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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. 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.

  3. An Interdisciplinary Approach for Designing Kinetic Models of the Ras/MAPK Signaling Pathway.

    PubMed

    Reis, Marcelo S; Noël, Vincent; Dias, Matheus H; Albuquerque, Layra L; Guimarães, Amanda S; Wu, Lulu; Barrera, Junior; Armelin, Hugo A

    2017-01-01

    We present in this article a methodology for designing kinetic models of molecular signaling networks, which was exemplarily applied for modeling one of the Ras/MAPK signaling pathways in the mouse Y1 adrenocortical cell line. The methodology is interdisciplinary, that is, it was developed in a way that both dry and wet lab teams worked together along the whole modeling process.

  4. 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.

  5. 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

  6. 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.

  7. RasIns: Genetically Encoded Intrabodies of Activated Ras Proteins.

    PubMed

    Cetin, Mehmet; Evenson, William E; Gross, Garrett G; Jalali-Yazdi, Farzad; Krieger, Daniel; Arnold, Don; Takahashi, Terry T; Roberts, Richard W

    2017-02-17

    K- and H-Ras are the most commonly mutated genes in human tumors and are critical for conferring and maintaining the oncogenic phenotype in tumors with poor prognoses. Here, we design genetically encoded antibody-like ligands (intrabodies) that recognize active, GTP-bound K- and H-Ras. These ligands, which use the 10th domain of human fibronectin as their scaffold, are stable inside the cells and when fused with a fluorescent protein label, the constitutively active G12V mutant H-Ras. Primary selection of ligands against Ras with mRNA display resulted in an intrabody (termed RasIn1) that binds with a KD of 2.1μM to H-Ras(G12V) (GTP), excellent state selectivity, and remarkable specificity for K- and H-Ras. RasIn1 recognizes residues in the Switch I region of Ras, similar to Raf-RBD, and competes with Raf-RBD for binding. An affinity maturation selection based on RasIn1 resulted in RasIn2, which binds with a KD of 120nM and also retains excellent state selectivity. Both of these intrabodies colocalize with H-Ras, K-Ras, and G12V mutants inside the cells, providing new potential tools to monitor and modulate Ras-mediated signaling. Finally, RasIn1 and Rasin2 both display selectivity for the G12V mutants as compared with wild-type Ras providing a potential route for mutant selective recognition of Ras. Copyright © 2016. Published by Elsevier Ltd.

  8. Determining the Factors for the Simulation of the Madden-Julian Oscillation: Use of NCEP CFS RAS Model

    NASA Astrophysics Data System (ADS)

    Seo, K.; Choi, J.; Wang, W.

    2010-12-01

    This study investigates the capability for simulating the Madden-Julian oscillation (MJO) in a series of atmosphere-ocean coupled and uncoupled simulations using NCEP operational general circulation models. The effect of air-sea coupling on the MJO is examined by comparing long-term simulations from the coupled Climate Forecast System (CFS T62) and the atmospheric Global Forecast System (GFS T62) models. Another coupled simulation with a higher horizontal resolution model (CFS T126) is performed to investigate the impact of model horizontal resolution. Furthermore, to examine the impact on a deep convection scheme, an additional coupled T126 run (CFS T126RAS) is conducted with the relaxed Arakawa-Schubert (RAS) scheme. The most important factors for the proper simulation of the MJO are investigated from these runs. The empirical orthogonal function, lagged regression and spectral analyses indicated that the interactive air-sea coupling greatly improved the coherence between convection, circulation and other surface fields on the intraseasonal time scale. In contrast to the model simulations using the simplified Arakawa-Schubert (SAS) cumulus scheme, CFS T126RAS produced statistically significant spectral peaks in the MJO frequency band, and greatly improved the strength of the MJO convection and circulation. Most importantly, the ability of MJO convection signal to penetrate into the Maritime Continent and western Pacific was demonstrated. In this simulation, an early-stage shallow heating and moistening preconditioned the atmosphere for subsequent intense MJO convection and a top-heavy vertical heating profile was formed by stratiform heating in the upper and middle troposphere, working to increase temperature anomalies and hence eddy available potential energy that sustains the MJO. The stratiform heating arose from convective detrainment of moisture to the environment and stratiform anvil clouds. Therefore, the following factors were analyzed to be most

  9. An innovative modeling approach using Qual2K and HEC-RAS integration to assess the impact of tidal effect on River Water quality simulation.

    PubMed

    Fan, Chihhao; Ko, Chun-Han; Wang, Wei-Shen

    2009-04-01

    Water quality modeling has been shown to be a useful tool in strategic water quality management. The present study combines the Qual2K model with the HEC-RAS model to assess the water quality of a tidal river in northern Taiwan. The contaminant loadings of biochemical oxygen demand (BOD), ammonia nitrogen (NH(3)-N), total phosphorus (TP), and sediment oxygen demand (SOD) are utilized in the Qual2K simulation. The HEC-RAS model is used to: (i) estimate the hydraulic constants for atmospheric re-aeration constant calculation; and (ii) calculate the water level profile variation to account for concentration changes as a result of tidal effect. The results show that HEC-RAS-assisted Qual2K simulations taking tidal effect into consideration produce water quality indices that, in general, agree with the monitoring data of the river. Comparisons of simulations with different combinations of contaminant loadings demonstrate that BOD is the most import contaminant. Streeter-Phelps simulation (in combination with HEC-RAS) is also performed for comparison, and the results show excellent agreement with the observed data. This paper is the first report of the innovative use of a combination of the HEC-RAS model and the Qual2K model (or Streeter-Phelps equation) to simulate water quality in a tidal river. The combination is shown to provide an alternative for water quality simulation of a tidal river when available dynamic-monitoring data are insufficient to assess the tidal effect of the river.

  10. Ras history

    PubMed Central

    2010-01-01

    Although the roots of Ras sprouted from the rich history of retrovirus research, it was the discovery of mutationally activated RAS genes in human cancer in 1982 that stimulated an intensive research effort to understand Ras protein structure, biochemistry and biology. While the ultimate goal has been developing anti-Ras drugs for cancer treatment, discoveries from Ras have laid the foundation for three broad areas of science. First, they focused studies on the origins of cancer to the molecular level, with the subsequent discovery of genes mutated in cancer that now number in the thousands. Second, elucidation of the biochemical mechanisms by which Ras facilitates signal transduction established many of our fundamental concepts of how a normal cell orchestrates responses to extracellular cues. Third, Ras proteins are also founding members of a large superfamily of small GTPases that regulate all key cellular processes and established the versatile role of small GTP-binding proteins in biology. We highlight some of the key findings of the last 28 years. PMID:21686117

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

    USDA-ARS?s Scientific Manuscript database

    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...

  12. 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

  13. 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.

  14. 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.

  15. Mechanisms of Ras membrane organization and signaling

    PubMed Central

    Abankwa, Daniel; Gorfe, Alemayehu A.; Hancock, John F.

    2009-01-01

    Understanding the signalling function of Ras GTPases has been the focus of much research for over 20 years. Both the catalytic domain and the membrane anchoring C terminal hypervariable region (HVR) of Ras are necessary for its cellular function. However, while the highly conserved catalytic domain has been characterized in atomic detail, the structure of the full-length membrane-bound Ras has remained elusive. Lack of structural knowledge on the full-length protein limited our understanding of Ras signalling. For example, structures of the Ras catalytic domain solved in complex with effectors do not provide a basis for the functional specificity of different Ras isoforms. Recent molecular dynamics simulations in combination with biophysical and cell biological experiments have shown that the HVR and parts of the G domain cofunction with the lipid tails to anchor H-ras to the plasma membrane. In the GTP-bound state, H-ras adopts an orientation that allows read out by Ras effectors and translation into corresponding MAPK signalling. Here we discuss details of an analysis that suggests a novel balance model for Ras functioning. The balance model rationalizes Ras membrane orientation and may help explain isoform specific interactions of Ras with its effectors and modulators. PMID:18758236

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Modeling and stochastic simulation of the Ras/cAMP/PKA pathway in the yeast Saccharomyces cerevisiae evidences a key regulatory function for intracellular guanine nucleotides pools.

    PubMed

    Cazzaniga, Paolo; Pescini, Dario; Besozzi, Daniela; Mauri, Giancarlo; Colombo, Sonia; Martegani, Enzo

    2008-02-01

    In the yeast Saccharomyces cerevisiae, the Ras/cAMP/PKA pathway is involved in the regulation of metabolism and cell cycle progression. The pathway is tightly regulated by several control mechanisms, as the feedback cycle ruled by the activity of phosphodiesterase. Here, we present a discrete mathematical model for the Ras/cAMP/PKA pathway that considers its principal cytoplasmic components and their mutual interactions. The tau-leaping algorithm is then used to perform stochastic simulations of the model. We investigate this system under various conditions, and we test how different values of several stochastic reaction constants affect the pathway behaviour. Finally, we show that the level of guanine nucleotides, GTP and GDP, could be relevant metabolic signals for the regulation of the whole pathway.

  3. 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

  4. 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.

  5. Importance of the REM (Ras exchange) domain for membrane interactions by RasGRP3.

    PubMed

    Czikora, Agnes; Kedei, Noemi; Kalish, Heather; Blumberg, Peter M

    2017-09-11

    RasGRP comprises a family of guanine nucleotide exchange factors, regulating the dissociation of GDP from Ras GTPases to enhance the formation of the active GTP-bound form. RasGRP1 possesses REM (Ras exchange), GEF (catalytic), EF-hand, C1, SuPT (suppressor of PT), and PT (plasma membrane-targeting) domains, among which the C1 domain drives membrane localization in response to diacylglycerol or phorbol ester and the PT domain recognizes phosphoinositides. The homologous family member RasGRP3 shows less plasma membrane localization. The objective of this study was to explore the role of the different domains of RasGRP3 in membrane translocation in response to phorbol esters. The full-length RasGRP3 shows limited translocation to the plasma membrane in response to PMA, even when the basic hydrophobic cluster in the PT domain, reported to be critical for RasGRP1 translocation to endogenous activators, is mutated to resemble that of RasGRP1. Moreover, exchange of the C-termini (SuPT-PT domain) of the two proteins had little effect on their plasma membrane translocation. On the other hand, while the C1 domain of RasGRP3 alone showed partial plasma membrane translocation, truncated RasGRP3 constructs, which contain the PT domain and are missing the REM, showed stronger translocation, indicating that the REM of RasGRP3 was a suppressor of its membrane interaction. The REM of RasGRP1 failed to show comparable suppression of RasGRP3 translocation. The marked differences between RasGRP3 and RasGRP1 in membrane interaction necessarily will contribute to their different behavior in cells and are relevant to the design of selective ligands as potential therapeutic agents. Published by Elsevier B.V.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. The renaissance of Ras.

    PubMed

    Milroy, Lech-Gustav; Ottmann, Christian

    2014-11-21

    Increased signaling by the small G protein Ras is found in many human cancers and is often caused by direct mutation of this protein. Hence, small-molecule attenuation of pathological Ras activity is of utmost interest in oncology. However, despite nearly three decades of intense drug discovery efforts, no clinically viable option for Ras inhibition has been developed. Very recently, reports of a number of new approaches of addressing Ras activity have led to the revival of this molecular target with the prospect of finally fulfilling the therapy promises associated with this important protein.

  17. Simulation of a class of hazardous situations in the ICS «INM RAS - Baltic Sea»

    NASA Astrophysics Data System (ADS)

    Zakharova, Natalia; Agoshkov, Valery; Aseev, Nikita; Parmuzin, Eugene; Sheloput, Tateana; Shutyaev, Victor

    2017-04-01

    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, scientific computing and processing of satellite data. In this work the results on the ICS development for PC-ICS "INM RAS - Baltic Sea" are presented. We discuss practical problems studied by ICS. The System includes numerical model of the Baltic Sea thermodynamics, the new oil spill model describing the propagation of a slick at the Sea surface (Agoshkov, Aseev et al., 2014) and the optimal ship route calculating block (Agoshkov, Zayachkovsky et al., 2014). The ICS is based on the INMOM numerical model of the Baltic Sea thermodynamics (Zalesny et al., 2013). It is possible to calculate main hydrodynamic parameters (temperature, salinity, velocities, sea level) using user-friendly interface of the ICS. The System includes data assimilation procedures (Agoshkov, 2003, Parmuzin, Agoshkov, 2012) and one can use the block of variational assimilation of the sea surface temperature in order to obtain main hydrodynamic parameters. Main possibilities of the ICS and several numerical experiments are presented in the work. By the problem of risk control is meant a problem of determination of optimal resources quantity which are necessary for decreasing the risk to some acceptable value. Mass of oil slick is chosen as a function of control. For the realization of the random variable the quadratic "functional of cost" is introduced. It comprises cleaning costs and deviation of damage of oil pollution from its acceptable value. The problem of minimization of this functional is solved based on the methods of optimal control and the theory of adjoint equations. The solution of this problem is

  18. Computational design for electromagnetic simulations

    NASA Astrophysics Data System (ADS)

    Glasby, Ryan Steven

    An automatic computational procedure has been developed to efficiently and accurately design the shape of complicated electromagnetic objects. These electromagnetic objects can be simulated for operation at high frequencies (˜10 GHz), and can be comprised of dissimilar materials. The automated design procedure consists of linking together an original electromagnetic field simulation tool, an original adjoint routine for obtaining sensitivity derivatives, and an original grid-smoothing tool with an existing optimization package. The electromagnetic field simulation software employs a temporally and spatially higher-order accurate Streamline Upwind/Petrov-Galerkin finite-element method that numerically solves Maxwell's equations in the time domain using implicit time stepping. The software for computing sensitivity derivatives employs a reverse-mode time-accurate discrete adjoint methodology that is formulated to automatically maintain consistency with the electromagnetic field simulation software. Grid smoothing is achieved using a spatially higher-order accurate Galerkin finite-element method that generates a numerical solution to the linear elastic equations. All computational solutions to the linear systems present in each software tool are obtained using the Generalized Minimum Residual algorithm with block diagonal preconditioning. Each software tool is implemented using a parallel processing paradigm and is therefore capable of being executed on a distributed memory supercomputer. The order of accuracy of the electromagnetic field simulation software has been determined by using comparisons with exact solutions. The field software's results were compared to the exact solution of a rectangular resonant cavity. In all cases, the order properties of the field software exceed theoretical expectations when linear, quadratic, and cubic tetrahedral elements are employed to discretize the field. To demonstrate the consistency of the adjoint-based sensitivity

  19. Surgical Simulator Design and Development

    PubMed Central

    2007-01-01

    With the introduction of minimally invasive surgery (MIS), it became necessary to develop training methods to learn skills outside the operating room. Several training simulators have become commercially available, but fundamental research into the requirements for effective and efficient training in MIS is still lacking. Three aspects of developing a training program are investigated here: what should be trained, how it should be trained, and how to assess the results of training. In addition, studies are presented that have investigated the role of force feedback in surgical simulators. Training should be adapted to the level of behavior: skill-based, rule-based, or knowledge-based. These levels can be used to design and structure a training program. Extra motivation for training can be created by assessment. During MIS, force feedback is reduced owing to friction in the laparoscopic instruments and within the trocar. The friction characteristics vary largely among instruments and trocars. When force feedback is incorporated into training, it should include the large variation in force feedback properties as well. Training different levels of behavior requires different training methods. Although force feedback is reduced during MIS, it is needed for tissue manipulation, and therefore force application should be trained as well. PMID:17653587

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Space shuttle visual simulation system design study

    NASA Technical Reports Server (NTRS)

    1973-01-01

    A recommendation and a specification for the visual simulation system design for the space shuttle mission simulator are presented. A recommended visual system is described which most nearly meets the visual design requirements. The cost analysis of the recommended system covering design, development, manufacturing, and installation is reported. Four alternate systems are analyzed.

  5. 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.

  6. 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.

  7. 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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  9. Targeting N-RAS as a Therapeutic Approach for Melanoma

    DTIC Science & Technology

    2014-12-01

    targeted cytotoxicity in these tumors. The Specific Aims/Study Design of this Discovery Proposal are: Test the hypothesis that inhibition or down...downstream of RAS (in the setting of wild-type RAS alleles) will similarly sensitize human melanoma cells to PKCd inhibition; 3) Test this targeted...3’ 7 TASK 1: Testing N-RAS-mutant human melanoma cells for apoptosis after inhibition or down- regulation of PKCδ: Status: Completed. Please

  10. 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

  11. 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…

  12. 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…

  13. 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.

  14. 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.

  15. 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.

  16. What makes Ras an efficient molecular switch: a computational, biophysical, and structural study of Ras-GDP interactions with mutants of Raf.

