Science.gov

Sample records for advanced pathway guidance

  1. Advanced Pathway Guidance Evaluations on a Synthetic Vision Head-Up Display

    NASA Technical Reports Server (NTRS)

    Kramer, Lynda J.; Prinzel, Lawrence J., III; Arthur, Jarvis J., III; Bailey, Randall E.

    2005-01-01

    NASA's Synthetic Vision Systems (SVS) project is developing technologies with practical applications to potentially eliminate low visibility conditions as a causal factor to civil aircraft accidents while replicating the operational benefits of clear day flight operations, regardless of the actual outside visibility condition. A major thrust of the SVS project involves the development/demonstration of affordable, certifiable display configurations that provide intuitive out-the-window terrain and obstacle information with advanced guidance for commercial and business aircraft. This experiment evaluated the influence of different pathway and guidance display concepts upon pilot situation awareness (SA), mental workload, and flight path tracking performance for Synthetic Vision display concepts using a Head-Up Display (HUD). Two pathway formats (dynamic and minimal tunnel presentations) were evaluated against a baseline condition (no tunnel) during simulated instrument meteorological conditions approaches to Reno-Tahoe International airport. Two guidance cues (tadpole, follow-me aircraft) were also evaluated to assess their influence. Results indicated that the presence of a tunnel on an SVS HUD had no effect on flight path performance but that it did have significant effects on pilot SA and mental workload. The dynamic tunnel concept with the follow-me aircraft guidance symbol produced the lowest workload and provided the highest SA among the tunnel concepts evaluated.

  2. Advances in spacecraft atmospheric entry guidance

    NASA Astrophysics Data System (ADS)

    Benito Manrique, Joel

    In order to advance entry guidance technology two different research areas have been explored with the objective of increasing the reachable landing area and the landing accuracy for future Mars missions. Currently only the northern hemisphere of Mars is available for landing due to its low elevation. Only low elevation landing sites have the necessary atmospheric density to allow landing using current Entry, Descent and Landing (EDL) technology. In order to reach most of the Ancient Highlands, the majority of the southern hemisphere, advanced EDL technology is needed in multiple fields, including entry guidance. The first research area is the definition and applications of reachable and controllable sets for entry. The definition of the reachable and controllable sets provides a framework for the study of the capabilities of an entry vehicle in a given planet. Reachable and controllable sets can be used to comprehensively characterize the envelope of trajectories that a vehicle can fly, the sites it can reach and the entry states that can be accommodated. The sets can also be used for the evaluation of trajectory planning algorithms and to assist in the selection of the entry or landing sites. In essence, the reachable and controllable sets offer a powerful vehicle and trajectory analysis and design framework that allows for better mission design choices. In order to illustrate the use of the sets, they are computed for a representative Mars mission using two different vehicle configurations. The sets characterize the impact of the vehicle configuration on the entry capability. Furthermore, the sets are used to find the best skip-entry trajectory for a return from the Moon mission, highlighting the utility of the sets in atmospheric maneuvers other than entry. The second research area is the development of the components of an entry guidance algorithm that allow high elevation landing and provide as well high landing accuracy. The approach taken follows the

  3. Control Software for Advanced Video Guidance Sensor

    NASA Technical Reports Server (NTRS)

    Howard, Richard T.; Book, Michael L.; Bryan, Thomas C.

    2006-01-01

    Embedded software has been developed specifically for controlling an Advanced Video Guidance Sensor (AVGS). A Video Guidance Sensor is an optoelectronic system that provides guidance for automated docking of two vehicles. Such a system includes pulsed laser diodes and a video camera, the output of which is digitized. From the positions of digitized target images and known geometric relationships, the relative position and orientation of the vehicles are computed. The present software consists of two subprograms running in two processors that are parts of the AVGS. The subprogram in the first processor receives commands from an external source, checks the commands for correctness, performs commanded non-image-data-processing control functions, and sends image data processing parts of commands to the second processor. The subprogram in the second processor processes image data as commanded. Upon power-up, the software performs basic tests of functionality, then effects a transition to a standby mode. When a command is received, the software goes into one of several operational modes (e.g. acquisition or tracking). The software then returns, to the external source, the data appropriate to the command.

  4. Next Generation Advanced Video Guidance Sensor

    NASA Technical Reports Server (NTRS)

    Lee, Jimmy; Spencer, Susan; Bryan, Tom; Johnson, Jimmie; Robertson, Bryan

    2008-01-01

    The first autonomous rendezvous and docking in the history of the U.S. Space Program was successfully accomplished by Orbital Express, using the Advanced Video Guidance Sensor (AVGS) as the primary docking sensor. The United States now has a mature and flight proven sensor technology for supporting Crew Exploration Vehicles (CEV) and Commercial Orbital Transport. Systems (COTS) Automated Rendezvous and Docking (AR&D). AVGS has a proven pedigree, based on extensive ground testing and flight demonstrations. The AVGS on the Demonstration of Autonomous Rendezvous Technology (DART)mission operated successfully in "spot mode" out to 2 km. The first generation rendezvous and docking sensor, the Video Guidance Sensor (VGS), was developed and successfully flown on Space Shuttle flights in 1997 and 1998. Parts obsolescence issues prevent the construction of more AVGS. units, and the next generation sensor must be updated to support the CEV and COTS programs. The flight proven AR&D sensor is being redesigned to update parts and add additional. capabilities for CEV and COTS with the development of the Next, Generation AVGS (NGAVGS) at the Marshall Space Flight Center. The obsolete imager and processor are being replaced with new radiation tolerant parts. In addition, new capabilities might include greater sensor range, auto ranging, and real-time video output. This paper presents an approach to sensor hardware trades, use of highly integrated laser components, and addresses the needs of future vehicles that may rendezvous and dock with the International Space Station (ISS) and other Constellation vehicles. It will also discuss approaches for upgrading AVGS to address parts obsolescence, and concepts for minimizing the sensor footprint, weight, and power requirements. In addition, parts selection and test plans for the NGAVGS will be addressed to provide a highly reliable flight qualified sensor. Expanded capabilities through innovative use of existing capabilities will also be

  5. Orbital Express Advanced Video Guidance Sensor

    NASA Technical Reports Server (NTRS)

    Howard, Ricky; Heaton, Andy; Pinson, Robin; Carrington, Connie

    2008-01-01

    In May 2007 the first US fully autonomous rendezvous and capture was successfully performed by DARPA's Orbital Express (OE) mission. Since then, the Boeing ASTRO spacecraft and the Ball Aerospace NEXTSat have performed multiple rendezvous and docking maneuvers to demonstrate the technologies needed for satellite servicing. MSFC's Advanced Video Guidance Sensor (AVGS) is a primary near-field proximity operations sensor integrated into ASTRO's Autonomous Rendezvous and Capture Sensor System (ARCSS), which provides relative state knowledge to the ASTRO GN&C system. This paper provides an overview of the AVGS sensor flying on Orbital Express, and a summary of the ground testing and on-orbit performance of the AVGS for OE. The AVGS is a laser-based system that is capable of providing range and bearing at midrange distances and full six degree-of-freedom (6DOF) knowledge at near fields. The sensor fires lasers at two different frequencies to illuminate the Long Range Targets (LRTs) and the Short Range Targets (SRTs) on NEXTSat. Subtraction of one image from the other image removes extraneous light sources and reflections from anything other than the corner cubes on the LRTs and SRTs. This feature has played a significant role for Orbital Express in poor lighting conditions. The very bright spots that remain in the subtracted image are processed by the target recognition algorithms and the inverse-perspective algorithms, to provide 3DOF or 6DOF relative state information. Although Orbital Express has configured the ASTRO ARCSS system to only use AVGS at ranges of 120 m or less, some OE scenarios have provided opportunities for AVGS to acquire and track NEXTSat at greater distances. Orbital Express scenarios to date that have utilized AVGS include a berthing operation performed by the ASTRO robotic arm, sensor checkout maneuvers performed by the ASTRO robotic arm, 10-m unmated operations, 30-m unmated operations, and Scenario 3-1 anomaly recovery. The AVGS performed very

