, and operation of equipment and facilities to process legacy radioactive waste slurries for safe, long-term disposal. The accomplishment of this mission requires the extensive use of physical and chemical simulants to represent the hazardous radioactive waste. Development and characterization of simulants can often be difficult to compare or utilize as questions exist as to the basis, techniques, or consistency associated with reported parameters. In addition, controversy has existed in the interpretation and application of the characterization data for the wastes that the simulants are intended to represent.

  18. Design of a nickel-hydrogen battery simulator for the NASA EOS testbed

    NASA Technical Reports Server (NTRS)

    Gur, Zvi; Mang, Xuesi; Patil, Ashok R.; Sable, Dan M.; Cho, Bo H.; Lee, Fred C.

    1992-01-01

    The hardware and software design of a nickel-hydrogen (Ni-H2) battery simulator (BS) with application to the NASA Earth Observation System (EOS) satellite is presented. The battery simulator is developed as a part of a complete testbed for the EOS satellite power system. The battery simulator involves both hardware and software components. The hardware component includes the capability of sourcing and sinking current at a constant programmable voltage. The software component includes the capability of monitoring the battery's ampere-hours (Ah) and programming the battery voltage according to an empirical model of the nickel-hydrogen battery stored in a computer.

  19. Space station Simulation Computer System (SCS) study for NASA/MSFC. Volume 4: Conceptual design report

    NASA Technical Reports Server (NTRS)

    1989-01-01

    The Simulation Computer System (SCS) is the computer hardware, software, and workstations that will support the Payload Training Complex (PTC) at Marshall Space Flight Center (MSFC). The PTC will train the space station payload scientists, station scientists, and ground controllers to operate the wide variety of experiments that will be onboard the Space Station Freedom. In the first step of this task, a methodology was developed to ensure that all relevant design dimensions were addressed, and that all feasible designs could be considered. The development effort yielded the following method for generating and comparing designs in task 4: (1) Extract SCS system requirements (functions) from the system specification; (2) Develop design evaluation criteria; (3) Identify system architectural dimensions relevant to SCS system designs; (4) Develop conceptual designs based on the system requirements and architectural dimensions identified in step 1 and step 3 above; (5) Evaluate the designs with respect to the design evaluation criteria developed in step 2 above. The results of the method detailed in the above 5 steps are discussed. The results of the task 4 work provide the set of designs which two or three candidate designs are to be selected by MSFC as input to task 5-refine SCS conceptual designs. The designs selected for refinement will be developed to a lower level of detail, and further analyses will be done to begin to determine the size and speed of the components required to implement these designs.

  20. Current and emerging opportunities for molecular simulations in structure-based drug design

    PubMed Central

    Michel, Julien

    2014-01-01

    An overview of the current capabilities and limitations of molecular simulation of biomolecular complexes in the context of computer-aided drug design is provided. Steady improvements in computer hardware coupled with more refined representations of energetics are leading to a new appreciation of the driving forces of molecular recognition. Molecular simulations are poised to more frequently guide the interpretation of biophysical measurements of biomolecular complexes. Ligand design strategies emerge from detailed analyses of computed structural ensembles. The feasibility of routine applications to ligand optimization problems hinges upon successful extensive large scale validation studies and the development of protocols to intelligently automate computations. PMID:24469595