    PubMed

    Filchtinski, Daniel; Sharabi, Oz; Rüppel, Alma; Vetter, Ingrid R; Herrmann, Christian; Shifman, Julia M

    2010-06-11

    Ras is a small GTP-binding protein that is an essential molecular switch for a wide variety of signaling pathways including the control of cell proliferation, cell cycle progression and apoptosis. In the GTP-bound state, Ras can interact with its effectors, triggering various signaling cascades in the cell. In the GDP-bound state, Ras looses its ability to bind to known effectors. The interaction of the GTP-bound Ras (Ras(GTP)) with its effectors has been studied intensively. However, very little is known about the much weaker interaction between the GDP-bound Ras (Ras(GDP)) and Ras effectors. We investigated the factors underlying the nucleotide-dependent differences in Ras interactions with one of its effectors, Raf kinase. Using computational protein design, we generated mutants of the Ras-binding domain of Raf kinase (Raf) that stabilize the complex with Ras(GDP). Most of our designed mutations narrow the gap between the affinity of Raf for Ras(GTP) and Ras(GDP), producing the desired shift in binding specificity towards Ras(GDP). A combination of our best designed mutation, N71R, with another mutation, A85K, yielded a Raf mutant with a 100-fold improvement in affinity towards Ras(GDP). The Raf A85K and Raf N71R/A85K mutants were used to obtain the first high-resolution structures of Ras(GDP) bound to its effector. Surprisingly, these structures reveal that the loop on Ras previously termed the switch I region in the Ras(GDP).Raf mutant complex is found in a conformation similar to that of Ras(GTP) and not Ras(GDP). Moreover, the structures indicate an increased mobility of the switch I region. This greater flexibility compared to the same loop in Ras(GTP) is likely to explain the natural low affinity of Raf and other Ras effectors to Ras(GDP). Our findings demonstrate that an accurate balance between a rigid, high-affinity conformation and conformational flexibility is required to create an efficient and stringent molecular switch. Copyright 2010 Elsevier Ltd

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Multivalent Small-Molecule Pan-RAS Inhibitors.

    PubMed

    Welsch, Matthew E; Kaplan, Anna; Chambers, Jennifer M; Stokes, Michael E; Bos, Pieter H; Zask, Arie; Zhang, Yan; Sanchez-Martin, Marta; Badgley, Michael A; Huang, Christine S; Tran, Timothy H; Akkiraju, Hemanth; Brown, Lewis M; Nandakumar, Renu; Cremers, Serge; Yang, Wan Seok; Tong, Liang; Olive, Kenneth P; Ferrando, Adolfo; Stockwell, Brent R

    2017-02-23

    Design of small molecules that disrupt protein-protein interactions, including the interaction of RAS proteins and their effectors, may provide chemical probes and therapeutic agents. We describe here the synthesis and testing of potential small-molecule pan-RAS ligands, which were designed to interact with adjacent sites on the surface of oncogenic KRAS. One compound, termed 3144, was found to bind to RAS proteins using microscale thermophoresis, nuclear magnetic resonance spectroscopy, and isothermal titration calorimetry and to exhibit lethality in cells partially dependent on expression of RAS proteins. This compound was metabolically stable in liver microsomes and displayed anti-tumor activity in xenograft mouse cancer models. These findings suggest that pan-RAS inhibition may be an effective therapeutic strategy for some cancers and that structure-based design of small molecules targeting multiple adjacent sites to create multivalent inhibitors may be effective for some proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. 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.

  5. Teaching Experiment Design by Computer Simulation

    ERIC Educational Resources Information Center

    Montgomery, David C.

    1973-01-01

    Describes an introductory physics experiment carried out by 24 students who used an IBM-360 Model-44 computer to stimulate Stokes' law. Discusses advantages of simulation programs in teaching experiment design. (CC)

  6. 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.

  7. Base Camp Design Simulation Training

    DTIC Science & Technology

    2011-07-01

    28 Location 2D Map View (note you are to select a location within the NW region of Yousel Khel) 29 3D Camera View...Figure 3: 2D Representation of Yousel Khel The scenario forces the student to conduct trade-off analysis as competing interests (proximity to a...reason, we designed a 600-man base camp on VBS2TM from an AutoCAD diagram found on the Theater Construction Management System (version 3.2). Known

  8. 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…

  9. 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.

  10. 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.

  11. Simulation optimizes noise jammer design

    NASA Astrophysics Data System (ADS)

    Knorr, J. B.; Karantanas, D. T.

    1985-05-01

    Direct noise amplification (DINA) and pseudo noise (modulated carrier - MC) are the two techniques used to approximate white Gaussian radar jamming noise. DINA is seldom employed because of its inefficient demands on the microwave amplifier. MC features modulation of a carrier signal to induce a Gaussian waveform at the victim receiver. The MC method attains a high efficiency with a carcinotron power oscillator, provided the Gaussian noise quality (GNQ), which is a function of the modulating signal parameters, is good. Results from a mainframe computer simulation indicate that the jammer bandwidth needs to be at least as wide as the victim bandwidth. The GNQ decreases with nearness to the edge of the jamming band but is independent of the jamer bandwidth.

  12. 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…

  13. 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…

  14. Spatial Segregation of Ras Signaling

    PubMed Central

    Chang, Eric C.; Philips, Mark R.

    2010-01-01

    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. PMID:16931912

  15. Analysis of Diffusion of Ras2 in Saccharomyces cerevisiae Using Fluorescence Recovery after Photobleaching

    PubMed Central

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

    2010-01-01

    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 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 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. PMID:20526029

  16. 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.

  17. 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.

  18. Design and simulation of a gyroklystron amplifier

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    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.

  19. ralGDS family members interact with the effector loop of ras p21.

    PubMed Central

    Kikuchi, A; Demo, S D; Ye, Z H; Chen, Y W; Williams, L T

    1994-01-01

    Using a yeast two-hybrid system, we identified a novel protein which interacts with ras p21. This protein shares 69% amino acid homology with ral guanine nucleotide dissociation stimulator (ralGDS), a GDP/GTP exchange protein for ral p24. We designated this protein RGL, for ralGDS-like. Using the yeast two-hybrid system, we found that an effector loop mutant of ras p21 was defective in interacting with the ras p21-interacting domain of RGL, suggesting that this domain binds to ras p21 through the effector loop of ras p21. Since ralGDS contained a region highly homologous with the ras p21-interacting domain of RGL, we examined whether ralGDS could interact with ras p21. In the yeast two-hybrid system, ralGDS failed to interact with an effector loop mutant of ras p21. In insect cells, ralGDS made a complex with v-ras p21 but not with a dominant negative mutant of ras p21. ralGDS interacted with the GTP-bound form of ras p21 but not with the GDP-bound form in vitro. ralGDS inhibited both the GTPase-activating activity of the neurofibromatosis gene product (NF1) for ras p21 and the interaction of Raf with ras p21 in vitro. These results demonstrate that ralGDS specifically interacts with the active form of ras p21 and that ralGDS can compete with NF1 and Raf for binding to the effector loop of ras p21. Therefore, ralGDS family members may be effector proteins of ras p21 or may inhibit interactions between ras p21 and its effectors. Images PMID:7935463

  20. 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.

  1. 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.

  2. Novel Methods for Electromagnetic Simulation and Design

    DTIC Science & Technology

    2016-08-03

    AFRL-AFOSR-VA-TR-2016-0272 NOVEL METHODS FOR ELECTROMAGNETIC SIMULATION AND DESIGN Leslie Greengard NEW YORK UNIVERSITY 70 WASHINGTON SQUARE S NEW...METHODS FOR ELECTROMAGNETIC SIMULATION AND DESIGN 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA9550-10-1-0180 5c.  PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S... electromagnetic scattering in realistic environments involving complex geometry. During the six year performance period (including a one-year no cost extension

  3. Memory interface simulator: A computer design aid

    NASA Technical Reports Server (NTRS)

    Taylor, D. S.; Williams, T.; Weatherbee, J. E.

    1972-01-01

    Results are presented of a study conducted with a digital simulation model being used in the design of the Automatically Reconfigurable Modular Multiprocessor System (ARMMS), a candidate computer system for future manned and unmanned space missions. The model simulates the activity involved as instructions are fetched from random access memory for execution in one of the system central processing units. A series of model runs measured instruction execution time under various assumptions pertaining to the CPU's and the interface between the CPU's and RAM. Design tradeoffs are presented in the following areas: Bus widths, CPU microprogram read only memory cycle time, multiple instruction fetch, and instruction mix.

  4. Expert systems for design and simulation

    SciTech Connect

    Aldridge, J.; Cerutti, J.; Draisin, W.; Steuerwalt, M.

    1985-01-01

    We discuss work in progress on two expert systems. We are developing systems that use artificial intelligence techniques to simplify the use of large simulation codes and to help design complicated physical devices. The simulation codes are used in analyzing and designing weapons, and the devices are themselves part of weapon systems. But we focus not only on the particular applications, but also on the broader issues common to design problems: large solution spaces and tentative reasoning. We also discuss some practical difficulties encountered during the project. One expert system provides an interface between users and several simulation codes. It checks input for errors, builds input files for the codes, and submits jobs to a central computing facility. The other expert system helps turn a description of a device into a particular design. Currently this expert system includes three major parts: a translator of descriptions into designs, a graphics interface that presents the design to the user and allows him to manipulate it, and a refiner of designs. The latter is the ''smartest'' part of the system, and the target of much of our present efforts.

  5. 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)

  6. [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.

  7. Dynamic Process Simulation for Analysis and Design.

    ERIC Educational Resources Information Center

    Nuttall, Herbert E., Jr.; Himmelblau, David M.

    A computer program for the simulation of complex continuous process in real-time in an interactive mode is described. The program is user oriented, flexible, and provides both numerical and graphic output. The program has been used in classroom teaching and computer aided design. Typical input and output are illustrated for a sample problem to…

  8. 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…

  9. Constructive simulation and topological design of protocols

    NASA Astrophysics Data System (ADS)

    Jaffe, Arthur; Liu, Zhengwei; Wozniakowski, Alex

    2017-06-01

    We give a topological simulation for tensor networks that we call the two-string model. In this approach we give a new way to design protocols, and we discover a new multipartite quantum communication protocol. We introduce the notion of topologically compressed transformations. Our new protocol can implement multiple, non-local compressed transformations among multi-parties using one multipartite resource state.

  10. 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…

  11. Deconstruction of the Ras switching cycle through saturation mutagenesis

    PubMed Central

    Bandaru, Pradeep; Shah, Neel H; Bhattacharyya, Moitrayee; Barton, John P; Kondo, Yasushi; Cofsky, Joshua C; Gee, Christine L; Chakraborty, Arup K; Kortemme, Tanja; Ranganathan, Rama; Kuriyan, John

    2017-01-01

    Ras proteins are highly conserved signaling molecules that exhibit regulated, nucleotide-dependent switching between active and inactive states. The high conservation of Ras requires mechanistic explanation, especially given the general mutational tolerance of proteins. Here, we use deep mutational scanning, biochemical analysis and molecular simulations to understand constraints on Ras sequence. Ras exhibits global sensitivity to mutation when regulated by a GTPase activating protein and a nucleotide exchange factor. Removing the regulators shifts the distribution of mutational effects to be largely neutral, and reveals hotspots of activating mutations in residues that restrain Ras dynamics and promote the inactive state. Evolutionary analysis, combined with structural and mutational data, argue that Ras has co-evolved with its regulators in the vertebrate lineage. Overall, our results show that sequence conservation in Ras depends strongly on the biochemical network in which it operates, providing a framework for understanding the origin of global selection pressures on proteins. DOI: http://dx.doi.org/10.7554/eLife.27810.001 PMID:28686159

  12. ALT-3 target design and simulations

    SciTech Connect

    Peterson, Jeffrey H

    2011-01-12

    ALT-3 is an experiment being designed in collaboration between Russian VNIIEF scientists and LANL that aims to conduct high velocity material experiments to measure shock velocities and pressures near 1 TPa. The DEMG (Disck Explosive Magnetic Generator) is used to drive> 60MA currents to accelerate an aluminum liner to speeds in excess of 20 km/s. 1-D and 2-D simulations of the aluminum target are presented with information on the free surface velocity profile, the state of the target, and the shock velocity in the target. 2-D simulations are presented showing the different targets available as well as a scenario with a perturbed liner impacter.

  13. 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.

  14. Orbit Design and Simulation for Kufasat Nanosatellite

    NASA Astrophysics Data System (ADS)

    Mahdi, Mohammed Chessab

    2015-12-01

    Orbit design for KufaSat Nano-satellites is presented. Polar orbit is selected for the KufaSat mission. The orbit was designed with an Inclination which enables the satellite to see every part of the earth. KufaSat has a payload for imaging purposes which require a large amount of power, so the orbit is determined to be sun synchronous in order to provide the power through solar panels. The KufaSat mission is designed for the low earth orbit. The six initial Keplerian Elements of KufaSat are calculated. The orbit design of KufaSat according to the calculated Keplerian elements has been simulated and analyzed by using MATLAB first and then by using General Mission Analysis Tool.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. IAA RAS Radio Telescope Monitoring System

    NASA Astrophysics Data System (ADS)

    Mikhailov, A.; Lavrov, A.

    2007-07-01

    Institute of Applied Astronomy of the Russian Academy of Sciences (IAA RAS) has three identical radio telescopes, the receiving complex of which consists of five two-channel receivers of different bands, six cryogen systems, and additional devices: four local oscillators, phase calibration generators and IF commutator. The design, hardware and data communication protocol are described. The most convenient way to join the devices of the receiving complex into the common monitoring system is to use the interface which allows to connect numerous devices to the data bus. For the purpose of data communication regulation and to exclude conflicts, a data communication protocol has been designed, which operates with complex formatted data sequences. Formation of such sequences requires considerable data processing capability. That is provided by a microcontroller chip in each slave device. The test version of the software for the central computer has been developed in IAA RAS. We are developing the Mark IV FS software extension modules, which will allow us to control the receiving complex of the radio telescope by special SNAP commands from both operator input and schedule files. We are also developing procedures of automatic measurements of SEFD, system noise temperature and other parameters, available both in VLBI and single-dish modes of operation. The system described has been installed on all IAA RAS radio telescopes at "Svetloe", "Zelenchukskaya" and "Badary" observatories. It has proved to be working quite reliably and to show the perfonmance expected.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Simulation-based disassembly systems design

    NASA Astrophysics Data System (ADS)

    Ohlendorf, Martin; Herrmann, Christoph; Hesselbach, Juergen

    2004-02-01

    Recycling of Waste of Electrical and Electronic Equipment (WEEE) is a matter of actual concern, driven by economic, ecological and legislative reasons. Here, disassembly as the first step of the treatment process plays a key role. To achieve sustainable progress in WEEE disassembly, the key is not to limit analysis and planning to merely disassembly processes in a narrow sense, but to consider entire disassembly plants including additional aspects such as internal logistics, storage, sorting etc. as well. In this regard, the paper presents ways of designing, dimensioning, structuring and modeling different disassembly systems. Goal is to achieve efficient and economic disassembly systems that allow recycling processes complying with legal requirements. Moreover, advantages of applying simulation software tools that are widespread and successfully utilized in conventional industry sectors are addressed. They support systematic disassembly planning by means of simulation experiments including consecutive efficiency evaluation. Consequently, anticipatory recycling planning considering various scenarios is enabled and decisions about which types of disassembly systems evidence appropriateness for specific circumstances such as product spectrum, throughput, disassembly depth etc. is supported. Furthermore, integration of simulation based disassembly planning in a holistic concept with configuration of interfaces and data utilization including cost aspects is described.

  6. LSST Survey Strategy: Cadence Design and Simulation

    NASA Astrophysics Data System (ADS)

    Pinto, Philip A.; Cook, K. H.; Delgado, F.; Miller, M.; Denneau, L.; Saha, A.; Gee, P. A.; Tyson, J. A.; Ivezic, Z.; LSST Collaboration

    2006-12-01

    The LSST will allow a wide variety of science to be done using data from a single survey. A large part of ensuring this claim is designing a smart and adaptive algorithm for scheduling observations, one which can effectively merge multiple requirements into a single program of observations while maximizing time on the sky and coping effectively with changing conditions in real time. Diverse requirements include multiband imaging of 30,000 square degrees of sky, achieving a uniform depth of exposure across 20,000 square degrees in each of six filters, allowing effective search strategies for NEO's and shortand long-period variables, and providing frequent, deep exposures to characterize faint transients and moving objects. The LSST operations simulator includes a detailed model of seeing and sky transparency derived from data obtained at its site on Cerro Pachon, Chile. It also includes a detailed model of the delays incurred by readout of the camera, filter changes, active optics acquisition, and movements of the dome and telescope. We describe current progress in the LSST scheduler design and present simulations of a prototype ten-year LSST mission which demonstrate that all of the science requirements and constraints can be accomodated successfully into a single survey.

  7. R-Ras C-terminal sequences are sufficient to confer R-Ras specificity to H-Ras.

    PubMed

    Hansen, Malene; Rusyn, Elena V; Hughes, Paul E; Ginsberg, Mark H; Cox, Adrienne D; Willumsen, Berthe M

    2002-06-27

    Activated versions of the similar GTPases, H-Ras and R-Ras, have differing effects on biological phenotypes: Activated H-Ras strongly transforms many fibroblast cell lines causing dramatic changes in cell shape and cytoskeletal organization. In contrast, R-Ras transforms fewer cell lines and the transformed cells display only some of the morphological changes associated with H-Ras transformation. H-Ras cells can survive in the absence of serum whereas R-Ras cells seem to die by an apoptotic-like mechanism in response to removal of serum. H-Ras can suppress integrin activation and R-Ras specifically antagonizes this effect. To map sequences responsible for these differences we have generated and investigated a panel of H-Ras and R-Ras chimeras. We found that the C-terminal 53 amino acids of R-Ras were necessary and sufficient to specify the contrasting biological properties of R-Ras with respect to focus morphology, reactive oxygen species (ROS) production and reversal of H-Ras-induced integrin suppression. Surprisingly, we found chimeras in which the focus formation and integrin-mediated phenotypes were separated, suggesting that different effectors could be involved in mediating these responses. An integrin profile of H-Ras and R-Ras cell pools showed no significant differences; both activated H-Ras and R-Ras expressing cells were found to have reduced beta(1) activity, suggesting that the activity state of the beta(1) subunit is not sufficient to direct an H-Ras transformed cell morphology.