  6. 78 FR 70624 - Guidance on Supervisory Concerns and Expectations Regarding Deposit Advance Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-26

    ... Expectations Regarding Deposit Advance Products'' (Guidance), which addresses safe and sound banking practices... Guidance to clarify the OCC's application of principles of safe and sound banking [[Page 70625

  7. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

    PubMed Central

    Biankin, Andrew V.; Waddell, Nicola; Kassahn, Karin S.; Gingras, Marie-Claude; Muthuswamy, Lakshmi B.; Johns, Amber L.; Miller, David K.; Wilson, Peter J.; Patch, Ann-Marie; Wu, Jianmin; Chang, David K.; Cowley, Mark J.; Gardiner, Brooke B.; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J.; Gill, Anthony J.; Pinho, Andreia V.; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J. Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R. Scott; Humphris, Jeremy L.; Kaplan, Warren; Jones, Marc D.; Colvin, Emily K.; Nagrial, Adnan M.; Humphrey, Emily S.; Chou, Angela; Chin, Venessa T.; Chantrill, Lorraine A.; Mawson, Amanda; Samra, Jaswinder S.; Kench, James G.; Lovell, Jessica A.; Daly, Roger J.; Merrett, Neil D.; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q.; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M.; Fisher, William E.; Brunicardi, F. Charles; Hodges, Sally E.; Reid, Jeffrey G.; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R.; Dinh, Huyen; Buhay, Christian J.; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E.; Yung, Christina K.; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A.; Petersen, Gloria M.; Gallinger, Steven; Hruban, Ralph H.; Maitra, Anirban; Iacobuzio-Donahue, Christine A.; Schulick, Richard D.; Wolfgang, Christopher L.; Morgan, Richard A.; Lawlor, Rita T.; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A.; Mann, Karen M.; Jenkins, Nancy A.; Perez-Mancera, Pedro A.; Adams, David J.; Largaespada, David A.; Wessels, Lodewyk F. A.; Rust, Alistair G.; Stein, Lincoln D.; Tuveson, David A.; Copeland, Neal G.; Musgrove, Elizabeth A.; Scarpa, Aldo; Eshleman, James R.; Hudson, Thomas J.; Sutherland, Robert L.; Wheeler, David A.; Pearson, John V.; McPherson, John D.; Gibbs, Richard A.; Grimmond, Sean M.

    2012-01-01

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis. PMID:23103869

  8. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    PubMed

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  9. Robust Neighboring Optimal Guidance for the Advanced Launch System

    NASA Technical Reports Server (NTRS)

    Hull, David G.

    1993-01-01

    In recent years, optimization has become an engineering tool through the availability of numerous successful nonlinear programming codes. Optimal control problems are converted into parameter optimization (nonlinear programming) problems by assuming the control to be piecewise linear, making the unknowns the nodes or junction points of the linear control segments. Once the optimal piecewise linear control (suboptimal) control is known, a guidance law for operating near the suboptimal path is the neighboring optimal piecewise linear control (neighboring suboptimal control). Research conducted under this grant has been directed toward the investigation of neighboring suboptimal control as a guidance scheme for an advanced launch system.

  10. Robust neighboring extremal guidance for the advanced launch system

    NASA Technical Reports Server (NTRS)

    Bain, John; Speyer, Jason L.

    1993-01-01

    With the availability of modern flight computers, realtime neighboring extremal guidance seems feasible. To overcome sensitivity to unknown system parameters and environmental uncertainties, a robust neighboring extremal guidance scheme is proposed. About the optimal trajectory, the accessory problem in the calculus of variations is formed, generating a quadratic cost criterion in the perturbed states and controls. By formulating a disturbance attenuation problem based upon the second variation cost criterion, a differential game is formulated. The game theoretic cost criterion is minimized with respect to the perturbed control but maximized with respect to the unknown parameters in the linearized dynamics. The resulting differential game problem gives rise to a two-point boundary-value problem solved using the sweep method. The sweep method solution provides a linear robust neighboring extremal guidance scheme that is applied to the Advanced Launch System.

  11. Next Generation Advanced Video Guidance Sensor Development and Test

    NASA Technical Reports Server (NTRS)

    Howard, Richard T.; Bryan, Thomas C.; Lee, Jimmy; Robertson, Bryan

    2009-01-01

    The Advanced Video Guidance Sensor (AVGS) was the primary docking sensor for the Orbital Express mission. The sensor performed extremely well during the mission, and the technology has been proven on orbit in other flights too. Parts obsolescence issues prevented the construction of more AVGS units, so the next generation of sensor was designed with current parts and updated to support future programs. The Next Generation Advanced Video Guidance Sensor (NGAVGS) has been tested as a breadboard, two different brassboard units, and a prototype. The testing revealed further improvements that could be made and demonstrated capability beyond that ever demonstrated by the sensor on orbit. This paper presents some of the sensor history, parts obsolescence issues, radiation concerns, and software improvements to the NGAVGS. In addition, some of the testing and test results are presented. The NGAVGS has shown that it will meet the general requirements for any space proximity operations or docking need.

  12. Advanced Guidance and Control for Hypersonics and Space Access

    NASA Technical Reports Server (NTRS)

    Hanson, John M.; Hall, Charles E.; Mulqueen, John A.; Jones, Robert E.

    2003-01-01

    Advanced guidance and control (AG&C) technologies are critical for meeting safety, reliability, and cost requirements for the next generation of reusable launch vehicle (RLV), whether it is fully rocket-powered or has air- breathing components. This becomes clear upon examining the number of expendable launch vehicle failures in the recent past where AG&C technologies could have saved a RLV with the same failure mode, the additional vehicle problems where t h i s technology applies, and the costs and time associated with mission design with or without all these failure issues. The state-of-the-art in guidance and control technology, as well as in computing technology, is the point where we can look to the possibility of being able to safely return a RLV in any situation where it can physically be recovered. This paper outlines reasons for AWC, current technology efforts, and the additional work needed for making this goal a reality. There are a number of approaches to AG&C that have the potential for achieving the desired goals. For some of these methods, we compare the results of tests designed to demonstrate the achievement of the goals. Tests up to now have been focused on rocket-powered vehicles; application to hypersonic air-breathers is planned. We list the test cases used to demonstrate that the desired results are achieved, briefly describe an automated test scoring method, and display results of the tests. Some of the technology components have reached the maturity level where they are ready for application to a new vehicle concept, while others are not far along in development.

  13. Simulation and ground testing with the Advanced Video Guidance Sensor

    NASA Technical Reports Server (NTRS)

    Howard, Richard T.; Johnston, Albert S.; Bryan, Thomas C.; Book, Michael L.

    2005-01-01

    The Advanced Video Guidance Sensor (AVGS), an active sensor system that provides near-range 6-degree-of-freedom sensor data, has been developed as part of an automatic rendezvous and docking system for the Demonstration of Autonomous Rendezvous Technology (DART). The sensor determines the relative positions and attitudes between the active sensor and the passive target at ranges up to 300 meters. The AVGS uses laser diodes to illuminate retro-reflectors in the target, a solid-state imager to detect the light returned from the target, and image capture electronics and a digital signal processor to convert the video information into the relative positions and attitudes. The development of the sensor, through initial prototypes, final prototypes, and three flight units, has required a great deal of testing at every phase, and the different types of testing, their effectiveness, and their results, are presented in this paper, focusing on the testing of the flight units. Testing has improved the sensor's performance.

  14. ADVANCES IN INDOOR AIR VAPOR INTRUSION: GUIDANCE AND APPLICATION

    EPA Science Inventory

    Ongoing efforts between the Office of Research and Development and the Office of Solid Waste and Emergency Response have included technical guidance support, field demonstration activities, data analysis, and technology transfer activities in evaluating the impacts of vapor intru...

  15. Advanced Guidance and Control Project for Reusable Launch Vehicles

    NASA Technical Reports Server (NTRS)

    Hanson, John M.

    2000-01-01

    The goals of this project are to significantly reduce the time and cost associated with guidance and control design for reusable launch vehicles, and to increase their safety and reliability. Success will lead to reduced cycle times during vehicle design and to reduced costs associated with flying to new orbits, with new payloads, and with modified vehicles. Success will also lead to more robustness to unforeseen circumstances in flight thereby enhancing safety and reducing risk. There are many guidance and control methods available that hold some promise for improvement in the desired areas. Investigators are developing a representative set of independent guidance and control methods for this project. These methods are being incorporated into a high-fidelity off is being conducted across a broad range of flight requirements. The guidance and control methods that perform the best will have demonstrated the desired qualities.

  16. Next Generation Advanced Video Guidance Sensor: Low Risk Rendezvous and Docking Sensor

    NASA Technical Reports Server (NTRS)

    Lee, Jimmy; Carrington, Connie; Spencer, Susan; Bryan, Thomas; Howard, Ricky T.; Johnson, Jimmie

    2008-01-01

    The Next Generation Advanced Video Guidance Sensor (NGAVGS) is being built and tested at MSFC. This paper provides an overview of current work on the NGAVGS, a summary of the video guidance heritage, and the AVGS performance on the Orbital Express mission. This paper also provides a discussion of applications to ISS cargo delivery vehicles, CEV, and future lunar applications.

  17. A Study Into the Effects of Kalman Filtered Noise in Advanced Guidance Laws of Missile Navigation

    DTIC Science & Technology

    2014-03-01

    air-to-air missile APN augmented proportional navigation AWG air weapons guidance DG differential geometry DOF degrees of freedom F fighter...not a viable substitute. The Phoenix was a long range missile with an advanced radar guidance system based heavily on the Tomcat AWG -9 radar. Using

  18. Approximate optimal guidance for the advanced launch system

    NASA Technical Reports Server (NTRS)

    Feeley, T. S.; Speyer, J. L.

    1993-01-01

    A real-time guidance scheme for the problem of maximizing the payload into orbit subject to the equations of motion for a rocket over a spherical, non-rotating earth is presented. An approximate optimal launch guidance law is developed based upon an asymptotic expansion of the Hamilton - Jacobi - Bellman or dynamic programming equation. The expansion is performed in terms of a small parameter, which is used to separate the dynamics of the problem into primary and perturbation dynamics. For the zeroth-order problem the small parameter is set to zero and a closed-form solution to the zeroth-order expansion term of Hamilton - Jacobi - Bellman equation is obtained. Higher-order terms of the expansion include the effects of the neglected perturbation dynamics. These higher-order terms are determined from the solution of first-order linear partial differential equations requiring only the evaluation of quadratures. This technique is preferred as a real-time, on-line guidance scheme to alternative numerical iterative optimization schemes because of the unreliable convergence properties of these iterative guidance schemes and because the quadratures needed for the approximate optimal guidance law can be performed rapidly and by parallel processing. Even if the approximate solution is not nearly optimal, when using this technique the zeroth-order solution always provides a path which satisfies the terminal constraints. Results for two-degree-of-freedom simulations are presented for the simplified problem of flight in the equatorial plane and compared to the guidance scheme generated by the shooting method which is an iterative second-order technique.

  19. The Hedgehog Signalling Pathway in Cell Migration and Guidance: What We Have Learned from Drosophila melanogaster

    PubMed Central

    Araújo, Sofia J.

    2015-01-01

    Cell migration and guidance are complex processes required for morphogenesis, the formation of tumor metastases, and the progression of human cancer. During migration, guidance molecules induce cell directionality and movement through complex intracellular mechanisms. Expression of these molecules has to be tightly regulated and their signals properly interpreted by the receiving cells so as to ensure correct navigation. This molecular control is fundamental for both normal morphogenesis and human disease. The Hedgehog (Hh) signaling pathway is evolutionarily conserved and known to be crucial for normal cellular growth and differentiation throughout the animal kingdom. The relevance of Hh signaling for human disease is emphasized by its activation in many cancers. Here, I review the current knowledge regarding the involvement of the Hh pathway in cell migration and guidance during Drosophila development and discuss its implications for human cancer origin and progression. PMID:26445062

  20. Advanced information processing system: Hosting of advanced guidance, navigation and control algorithms on AIPS using ASTER

    NASA Technical Reports Server (NTRS)

    Brenner, Richard; Lala, Jaynarayan H.; Nagle, Gail A.; Schor, Andrei; Turkovich, John

    1994-01-01

    This program demonstrated the integration of a number of technologies that can increase the availability and reliability of launch vehicles while lowering costs. Availability is increased with an advanced guidance algorithm that adapts trajectories in real-time. Reliability is increased with fault-tolerant computers and communication protocols. Costs are reduced by automatically generating code and documentation. This program was realized through the cooperative efforts of academia, industry, and government. The NASA-LaRC coordinated the effort, while Draper performed the integration. Georgia Institute of Technology supplied a weak Hamiltonian finite element method for optimal control problems. Martin Marietta used MATLAB to apply this method to a launch vehicle (FENOC). Draper supplied the fault-tolerant computing and software automation technology. The fault-tolerant technology includes sequential and parallel fault-tolerant processors (FTP & FTPP) and authentication protocols (AP) for communication. Fault-tolerant technology was incrementally incorporated. Development culminated with a heterogeneous network of workstations and fault-tolerant computers using AP. Draper's software automation system, ASTER, was used to specify a static guidance system based on FENOC, navigation, flight control (GN&C), models, and the interface to a user interface for mission control. ASTER generated Ada code for GN&C and C code for models. An algebraic transform engine (ATE) was developed to automatically translate MATLAB scripts into ASTER.

  1. Optimal guidance law development for an advanced launch system

    NASA Technical Reports Server (NTRS)

    Calise, Anthony J.; Leung, Martin S. K.

    1995-01-01

    The objective of this research effort was to develop a real-time guidance approach for launch vehicles ascent to orbit injection. Various analytical approaches combined with a variety of model order and model complexity reduction have been investigated. Singular perturbation methods were first attempted and found to be unsatisfactory. The second approach based on regular perturbation analysis was subsequently investigated. It also fails because the aerodynamic effects (ignored in the zero order solution) are too large to be treated as perturbations. Therefore, the study demonstrates that perturbation methods alone (both regular and singular perturbations) are inadequate for use in developing a guidance algorithm for the atmospheric flight phase of a launch vehicle. During a second phase of the research effort, a hybrid analytic/numerical approach was developed and evaluated. The approach combines the numerical methods of collocation and the analytical method of regular perturbations. The concept of choosing intelligent interpolating functions is also introduced. Regular perturbation analysis allows the use of a crude representation for the collocation solution, and intelligent interpolating functions further reduce the number of elements without sacrificing the approximation accuracy. As a result, the combined method forms a powerful tool for solving real-time optimal control problems. Details of the approach are illustrated in a fourth order nonlinear example. The hybrid approach is then applied to the launch vehicle problem. The collocation solution is derived from a bilinear tangent steering law, and results in a guidance solution for the entire flight regime that includes both atmospheric and exoatmospheric flight phases.