  8. 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.

  9. 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.

  10. Muon RLA - design status and simulations

    SciTech Connect

    Beard, Kevin B.; Bogacz, Slawomir A.; Morozov, Vasiliy S.; Roblin, Yves R.

    2013-02-01

    The Neutrino Factory baseline design involves a complex chain of accelerators beginning with a linac. This first pre-linac follows the capture and bunching section and accelerates the muons from about 244 to 900 MeV and must accept a high emittance beam about 30 cm wide with a 10% energy spread. It uses counterwound, shielded superconducting solenoids and 201 MHz superconducting cavities, and currently consists of 24 3 m and 24 5 m long cryomodules. The next stage is a 1st dogbone-shaped RLA that takes the total energy from 900 MeV to 3.6 GeV in 4.5 passes, followed by a 2nd RLA that takes the energy from 3.6 to 12.6 GeV in 4.5 passes. Simulations are in progress to optimize the optics and determine the radiation loads from beam loss and muon decay.

  11. A computer simulator for development of engineering system design methodologies

    NASA Technical Reports Server (NTRS)

    Padula, S. L.; Sobieszczanski-Sobieski, J.

    1987-01-01

    A computer program designed to simulate and improve engineering system design methodology is described. The simulator mimics the qualitative behavior and data couplings occurring among the subsystems of a complex engineering system. It eliminates the engineering analyses in the subsystems by replacing them with judiciously chosen analytical functions. With the cost of analysis eliminated, the simulator is used for experimentation with a large variety of candidate algorithms for multilevel design optimization to choose the best ones for the actual application. Thus, the simulator serves as a development tool for multilevel design optimization strategy. The simulator concept, implementation, and status are described and illustrated with examples.

  12. 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.

  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. 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.

  15. Hygrothermal Simulation: A Tool for Building Envelope Design Analysis

    Treesearch

    Samuel V. Glass; Anton TenWolde; Samuel L. Zelinka

    2013-01-01

    Is it possible to gauge the risk of moisture problems while designing the building envelope? This article provides a brief introduction to computer-based hygrothermal (heat and moisture) simulation, shows how simulation can be useful as a design tool, and points out a number of im-portant considerations regarding model inputs and limita-tions. Hygrothermal simulation...

  16. 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

  17. 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

  18. LSST Operational Cadence Simulation and Design

    NASA Astrophysics Data System (ADS)

    Cook, K. H.; Saha, A.; Pierfedrici, F.; Allsman, R.; Delgado, F.; Pinto, P. A.

    2004-12-01

    With its unprecedented combination of collecting area and field of view, the LSST will image large areas of the sky frequently and to great depth. The cadence of these observations, the order in which different fields of view are observed in each color and the frequency with which they are revisited, will determine just how much sky will be covered, to what depth, and with what temporal sampling. This in turn will determine how useful LSST data will be to different investigations. The development of observing cadences is thus an important part of the LSST design process. A great many scientific programs require multiple, short exposures. As a result, detailed simulations of a decade of LSST operation demonstrate cadences which will satisfy a wide variety of scientific requirements simultaneously. They also demonstrate that there is surprisingly little conflict among the cadence demands of projects as diverse as whole-sky weak lens surveys, near-Earth asteroid, outer solar system, and supernova searches, and catching transients and characterizing variability on a wide variety of timescales. This shows that the LSST need not be "over-engineered" for any given project to be useful for doing many at the same time.

  19. 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

  20. Telecom Link--A Competitive Simulated Design Exercise.

    ERIC Educational Resources Information Center

    Freeman, J.; Allen, J.

    1982-01-01

    Telecom link is a structured design exercise concerned with building a telecommunications link between London and Amsterdam. Designed for A-level physics, the simulation requires a minimum of 10 hours. Aims of the exercise, design specifications and technical aspects, and summaries of four possible technologies used in the simulation are…

  1. Designing with Ada for satellite simulation: A case study

    NASA Technical Reports Server (NTRS)

    Agresti, W. W.; Church, V. E.; Card, D. N.; Lo, P. L.

    1986-01-01

    A FORTRAN oriented and an Ada oriented design for the same system are compared to learn whether an essentially different design was produced using Ada. The designs were produced by an experiment that involves the parallel development of software for a spacecraft dynamics simulator. Design differences are identified in the use of abstractions, system structure, and simulator operations. Although the designs were vastly different, this result may be influenced by some special characteristics discussed.

  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. 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

  4. Designing and conducting simulation-based research.

    PubMed

    Cheng, Adam; Auerbach, Marc; Hunt, Elizabeth A; Chang, Todd P; Pusic, Martin; Nadkarni, Vinay; Kessler, David

    2014-06-01

    As simulation is increasingly used to study questions pertaining to pediatrics, it is important that investigators use rigorous methods to conduct their research. In this article, we discuss several important aspects of conducting simulation-based research in pediatrics. First, we describe, from a pediatric perspective, the 2 main types of simulation-based research: (1) studies that assess the efficacy of simulation as a training methodology and (2) studies where simulation is used as an investigative methodology. We provide a framework to help structure research questions for each type of research and describe illustrative examples of published research in pediatrics using these 2 frameworks. Second, we highlight the benefits of simulation-based research and how these apply to pediatrics. Third, we describe simulation-specific confounding variables that serve as threats to the internal validity of simulation studies and offer strategies to mitigate these confounders. Finally, we discuss the various types of outcome measures available for simulation research and offer a list of validated pediatric assessment tools that can be used in future simulation-based studies. Copyright © 2014 by the American Academy of Pediatrics.

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

    PubMed

    Coyle, Scott M; Lim, Wendell A

    2016-01-14

    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.

  6. 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.

  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. 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.

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

    PubMed Central

    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

    2012-01-01

    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. PMID:21968647

  12. Integrated simulation environment for lighting design

    SciTech Connect

    Pal, Vineeta; Papamichael, Konstantinos

    2001-05-24

    Lighting design involves the consideration of multiple performance criteria, from the earliest stages of conceptual design, through various stages of controls and operation in a project's life cycle. These criteria include: (1) the quantitative analysis of illuminance and luminance distribution due to daylighting and electric lighting; (2) qualitative analysis of the lighting design with photometrically accurate renderings of the designed environment; (3) analysis of energy implications of daylighting and electric lighting design and operation;, and (4) analysis of control strategies and sensor placement for maximizing energy savings from lighting control while providing visual comfort. In this paper we describe the development of an integrated decision-making environment that brings together several different tools, and provides the data management and process control required for a multi-criterion support of the design and operation of daylighting and electric lighting systems. The result is a powerful design and decision-making environment to meet the diverse and evolving needs of lighting designers and operators.

  13. 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.

  14. 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…

  15. 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…

  16. 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.

  17. 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

  18. Simulation Design: Engaging Large Groups of Nurse Practitioner Students.

    PubMed

    Garnett, Susan; Weiss, Josie A; Winland-Brown, Jill E

    2015-09-01

    Little has been written about using human patient simulation to teach primary care management to large groups of nurse practitioner (NP) students. This article describes an innovative design for simulated clinical experiences based on a game show format. This large-group design was conceived as a way to overcome several challenges, particularly limited faculty resources, to integrating simulation into NP education. Progressive variations evolved from this foundation, including the use of observer-participant groups; initial and follow-up visits on the same simulated patient; and mentor-mentee collaborations. Student comments, while consistently positive about the simulated clinical experiences, have been used to guide revisions to strengthen the simulation program. The innovative large-group design enabled faculty to use simulation to enhance students' skills in primary care management. Faculties with similar challenges might find these strategies useful to replicate or adapt. Copyright 2015, SLACK Incorporated.

  19. 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.

  20. 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

  1. 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.

  2. Ras in Cancer and Developmental Diseases

    PubMed Central

    Fernández-Medarde, Alberto; Santos, Eugenio

    2011-01-01

    Somatic, gain-of-function mutations in ras genes were the first specific genetic alterations identified in human cancer about 3 decades ago. Studies during the last quarter century have characterized the Ras proteins as essential components of signaling networks controlling cellular proliferation, differentiation, or survival. The oncogenic mutations of the H-ras, N-ras, or K-ras genes frequently found in human tumors are known to throw off balance the normal outcome of those signaling pathways, thus leading to tumor development. Oncogenic mutations in a number of other upstream or downstream components of Ras signaling pathways (including membrane RTKs or cytosolic kinases) have been detected more recently in association with a variety of cancers. Interestingly, the oncogenic Ras mutations and the mutations in other components of Ras/MAPK signaling pathways appear to be mutually exclusive events in most tumors, indicating that deregulation of Ras-dependent signaling is the essential requirement for tumorigenesis. In contrast to sporadic tumors, separate studies have identified germline mutations in Ras and various other components of Ras signaling pathways that occur in specific association with a number of different familial, developmental syndromes frequently sharing common phenotypic cardiofaciocutaneous features. Finally, even without being a causative force, defective Ras signaling has been cited as a contributing factor to many other human illnesses, including diabetes and immunological and inflammatory disorders. We aim this review at summarizing and updating current knowledge on the contribution of Ras mutations and altered Ras signaling to development of various tumoral and nontumoral pathologies. PMID:21779504

  3. 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.

  4. Design of a Small-Scale Unmanned Helicopter Simulation System

    NASA Astrophysics Data System (ADS)

    Deng, Hong-Bin; Wang, Jin-Hua; Liu, Pei-Zhi; Peng, Yu-Hua; Tang, Xiao-Ying; Li, Han-Jun; Zeng, Yan-Jun

    This paper investigates the design of an unmanned helicopter simulation system with Matlab, and completes the development of modeling, the navigation system, device input system, control system and virtual reality system, eventually accomplishing a simulation system which can freely alternate between manned mode and unmanned mode. Based on flight tests, it is shown that the simulation and test results agree well, indicating that the simulation system accurately describes the characteristics of helicopter dynamics and the control system.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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…

  15. 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.

  16. 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.

  17. 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.

  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. 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.

  1. 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.

  2. 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.

  3. Enhanced Ras activity in pyramidal neurons induces cellular hypertrophy and changes in afferent and intrinsic connectivity in synRas mice.

    PubMed

    Gärtner, Ulrich; Alpár, Alán; Seeger, Gudrun; Heumann, Rolf; Arendt, Thomas

    2004-05-01

    Neurotrophic actions are critically controlled and transmitted to cellular responses by the small G protein Ras which is therefore essential for normal functioning and plasticity of the nervous system. The present study summarises findings of recent studies on morphological changes in the neocortex of synRas mice expressing Val12-Ha-Ras in vivo under the control of the rat synapsin I promoter. In the here reported model (introduced by Heumann et al. [J. Cell Biol. 151 (2000) 1537]), transgenic Val12-Ha-Ras expression is confined to the pyramidal cell population and starts postnatally at a time, when neurons are postmitotic and their developmental maturation has been basically completed. Expression of Val12-Ha-Ras results in a significant enlargement of pyramidal neurons. Size, complexity and spine density of dendritic trees are increased, which leads, finally, to cortical expansion. However, the main morphological design principles of 'transgenic' pyramidal cells remain preserved. In addition to somato-dendritic changes, expression of Val12-Ha-Ras in pyramidal cells induces augmented axon calibres and upregulates the establishment of efferent boutons. Despite the enlargement of cortical size, the overall density of terminals representing intra- or interhemispheric, specific and non-specific afferents is unchanged or even higher in transgenic mice suggesting a significant increase in the total afferent input to the neocortex. Although interneurons do not express the transgene and are therefore excluded from direct, intrinsic Val12-Ha-Ras effects, they respond with morphological adaptations to structural changes. Thus, dendritic arbours of interneurons are extended to follow the cortical expansion and basket cells establish a denser inhibitory innervation of 'transgenic' pyramidal cells perikarya. It is concluded that expression of Val12-Ha-Ras in pyramidal neurons results in remodelling of neocortical structuring which strongly implicates a crucial involvement of

  4. 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.

  5. Symplectic molecular dynamics simulations on specially designed parallel computers.

    PubMed

    Borstnik, Urban; Janezic, Dusanka

    2005-01-01

    We have developed a computer program for molecular dynamics (MD) simulation that implements the Split Integration Symplectic Method (SISM) and is designed to run on specialized parallel computers. The MD integration is performed by the SISM, which analytically treats high-frequency vibrational motion and thus enables the use of longer simulation time steps. The low-frequency motion is treated numerically on specially designed parallel computers, which decreases the computational time of each simulation time step. The combination of these approaches means that less time is required and fewer steps are needed and so enables fast MD simulations. We study the computational performance of MD simulation of molecular systems on specialized computers and provide a comparison to standard personal computers. The combination of the SISM with two specialized parallel computers is an effective way to increase the speed of MD simulations up to 16-fold over a single PC processor.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Ras Regulates Rb via NORE1A*

    PubMed Central

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

    2016-01-01

    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. PMID:26677227

  14. CAGE IIIA Distributed Simulation Design Methodology

    DTIC Science & Technology

    2014-05-01

    Greenach Mean Time GOTS Government Off The Shelf GPS Global Positioning System GW Gate Way HD Hard Drive HICON Higher Control HOA Horn of Africa HQ...Organisation SF Special Forces SME Subject Matter Expert SOCET GXP SOCET GXP is a geospatial-intelligence software package that uses imagery...Implementing Defence Experimentation (GUIDEx). The key challenges for this methodology are with understanding how to: • design it o define the

  15. 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…

  16. 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.

  17. 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…

  18. 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…

  19. 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…

  20. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    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.

  3. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2011-01-01

    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. PMID:21945529

  5. 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.

  6. Clinical Validation of a Multiplex Kit for RAS Mutations in Colorectal Cancer: Results of the RASKET (RAS KEy Testing) Prospective, Multicenter Study

    PubMed Central

    Yoshino, Takayuki; Muro, Kei; Yamaguchi, Kensei; Nishina, Tomohiro; Denda, Tadamichi; Kudo, Toshihiro; Okamoto, Wataru; Taniguchi, Hiroya; Akagi, Kiwamu; Kajiwara, Takeshi; Hironaka, Shuichi; Satoh, Taroh

    2015-01-01

    Background RAS (KRAS and NRAS) testing is required to predict anti-epidermal growth factor receptor (EGFR) treatment efficacy in metastatic colorectal cancer (CRC). Although direct sequencing (DS) with manual microdissection (MMD) is widely used, a diagnostic kit providing rapid detections of RAS mutations would be clinically beneficial. We evaluated the MEBGENTM RASKET KIT (RASKET KIT), a multiplex assay using PCR-reverse sequence specific oligonucleotide and xMAP® technology to concurrently detect exon 2, 3, and 4 RAS mutations in a short turnaround time (4.5 h/96-specimens). Methods Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 308 consenting patients with histologically-confirmed CRC at six hospitals in Japan. For the RASKET KIT, we used only 50–100 ng DNA from each FFPE specimen not processed by MMD. The primary endpoint was the concordance rate between RAS mutations identified with the RASKET KIT and two reference assays (DS with MMD and TheraScreen® K-RAS Mutation Kit). As the secondary endpoints, we evaluated the concordance rate between DS and the RASKET KIT for RAS mutations in the wild-type KRAS exon 2 population and the genotyping performance of the RASKET KIT compared with DS. Findings Among 307 analyzable specimens, the reference assays detected 140 (45.6%, 140/307) RAS mutations: 111 KRAS exon 2 and 29 other (minor) RAS mutations. The RASKET KIT detected 143 (46.6%, 143/307) mutations: 114 KRAS exon 2 and 29 minor RAS mutations. The between-method concordance rate was 96.7% (297/307) (95% CI: 94.1–98.4%). Minor RAS mutations were detected in 15.7% (30/191) of the wild-type KRAS exon 2 population (n = 191); the concordance rate was 98.4% (188/191) (95% CI: 95.5–99.7%). The concordance rate of RAS genotyping was 100% (139/139) (95% CI: 97–100%). Interpretation The RASKET KIT provides rapid and precise detections of RAS mutations and consequently, quicker and more effective anti-EGFR therapy for CRC (Study ID: UMIN

  7. K-ras-driven engineered mouse models for pancreatic cancer.

    PubMed

    Yin, Xuyuan; Su, Jingna; Zhou, Xiuxiao; Guo, Jianping; Wei, Wenyi; Wang, Zhiwei

    2015-01-01

    Pancreatic cancer (PC) is one of the most fatal cancers largely due to the lack of early diagnosis and effective therapies. Therefore, further understanding the underlying molecular mechanisms of PC development and progression is pivotal to the development of more effective targeted therapies. Emerging evidence has suggested that using mouse models, especially genetically engineered mouse models, is ideal to explore the mechanisms of pancreatic tumorigenesis. To this end, it has been known that a K-ras mutation on codon 12 (K-ras G12D) plays a critical role in the PC development. Thus, most mouse models of PC have been developed by targeting a conditionally mutated K-ras (G12D) together with concomitant deletion or mutation of other key genes to recapitulate the PC progression in human patients. Here, we summarize a number of K-ras-driven engineered mouse models to provide molecular insights into PC disease development and progression. We hope that these mouse models will help design a novel therapeutic strategy and to further improve the treatment of PC patients.