  2. Advanced entry guidance algorithm with landing footprint computation

    NASA Astrophysics Data System (ADS)

    Leavitt, James Aaron

    The design and performance evaluation of an entry guidance algorithm for future space transportation vehicles is presented. The algorithm performs two functions: on-board trajectory planning and trajectory tracking. The planned longitudinal path is followed by tracking drag acceleration, as is done by the Space Shuttle entry guidance. Unlike the Shuttle entry guidance, lateral path curvature is also planned and followed. A new trajectory planning function for the guidance algorithm is developed that is suitable for suborbital entry and that significantly enhances the overall performance of the algorithm for both orbital and suborbital entry. In comparison with the previous trajectory planner, the new planner produces trajectories that are easier to track, especially near the upper and lower drag boundaries and for suborbital entry. The new planner accomplishes this by matching the vehicle's initial flight path angle and bank angle, and by enforcing the full three-degree-of-freedom equations of motion with control derivative limits. Insights gained from trajectory optimization results contribute to the design of the new planner, giving it near-optimal downrange and crossrange capabilities. Planned trajectories and guidance simulation results are presented that demonstrate the improved performance. Based on the new planner, a method is developed for approximating the landing footprint for entry vehicles in near real-time, as would be needed for an on-board flight management system. The boundary of the footprint is constructed from the endpoints of extreme downrange and crossrange trajectories generated by the new trajectory planner. The footprint algorithm inherently possesses many of the qualities of the new planner, including quick execution, the ability to accurately approximate the vehicle's glide capabilities, and applicability to a wide range of entry conditions. Footprints can be generated for orbital and suborbital entry conditions using a pre

  3. 78 FR 25268 - Proposed Guidance on Deposit Advance Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-30

    ... losses. Compliance with applicable federal consumer protection statutes, management's oversight, and... safe and sound banking practices and consumer protection in connection with deposit advance credit... Management Policy, (202) 898-3898; Surya Sen, Section Chief, Supervisory Policy, (202) 898-6699;...

  4. 78 FR 70552 - Guidance on Supervisory Concerns and Expectations Regarding Deposit Advance Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-26

    ... and sound banking practices and consumer protection in connection with deposit advance products. FOR... Guidance to clarify the FDIC's application of principles of safe and sound banking practices and consumer... safe and sound manner and does not engage in practices that would increase these risks. III....

  5. Advances in Orion's On-Orbit Guidance and Targeting System Architecture

    NASA Technical Reports Server (NTRS)

    Scarritt, Sara K.; Fill, Thomas; Robinson, Shane

    2015-01-01

    NASA's manned spaceflight programs have a rich history of advancing onboard guidance and targeting technology. In order to support future missions, the guidance and targeting architecture for the Orion Multi-Purpose Crew Vehicle must be able to operate in complete autonomy, without any support from the ground. Orion's guidance and targeting system must be sufficiently flexible to easily adapt to a wide array of undecided future missions, yet also not cause an undue computational burden on the flight computer. This presents a unique design challenge from the perspective of both algorithm development and system architecture construction. The present work shows how Orion's guidance and targeting system addresses these challenges. On the algorithm side, the system advances the state-of-the-art by: (1) steering burns with a simple closed-loop guidance strategy based on Shuttle heritage, and (2) planning maneuvers with a cutting-edge two-level targeting routine. These algorithms are then placed into an architecture designed to leverage the advantages of each and ensure that they function in concert with one another. The resulting system is characterized by modularity and simplicity. As such, it is adaptable to the on-orbit phases of any future mission that Orion may attempt.

  6. Guidance on offsite emergency radiation measurement systems. Phase 2: The milk pathway

    SciTech Connect

    Not Available

    1984-04-01

    This document provides guidance to State and local governments and to Federal agencies on offsite emergency measurement of radionuclides after an accident involving a light-water nuclear power plant; in particular, this document provides guidance on determining the dose commitment from the milk pathway. Protective action levels proposed by the Food and Drug Administration (FDA) for milk are used as the basis for monitoring requirements. Measurement of radionuclides in milk should be made at the earliest practical point in the production chain: dairy farms, receiving and transfer stations, processing plants or marketing facilities. Early monitoring will provide data to keep significantly contaminated milk out of distribution and will provide the basis for the most timely emergency response action. Radioiodine plus four other radionuclides, cesium-134, cesium-137, strontium-89, and strontium-90, contribute significantly to dose via the milk pathway; of the most severe potential accident, the short-term dose via the milk pathway from radioiodine is significantly greater than that of cesium or strontium. There is no emergency field monitoring instrumentation available for accurately monitoring cesium and strontium, particularly in the presence of radioiodine. Radioiodine can be a potential contamination problem in liquid milk, whereas radiocesium and radiostrontium can be a contamination problem in processed milk products. Monitoring for the long half-life nuclides such as cesium and strontium requires sophisticated equipment or chemistry procedures which are only available in a laboratory. 2 references, 21 figures, 21 tables.

  7. TRIM-9 functions in the UNC-6/UNC-40 pathway to regulate ventral guidance.

    PubMed

    Song, Song; Ge, Qinglan; Wang, Jinbo; Chen, Haiyang; Tang, Sanyuan; Bi, Junfeng; Li, Xia; Xie, Qi; Huang, Xun

    2011-01-01

    TRIpartite Motif (TRIM) family proteins are ring finger domain-containing, multi-domain proteins implicated in many biological processes. Members of the TRIM-9/C-I subfamily of TRIM proteins, including TRIM-9, MID1 and MID2, have neuronal functions and are associated with neurological diseases. To explore whether the functions of C-I TRIM proteins are conserved in invertebrates, we analyzed Caenorhabditis elegans and Drosophila trim-9 mutants. C. elegans trim-9 mutants exhibit defects in the ventral guidance of hermaphrodite specific neuron (HSN) and the touch neuron AVM. Further genetic analyses indicate that TRIM-9 participates in the UNC-6-UNC-40 attraction pathway. Asymmetric distribution of UNC-40 during HSN development is normal in trim-9 mutants. However, the asymmetric localization of MIG-10, a downstream effector of UNC-40, is abolished in trim-9 mutants. These results suggest that TRIM-9 functions upstream of MIG-10 in the UNC-40 pathway. Moreover, we showed that TRIM-9 exhibits E3 ubiquitin ligase activity in vitro and this activity is important for TRIM-9 function in vivo. Additionally, we found that Drosophila trim-9 is required for the midline attraction of a group of sensory neuron axons. Over-expression of the Netrin/UNC-6 receptor Frazzled suppresses the guidance defects in trim-9 mutants. Our study reveals an evolutionarily conserved function of TRIM-9 in the UNC-40/Frazzled-mediated UNC-6/Netrin attraction pathway.

  8. DEVELOPMENT OF HUMAN FACTORS ENGINEERING GUIDANCE FOR SAFETY EVALUATIONS OF ADVANCED REACTORS.

    SciTech Connect

    O'HARA, J.; PERSENSKY, J.; SZABO, A.

    2006-10-01

    Advanced reactors are expected to be based on a concept of operations that is different from what is currently used in today's reactors. Therefore, regulatory staff may need new tools, developed from the best available technical bases, to support licensing evaluations. The areas in which new review guidance may be needed and the efforts underway to address the needs will be discussed. Our preliminary results focus on some of the technical issues to be addressed in three areas for which new guidance may be developed: automation and control, operations under degraded conditions, and new human factors engineering methods and tools.

  9. Advanced Information Systems Design: Technical Basis and Human Factors Review Guidance

    DTIC Science & Technology

    2000-03-01

    H^ NUREG /CR-6633 BNL- NUREG -52563 Advanced Information Systems Design: Technical Basis and Human Factors Review Guidance Brookhaven National...AVAILABILITY NOTICE Availability of Reference Materials Cited in NRC Publications NRC publications in the NUREG series, NRC regu- lations, and Title...Information Service Springfield, VA 22161 -0002 <http://www.ntis.gov> 1 -800-553-6847 or locally 703-605-6000 The NUREG series comprises (1) brochures

  10. Guidance for Developing Principal Design Criteria for Advanced (Non-Light Water) Reactors

    SciTech Connect

    Holbrook, Mark; Kinsey, Jim

    2015-03-01

    In July 2013, the US Department of Energy (DOE) and US Nuclear Regulatory Commission (NRC) established a joint initiative to address a key portion of the licensing framework essential to advanced (non-light water) reactor technologies. The initiative addressed the “General Design Criteria for Nuclear Power Plants,” Appendix A to10 Code of Federal Regulations (CFR) 50, which were developed primarily for light water reactors (LWRs), specific to the needs of advanced reactor design and licensing. The need for General Design Criteria (GDC) clarifications in non-LWR applications has been consistently identified as a concern by the industry and varied stakeholders and was acknowledged by the NRC staff in their 2012 Report to Congress1 as an area for enhancement. The initiative to adapt GDC requirements for non-light water advanced reactor applications is being accomplished in two phases. Phase 1, managed by DOE, consisted of reviews, analyses and evaluations resulting in recommendations and deliverables to NRC as input for NRC staff development of regulatory guidance. Idaho National Laboratory (INL) developed this technical report using technical and reactor technology stakeholder inputs coupled with analysis and evaluations provided by a team of knowledgeable DOE national laboratory personnel with input from individual industry licensing consultants. The DOE national laboratory team reviewed six different classes of emerging commercial reactor technologies against 10 CFR 50 Appendix A GDC requirements and proposed guidance for their adapted use in non-LWR applications. The results of the Phase 1 analysis are contained in this report. A set of draft Advanced Reactor Design Criteria (ARDC) has been proposed for consideration by the NRC in the establishment of guidance for use by non-LWR designers and NRC staff. The proposed criteria were developed to preserve the underlying safety bases expressed by the original GDC, and recognizing that advanced reactors may take

  11. Guidance on offsite emergency radiation measurement systems. Phase 3. Water and non-dairy food pathway

    SciTech Connect

    Salmonson, B.J.; Hoffman, L.G.; Honkus, R.J.; Keller, J.H.

    1984-10-01

    This document provides guidance to State and local governments and to federal agencies on offsite emergency measurement of radionuclides in non-dairy food and potable water to determine dose commitment after an accident involving a light-water nuclear power plant. In the early emergency phase of an accident, monitoring of the ingestion pathway should be primarily directed toward controlling the human ingestion of deposited airborne contamination. Ingestion of edible plants is the non-dairy food pathway of primary concern. The importance of this pathway is dependent on the time of year the nuclide release occurs (e.g. deposition of radionuclides on plants just prior to or during harvest presents the greatest hazard). The greatest immediate concern following a release may be from the radioiodines; however, because of their short half-life, the hazard diminishes rapidly and the longer lived radionuclides of strontium and cesium become important. Protective actions and monitoring requirements are discussed. Several alternatives for field monitoring of foodstuffs and water are presented. However, the recommended procedure for monitoring foodstuffs is field sampling in predetermined areas followed by laboratory analyses. The recommended procedure for monitoring water is collection of samples at water purification plants followed by analyses performed by experienced technical personnel. 32 references, 2 figures, 9 tables.

  12. The Next Generation Advanced Video Guidance Sensor: Flight Heritage and Current Development

    NASA Astrophysics Data System (ADS)

    Howard, Richard T.; Bryan, Thomas C.

    2009-03-01

    The Next Generation Advanced Video Guidance Sensor (NGAVGS) is the latest in a line of sensors that have flown four times in the last 10 years. The NGAVGS has been under development for the last two years as a long-range proximity operations and docking sensor for use in an Automated Rendezvous and Docking (AR&D) system. The first autonomous rendezvous and docking in the history of the U.S. Space Program was successfully accomplished by Orbital Express, using the Advanced Video Guidance Sensor (AVGS) as the primary docking sensor. That flight proved that the United States now has a mature and flight proven sensor technology for supporting Crew Exploration Vehicles (CEV) and Commercial Orbital Transport Systems (COTS) Automated Rendezvous and Docking (AR&D). NASA video sensors have worked well in the past: the AVGS used on the Demonstration of Autonomous Rendezvous Technology (DART) mission operated successfully in "spot mode" out to 2 km, and the first generation rendezvous and docking sensor, the Video Guidance Sensor (VGS), was developed and successfully flown on Space Shuttle flights in 1997 and 1998.

  13. A Plan for Advanced Guidance and Control Technology for 2nd Generation Reusable Launch Vehicles

    NASA Technical Reports Server (NTRS)

    Hanson, John M.; Fogle, Frank (Technical Monitor)

    2002-01-01

    Advanced guidance and control (AG&C) technologies are critical for meeting safety/reliability and cost requirements for the next generation of reusable launch vehicle (RLV). This becomes clear upon examining the number of expendable launch vehicle failures in the recent past where AG&C technologies would have saved a RLV with the same failure mode, the additional vehicle problems where this technology applies, and the costs associated with mission design with or without all these failure issues. The state-of-the-art in guidance and control technology, as well as in computing technology, is at the point where we can took to the possibility of being able to safely return a RLV in any situation where it can physically be recovered. This paper outlines reasons for AG&C, current technology efforts, and the additional work needed for making this goal a reality.

  14. Learning guide for the terminal configured vehicle advanced guidance and control system mode select panel

    NASA Technical Reports Server (NTRS)

    Anderson, M. A.; Callahan, R.

    1981-01-01

    This learning guide is designed to assist pilots in taking the PLATO presimulator training course on the advanced guidance and control system mode select panel. The learning guide is divided into five sections. The first section, the introduction, presents the course goals, prerequisites, definition of PLATO activities, and a suggested approach to completing the course. The remaining four sections present the purpose, learning activities and summary of each lesson of the AGCS PLATO course, which consists of (1) AGCS introduction; (2) lower order modes; (3) higher order modes; and (4) an arrival route exercise.

  15. The Next Generation Advanced Video Guidance Sensor: Flight Heritage and Current Development

    NASA Technical Reports Server (NTRS)

    Howard, Richard T.; Bryan, Thomas C.

    2009-01-01

    The Next Generation Advanced Video Guidance Sensor (NGAVGS) is the latest in a line of sensors that have flown four times in the last 10 years. The NGAVGS has been under development for the last two years as a long-range proximity operations and docking sensor for use in an Automated Rendezvous and Docking (AR&D) system. The first autonomous rendezvous and docking in the history of the U.S. Space Program was successfully accomplished by Orbital Express, using the Advanced Video Guidance Sensor (AVGS) as the primary docking sensor. That flight proved that the United States now has a mature and flight proven sensor technology for supporting Crew Exploration Vehicles (CEV) and Commercial Orbital Transport Systems (COTS) Automated Rendezvous and Docking (AR&D). NASA video sensors have worked well in the past: the AVGS used on the Demonstration of Autonomous Rendezvous Technology (DART) mission operated successfully in "spot mode" out to 2 km, and the first generation rendezvous and docking sensor, the Video Guidance Sensor (VGS), was developed and successfully flown on Space Shuttle flights in 1997 and 1998. This paper presents the flight heritage and results of the sensor technology, some hardware trades for the current sensor, and discusses the needs of future vehicles that may rendezvous and dock with the International Space Station (ISS) and other Constellation vehicles. It also discusses approaches for upgrading AVGS to address parts obsolescence, and concepts for minimizing the sensor footprint, weight, and power requirements. In addition, the testing of the various NGAVGS development units will be discussed along with the use of the NGAVGS as a proximity operations and docking sensor.

  16. MIG-10 functions with ABI-1 to mediate the UNC-6 and SLT-1 axon guidance signaling pathways.

    PubMed

    Xu, Yan; Quinn, Christopher C

    2012-01-01

    Extracellular guidance cues steer axons towards their targets by eliciting morphological changes in the growth cone. A key part of this process is the asymmetric recruitment of the cytoplasmic scaffolding protein MIG-10 (lamellipodin). MIG-10 is thought to asymmetrically promote outgrowth by inducing actin polymerization. However, the mechanism that links MIG-10 to actin polymerization is not known. We have identified the actin regulatory protein ABI-1 as a partner for MIG-10 that can mediate its outgrowth-promoting activity. The SH3 domain of ABI-1 binds to MIG-10, and loss of function of either of these proteins causes similar axon guidance defects. Like MIG-10, ABI-1 functions in both the attractive UNC-6 (netrin) pathway and the repulsive SLT-1 (slit) pathway. Dosage sensitive genetic interactions indicate that MIG-10 functions with ABI-1 and WVE-1 to mediate axon guidance. Epistasis analysis reveals that ABI-1 and WVE-1 function downstream of MIG-10 to mediate its outgrowth-promoting activity. Moreover, experiments with cultured mammalian cells suggest that the interaction between MIG-10 and ABI-1 mediates a conserved mechanism that promotes formation of lamellipodia. Together, these observations suggest that MIG-10 interacts with ABI-1 and WVE-1 to mediate the UNC-6 and SLT-1 guidance pathways.