  8. 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

  9. 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."

  10. 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.

  11. 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…

  12. 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…

  13. 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…

  14. 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…

  15. 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…

  16. 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.

  17. Design by dragging: an interface for creative forward and inverse design with simulation ensembles.

    PubMed

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

    2013-12-01

    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.

  18. 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

  19. Design of simulation-based medical education and advantages and disadvantages of in situ simulation versus off-site simulation.

    PubMed

    Sørensen, Jette Led; Østergaard, Doris; LeBlanc, Vicki; Ottesen, Bent; Konge, Lars; Dieckmann, Peter; Van der Vleuten, Cees

    2017-01-21

    Simulation-based medical education (SBME) has traditionally been conducted as off-site simulation in simulation centres. Some hospital departments also provide off-site simulation using in-house training room(s) set up for simulation away from the clinical setting, and these activities are called in-house training. In-house training facilities can be part of hospital departments and resemble to some extent simulation centres but often have less technical equipment. In situ simulation, introduced over the past decade, mainly comprises of team-based activities and occurs in patient care units with healthcare professionals in their own working environment. Thus, this intentional blend of simulation and real working environments means that in situ simulation brings simulation to the real working environment and provides training where people work. In situ simulation can be either announced or unannounced, the latter also known as a drill. This article presents and discusses the design of SBME and the advantage and disadvantage of the different simulation settings, such as training in simulation-centres, in-house simulations in hospital departments, announced or unannounced in situ simulations. Non-randomised studies argue that in situ simulation is more effective for educational purposes than other types of simulation settings. Conversely, the few comparison studies that exist, either randomised or retrospective, show that choice of setting does not seem to influence individual or team learning. However, hospital department-based simulations, such as in-house simulation and in situ simulation, lead to a gain in organisational learning. To our knowledge no studies have compared announced and unannounced in situ simulation. The literature suggests some improved organisational learning from unannounced in situ simulation; however, unannounced in situ simulation was also found to be challenging to plan and conduct, and more stressful among participants. The importance of

  20. 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

  1. 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

  2. Optimizing depuration of salmon in RAS

    USDA-ARS?s Scientific Manuscript database

    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. ...

  3. 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.

  4. 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.

  5. Molecular interaction between K-Ras and H-REV107 in the Ras signaling pathway.

    PubMed

    Han, Chang Woo; Jeong, Mi Suk; Jang, Se Bok

    2017-09-16

    Ras proteins are small GTPases that serve as master moderators of a large number of signaling pathways involved in various cellular processes. Activating mutations in Ras are found in about one-third of cancers. H-REV107, a K-Ras binding protein, plays an important role in determining K-Ras function. H-REV107 is a member of the HREV107 family of class II tumor suppressor genes and a growth inhibitory Ras target gene that suppresses cellular growth, differentiation, and apoptosis. Expression of H-REV107 was strongly reduced in about 50% of human carcinoma cell lines. However, the specific molecular mechanism by which H-REV107 inhibits Ras is still unknown. In the present study, we suggest that H-REV107 forms a strong complex with activating oncogenic mutation Q61H K-Ras from various biochemical binding assays and modeled structures. In addition, the interaction sites between K-Ras and H-REV107 were predicted based on homology modeling. Here, we found that some structure-based mutants of the K-Ras disrupted the complex formation with H-REV107. Finally, a novel molecular mechanism describing K-Ras and H-REV107 binding is suggested and insights into new K-Ras effector target drugs are provided. Copyright © 2017 Elsevier Inc. All rights reserved.

  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. SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation.

    PubMed

    Zhang, Xiaoyu; Spiegelman, Nicole A; Nelson, Ornella D; Jing, Hui; Lin, Hening

    2017-04-13

    The Ras family of GTPases are important in cell signaling and frequently mutated in human tumors. Understanding their regulation is thus important for studying biology and human diseases. Here, we report that a novel posttranslational mechanism, reversible lysine fatty acylation, regulates R-Ras2, a member of the Ras family. SIRT6, a sirtuin with established tumor suppressor function, regulates the lysine fatty acylation of R-Ras2. In mouse embryonic fibroblasts (MEFs), Sirt6 knockout (KO) increased R-Ras2 lysine fatty acylation. Lysine fatty acylation promotes the plasma membrane localization of R-Ras2 and its interaction with phosphatidylinositol 3-kinase PI3K, leading to activated Akt and increased cell proliferation. Our study establishes lysine fatty acylation as a previously unknown mechanism that regulates the Ras family of GTPases and provides an important mechanism by which SIRT6 functions as a tumor suppressor.

  8. 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.

  9. 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.

  10. 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.

  11. Design-Based Comparison of Spine Surgery Simulators: Optimizing Educational Features of Surgical Simulators.

    PubMed

    Ryu, Won Hyung A; Mostafa, Ahmed E; Dharampal, Navjit; Sharlin, Ehud; Kopp, Gail; Jacobs, W Bradley; Hurlbert, R John; Chan, Sonny; Sutherland, Garnette R

    2017-10-01

    Simulation-based education has made its entry into surgical residency training, particularly as an adjunct to hands-on clinical experience. However, one of the ongoing challenges to wide adoption is the capacity of simulators to incorporate educational features required for effective learning. The aim of this study was to identify strengths and limitations of spine simulators to characterize design elements that are essential in enhancing resident education. We performed a mixed qualitative and quantitative cohort study with a focused survey and interviews of stakeholders in spine surgery pertaining to their experiences on 3 spine simulators. Ten participants were recruited spanning all levels of training and expertise until qualitative analysis reached saturation of themes. Participants were asked to perform lumbar pedicle screw insertion on 3 simulators. Afterward, a 10-item survey was administrated and a focused interview was conducted to explore topics pertaining to the design features of the simulators. Overall impressions of the simulators were positive with regards to their educational benefit, but our qualitative analysis revealed differing strengths and limitations. Main design strengths of the computer-based simulators were incorporation of procedural guidance and provision of performance feedback. The synthetic model excelled in achieving more realistic haptic feedback and incorporating use of actual surgical tools. Stakeholders from trainees to experts acknowledge the growing role of simulation-based education in spine surgery. However, different simulation modalities have varying design elements that augment learning in distinct ways. Characterization of these design characteristics will allow for standardization of simulation curricula in spinal surgery, optimizing educational benefit. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2015-01-01

    RAS proteins require membrane association for their biological 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 (FTIs) were developed as potential anti-RAS drugs. The lack of efficacy of FTIs as anti-cancer 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 post-translational 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. PMID:25878363

  13. 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.

  14. Vestibular models for design and evaluation of flight simulator motion

    NASA Technical Reports Server (NTRS)

    Bussolari, S. R.; Sullivan, R. B.; Young, L. R.

    1986-01-01

    The use of spatial orientation models in the design and evaluation of control systems for motion-base flight simulators is investigated experimentally. The development of a high-fidelity motion drive controller using an optimal control approach based on human vestibular models is described. The formulation and implementation of the optimal washout system are discussed. The effectiveness of the motion washout system was evaluated by studying the response of six motion washout systems to the NASA/AMES Vertical Motion Simulator for a single dash-quick-stop maneuver. The effects of the motion washout system on pilot performance and simulator acceptability are examined. The data reveal that human spatial orientation models are useful for the design and evaluation of flight simulator motion fidelity.

  15. 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.

  16. LEGO - A Class Library for Accelerator Design and Simulation

    SciTech Connect

    Cai, Yunhai

    1998-11-19

    An object-oriented class library of accelerator design and simulation is designed and implemented in a simple and modular fashion. All physics of single-particle dynamics is implemented based on the Hamiltonian in the local frame of the component. Symplectic integrators are used to approximate the integration of the Hamiltonian. A differential algebra class is introduced to extract a Taylor map up to arbitrary order. Analysis of optics is done in the same way both for the linear and non-linear cases. Recently, Monte Carlo simulation of synchrotron radiation has been added into the library. The code is used to design and simulate the lattices of the PEP-II and SPEAR3. And it is also used for the commissioning of the PEP-II. Some examples of how to use the library will be given.

  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. 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.

  19. The navigation receiver simulation and estimate software system design

    NASA Astrophysics Data System (ADS)

    Yi, Xiaoxiao; Zhao, Yan

    2006-11-01

    Developing the satellite positioning and navigation system independently is a huge project. Establishing the simulation and estimate software system for navigation receivers can supply reference data for developing and improving real receivers. This paper analyzed the general structure of the receiver, presented a more feasible design method for the receiver simulation and estimate software system, introduced some estimate items and the data or algorithms which the items needed, and proposed a solution to C/A code rapid acquisition with inertial navigation system (INS) assisting. This software system consists of a signal simulator, a navigation receiver simulator and a receiver estimate software and is based on MATLAB/SIMULINK. It helps to configure a precise receiver simulation and estimate system.

  20. 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.

  1. 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.

  2. Software Design for Interactive Graphic Radiation Treatment Simulation Systems*

    PubMed Central

    Kalet, Ira J.; Sweeney, Christine; Jacky, Jonathan

    1990-01-01

    We examine issues in the design of interactive computer graphic simulation programs for radiation treatment planning (RTP), as well as expert system programs that automate parts of the RTP process, in light of ten years of experience at designing, building and using such programs. An experiment in object-oriented design using standard Pascal shows that while some advantage is gained from the design, it is still difficult to achieve modularity and to integrate expert system components. A new design based on the Common LISP Object System (CLOS) is described. This series of designs for RTP software shows that this application benefits in specific ways from object-oriented design methods and appropriate languages and tools.

  3. 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.

  4. Design and simulation challenges for FERMI@elettra

    NASA Astrophysics Data System (ADS)

    Di Mitri, S.; Allaria, E.; Badano, L.; Bontoiu, C.; Cornacchia, M.; Craievich, P.; Danailov, M.; De Ninno, G.; Diviacco, B.; Ferrando, O.; Ferry, S.; Iazzourene, F.; Milton, S. V.; Penco, G.; Spampinati, S.; Trovo', M.; Veronese, M.; Fawley, W.; Lidia, S.; Penn, G.; Qiang, J.; Sonnad, K. G.; Venturini, M.; Warnock, R.; Zholents, A. A.; Pogorelov, I. V.; Borland, M.; Bassi, G.; Ellison, J. A.; Heinemann, K.; Fiorito, R.; Shkvarunets, A.; Tobin, J. C.

    2009-09-01

    FERMI@elettra is a fourth-generation light source user facility under construction at the Elettra Laboratory in Trieste, Italy. The high-quality 1.2 GeV electron beam drives two-seeded Free Electron Lasers (FELs) in the wavelength range 100-10 nm. Wavelength tunability, variable polarization and higher electron beam energies to reach even shorter output wavelengths are also in the machine delivery plan. This paper describes the physics processes that have been modelled to simulate FERMI@elettra and the computer codes used to optimize the machine design. The paper focuses on several design challenges and how these translate into modelling and simulation challenges.

  5. 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.

  6. Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence*

    PubMed Central

    Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L.; Embrey, Kevin J.; Golovanov, Alexander P.

    2016-01-01

    The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly 15N-labeled Ras as well as [13C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. PMID:26565026

  7. Optimization of a neutron detector design using adjoint transport simulation

    SciTech Connect

    Yi, C.; Manalo, K.; Huang, M.; Chin, M.; Edgar, C.; Applegate, S.; Sjoden, G.

    2012-07-01

    A synthetic aperture approach has been developed and investigated for Special Nuclear Materials (SNM) detection in vehicles passing a checkpoint at highway speeds. SNM is postulated to be stored in a moving vehicle and detector assemblies are placed on the road-side or in chambers embedded below the road surface. Neutron and gamma spectral awareness is important for the detector assembly design besides high efficiencies, so that different SNMs can be detected and identified with various possible shielding settings. The detector assembly design is composed of a CsI gamma-ray detector block and five neutron detector blocks, with peak efficiencies targeting different energy ranges determined by adjoint simulations. In this study, formulations are derived using adjoint transport simulations to estimate detector efficiencies. The formulations is applied to investigate several neutron detector designs for Block IV, which has its peak efficiency in the thermal range, and Block V, designed to maximize the total neutron counts over the entire energy spectrum. Other Blocks detect different neutron energies. All five neutron detector blocks and the gamma-ray block are assembled in both MCNP and deterministic simulation models, with detector responses calculated to validate the fully assembled design using a 30-group library. The simulation results show that the 30-group library, collapsed from an 80-group library using an adjoint-weighting approach with the YGROUP code, significantly reduced the computational cost while maintaining accuracy. (authors)

  8. 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

  9. 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."

  10. Improved Pyrolysis Micro reactor Design via Computational Fluid Dynamics Simulations

    DTIC Science & Technology

    2017-05-23

    NUMBER (Include area code) 23 May 2017 Briefing Charts 25 April 2017 - 23 May 2017 Improved Pyrolysis Micro-reactor Design via Computational Fluid... PYROLYSIS MICRO-REACTOR DESIGN VIA COMPUTATIONAL FLUID DYNAMICS SIMULATIONS Ghanshyam L. Vaghjiani* DISTRIBUTION A: Approved for public release...Approved for public release, distribution unlimited. PA Clearance 17247 Chen-Source (>240 references from SciFinder as of 5/1/17): Flash pyrolysis

  11. 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.

  12. 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

  13. Structured Analysis and Design of a Satellite Simulator

    DTIC Science & Technology

    1977-09-01

    Conatraints ... 6 Functional Specifications „.... 7 Summary ...... • 9 III . Preliminary Design ..... 11 Introduction ........ ... 11...iv List of Fl.’:ur’’". Figura 26 Sequence Errors . , 27 Current Statue Data ••••.•...••••••••• 28 Vehicle Message Data 29 Output Messages 50a...emphasis placed on the functional specifications. Chapter III presents a Preliminary Design of the simulator in the form of activity and data models

  14. 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.

  15. 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.

  16. 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

  17. Black Blizzard: Designing Role-Play Simulations for Education

    ERIC Educational Resources Information Center

    Linser, Roni; Ree-Lindstad, Nina; Vold, Tone

    2007-01-01

    This paper outlines and analyses some key design issues we encountered in the process of creating an online role-play simulation (RPS) for a course targeting personnel involved in crisis management. Titled "Black Blizzard" the RPS aims to enable an exploration of typical issues and problems that arise in cross and multi-cultural international…

  18. 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

  19. 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.

  20. 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.

  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. 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.

  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. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Enzymatic and antisense effects of a specific anti-Ki-ras ribozyme in vitro and in cell culture.

    PubMed Central

    Giannini, C D; Roth, W K; Piiper, A; Zeuzem, S

    1999-01-01

    Due to their mode of action, ribozymes show antisense effects in addition to their specific cleavage activity. In the present study we investigated whether a hammerhead ribozyme is capable of cleaving mutated Ki-ras mRNA in a pancreatic carcinoma cell line and whether antisense effects contribute to the activity of the ribozyme. A 2[prime]-O-allyl modified hammerhead ribozyme was designed to cleave specifically the mutated form of the Ki- ras mRNA (GUU motif in codon 12). The activity was monitored by RT-PCR on Ki- ras RNA expression by determination of the relative amount of wild type to mutant Ki-ras mRNA, by 5-bromo-2[prime]-deoxy-uridine incorporation on cell proliferation and by colony formation in soft agar on malignancy in the human pancreatic adenocarcinoma cell line CFPAC-1, which is heterozygous for the Ki-ras mutation. A catalytically inactive ribozyme was used as control to differentiate between antisense and cleavage activity and a ribozyme with random guide sequences as negative control. The catalytically active anti-Ki-ras ribozyme was at least 2-fold more potent in decreasing cellular Ki-ras mRNA levels, inhibiting cell proliferation and colony formation in soft agar than the catalytically inactive ribozyme. The catalytically active anti-Ki-ras ribozyme, but not the catalytically inactive or random ribozyme, increased the ratio of wild type to mutated Ki-ras mRNA in CFPAC-1 cells. In conclusion, both cleavage activity and antisense effects contribute to the activity of the catalytically active anti-Ki-ras hammerhead ribozyme. Specific ribozymes might be useful in the treatment of pancreatic carcinomas containing an oncogenic GTT mutation in codon 12 of the Ki-ras gene. PMID:10373591

  12. 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

  13. 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.

  14. 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

  15. Microelectronics package design using experimentally-validated modeling and simulation.

    SciTech Connect

    Johnson, Jay Dean; Young, Nathan Paul; Ewsuk, Kevin Gregory

    2010-11-01

    Packaging high power radio frequency integrated circuits (RFICs) in low temperature cofired ceramic (LTCC) presents many challenges. Within the constraints of LTCC fabrication, the design must provide the usual electrical isolation and interconnections required to package the IC, with additional consideration given to RF isolation and thermal management. While iterative design and prototyping is an option for developing RFIC packaging, it would be expensive and most likely unsuccessful due to the complexity of the problem. To facilitate and optimize package design, thermal and mechanical simulations were used to understand and control the critical parameters in LTCC package design. The models were validated through comparisons to experimental results. This paper summarizes an experimentally-validated modeling approach to RFIC package design, and presents some results and key findings.