  17. 78 FR 25353 - Proposed Guidance on Deposit Advance Products; Withdrawal of Proposed Guidance on Deposit-Related...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-30

    ... Bulletin, 2001-47, ``Third-Party Relationships: Risk Management Principles for Third-Party Relationships... protection statutes, management's oversight, and relationships with third parties will also be assessed... Proposed Guidance on Deposit-Related Consumer Credit Products AGENCIES: Office of the Comptroller of...

  18. Advanced navigation and guidance for high-precision planetary landing on Mars

    NASA Astrophysics Data System (ADS)

    Levesque, Jean-Francois

    Several international missions scheduled for years 2011--2013 have as objective a Mars surface sample return to Earth. In order to gather samples of high scientific quality, these missions require precise landing at preselected locations on Mars. Since the previous missions on Mars have flown unguided and highly inaccurate atmospheric entry, a new generation of landing systems must be developed. It was demonstrated by Wolf et al., [2004] that the most efficient way to increase the landing accuracy is achieved during the atmospheric entry by steering the vehicle trajectory in order to eliminate the dispersions caused at entry and accumulated during the hypersonic phase. Thus, the research project proposed here will investigate the problem and bring advances on atmospheric entry navigation, guidance and control techniques applied to atmospheric entry on Mars. The state-of-the-art revealed several limitations on the current techniques such as the lack of proper navigation system and the inability to guide the trajectory efficiently in presence of disturbances and entry conditions uncertainties. On the theoretical side, the nonlinear state estimators required for navigation use algorithms that are a heavy computational burden for the onboard processor. Following these limitations, the research presented in this document is conducted along three paths: estimation theory, entry navigation techniques and entry guidance techniques in order to investigate on advances to achieve high precision landing. After an in-depth investigation of the theoretical background required to understand the atmospheric entry dynamics, a number of issues are addressed and the following substantial contributions regarding Mars atmospheric entry navigation and guidance are achieved. (C1) A theoretical improvement of the unscented Kalman Filter by merging two variants in the literature. The resulting technique has the advantages of both former algorithms. (C2) Four navigation concepts using

  19. Human factors engineering guidance for the review of advanced alarm systems

    SciTech Connect

    O`Hara, J.M.; Brown, W.S.; Higgins, J.C.; Stubler, W.F.

    1994-09-01

    This report provides guidance to support the review of the human factors aspects of advanced alarm system designs in nuclear power plants. The report is organized into three major sections. The first section describes the methodology and criteria that were used to develop the design review guidelines. Also included is a description of the scope, organization, and format of the guidelines. The second section provides a systematic review procedure in which important characteristics of the alarm system are identified, described, and evaluated. The third section provides the detailed review guidelines. The review guidelines are organized according to important characteristics of the alarm system including: alarm definition; alarm processing and reduction; alarm prioritization and availability; display; control; automated; dynamic, and modifiable characteristics; reliability, test, maintenance, and failure indication; alarm response procedures; and control-display integration and layout.

  20. Orbital Express Advanced Video Guidance Sensor: Ground Testing, Flight Results and Comparisons

    NASA Technical Reports Server (NTRS)

    Pinson, Robin M.; Howard, Richard T.; Heaton, Andrew F.

    2008-01-01

    Orbital Express (OE) was a successful mission demonstrating automated rendezvous and docking. The 2007 mission consisted of two spacecraft, the Autonomous Space Transport Robotic Operations (ASTRO) and the Next Generation Serviceable Satellite (NEXTSat) that were designed to work together and test a variety of service operations in orbit. The Advanced Video Guidance Sensor, AVGS, was included as one of the primary proximity navigation sensors on board the ASTRO. The AVGS was one of four sensors that provided relative position and attitude between the two vehicles. Marshall Space Flight Center was responsible for the AVGS software and testing (especially the extensive ground testing), flight operations support, and analyzing the flight data. This paper briefly describes the historical mission, the data taken on-orbit, the ground testing that occurred, and finally comparisons between flight data and ground test data for two different flight regimes.

  1. Advancing the educational and career pathway for clinical trials nurses.

    PubMed

    Scott, Kathleen; White, Kathryn; Roydhouse, Jessica K

    2013-04-01

    Clinical trials nurses play a pivotal role in the conduct of clinical research, but the educational and career pathway for these nurses remains unclear. This article reports findings from a survey of nurses working in cancer clinical trials research in Australia. Most participants held postgraduate qualifications (42 of 61); however, clinical trials education was primarily attained through short professional development courses. Interest in pursuing trial-specific postgraduate education was high, but barriers were identified, including cost, time, and unclear benefit for career advancement. Job titles varied substantially, which is indicative of an unclear employment pathway. These findings suggest that initiatives to improve the educational and career pathway for clinical trials nurses are needed and should include the following: formal educational preparation, greater consistency in employment status, and clearer career progression. These strategies should be underpinned by broad professional recognition of the clinical trials nurse as a specialized nursing role.

  2. Targeting stem cell signaling pathways for drug discovery: advances in the Notch and Wnt pathways.

    PubMed

    An, Songzhu Michael; Ding, Qiang; Zhang, Jie; Xie, JingYi; Li, LingSong

    2014-06-01

    Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions. In stem cells, a small number of pathways, notably those of TGF-β/BMP, Hedgehog, Notch, and Wnt, are responsible for the regulation of pluripotency and differentiation. During embryonic development, these pathways govern cell fate specifications as well as the formation of tissues and organs. In adulthood, their normal functions are important for tissue homeostasis and regeneration, whereas aberrations result in diseases, such as cancer and degenerative disorders. In complex biological systems, stem cell signaling pathways work in concert as a network and exhibit crosstalk, such as the negative crosstalk between Wnt and Notch. Over the past decade, genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways. Indeed, discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry. Remarkable progress has been made and several promising drug candidates have entered into clinical trials. This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.

  3. The Advanced Video Guidance Sensor: Orbital Express and the Next Generation

    NASA Technical Reports Server (NTRS)

    Howard, Richard T.; Heaton, Andrew F.; Pinson, Robin M.; Carrington, Connie L.; Lee, James E.; Bryan, Thomas C.; Robertson, Bryan A.; Spencer, Susan H.; Johnson, Jimmie E.

    2008-01-01

    The Orbital Express (OE) mission performed the first autonomous rendezvous and docking in the history of the United States on May 5-6, 2007 with the Advanced Video Guidance Sensor (AVGS) acting as one of the primary docking sensors. Since that event, the OE spacecraft performed four more rendezvous and docking maneuvers, each time using the AVGS as one of the docking sensors. The Marshall Space Flight Center's (MSFC's) AVGS is a nearfield proximity operations sensor that was integrated into the Autonomous Rendezvous and Capture Sensor System (ARCSS) on OE. The ARCSS provided the relative state knowledge to allow the OE spacecraft to rendezvous and dock. The AVGS is a mature sensor technology designed to support Automated Rendezvous and Docking (AR&D) operations. It is a video-based laser-illuminated sensor that can determine the relative position and attitude between itself and its target. Due to parts obsolescence, the AVGS that was flown on OE can no longer be manufactured. MSFC has been working on the next generation of AVGS for application to future Constellation missions. This paper provides an overview of the performance of the AVGS on Orbital Express and discusses the work on the Next Generation AVGS (NGAVGS).

  4. Guidance for Professionals Working with Newborns and Their Families: Pathways to Positive Parenting

    ERIC Educational Resources Information Center

    Pearson, Jolene

    2016-01-01

    Parents of newborns and infants are especially open to learning, and many new parents are actively seeking information. What do professionals teach them? How do they teach them? "Pathways" is an educator's guide to educating and supporting new parents. "Pathways" guides professionals in developing an approach to parent…

  5. An advanced arrangement of the combined propulsion, levitation and guidance system of superconducting Maglev

    SciTech Connect

    Fujie, Junji

    1999-09-01

    The PLG (combined Propulsion, Levitation and Guidance) method was proposed for a more favorable Maglev ground coil system, combining the functions of propulsion, levitation, and guidance of the vehicle into one coil. Research and development is currently being conducted on this method. In this paper, the characteristics of a newly-structured system for the PLG method is examined. The discussed characteristics include propulsion, levitation-guidance, vehicle dynamics in the cases of problems with the superconducting magnets, and the magnetic field on board the vehicle.

  6. Advances in mechanisms and signaling pathways of carbon nanotube toxicity.

    PubMed

    Dong, Jie; Ma, Qiang

    2015-01-01

    Carbon nanotubes (CNT) have been developed into new materials with a variety of industrial and commercial applications. In contrast, the physicochemical properties of CNT at the nanoscale render them the potency to generate toxic effects. Indeed, the potential health impacts of CNT have drawn a great deal of attention in recent years, owing to their identified toxicological and pathological consequences including cytotoxicity, inflammation, fibrosis, genotoxicity, tumorigenesis, and immunotoxicity. Understanding the mechanisms by which CNT induce toxicity and pathology is thus urgently needed for accurate risk assessment of CNT exposure in humans, and for safe and responsible development and commercialization of nanotechnology. Here, we summarize and discuss recent advances in this area with a focus on the molecular interactions between CNT and mammalian systems, and the signaling pathways important for the development of CNT toxicity such as the NF-κB, NLRP3 inflammasome, TGF-β1, MAPK, and p53 signaling cascades. With the current mechanistic evidence summarized in this review, we expect to provide new insights into CNT toxicology at the molecular level and offer new clues to the prevention of health effects resulting from CNT exposure. Moreover, we disclose questions and issues that remain in this rapidly advancing field of nanotoxicology, which would facilitate ascertaining future research directions.

  7. Advances in mechanisms and signaling pathways of carbon nanotube toxicity

    PubMed Central

    Dong, Jie; Ma, Qiang

    2015-01-01

    Carbon nanotubes (CNT) have been developed into new materials with a variety of industrial and commercial applications. In contrast, the physicochemical properties of CNT at the nanoscale render them the potency to generate toxic effects. Indeed, the potential health impacts of CNT have drawn a great deal of attention in recent years, owing to their identified toxicological and pathological consequences including cytotoxicity, inflammation, fibrosis, genotoxicity, tumorigenesis, and immunotoxicity. Understanding the mechanisms by which CNT induce toxicity and pathology is thus urgently needed for accurate risk assessment of CNT exposure in humans, and for safe and responsible development and commercialization of nanotechnology. Here, we summarize and discuss recent advances in this area with a focus on the molecular interactions between CNT and mammalian systems, and the signaling pathways important for the development of CNT toxicity such as the NF-κB, NLRP3 inflammasome, TGF-β1, MAPK, and p53 signaling cascades. With the current mechanistic evidence summarized in this review, we expect to provide new insights into CNT toxicology at the molecular level and offer new clues to the prevention of health effects resulting from CNT exposure. Moreover, we disclose questions and issues that remain in this rapidly advancing field of nanotoxicology, which would facilitate ascertaining future research directions. PMID:25676622

  8. The combination of transcriptomics and informatics identifies pathways targeted by miR-204 during neurogenesis and axon guidance

    PubMed Central

    Conte, Ivan; Merella, Stefania; Garcia-Manteiga, Jose Manuel; Migliore, Chiara; Lazarevic, Dejan; Carrella, Sabrina; Marco-Ferreres, Raquel; Avellino, Raffaella; Davidson, Nathan Paul; Emmett, Warren; Sanges, Remo; Bockett, Nicholas; Van Heel, David; Meroni, Germana; Bovolenta, Paola; Stupka, Elia; Banfi, Sandro

    2014-01-01

    Vertebrate organogenesis is critically sensitive to gene dosage and even subtle variations in the expression levels of key genes may result in a variety of tissue anomalies. MicroRNAs (miRNAs) are fundamental regulators of gene expression and their role in vertebrate tissue patterning is just beginning to be elucidated. To gain further insight into this issue, we analysed the transcriptomic consequences of manipulating the expression of miR-204 in the Medaka fish model system. We used RNA-Seq and an innovative bioinformatics approach, which combines conventional differential expression analysis with the behavior expected by miR-204 targets after its overexpression and knockdown. With this approach combined with a correlative analysis of the putative targets, we identified a wider set of miR-204 target genes belonging to different pathways. Together, these approaches confirmed that miR-204 has a key role in eye development and further highlighted its putative function in neural differentiation processes, including axon guidance as supported by in vivo functional studies. Together, our results demonstrate the advantage of integrating next-generation sequencing and bioinformatics approaches to investigate miRNA biology and provide new important information on the role of miRNAs in the control of axon guidance and more broadly in nervous system development. PMID:24895435

  9. [Advance studies of Slit-Robo signal pathway and its roles in ocular neovascularisation].

    PubMed

    Kong, Yichun; Zhao, Kanxing

    2014-05-01

    The migration and patterning of axons and blood vessels share similar guidance mechanisms. Slits and their Roundabout (Robo) receptors were initially characterized as repulsive guidance cues for neuronal axons and mediate the migration of neuronal precursor cells during neural development. In recent years, the research of Slit/Robo signal pathway on neovascularization has become one of hot topics. This review will focus on the role of Slit/Robo signal pathway in ocular neovascularization to promote the research of Slit/Robo signaling on ophthalmology.

  10. Advancing Ambitions: The Role of Career Guidance in Supporting Social Mobility

    ERIC Educational Resources Information Center

    Hooley, Tristram; Matheson, Jesse; Watts, A. G.

    2014-01-01

    Career guidance describes activities that support individuals in learning about education and employment, and in planning for their future lives, learning, and work. These activities contribute to social mobility, which helps people discover and access opportunities that might exist outside of their immediate networks. Changes in funding and in…

  11. Mission analysis and guidance, navigation, and control design for rendezvous and docking phase of advanced reentry vehicle mission

    NASA Astrophysics Data System (ADS)

    Strippoli, L.; Colmenarejo, P.; Strauch, H.

    2013-12-01

    Advanced Reentry Vehicle (ARV) belongs to the family of vehicles designed to perform rendezvous and docking (RvD) with the International space station (ISS) [1]. Differently from its predecessor ATV (Automated Transfer Vehicle), the ARV will transport a reentry capsule, equipped with a heatshield and able to bring back cargo, experiments, or, as a possible future development, even crew, being this latter scenario very attracting in view of the Space Shuttle retirement. GMV, as subcontractor of EADS-Astrium Germany, is in charge of the RvD and departure mission analysis and GNC (Guidance, Navigation, and Control) design of ARV mission. This paper will present the main outcomes of the study.

  12. Computer-based written emotional disclosure: the effects of advance or real-time guidance and moderation by Big 5 personality traits.

    PubMed

    Beyer, Jonathan A; Lumley, Mark A; Latsch, Deborah V; Oberleitner, Lindsay M S; Carty, Jennifer N; Radcliffe, Alison M

    2014-01-01

    Standard written emotional disclosure (WED) about stress, which is private and unguided, yields small health benefits. The effect of providing individualized guidance to writers may enhance WED, but has not been tested. This trial of computer-based WED compared two novel therapist-guided forms of WED - advance guidance (before sessions) and real-time guidance (during sessions, through instant messaging) - to both standard WED and control writing; it also tested Big 5 personality traits as moderators of guided WED. Young adult participants (n = 163) with unresolved stressful experiences were randomized to conditions, had three, 30-min computer-based writing sessions, and were reassessed six weeks later. Contrary to hypotheses, real-time guidance WED had poorer outcomes than the other conditions on several measures, and advance guidance WED also showed some poorer outcomes. Moderator analyses revealed that participants with low baseline agreeableness, low extraversion, or high conscientiousness had relatively poor responses to guidance. We conclude that providing guidance for WED, especially in real-time, may interfere with emotional processing of unresolved stress, particularly for people whose personalities have poor fit with this interactive form of WED.