  16. 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.

  17. 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.

  18. Comparing simulated emission from molecular clouds using experimental design

    SciTech Connect

    Yeremi, Miayan; Flynn, Mallory; Loeppky, Jason; Rosolowsky, Erik; Offner, Stella

    2014-03-10

    We propose a new approach to comparing simulated observations that enables us to determine the significance of the underlying physical effects. We utilize the methodology of experimental design, a subfield of statistical analysis, to establish a framework for comparing simulated position-position-velocity data cubes to each other. We propose three similarity metrics based on methods described in the literature: principal component analysis, the spectral correlation function, and the Cramer multi-variate two-sample similarity statistic. Using these metrics, we intercompare a suite of mock observational data of molecular clouds generated from magnetohydrodynamic simulations with varying physical conditions. Using this framework, we show that all three metrics are sensitive to changing Mach number and temperature in the simulation sets, but cannot detect changes in magnetic field strength and initial velocity spectrum. We highlight the shortcomings of one-factor-at-a-time designs commonly used in astrophysics and propose fractional factorial designs as a means to rigorously examine the effects of changing physical properties while minimizing the investment of computational resources.

  19. 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.

  20. Ras GTPases’ interaction with effector domains

    PubMed Central

    Patel, Manishha; Côté, Jean-François

    2013-01-01

    The Ras superfamily of proteins consists of five branches: Ras, Rho, Arf, Rab and Ran subfamilies. These proteins are involved in a plethora of biological functions spanning cytoskeletal organization, cell proliferation, transcription and intracellular trafficking. Ras-Binding Domains (RBDs) have classically been identified as autonomous ubiquitin-like folded regions that bind certain activated Ras GTPases of the Ras subfamily. In general, RBDs in many proteins have been tagged with membrane-targeting functions as in the case of the well-characterized c-Raf-RBD/Ras interaction. However, it is becoming apparent that the definition and functions of RBDs need to be revamped in order to reflect the new discoveries associated with this domain. Here, we discuss in more detail the recent advances associated with these RBDs. We highlight research identifying RBDs in formins, ELMOs and the RhoGEF, Syx and discuss the emerging role for RBDs in controlling autoinhibition relief and the newly recognized versatility of RBDs to interact with Rho and Arf family GTPases. In addition, these recent findings raise the exciting hypothesis that functional RBDs remain hidden in the proteome and are ready to be uncovered. PMID:23986800

  1. Simulation and optimal design for deformable mirror supporting structure

    NASA Astrophysics Data System (ADS)

    Zhao, Fu; Wang, Ping; Gong, Yanjue; Lin, Jianlong; Xiang, Huiyu

    2009-11-01

    This article takes a kind of special supporting structure of deformable mirror as an example to make deeply study on its optimal design and validity simulation based on finite element analysis. The original resonance frequency and modes shape of the supporting structure are obtained with the FEA method and the dynamic theory. Then a group of optimized structure parameters are determined with the BP networks and Genetic Algorithm optimal methods. The simulation analyses including random vibration, harmonic response and fatigue life are carried out to demonstrate that the dynamic stiffness of the optimized supporting structure has been improved greatly by the presented optimization method.

  2. 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.

  3. Design of a Hospital Simulation Software for Nursing Education.

    PubMed

    Cervi, Gustavo Henrique; Flores, Cecília Dias; Somensi, Rute Merlo; Caregnato, Rita Catalina Aquino

    2016-01-01

    This work aims to describe the inception and design for a hospital simulator based on data and cases provided by teachers and other randomized data. The main goal is to develop a computer software tool that simulates a hospital as a tool for nursing student. The system is based on a multi-agent model and multi threaded parallel processing. Other parts includes the interfaces for teacher and student, reports and fixed constraints like Laws and other rules. This is a work in progress project and will be released as open source software after the final validation.

  4. 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.

  5. 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.

  6. Simulation-Guided DNA Probe Design for Consistently Ultraspecific Hybridization

    PubMed Central

    Wang, J. Sherry; Zhang, David Yu

    2015-01-01

    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 for analyzing nucleic acids. Thermodynamics-guided probe design and empirical optimization of reaction conditions have been used to enable discrimination of single nucleotide variants, but typically these approaches provide only an approximate 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 different target single nucleotide variants sequences showed between 200- and 3000-fold (median 890) higher binding affinity than their corresponding wildtype sequences. As a demonstration of the usefulness of this simulation-guided design approach we developed probes which, in combination with PCR amplification, we use to detect low concentrations of variant alleles (1%) in human genomic DNA. PMID:26100802

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

    PubMed

    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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Design and simulation of HTS bulk linear synchronous motor

    NASA Astrophysics Data System (ADS)

    Yoshida, K.; Matsumoto, H.

    2002-10-01

    A new type high temperature superconducting (HTS) bulk linear synchronous motor (LSM) theory is proposed by authors which is based on an idea of considering the pinning force as a synchronizing one in using current-carrying-armature-winding instead of permanent magnets. Electromagnetic force which HTS bulk produces depends on strongly the space distribution of an applied magnetic field under field cooling. LSM thrust force distribution on HTS bulk which is essentially different from that on a permanent magnet. It is generally difficult to design HTS bulk LSM. This paper presents a design of HTS bulk LSM by the finite element method (FEM) and its dynamics simulation of propulsion motion. Dynamics simulation is carried out using an instantaneous-maximum-thrust-force control method proposed here which is based on an analytical formula of LSM thrust force derived from the FEM capable of modeling HTS bulk.

  2. 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.

  3. 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.

  4. Flexible Space-Filling Designs for Complex System Simulations

    DTIC Science & Technology

    2013-06-01

    ACKNOWLEDGEMENTS I want to thank Gene Paulo for supporting me as my Dissertation Advisor, but also for being such a good friend and mentor. I hope we can...two uniform grids of 11 points 71 that range from –1 to 1, one grid for the true model and one grid for the predicted model ( Goel , Tushar, Raphael...simulation models early in the architectural design of a ship. The traditional naval architect paradigm is to design the weapon systems, radars , or any

  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. 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.

  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. 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

  9. 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.

  10. 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.

  11. Design of an immersive simulator for assisted power wheelchair driving.

    PubMed

    Devigne, Louise; Babel, Marie; Nouviale, Florian; Narayanan, Vishnu K; Pasteau, Francois; Gallien, Philippe

    2017-07-01

    Driving a power wheelchair is a difficult and complex visual-cognitive task. As a result, some people with visual and/or cognitive disabilities cannot access the benefits of a power wheelchair because their impairments prevent them from driving safely. In order to improve their access to mobility, we have previously designed a semi-autonomous assistive wheelchair system which progressively corrects the trajectory as the user manually drives the wheelchair and smoothly avoids obstacles. Developing and testing such systems for wheelchair driving assistance requires a significant amount of material resources and clinician time. With Virtual Reality technology, prototypes can be developed and tested in a risk-free and highly flexible Virtual Environment before equipping and testing a physical prototype. Additionally, users can "virtually" test and train more easily during the development process. In this paper, we introduce a power wheelchair driving simulator allowing the user to navigate with a standard wheelchair in an immersive 3D Virtual Environment. The simulation framework is designed to be flexible so that we can use different control inputs. In order to validate the framework, we first performed tests on the simulator with able-bodied participants during which the user's Quality of Experience (QoE) was assessed through a set of questionnaires. Results show that the simulator is a promising tool for future works as it generates a good sense of presence and requires rather low cognitive effort from users.

  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 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

  15. 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

  16. 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.

  17. Micro-Venturi injector: design, experimental and simulative examination

    NASA Astrophysics Data System (ADS)

    Degenhardt, S.; Cheriguen, Y.; Geiling, T.; Hoffmann, M.

    2016-10-01

    This paper reports the first factorial design of a micro Venturi injector completed by a simulative investigation of the device. For the first time, a comprehensive correlation between the point of the maximum vacuum pressure generated by the Venturi nozzle and the variation of the inlet pressure is shown. The device reported in this contribution enables a new solution for robust low-pressure generation in parallel fluidic channels.

  18. 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.

  19. Monte Carlo simulations for design of the KFUPM PGNAA facility

    NASA Astrophysics Data System (ADS)

    Naqvi, A. A.; Nagadi, M. M.; Khateeb-ur-Rehman; Maslehuddin, M.; Kidwai, S.

    2003-02-01

    Monte Carlo simulations were carried out to design a 2.8 MeV neutron-based prompt gamma ray neutron activation analysis (PGNAA) setup for elemental analysis of cement samples. The elemental analysis was carried out using prompt gamma rays produced through capture of thermal neutrons in sample nuclei. The basic design of the PGNAA setup consists of a cylindrical cement sample enclosed in a cylindrical high-density polyethylene moderator placed between a neutron source and a gamma ray detector. In these simulations the predominant geometrical parameters of the PGNAA setup were optimized, including moderator size, sample size and shielding of the detector. Using the results of the simulations, an experimental PGNAA setup was then fabricated at the 350 kV Accelerator Laboratory of this University. The design calculations were checked experimentally through thermal neutron flux measurements inside the PGNAA moderator. A test prompt gamma ray spectrum of the PGNAA setup was also acquired from a Portland cement sample, using a pulsed beam of 2.8 MeV neutrons. Prompt gamma ray peaks due to the calcium, silicon and iron content of the Portland cement were detected.

  20. A Systems Approach to Designing Effective Clinical Trials Using Simulations

    PubMed Central

    Fusaro, Vincent A.; Patil, Prasad; Chi, Chih-Lin; Contant, Charles F.; Tonellato, Peter J.

    2013-01-01

    Background Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit compared to standard clinical therapy. This study demonstrates a computational framework to systematically evaluate pre-clinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes. Methods and Results We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs. The framework includes options to create a patient population, multiple dosing strategies including genetic-based and non-genetic clinical-based, multiple dose adjustment protocols, pharmacokinetic/pharmacodynamics (PK/PD) modeling and international normalization ratio (INR) prediction, as well as various types of outcome measures. We validated the framework by conducting 1,000 simulations of the CoumaGen clinical trial primary endpoints. The simulation predicted a mean time in therapeutic range (TTR) of 70.6% and 72.2% (P = 0.47) in the standard and pharmacogenetic arms, respectively. Then, we evaluated another dosing protocol under the same original conditions and found a significant difference in TTR between the pharmacogenetic and standard arm (78.8% vs. 73.8%; P = 0.0065), respectively. Conclusions We demonstrate that this simulation framework is useful in the pre-clinical assessment phase to study and evaluate design options and provide evidence to optimize the clinical trial for patient efficacy and reduced risk. PMID:23261867

  1. 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.

  2. Factor Xa: Simulation studies with an eye to inhibitor design

    NASA Astrophysics Data System (ADS)

    Daura, Xavier; Haaksma, Eric; van Gunsteren, Wilfred F.

    2000-08-01

    Factor Xa is a serine protease which activates thrombin and plays a key regulatory role in the blood-coagulation cascade. Factor Xa is at the crossroads of the extrinsic and intrinsic pathways of coagulation and, hence, has become an important target for the design of anti-thrombotics (inhibitors). It is not known to be involved in other processes than hemostasis and its binding site is different to that of other serine proteases, thus facilitating selective inhibition. The design of high-affinity selective inhibitors of factor Xa requires knowledge of the structural and dynamical characteristics of its active site. The three-dimensional structure of factor Xa was resolved by X-ray crystallography and refined at 2.2 Å resolution by Padmanabhan and collaborators. In this article we present results from molecular dynamics simulations of the catalytic domain of factor Xa in aqueous solution. The simulations were performed to characterise the mobility and flexibility of the residues delimiting the unoccupied binding site of the enzyme, and to determine hydrogen bonding propensities (with protein and with solvent atoms) of those residues in the active site that could interact with a substrate or a potential inhibitor. The simulation data is aimed at facilitating the design of high-affinity selective inhibitors of factor Xa.

  3. Simulation design for the composition of zirconia composite ceramic tool

    NASA Astrophysics Data System (ADS)

    Chuanzhen, Huang; Jing, Sun; Hanlian, Liu; Bin, Zou; Xing, Ai; Wang, Jun

    2004-04-01

    The relationship between the fracture toughness increment (ΔK IC) resulting from toughening mechanisms, such as phase transition, residual stress, geometry effect, and grain bridging, and the volume fraction of zirconia was established to simulate and design the composition of a zirconia-matrix composite tool, thereby avoiding “trial-and-error” experiments. The composition of the ZrO2/Al2O3 ceramic tool was simulated in accordance with the requirement for fracture toughness. It was shown that the simulated result was in agreement with experiment and that the established simulation model was to some extent valid in predicting the composition of the zirconia-matrix composite ceramic tool with dispersed α-Al2O3. Thus, a new type of ceramic tool material, a ZrO2/Al2O3 composite, was developed by adding α-Al2O3 to ZrO2 on the basis of the results of the computer simulation.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  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 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.

  10. 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.

  11. 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

  12. 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

  13. Guiding without feeling guided: Implicit scaffolding through interactive simulation design

    NASA Astrophysics Data System (ADS)

    Paul, Ariel; Podolefsky, Noah; Perkins, Katherine

    2013-01-01

    While PhET interactive simulations (sims) were historically designed for college students, they are used at lower grade levels, and we are currently developing sims targeted at middle school (MS). In studying how MS students interact with and learn from these sims, we have been extracting insights about design for the middle-grade-levels and across K-16. This collection of work has highlighted the importance of implicit scaffolding, a design framework that reduces the amount of explicit instruction needed to facilitate learning. We present a case study of redesigning a sim - Energy Skate Park (ESP) - for effective use in MS. We conducted think-aloud interviews with MS students to identify successful features, sources of confusion or unproductive distraction, as well as features inconsistent with gradeappropriate learning goals. Drawing on these data and the principle of implicit scaffolding, we developed Energy Skate Park Basics (ESPB). Interviews on ESPB demonstrate increased usability and learning for MS students.

  14. Design and simulation of turbine impeller in hydrovalve

    NASA Astrophysics Data System (ADS)

    Shi, Yunxu

    2008-10-01

    The water level in refrigerator must be controlled accurately in order to adjust the refrigerator's temperature, namely, a flow sensor needs to be designed to precisely measure the water flow into the flume according to the structure of hydrovalve. So the mechanical model of the turbine impeller's vane was first done through the analysis of the vane's beard driving and dragging force torques, and the instrument constant of the flow sensor was deducted, the dynamic measurement characteristics of the flow sensor was then analyzed to analyze the measurement precision of the flow sensor. The structure of flow sensor has been designed according to the results of theoretical analysis, and the flow field simulation of the turbine flowmeter has been done using the software of FLUENT. The theoretical and experimental results show that the mechanical model of the turbine flowmeter is reasonable and the mathematical expression of the ideal instrument constant can be adopted as the design reference of the flow sensor.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. Design of a laboratory simulator to test exoplanet imaging polarimetry

    NASA Astrophysics Data System (ADS)

    Jeffers, S. V.; Miesen, N.; Rodenhuis, M.; Keller, C. U.

    2008-07-01

    Research on extrasolar planets is one of the most rapidly advancing fields of astrophysics. In just over a decade since the discovery of the first extra-solar planet orbiting around 51 Pegasi, 289 extrasolar planets have been discovered. This breakthrough is the result of the development of a wide range of new observational techniques and facilities for the detection and characterisation of extrasolar planets. In Utrecht we are building the Extreme Polarimeter (ExPo) to image extra-solar planets and circumstellar environments using polarimetry at contrast ratio of 10-9. To test and calibrate ExPo, we have built a laboratory-based simulator that mimics a star with a Jupiter-like exoplanet as seen by the 4.2m William Herschel Telescope. The star and planet are simulated using two single-mode fibres in close proximity that are fed with a broadband arc lamp with a contrast ratio down to 10-9. The planet is partially linearly polarized. The telescope is simulated with two lenses, and seeing can be included with a rotating glass plate covered with hairspray. In this paper we present the scientific requirements and the simulator design.

  4. Effects of an Experiential Learning Simulation Design on Clinical Nursing Judgment Development.

    PubMed

    Chmil, Joyce Victor; Turk, Melanie; Adamson, Katie; Larew, Charles

    2015-01-01

    Simulation design should be theory based and its effect on outcomes evaluated. This study (1) applied a model of experiential learning to design a simulation experience, (2) examined how this design affected clinical nursing judgment development, and (3) described the relationship between clinical nursing judgment development and student performance when using the experiential learning design. Findings suggest that using an experiential learning simulation design results in more highly developed nursing judgment and competency in simulation performance.

  5. 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.

  6. Co-Simulation for Advanced Process Design and Optimization

    SciTech Connect

    Stephen E. Zitney

    2009-01-01

    Meeting the increasing demand for clean, affordable, and secure energy is arguably the most important challenge facing the world today. Fossil fuels can play a central role in a portfolio of carbon-neutral energy options provided CO{sub 2} emissions can be dramatically reduced by capturing CO{sub 2} and storing it safely and effectively. Fossil energy industry faces the challenge of meeting aggressive design goals for next-generation power plants with CCS. Process designs will involve large, highly-integrated, and multipurpose systems with advanced equipment items with complex geometries and multiphysics. APECS is enabling software to facilitate effective integration, solution, and analysis of high-fidelity process/equipment (CFD) co-simulations. APECS helps to optimize fluid flow and related phenomena that impact overall power plant performance. APECS offers many advanced capabilities including ROMs, design optimization, parallel execution, stochastic analysis, and virtual plant co-simulations. NETL and its collaborative R&D partners are using APECS to reduce the time, cost, and technical risk of developing high-efficiency, zero-emission power plants with CCS.

  7. 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.

  8. Numerical simulation and rational design of optically anisotropic columnar films

    NASA Astrophysics Data System (ADS)

    Leontyev, Viktor A.; Hawkeye, Matthew M.; Wakefield, Nicholas G.; Tabunshchyk, Kyrylo; Sit, Jeremy C.; Kovalenko, Andriy; Brett, Michael J.

    2011-03-01

    Optical anisotropy is an inherent property of columnar dielectric films, such as those fabricated by the glancing angle deposition (GLAD) technique. This process utilizes physical vapor deposition combined with computer-controlled substrate motion to finely tune the direction of column growth and vital morphological parameters such as column cross-section and inter-columnar spacing. Control over the anisotropic properties of the porous film provides an opportunity to design polarization-selective photonic devices and films with improved band gap properties. Anisotropic defects in multilayer films also result in a polarization-sensitive position of resonant transmission modes. We employed the finite-difference time-domain and frequency-domain methods to theoretically analyze and design columnar films with unique band-gap properties. The following morphologies were considered: (i) S-shaped columnar films with polarization-dependent band-gap position and width. Using numerical simulations we have shown that the competitive effect of different sources of anisotropy can be used to engineer photonic band gaps with strong selectivity to linearly-polarized light; (ii) Rugate thin films with an anisotropic defect, which exhibit resonant mode splitting. Optical devices were fabricated using titanium dioxide because it has good transparency in the visible range of the optical spectrum and a large bulk refractive index. Experimental results were compared to simulations to verify the designs and understand the limitations of the fabrication process.

  9. 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.

  10. Design and simulation of plasmonic interference-based majority gate

    NASA Astrophysics Data System (ADS)

    Doevenspeck, Jonas; Zografos, Odysseas; Gurunarayanan, Surya; Lauwereins, R.; Raghavan, P.; Sorée, B.

    2017-06-01

    Major obstacles in current CMOS technology, such as the interconnect bottleneck and thermal heat management, can be overcome by employing subwavelength-scaled light in plasmonic waveguides and devices. In this work, a plasmonic structure that implements the majority (MAJ) gate function is designed and thoroughly studied through simulations. The structure consists of three merging waveguides, serving as the MAJ gate inputs. The information of the logic signals is encoded in the phase of transmitted surface plasmon polaritons (SPP). SPPs are excited at all three inputs and the phase of the output SPP is determined by the MAJ of the input phases. The operating dimensions are identified and the functionality is verified for all input combinations. This is the first reported simulation of a plasmonic MAJ gate and thus contributes to the field of optical computing at the nanoscale.

  11. 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.

  12. Design Studies of a Multicusp Ion Source with FEMLAB Simulation

    NASA Astrophysics Data System (ADS)

    Azadboni, Fatemeh Khodadadi; Sedaghatizade, Mahmood; Sepanloo, Kamran

    2010-02-01

    Femlab simulations have been used to arrive at the first step in the design of an ion source. The goal is to optimize Magnetic multipole plasma confinement geometries, the increased area of constant magnetic field in the central region of the plasma volume and the increase in number of electrons which have stationary orbits within this region of the field. The confinement of electrons is essential for Multicusp ion source to produce intense beams of negative hydrogen ions (H-). A higher electron temperature and density given by a better plasma confinement leads to the higher efficiencies of the ionization and the production of highly charged ions. We have performed Femlab simulations of the magnetic flux density from permanent magnet used for a Multicusp ion source, plasma confinement and trapping of fast electrons by the magnetic field.

  13. 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.

  14. 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.

  15. 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

  16. Design and simulation on the morphing composite propeller (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Chen, Fanlong; Li, Qinyu; Liu, Liwu; Lan, Xin; Liu, Yanju; Leng, Jinsong

    2017-04-01

    As one of the most crucial part of the unmanned underwater vehicle (UUV), the composite propeller plays an important role on the UUV's performance. As the composite propeller behaves excellent properties in hydroelastic facet and acoustic suppression, it attracts increasing attentions all over the globe. This paper goes a step further based on this idea, and comes up with a novel concept of "morphing composite propeller" (MCP) to improve the performance of the conventional composite propeller (CCP) to anticipate the improved propeller can perform better to propel the UUV. Based on the new concept, a novel MCP is designed. Each blade of the propeller is assembled with an active rotatable flap (ARF) to change the blade's local camber with flap rotation. Then the transmission mechanism (TM) has been designed and housed in the propeller blade to push the ARF. With the ARF rotating, the UUV can be propelled by different thrusts under certain rotation velocities of the propeller. Based on the design, the Fluent is exploited to analyze the fluid dynamics around the propeller. Finally, based on the design and hydrodynamic analysis, the structural response for the novel morphing composite propeller is calculated. The propeller blade is simplified and layered with composite materials. And the structure response of an MCP is obtained with various rotation angle under the hydrodynamic pressure. This simulation can instruct the design and fabrication techniques of the MCP.

  17. Force model for laparoscopic graspers: implications for virtual simulator design.

    PubMed

    Susmitha Wils, K; Devasahayam, Suresh R; Manivannan, M; Mathew, George

    2017-04-01

    Laparoscopic graspers limit haptic perception, which in turn leads to tissue damage. Using virtual simulators to train surgeons in handling these instruments would ensure safer grasp. The design of a laparoscopic virtual simulator with force feedback depends on effective implementation of the grasper force model. To develop a laparoscopic grasper tip force model theoretically from grasper mechanics and validate the same experimentally during laparoscopic pinching. We developed a force model for double and single jaw action graspers using grasper mechanics. For experimental validation, the handle angle and the forces at the tip and the handle of the instrumented graspers during laparoscopic pinching of porcine abdominal tissues were measured. The intra-class correlation coefficient (ICC) between experimental and calculated tip force was calculated. Excellent ICC (ICC ≥0.8, p<.001) between calculated and experimental tip force was obtained for both graspers for all grasped tissues. Mean absolute forces for all trials while using double and single jaw action graspers were ((FTc = 1.7N, FTe = 1.8N) and (FTc = 2.2N, FTe = 2.8N)) for gall bladder, ((FTc = 3.4N, FTe = 4.4N) and (FTc = 3.3N, FTe = 3.4N)) for liver and ((FTc = 4.2N, FTe = 4.5N) and (FTc = 2.3N, FTe = 2.6N)) for spleen, respectively. The proposed model may be used for the design of laparoscopic pinching action in a virtual simulator with force feedback and also for better ergonomic design of laparoscopic graspers.

  18. 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.

  19. 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.

  20. Standard Simulator Data Base (SSDB) Interchange Format (SIF) Design Standard

    DTIC Science & Technology

    1993-06-17

    Technology NITP National Imagery Transmission Format PDR Preliminary Design Review RGB Red-Green- Blue SDBF Simulator Data Bane Facility SIr SSDB Interchange...File. The SIF/BDI implementation of the NITF standard shall store the actual band value(s) at each texel position (e.g., the red, green, and blue ...Encodina. A single SMC/FDC code shall require six bytes of storage, in one band of data. The high-order byte whall represent the SMC value in simple binary

  1. Application of Regression Designs for Simulation of Laser Cladding

    NASA Astrophysics Data System (ADS)

    Zhang, Qunli; Anyakin, Mykola; Zhuk, Ruslan; Pan, Yi; Kovalenko, Volodymyr; Yao, Jianhua

    Laser cladding is a complicated process controlled by most parameters such as laser beam, properties of matrix and powder, treatment status of base material, laser cladding parameters etc. The best way to choose the working conditions cheaply and fast is to use the processing simulation. The statistical modeling was used in this paper, which was developed after regression design based on the experimental results of 2Cr13 steel cladding with diode laser robotized system. The influence degrees of technological factors (laser power, laser scanning speed, defocusing amount and powder feeding rate) on the dimensions and hardness of laser clad layers were investigated.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Numerical simulations supporting the process design of ring rolling processes

    NASA Astrophysics Data System (ADS)

    Jenkouk, V.; Hirt, G.; Seitz, J.

    2013-05-01

    In conventional Finite Element Analysis (FEA) of radial-axial ring rolling (RAR) the motions of all tools are usually defined prior to simulation in the preprocessing step. However, the real process holds up to 8 degrees of freedom (DOF) that are controlled by industrial control systems according to actual sensor values and preselected control strategies. Since the histories of the motions are unknown before the experiment and are dependent on sensor data, the conventional FEA cannot represent the process before experiment. In order to enable the usage of FEA in the process design stage, this approach integrates the industrially applied control algorithms of the real process including all relevant sensors and actuators into the FE model of ring rolling. Additionally, the process design of a novel process 'the axial profiling', in which a profiled roll is used for rolling axially profiled rings, is supported by FEA. Using this approach suitable control strategies can be tested in virtual environment before processing.

  11. 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.

  12. Designing optimal number of receiving traces based on simulation model

    NASA Astrophysics Data System (ADS)

    Zhao, Hu; Wu, Si-Hai; Yang, Jing; Ren, Da; Xu, Wei-Xiu; Liu, Di-Ou; Zhu, Peng-Yu

    2017-03-01

    Currently, the selection of receiving traces in geometry design is mostly based on the horizontal layered medium hypothesis, which is unable to meet survey requirements in a complex area. This paper estimates the optimal number of receiving traces in field geometry using a numerical simulation based on a field test conducted in previous research (Zhu et al., 2011). A mathematical model is established for total energy and average efficiency energy using fixed trace spacing and optimal receiving traces are estimated. Seismic data acquired in a complex work area are used to verify the correctness of the proposed method. Results of model data calculations and actual data processing show that results are in agreement. This indicates that the proposed method is reasonable, correct, sufficiently scientific, and can be regarded as a novel method for use in seismic geometry design in complex geological regions.

  13. 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.

  14. 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.”

  15. 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.

  16. 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

  17. 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.

  18. Honokiol Suppresses Survival Signals Mediated by Ras-Dependent Phospholipase D Activity in Human Cancer Cells

    PubMed Central

    Garcia, Avalon; Zheng, Yang; Zhao, Chen; Toschi, Alfredo; Fan, Judy; Shraibman, Natalie; Brown, H. Alex; Bar-Sagi, Dafna; Foster, David A.; Arbiser, Jack L.

    2009-01-01

    Purpose Elevated phospholipase D (PLD) activity provides a survival signal in several human cancer cell lines and suppresses apoptosis when cells are subjected to the stress of serum withdrawal. Thus, targeting PLD survival signals has potential to suppress survival in cancer cells that depend on PLD for survival. Honokiol is a compound that suppresses tumor growth in mouse models. The purpose of this study was to investigate the effect of honokiol on PLD survival signals and the Ras dependence of these signals. Experimental Design The effect of honokiol upon PLD activity was examined in human cancer cell lines where PLD activity provides a survival signal. The dependence of PLD survival signals on Ras was investigated, as was the effect of honokiol on Ras activation. Results We report here that honokiol suppresses PLD activity in human cancer cells where PLD has been shown to suppress apoptosis. PLD activity is commonly elevated in response to the stress of serum withdrawal, and, importantly, the stress-induced increase in PLD activity is selectively suppressed by honokiol. The stress-induced increase in PLD activity was accompanied by increased Ras activation, and the stress-induced increase in PLD activity in MDA-MB-231 breast cancer cells was dependent on a Ras. The PLD activity was also dependent on the GTPases RalA and ADP ribosylation factor. Importantly, honokiol suppressed Ras activation. Conclusion The data provided here indicate that honokiol may be a valuable therapeutic reagent for targeting a large number of human cancers that depend on Ras and PLD for their survival. PMID:18594009

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Design, simulation, and testing of IDT-based MEMS gyroscope

    NASA Astrophysics Data System (ADS)

    Suh, William D.; Jose, K. A.; Xavier, Pascal B.; Varadan, Vijay K.; Varadan, Vasundara V.

    2001-08-01

    The design and simulation of a Surface Acoustic Wave (SAW) MEMS gyroscope using HP EESOF is presented in this paper. This SAW gyroscope is an integration of a SAW resonator and a SAW sensor. The SAW resonator is designed and optimized using coupling-of-modes theory. The SAW resonator is used to setup the stable reference vibration. A SAW sensor arranged in orthogonal to the resonator. Further to this resonator, strategically positioned metallic dots that form an array along the standing wave anti-node locations are subjected to the reference vibratory motion. These vibrating dot arrays through the Coriolis effect will generate secondary SAW in orthogonal direction under rotation, which can then be picked up by the SAW sensor. Numerical simulation using HP EESOF is used to optimize this gyroscope. This SAW gyroscope can be competitively priced, inherently rugged, reliable and very sensitive, which is capable of being wirelessly interrogated, without any sensor power source. In view of its one-layer planar configuration, this gyroscope can be implemented easily for applications requiring conformal mounting onto a surface of interest.

  6. 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.

  7. 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.

  8. 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.

  9. Operationalising elaboration theory for simulation instruction design: a Delphi study.

    PubMed

    Haji, Faizal A; Khan, Rabia; Regehr, Glenn; Ng, Gary; de Ribaupierre, Sandrine; Dubrowski, Adam

    2015-06-01

    The aim of this study was to assess the feasibility of incorporating the Delphi process within the simplifying conditions method (SCM) described in elaboration theory (ET) to identify conditions impacting the complexity of procedural skills for novice learners. We generated an initial list of conditions impacting the complexity of lumbar puncture (LP) from key informant interviews (n = 5) and a literature review. Eighteen clinician-educators from six different medical specialties were subsequently recruited as expert panellists. Over three Delphi rounds, these panellists rated: (i) their agreement with the inclusion of the simple version of the conditions in a representative ('epitome') training scenario, and (ii) how much the inverse (complex) version increases LP complexity for a novice. Cronbach's α-values were used to assess inter-rater agreement. All panellists completed Rounds 1 and 2 of the survey and 17 completed Round 3. In Round 1, Cronbach's α-values were 0.89 and 0.94 for conditions that simplify and increase LP complexity, respectively; both values increased to 0.98 in Rounds 2 and 3. With the exception of 'high CSF (cerebral spinal fluid) pressure', panellists agreed with the inclusion of all conditions in the simplest (epitome) training scenario. Panellists rated patient movement, spinal anatomy, patient cooperativeness, body habitus, and the presence or absence of an experienced assistant as having the greatest impact on the complexity of LP. This study demonstrated the feasibility of using expert consensus to establish conditions impacting the complexity of procedural skills, and the benefits of incorporating the Delphi method into the SCM. These data can be used to develop and sequence simulation scenarios in a progressively challenging manner. If the theorised learning gains associated with ET are realised, the methods described in this study may be applied to the design of simulation training for other procedural and non-procedural skills

  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 Symposium Draws Hundreds of Attendees | FNLCR

    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, in

  12. 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

  13. 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.

  14. Demonstration of pb-PSHA with Ras-Elhekma earthquake, Egypt

    NASA Astrophysics Data System (ADS)

    Fergany, Elsayed; Hutchings, Lawrence

    2017-06-01

    The main goal of this work is to: (1) argue for the importance of a physically-based probabilistic seismic hazard analysis (pb-PSHA) methodology and show examples to support the argument from recent events, (2) demonstrate the methodology with the ground motion simulations of May 28, 1998, Mw = 5.5 Ras-Elhekma earthquake, north Egypt. The boundaries for the possible rupture parameters that may have been identified prior to the 1998 Ras-Elhekma earthquake were estimated. A range of simulated ground-motions for the Ras-Elhekma earthquake was ;predicted; for frequency 0.5-25 Hz at three sites, where the large earthquake was recorded, with average epicentral distances of 220 km. The best rupture model of the 1998 Ras-Elhekma earthquake was identified by calculated the goodness of fit between observed and synthesized records at sites FYM, HAG, and KOT. We used the best rupture scenario of the 1998 earthquake to synthesize the ground motions at interested sites where the main shock was not recorded. Based on the good fit of simulated and observed seismograms, we concluded that this methodology can provide realistic ground motion of an earthquake and highly recommended for engineering purposes in advance or foregoing large earthquakes at non record sites. We propose that there is a need for this methodology for good-representing the true hazard with reducing uncertainties.

  15. Design and simulation of advanced charge recovery piezoactuator drivers

    NASA Astrophysics Data System (ADS)

    Biancuzzi, G.; Lemke, T.; Woias, P.; Ruthmann, O.; Schrag, H. J.; Vodermayer, B.; Schmid, T.; Goldschmidtboeing, F.

    2010-10-01

    The German Artificial Sphincter System project aims at the development of an implantable sphincter prosthesis driven by a piezoelectrically actuated micropump. The system has been designed to be fully implantable, i.e. the power supply is provided by a rechargeable lithium polymer battery. In order to provide sufficient battery duration and to limit battery dimensions, special effort has to be made to minimize power consumption of the whole system and, in particular, of the piezoactuator driver circuitry. Inductive charge recovery can be used to recover part of the charge stored within the actuator. We are going to present a simplified inductor-based circuit capable of voltage inversion across the actuator without the need of an additional negative voltage source. The dimension of the inductors required for such a concept is nevertheless significant. We therefore present a novel alternative concept, called direct switching, where the equivalent capacitance of the actuator is charged directly by a step-up converter and discharged by a step-down converter. We achieved superior performance compared to a simple inductor-based driver with the advantage of using small-size chip inductors. As a term of comparison, the performance of the aforementioned drivers is compared to a conventional driver that does not implement any charge recovery technique. With our design we have been able to achieve more than 50% reduction in power consumption compared to the simplest conventional driver. The new direct switching driver performs 15% better than an inductor-based driver. A novel, whole-system SPICE simulation is presented, where both the driving circuit and the piezoactuator are modeled making use of advanced nonlinear models. Such a simulation is a precious tool to design and optimize piezoactuator drivers.

  16. 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

  17. 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

  18. 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

  19. 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

  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. 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.

  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. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Advanced Diagnostic Design for Paul Trap Simulator Experiment (PTSX)

    NASA Astrophysics Data System (ADS)

    Godbehere, A. B.; Chung, M.; Davidson, R. C.; Gilson, E. P.

    2007-11-01

    The Paul Trap Simulator Experiment (PTSX) is a compact laboratory Paul trap that uses a pure-ion plasma to simulate a long, thin charged particle bunch coasting through a kilometers-long magnetic alternating-gradient transport system. Current PTSX experiments are exploring the limits of the smooth focusing model, and using the detection of collective mode oscillations to infer key bunch properties such as the line density and transverse temperature. These experiments require the use of advanced diagnostics to measure the transverse distribution of the plasma perticles at a given instant in time. One set of experimental diagnostics uses a CCD camera with a short exposure time to collect light from Laser Induced Fluorescence (LIF) of the cross section of a barium plasma beam. A second set of experimental diagnostics utilizes capacitive coupling of the ions with four electrodes, which are connected to high- input-impedance active filters. Details of the design and performance of the laser system, CCD camera system, and collective mode diagnostic electronics will be presented.

  12. 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.

  13. Design of observation / telecommunication constellations : Synergy through a simulation platform

    NASA Astrophysics Data System (ADS)

    Rainjonneau, S.; Gaertner, S.; Froment, F.; Raffier, B.

    2002-07-01

    Some new world-wide telecommunication or observation systems are based on LEO or MEO satellite constellations, used as relay between terminals or imaging target and gateways or ground stations, in order to provide telephony, high data rate or ground imaging to the end user. Such complex systems are characterized by several system constraints, due to the huge number of users or requests, and the movement of the satellites with regards to the Earth. The design of such whole system can be also considered as a complex problem. It has to be realized thanks to simulators, taking into account a part more or less important of the system constraints. This article presents a complete set of simulation tools, developed by Alcatel Space Industries, in the framework of different telecommunication and observation projects. These tools are regrouped inside a common workshop and based on a generic representation of new telecommunication and observation systems. Two major key points can be highlighted in this approach : two phases correspond to 0/A and A/B project phases and for each phase, five generic steps are followed to conduct to the system design. Such a complete tool chain allows to define and analyze the constellation behavior during the first project levels, when an important system engineering activity is required, in order to support system trade-offs and to determine the best system architecture to guarantee the largest coverage and capacity over the targeted countries. Hence these tools can be considered as very interesting prototypes for operational mission planning services too. The paper will illustrate all these principles by presenting the workshop architecture and by delivering several outputs and visualizations issued from the different tools. The use cases will be chosen among potential or fictitious architectures.

  14. 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.

  15. Early regulation of membrane excitability by ras oncogene proteins.

    PubMed Central

    Collin, C; Papageorge, A G; Sakakibara, M; Huddie, P L; Lowy, D R; Alkon, D L

    1990-01-01

    Two electrode voltage clamp conditions were used to study the early effects on ionic membrane channels of the intracellularly injected proto-oncogenic form of c-Ha-ras (c-ras) and its oncogenic counterpart v-Ha-ras (v-ras). These experiments were conducted on isolated somata of identified fully differentiated neurons of the sea snail Hermissenda. 20 min after c-ras, and 10 min after v-ras intracellular injections into type B medial photoreceptors of Hermissenda, the peak amplitude of two outward potassium currents (IA and IC), across the isolated Type B soma membrane begin to decrease. These two currents have been previously isolated by differences in activation and inactivation kinetics and their response to pharmacological blockers. c- or v-ras injections did not have any effect on a voltage-dependent inward calcium current. Reduction of IA preceded that of IC. Current reductions due to c-ras, but not to v-ras injection reversed spontaneously after 40 min. The voltage dependence of the steady state inactivation of IA shifted toward more negative potentials with ras injections. Ras-mediated cell transformations therefore, could involve, perhaps as initial events, prolonged modification of membrane currents. PMID:2207264

  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. Isochronous (CW) Non-Scaling FFAGs: Design and Simulation

    SciTech Connect

    Johnstone, C.; Berz, M.; Makino, K.; Snopok, P.

    2010-11-04

    The drive for higher beam power, high duty cycle, and reliable beams at reasonable cost has focused international attention and design effort on fixed field accelerators, notably Fixed-Field Alternating Gradient accelerators (FFAGs). High-intensity GeV proton drivers encounter duty cycle and space-charge limits in the synchrotron and machine size concerns in the weaker-focusing cyclotrons. A 10-20 MW proton driver is challenging, if even technically feasible, with conventional accelerators--with the possible exception of a SRF linac, which has a large associated cost and footprint. Recently, the concept of isochronous orbits has been explored and developed for nonscaling FFAGs using powerful new methodologies in FFAG accelerator design and simulation. The property of isochronous orbits enables the simplicity of fixed RF and, by tailoring a nonlinear radial field profile, the FFAG can remain isochronous beyond the energy reach of cyclotrons, well into the relativistic regime. With isochronous orbits, the machine proposed here has the high average current advantage and duty cycle of the cyclotron in combination with the strong focusing, smaller losses, and energy variability that are more typical of the synchrotron. This paper reports on these new advances in FFAG accelerator technology and presents advanced modeling tools for fixed-field accelerators unique to the code COSY INFINITY.

  19. 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%.

  20. 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.

  1. Sprouty, an intracellular inhibitor of Ras signaling.

    PubMed

    Casci, T; Vinós, J; Freeman, M

    1999-03-05

    Sprouty was identified in a genetic screen as an inhibitor of Drosophila EGF receptor signaling. The Egfr triggers cell recruitment in the eye, and sprouty- eyes have excess photoreceptors, cone cells, and pigment cells. Sprouty's function is, however, more widespread. We show that it also interacts genetically with the receptor tyrosine kinases Torso and Sevenless, and it was first discovered through its effect on FGF receptor signaling. In contrast to an earlier proposal that Sprouty is extracellular, we show by biochemical analysis that Sprouty is an intracellular protein, associated with the inner surface of the plasma membrane. Sprouty binds to two intracellular components of the Ras pathway, Drk and Gap1. Our results indicate that Sprouty is a widespread inhibitor of Ras pathway signal transduction.

  2. 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

  3. Ras-Independent Function of NF1

    DTIC Science & Technology

    2013-05-01

    required to fulfill this process. Moreover, the skin disease we observed in those mice is psoriasis . 15. SUBJECT TERMS Neurofibromin (NF1), Ras...factor such as age contributes to the process. 3d. Proposed work: Determine the relation between NF1 and psoriasis (months 13-24). We will collect...several psoriasis related genes, such as Th17, IL22, IL23, CD68, CXCL8, CCL2, defensin-2 by quantitative PCR in the skin samples from the lesions

  4. 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.

  5. RAS signaling dysregulation in human embryonal Rhabdomyosarcoma.

    PubMed

    Martinelli, Simone; McDowell, Heather P; Vigne, Silvia Delle; Kokai, George; Uccini, Stefania; Tartaglia, Marco; Dominici, Carlo

    2009-11-01

    Rhabdomyosarcoma (RMS) is a common childhood solid tumor, resulting from dysregulation of the skeletal myogenesis program. Two major histological subtypes occur in childhood RMS, embryonal and alveolar. While chromosomal rearrangements account for the majority of alveolar tumors, the genetic defects underlying the pathogenesis of embryonal RMS remain largely undetermined. A few studies performed on small series of embryonal tumors suggest that dysregulation of RAS function may be relevant to disease pathogenesis. To explore further the biological and clinical relevance of mutations with perturbing consequences on RAS signaling in embryonal RMS, we investigated the prevalence of PTPN11, HRAS, KRAS, NRAS, BRAF, MEK1, and MEK2 mutations in a relatively large cohort of primary tumors. While HRAS and KRAS were found to be rarely mutated, we identified somatic NRAS lesions in 20% of cases. All mutations were missense and affected codon 61, with the introduction of a positive charged amino acid residue representing the most common event. PTPN11 was found mutated in one tumor specimen, confirming that somatic defects in this gene are relatively uncommon in RMS, while no mutation was observed in BRAF and MEK genes. Although no clear association of mutations with any clinical variable was observed, comparison of the outcome between mutation-positive and mutation-negative cases indicated a trend for a higher percentage of patients exhibiting a better outcome in the former. Our findings provide evidence that dysregulation of RAS signaling is a major event contributing to embryonal RMS pathogenesis. Copyright 2009 Wiley-Liss, Inc.

  6. 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

  7. Src promotes GTPase activity of Ras via tyrosine 32 phosphorylation

    PubMed Central

    Bunda, Severa; Heir, Pardeep; Srikumar, Tharan; Cook, Jonathan D.; Burrell, Kelly; Kano, Yoshihito; Lee, Jeffrey E.; Zadeh, Gelareh; Raught, Brian; Ohh, Michael

    2014-01-01

    Mutations in Ras GTPase and various other components of the Ras signaling pathways are among the most common genetic alterations in human cancers and also have been identified in several familial developmental syndromes. Over the past few decades it has become clear that the activity or the oncogenic potential of Ras is dependent on the nonreceptor tyrosine kinase Src to promote the Ras/Raf/MAPK pathway essential for proliferation, differentiation, and survival of eukaryotic cells. However, no direct relationship between Ras and Src has been established. We show here that Src binds to and phosphorylates GTP-, but not GDP-, loaded Ras on a conserved Y32 residue within the switch I region in vitro and that in vivo, Ras-Y32 phosphorylation markedly reduces the binding to effector Raf and concomitantly increases binding to GTPase-activating proteins and the rate of GTP hydrolysis. These results suggest that, in the context of predetermined crystallographic structures, Ras-Y32 serves as an Src-dependent keystone regulatory residue that modulates Ras GTPase activity and ensures unidirectionality to the Ras GTPase cycle. PMID:25157176

  8. 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

  9. Nuclear Ras2-GTP controls invasive growth in Saccharomyces cerevisiae.

    PubMed

    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.

  10. Cytosolic Ras Supports Eye Development in Drosophila ▿

    PubMed Central

    Sung, Pamela J.; Rodrigues, Aloma B.; Kleinberger, Andrew; Quatela, Steven; Bach, Erika A.; Philips, Mark R.

    2010-01-01

    Ras proteins associate with cellular membranes as a consequence of a series of posttranslational modifications of a C-terminal CAAX sequence that include prenylation and are thought to be required for biological activity. In Drosophila melanogaster, Ras1 is required for eye development. We found that Drosophila Ras1 is inefficiently prenylated as a consequence of a lysine in the A1 position of its CAAX sequence such that a significant pool remains soluble in the cytosol. We used mosaic analysis with a repressible cell marker (MARCM) to assess if various Ras1 transgenes could restore photoreceptor fate to eye disc cells that are null for Ras1. Surprisingly, we found that whereas Ras1 with an enhanced efficiency of membrane targeting could not rescue the Ras1 null phenotype, Ras1 that was not at all membrane targeted by virtue of a mutation of the CAAX cysteine was able to fully rescue eye development. In addition, constitutively active Ras112V,C186S not targeted to membranes produced a hypermorphic phenotype and stimulated mitogen-activated protein kinase (MAPK) signaling in S2 cells. We conclude that the membrane association of Drosophila Ras1 is not required for eye development. PMID:20937772

  11. 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

  12. 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…

  13. 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…

  14. 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…

  15. 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.

  16. 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.

  17. Heat-load simulator for heat sink design

    NASA Technical Reports Server (NTRS)

    Dunleavy, A. M.; Vaughn, T. J.

    1968-01-01

    Heat-load simulator is fabricated from 1/4-inch aluminum plate with a contact surface equal in dimensions and configuration to those of the electronic installation. The method controls thermal output to simulate actual electronic component thermal output.

  18. Algorithm design for a gun simulator based on image processing

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Wei, Ping; Ke, Jun

    2015-08-01

    In this paper, an algorithm is designed for shooting games under strong background light. Six LEDs are uniformly distributed on the edge of a game machine screen. They are located at the four corners and in the middle of the top and the bottom edges. Three LEDs are enlightened in the odd frames, and the other three are enlightened in the even frames. A simulator is furnished with one camera, which is used to obtain the image of the LEDs by applying inter-frame difference between the even and odd frames. In the resulting images, six LED are six bright spots. To obtain the LEDs' coordinates rapidly, we proposed a method based on the area of the bright spots. After calibrating the camera based on a pinhole model, four equations can be found using the relationship between the image coordinate system and the world coordinate system with perspective transformation. The center point of the image of LEDs is supposed to be at the virtual shooting point. The perspective transformation matrix is applied to the coordinate of the center point. Then we can obtain the virtual shooting point's coordinate in the world coordinate system. When a game player shoots a target about two meters away, using the method discussed in this paper, the calculated coordinate error is less than ten mm. We can obtain 65 coordinate results per second, which meets the requirement of a real-time system. It proves the algorithm is reliable and effective.

  19. 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.

  20. 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)

  1. 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

  2. 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

  3. 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.

  4. Overexpressed Galectin-3 in Pancreatic Cancer Induces Cell Proliferation and Invasion by Binding Ras and Activating Ras Signaling

    PubMed Central

    Song, Shumei; Ji, Baoan; Ramachandran, Vijaya; Wang, Huamin; Hafley, Margarete; Logsdon, Craig; Bresalier, Robert S.

    2012-01-01

    Pancreatic cancer (PDAC) is a lethal disease with a five-year survival of 3–5%. Mutations in K-Ras are found in nearly all cases, but K-Ras mutations alone are not sufficient for the development of PDAC. Additional factors contribute to activation of Ras signaling and lead to tumor formation. Galectin-3 (Gal-3), a multifunctional β-galactoside-binding protein, is highly expressed in PDAC. We therefore investigated the functional role of Gal-3 in pancreatic cancer progression and its relationship to Ras signaling. Expression of Gal-3 was determined by immunohistochemistry, Q-PCR and immunoblot. Functional studies were performed using pancreatic cell lines genetically engineered to express high or low levels of Gal-3. Ras activity was examined by Raf pull-down assays. Co-immunoprecipitation and immunofluorescence were used to assess protein-protein interactions. In this study, we demonstrate that Gal-3 was highly up-regulated in human tumors and in a mutant K-Ras mouse model of PDAC. Down-regulation of Gal-3 by lentivirus shRNA decreased PDAC cell proliferation and invasion in vitro and reduced tumor volume and size in an orthotopic mouse model. Gal-3 bound Ras and maintained Ras activity; down-regulation of Gal-3 decreased Ras activity as well as Ras down-stream signaling including phosphorylation of ERK and AKT and Ral A activity. Transfection of Gal-3 cDNA into PDAC cells with low-level Gal-3 augmented Ras activity and its down-stream signaling. These results suggest that Gal-3 contributes to pancreatic cancer progression, in part, by binding Ras and activating Ras signaling. Gal-3 may therefore be a potential novel target for this deadly disease. PMID:22900040

  5. 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

  6. 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.

  7. 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.

  8. 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).

  9. 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).

  10. 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.

  11. 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.

  12. 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.

  13. 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

  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. 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.

  16. Ras proteins control mitochondrial biogenesis and function in Saccharomyces cerevisiae.

    PubMed

    Hlavatá, L; Nyström, T

    2003-01-01

    The evolutionarily conserved Ras proteins function as a point of convergence for different signaling pathways in eukaryotes and have been implicated in both aging and cancer development. In Saccharomyces cerevisiae the plasma membrane proteins Ras1 and Ras2 are sensing the nutritional status of the environments, e.g., the abundance and quality of available carbon sources. The cAMP-protein kinase A pathway is the most explored signaling pathway controlled by Ras proteins; it affects a large number of genes, some of which are important to defend the cell against oxidative stress. In addition, recent analysis has shown that the Ras system of yeast is involved in the development of mitochondria and in regulating their activity. As a sensor of environmental status and an effector of mitochondrial activity, Ras serves as a Rosetta stone of cellular energy transduction. This review summarizes the physical and functional involvement of Ras proteins and Ras-dependent signaling pathways in mitochondrial function in S. cerevisiae. Since mitochondria produce harmful reactive oxygen species as an inevitable byproduct and are partly under control of Ras, illuminating these regulatory interactions may improve our understanding of both cancer and aging.

  17. 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

  18. Application of HEC-RAS for flood forecasting in perched river-A case study of hilly region, China

    NASA Astrophysics Data System (ADS)

    Sun, Pingping; Wang, Shuqian; Gan, Hong; Liu, Bin; Jia, Ling

    2017-04-01

    Flooding in small and medium rivers are seriously threatening the safety of human beings’ life and property. The simulation forecasting of the river flood and bank risk in hilly region has gradually become a hotspot. At present, there are few studies on the simulation of hilly perched river, especially in the case of lacking section flow data. And the method of how to determine the position of the levee breach along the river bank is not much enough. Based on the characteristics of the sections in hilly perched river, an attempt is applied in this paper which establishes the correlation between the flow profile computed by HEC-RAS model and the river bank. A hilly perched river in Lingshi County, Shanxi Province of China, is taken as the study object, the levee breach positions along the bank are simulated under four different design storm. The results show that the flood control standard of upper reach is high, which can withstand the design storm of 100 years. The current standard of lower reach is low, which is the flooding channel with high frequency. As the standard of current channel between the 2rd and the 11th section is low, levee along that channel of the river bank is considered to be heighten and reinforced. The study results can provide some technical support for flood proofing in hilly region and some reference for the reinforcement of river bank.

  19. Rapid Modeling, Assembly and Simulation in Design Optimization

    NASA Technical Reports Server (NTRS)

    Housner, Jerry

    1997-01-01

    A new capability for design is reviewed. This capability provides for rapid assembly of detail finite element models early in the design process where costs are most effectively impacted. This creates an engineering environment which enables comprehensive analysis and design optimization early in the design process. Graphical interactive computing makes it possible for the engineer to interact with the design while performing comprehensive design studies. This rapid assembly capability is enabled by the use of Interface Technology, to couple independently created models which can be archived and made accessible to the designer. Results are presented to demonstrate the capability.

  20. 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.

  1. An Integrated Design and Development System for Graphics Simulation.

    ERIC Educational Resources Information Center

    Richardson, J. Jeffrey

    In the training of maintenance and operations technicians, three enhancements to a basic, straightforward, fixed-sequence simulation system can be useful. The primary advantage of the resultant system is that the principal object of simulation is the task to be performed, which includes both the planning knowledge and the equipment actions…

  2. A Study of Educational Simulations Part II--Interface Design

    ERIC Educational Resources Information Center

    Adams, W.; Reid, S.; LeMaster, R.; McKagan, S.; Perkins, K.; Dubson, M.; Wieman, C.

    2008-01-01

    Interactive computer simulations with complex representations and sophisticated graphics are a relatively new addition to the classroom, and research in this area is limited. We have conducted over 200 individual student interviews during which the students described what they were thinking as they interacted with simulations. These interviews…

  3. Benefits of full scope simulators during solar thermal power plants design and construction

    NASA Astrophysics Data System (ADS)

    Gallego, José F.; Gil, Elena; Rey, Pablo

    2017-06-01

    In order to efficiently develop high-precision dynamic simulators for solar thermal power plants, Tecnatom adapted its simulation technology to consider solar thermal models. This effort and the excellent response of the simulation market have allowed Tecnatom to develop simulators with both parabolic trough and solar power tower technologies, including molten salt energy storage. These simulators may pursue different objectives, giving rise to training or engineering simulators. Solar thermal power market combines the need for the training of the operators with the potential benefits associated to the improvement of the design of the plants. This fact along with the simulation capabilities enabled by the current technology and the broad experience of Tecnatom present the development of an engineering+training simulator as a very advantageous option. This paper describes the challenge of the development and integration of a full scope simulator during the design and construction stages of a solar thermal power plant, showing the added value to the different engineering areas.

  4. Optimizing the design of a bioabsorbable metal stent using computer simulation methods.

    PubMed

    Grogan, James A; Leen, Sean B; McHugh, Peter E

    2013-11-01

    Computer simulation is used extensively in the design of permanent stents. In order to address new challenges that arise in the design of absorbable metal stents (AMSs), such as corrosion and the limited mechanical properties of bioabsorbable alloys, new simulation and design techniques are needed. In this study a new method for simulating AMS corrosion is developed to study the effects of corrosion on the mechanical performance of a range of stent designs. The corrosion model is combined with an optimization strategy to identify AMS features that give optimal corrosion performance in the body. It is found that strut width is the predominant geometrical factor in determining long-term AMS scaffolding performance. An AMS with superior scaffolding performance to a commercial design is identified, based on deployment and corrosion simulations in stenosed vessels. These simulation and design techniques give new insights into in-vivo AMS performance and the role of device geometry in determining long-term scaffolding performance.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. The Statistical Power of the Cluster Randomized Block Design with Matched Pairs--A Simulation Study

    ERIC Educational Resources Information Center

    Dong, Nianbo; Lipsey, Mark

    2010-01-01

    This study uses simulation techniques to examine the statistical power of the group- randomized design and the matched-pair (MP) randomized block design under various parameter combinations. Both nearest neighbor matching and random matching are used for the MP design. The power of each design for any parameter combination was calculated from…

  10. 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…

  11. 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…

  12. 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…

  13. 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.

  14. 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.

  15. 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…

  16. 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…

  17. 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.

  18. 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.

  19. Simulation design: A Teaching Technique for Political Science

    ERIC Educational Resources Information Center

    Deiner, John T.

    1974-01-01

    Goals, course structure, physical and technical problems, the running of a simulation and evaluation of students are described for a game representing the political system of Argentina in a university comparative government course. (Author/KM)

  20. 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.

  1. 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.

  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. Discrete-event simulation for the design and evaluation of physical protection systems

    SciTech Connect

    Jordan, S.E.; Snell, M.K.; Madsen, M.M.; Smith, J.S.; Peters, B.A.

    1998-08-01

    This paper explores the use of discrete-event simulation for the design and control of physical protection systems for fixed-site facilities housing items of significant value. It begins by discussing several modeling and simulation activities currently performed in designing and analyzing these protection systems and then discusses capabilities that design/analysis tools should have. The remainder of the article then discusses in detail how some of these new capabilities have been implemented in software to achieve a prototype design and analysis tool. The simulation software technology provides a communications mechanism between a running simulation and one or more external programs. In the prototype security analysis tool, these capabilities are used to facilitate human-in-the-loop interaction and to support a real-time connection to a virtual reality (VR) model of the facility being analyzed. This simulation tool can be used for both training (in real-time mode) and facility analysis and design (in fast mode).

  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. Ras chaperones: new targets for cancer and immunotherapy.

    PubMed

    Kloog, Yoel; Elad-Sfadia, Galit; Haklai, Roni; Mor, Adam

    2013-01-01

    The Ras inhibitor S-trans,trans-farnesylthiosalicylic acid (FTS, Salirasib®) interferes with Ras membrane interactions that are crucial for Ras-dependent signaling and cellular transformation. FTS had been successfully evaluated in clinical trials of cancer patients. Interestingly, its effect is mediated by targeting Ras chaperones that serve as key coordinators for Ras proper folding and delivery, thus offering a novel target for cancer therapy. The development of new FTS analogs has revealed that the specific modifications to the FTS carboxyl group by esterification and amidation yielded compounds with improved growth inhibitory activity. When FTS was combined with additional therapeutic agents its activity toward Ras was significantly augmented. FTS should be tested not only in cancer but also for genetic diseases associated with abnormal Ras signaling, as well as for various inflammatory and autoimmune disturbances, where Ras plays a major role. We conclude that FTS has a great potential both as a safe anticancer drug and as a promising immune modulator agent. © 2013 Elsevier Inc. All rights reserved.

  6. Regional scale flood modeling using NEXRAD rainfall, GIS, and HEC-HMS/RAS: a case study for the San Antonio River Basin Summer 2002 storm event.

    PubMed

    Knebl, M R; Yang, Z-L; Hutchison, K; Maidment, D R

    2005-06-01

    This paper develops a framework for regional scale flood modeling that integrates NEXRAD Level III rainfall, GIS, and a hydrological model (HEC-HMS/RAS). The San Antonio River Basin (about 4000 square miles, 10,000 km2) in Central Texas, USA, is the domain of the study because it is a region subject to frequent occurrences of severe flash flooding. A major flood in the summer of 2002 is chosen as a case to examine the modeling framework. The model consists of a rainfall-runoff model (HEC-HMS) that converts precipitation excess to overland flow and channel runoff, as well as a hydraulic model (HEC-RAS) that models unsteady state flow through the river channel network based on the HEC-HMS-derived hydrographs. HEC-HMS is run on a 4 x 4 km grid in the domain, a resolution consistent with the resolution of NEXRAD rainfall taken from the local river authority. Watershed parameters are calibrated manually to produce a good simulation of discharge at 12 subbasins. With the calibrated discharge, HEC-RAS is capable of producing floodplain polygons that are comparable to the satellite imagery. The modeling framework presented in this study incorporates a portion of the recently developed GIS tool named Map to Map that has been created on a local scale and extends it to a regional scale. The results of this research will benefit future modeling efforts by providing a tool for hydrological forecasts of flooding on a regional scale. While designed for the San Antonio River Basin, this regional scale model may be used as a prototype for model applications in other areas of the country.

  7. OR fire virtual training simulator: design and face validity.

    PubMed

    Dorozhkin, Denis; Olasky, Jaisa; Jones, Daniel B; Schwaitzberg, Steven D; Jones, Stephanie B; Cao, Caroline G L; Molina, Marcos; Henriques, Steven; Wang, Jinling; Flinn, Jeff; De, Suvranu

    2016-12-30

    The Virtual Electrosurgical Skill Trainer is a tool for training surgeons the safe operation of electrosurgery tools in both open and minimally invasive surgery. This training includes a dedicated team-training module that focuses on operating room (OR) fire prevention and response. The module was developed to allow trainees, practicing surgeons, anesthesiologist, and nurses to interact with a virtual OR environment, which includes anesthesia apparatus, electrosurgical equipment, a virtual patient, and a fire extinguisher. Wearing a head-mounted display, participants must correctly identify the "fire triangle" elements and then successfully contain an OR fire. Within these virtual reality scenarios, trainees learn to react appropriately to the simulated emergency. A study targeted at establishing the face validity of the virtual OR fire simulator was undertaken at the 2015 Society of American Gastrointestinal and Endoscopic Surgeons conference. Forty-nine subjects with varying experience participated in this Institutional Review Board-approved study. The subjects were asked to complete the OR fire training/prevention sequence in the VEST simulator. Subjects were then asked to answer a subjective preference questionnaire consisting of sixteen questions, focused on the usefulness and fidelity of the simulator. On a 5-point scale, 12 of 13 questions were rated at a mean of 3 or greater (92%). Five questions were rated above 4 (38%), particularly those focusing on the simulator effectiveness and its usefulness in OR fire safety training. A total of 33 of the 49 participants (67%) chose the virtual OR fire trainer over the traditional training methods such as a textbook or an animal model. Training for OR fire emergencies in fully immersive VR environments, such as the VEST trainer, may be the ideal training modality. The face validity of the OR fire training module of the VEST simulator was successfully established on many aspects of the simulation.

  8. 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.

  9. 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.

  10. 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

  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. 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.

  13. An intelligent simulation environment for control system design

    SciTech Connect

    Robinson, J.T.

    1989-01-01

    The Oak Ridge National Laboratory is currently assisting in the development of advanced control systems for the next generation of nuclear power plants. This paper presents a prototype interactive and intelligent simulation environment being developed to support this effort. The environment combines tools from the field of Artificial Intelligence; in particular object-oriented programming, a LISP programming environment, and a direct manipulation user interface; with traditional numerical methods for simulating combined continuous/discrete processes. The resulting environment is highly interactive and easy to use. Models may be created and modified quickly through a window oriented direct manipulation interface. Models may be modified at any time, even as the simulation is running, and the results observed immediately via real-time graphics. 8 refs., 3 figs.

  14. Recent changes in the landscape of combination RAS blockade.

    PubMed

    Epstein, Benjamin J; Smith, Steven M; Choksi, Rushab

    2009-11-01

    The renin-angiotensin system (RAS) is a prime target for cardiovascular drug therapy. Inhibition of the RAS lowers blood pressure and confers protection against cardiovascular and renal events. These latter benefits cannot be entirely attributed to blood pressure lowering. Angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor blockers (ARBs) have been studied extensively and, while there is irrefutable evidence that these agents mitigate the risk for cardiovascular and renal events, their protection is incomplete. In outcomes studies that have employed ACE-inhibitors or ARBs there has been a relatively high residual event rate in the treatment arm and this has been ascribed, by some, to the fact that neither ACE-inhibitors nor ARBs completely repress RAS. For this reason, combined RAS blockade with an ACE-inhibitor and ARB has emerged as a therapeutic option. In hypertension, combined RAS blockade elicits only a marginal incremental drop in blood pressure and it does not further lower the risk for cardiovascular events. In chronic heart failure and proteinuric renal disease, combining these agents in carefully selected patients is associated with a reduction in clinical events. Irrespective of the setting, dual RAS blockade is associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The emergence of the direct renin inhibitor, aliskiren, has afforded clinicians a new strategy for RAS blockade. Renin system blockade with aliskiren plus another RAS agent is the subject of ongoing large-scale clinical trials and early studies suggest promise for this strategy. Currently, combined RAS blockade with an ACE-inhibitor and an ARB should not be routinely employed for hypertension; however, the combination of an ACE-inhibitor or ARB with aliskiren might be considered in some patients given the more formidable blood pressure-lowering profile of this regimen. In carefully selected patients with heart

  15. 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

  16. 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).

  17. 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

  18. 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…

  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. 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…

  1. 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…

  2. 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.

  3. 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…

  4. 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…

  5. 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…

  6. 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.

  7. Towards Application of NASA Standard for Models and Simulations in Aeronautical Design Process

    NASA Astrophysics Data System (ADS)

    Vincent, Luc; Dunyach, Jean-Claude; Huet, Sandrine; Pelissier, Guillaume; Merlet, Joseph

    2012-08-01

    Even powerful computational techniques like simulation endure limitations in their validity domain. Consequently using simulation models requires cautions to avoid making biased design decisions for new aeronautical products on the basis of inadequate simulation results. Thus the fidelity, accuracy and validity of simulation models shall be monitored in context all along the design phases to build confidence in achievement of the goals of modelling and simulation.In the CRESCENDO project, we adapt the Credibility Assessment Scale method from NASA standard for models and simulations from space programme to the aircraft design in order to assess the quality of simulations. The proposed eight quality assurance metrics aggregate information to indicate the levels of confidence in results. They are displayed in management dashboard and can secure design trade-off decisions at programme milestones.The application of this technique is illustrated in aircraft design context with specific thermal Finite Elements Analysis. This use case shows how to judge the fitness- for-purpose of simulation as Virtual testing means and then green-light the continuation of Simulation Lifecycle Management (SLM) process.

  8. 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.

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

    PubMed

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

    2015-10-01

    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. 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. 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. The developed software will be useful in improving patient safety and clinical efficiency of proton therapy.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. News and Views: Cold comfort; RAS responds to new STFC priorities; RAS joint fellowship supports retraining

    NASA Astrophysics Data System (ADS)

    2010-02-01

    The announcement of the funding decisions made by the Science and Technology Facilities Council in December represent a narrowing of the horizons for UK astronomy, ending support for significant facilities and missions and permitting limited development of new projects. The RAS has teamed up with the Daphne Jackson Trust to offer a joint fellowship aimed at people wishing to return to research after a career break.

  16. Evolution of ephemerides EPM of IAA RAS

    NASA Astrophysics Data System (ADS)

    Pitjeva, E.

    2015-08-01

    The evolution of numerical EPM ephemerides of the IAA RAS from available EPM2004, EPM2008, EPM2011, to the new EPM2014 version is presented briefly. The comparison progress of ephemerides includes: the growing database of different types of observations from classical optical to radio technical of spacecraft from 1913 to 2014, enlarged up to more 800000 measurements; improved dynamical model from mutual perturbations of all planets, the Sun, the Moon, 301 largest asteroids to additional perturbations from of 30 largest trans-neptunian objects (TNO) and perturbations from remaining smaller asteroids and TNO modeled by the two-dimensional asteroid ring and the one-dimensional TNO ring; program software ERA-7 to ERA-8.

  17. 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.

  18. Targeting the RAS pathway in melanoma.

    PubMed

    Ji, Zhenyu; Flaherty, Keith T; Tsao, Hensin

    2012-01-01

    Metastatic melanoma is a highly lethal type of skin cancer and is often refractory to all traditional chemotherapeutic agents. Key insights into the genetic makeup of melanoma tumors have led to the development of promising targeted agents. An activated RAS pathway, anchored by oncogenic BRAF, appears to be the central motor driving melanoma proliferation. Although recent clinical trials have brought enormous hope to patients with melanoma, adverse effects and novel escape mechanisms of these inhibitors have already emerged. Definition of the limits of the first successful targeted therapies will provide the basis for further advances in management of disseminated melanoma. In this review, the current state of targeted therapy for melanoma is discussed, including the potent BRAF(V600E) inhibitor vemurafenib. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. 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.

  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