  13. A real-time simulation facility for advanced digital guidance and control system research

    NASA Technical Reports Server (NTRS)

    Bryant, W. H.; Downing, D. R.; Ostroff, A. J.

    1979-01-01

    A real-time simulation facility built at NASA's Langley Research Center to support digital guidance and control research and development activities is examined. The unit has recently been used to develop autoland systems for VTOL. The paper describes the autoland experiment and the flight environment, the simulation facility hardware and software, and presents typical simulation data to illustrate the type of data analysis carried out during software development. Finally, flight data for a later version of the autoland system are presented to demonstrate the simulation's capability to predict overall system behavior.

  14. The Primary Flight Display and Its Pathway Guidance: Workload, Performance, and Situation Awareness

    NASA Technical Reports Server (NTRS)

    Wickens, Christopher D.; Alexander, Amy L.; Hardy, Thomas J.

    2003-01-01

    In two experiments carried out in a high fidelity general aviation flight simulator, 42 instrument rated pilots flew a pathway-in-the-sky (tunnel) display through a series of multi-leg curved stepdown approaches through mountainous terrain. Both experiments examined how properties of the tunnel influenced flight path tracking performance, traffic awareness, terrain awareness and workload (assessed both by subjective and secondary task performance measures). Experiment 1, flown in simulated VMC, compared high and low intensity tunnels, with a less cluttered follow-me-airplane (FMA). The results revealed that both tunnels supported better flight path tracking than the FMA, because of the availability of more preview information. Increasing tunnel intensity, while reducing subjective workload, had no benefit on tracking, and degraded traffic detection performance. In Experiment 2, flown mostly in IMC, the low intensity tunnel was flown with a large (10 inch x 8 inch) and small (8 inch x 6.5 inch) display, representing a geometric field of view (GFOV) of either 30 degrees or 60 degrees. Most measures of flight path tracking performance favored the smaller display, and particularly the 60 degree GFOV, which presented a smaller appearing tunnel, and a wider range of terrain depiction. The larger GFOV also supported better terrain awareness, and yielded a lower secondary task assessment of workload. In both experiments, the final landing approach was terminated by a runway obstruction, and the tunnel guided pilots on a missed approach. In nearly all cases, pilots failed to notice an air hazard that lay in the missed approach path, but was only depicted in the outside view.

  15. Real-time approximate optimal guidance laws for the advanced launch system

    NASA Technical Reports Server (NTRS)

    Speyer, Jason L.; Feeley, Timothy; Hull, David G.

    1989-01-01

    An approach to optimal ascent guidance for a launch vehicle is developed using an expansion technique. The problem is to maximize the payload put into orbit subject to the equations of motion of a rocket over a rotating spherical earth. It is assumed that the thrust and gravitational forces dominate over the aerodynamic forces. It is shown that these forces can be separated by a small parameter epsilon, where epsilon is the ratio of the atmospheric scale height to the radius of the earth. The Hamilton-Jacobi-Bellman or dynamic programming equation is expanded in a series where the zeroth-order term (epsilon = 0) can be obtained in closed form. The zeroth-order problem is that of putting maximum payload into orbit subject to the equations of motion of a rocket in a vacuum over a flat earth. The neglected inertial and aerodynamic terms are included in higher order terms of the expansion, which are determined from the solution of first-order linear partial differential equations requiring only quadrature integrations. These quadrature integrations can be performed rapidly, so that real-time approximate optimization can be used to construct the launch guidance law.

  16. Systemic treatment approaches in her2-negative advanced breast cancer—guidance on the guidelines

    PubMed Central

    Joy, A.A.; Ghosh, M.; Fernandes, R.; Clemons, M.J.

    2015-01-01

    Despite advancements in the treatment of early-stage breast cancer, many patients still develop disease recurrence; others present with de novo metastatic disease. For most patients with advanced breast cancer, the primary treatment intent is noncurative—that is, palliative—in nature. The goals of treatment should therefore focus on maximizing symptom control and extending survival. Treatments should be evaluated on an individualized basis in terms of evidence, but also with full respect for the wishes of the patient in terms of acceptable toxicity. Given the availability of extensive reviews on the roles of endocrine therapy and her2 (human epidermal growth factor receptor 2)–targeted therapies for advanced disease, we focus here mainly on treatment guidelines for the non-endocrine management of her2-negative advanced breast cancer in a Canadian health care context. PMID:25848337

  17. Advancing adverse outcome pathways for integrated toxicology and regulatory applications

    EPA Science Inventory

    Recent regulatory efforts in many countries have focused on a toxicological pathway-based vision for human health assessments relying on in vitro systems and predictive models to generate the toxicological data needed to evaluate chemical hazard. A pathway-based vision is equally...

  18. Application of the adverse outcome pathway framework - advances and challenges

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework, while not new in concept, has gained attention in recent years as a set of organizing principles and tools that can help facilitate greater use of mechanistic or pathway-based data in risk assessment and regulatory decision-making. Reg...

  19. Piezoelectric ceramic (PZT) modulates axonal guidance growth of rat cortical neurons via RhoA, Rac1, and Cdc42 pathways.

    PubMed

    Wen, Jianqiang; Liu, Meili

    2014-03-01

    Electrical stimulation is critical for axonal connection, which can stimulate axonal migration and deformation to promote axonal growth in the nervous system. Netrin-1, an axonal guidance cue, can also promote axonal guidance growth, but the molecular mechanism of axonal guidance growth under indirect electric stimulation is still unknown. We investigated the molecular mechanism of axonal guidance growth under piezoelectric ceramic lead zirconate titanate (PZT) stimulation in the primary cultured cortical neurons. PZT induced marked axonal elongation. Moreover, PZT activated the excitatory postsynaptic currents (EPSCs) by increasing the frequency and amplitude of EPSCs of the cortical neurons in patch clamp assay. PZT downregulated the expression of Netrin-1 and its receptor Deleted in Colorectal Cancer (DCC). Rho GTPase signaling is involved in interactions of Netrin-1 and DCC. PZT activated RhoA. Dramatic decrease of Cdc42 and Rac1 was also observed after PZT treatment. RhoA inhibitor Clostridium botulinum C3 exoenzyme (C3-Exo) prevented the PZT-induced downregulation of Netrin-1 and DCC. We suggest that PZT can promote axonal guidance growth by downregulation of Netrin-1 and DCC to mediate axonal repulsive responses via the Rho GTPase signaling pathway. Obviously, piezoelectric materials may provide a new approach for axonal recovery and be beneficial for clinical therapy in the future.

  20. Advanced Sensors and Controls for Building Applications: Market Assessment and Potential R&D Pathways

    SciTech Connect

    Brambley, M. R.; Haves, P.; McDonald, S. C.; Torcellini, P.; Hansen, D.; Holmberg, D. R.; Roth, K. W.

    2005-04-01

    This document provides a market assessment of existing building sensors and controls and presents a range of technology pathways (R&D options) for pursuing advanced sensors and building control strategies.

  1. Using 3D printed models for planning and guidance during endovascular intervention: a technical advance

    PubMed Central

    Itagaki, Michael W.

    2015-01-01

    Three-dimensional (3D) printing applications in medicine have been limited due to high cost and technical difficulty of creating 3D printed objects. It is not known whether patient-specific, hollow, small-caliber vascular models can be manufactured with 3D printing, and used for small vessel endoluminal testing of devices. Manufacture of anatomically accurate, patient-specific, small-caliber arterial models was attempted using data from a patient’s CT scan, free open-source software, and low-cost Internet 3D printing services. Prior to endovascular treatment of a patient with multiple splenic artery aneurysms, a 3D printed model was used preoperatively to test catheter equipment and practice the procedure. A second model was used intraoperatively as a reference. Full-scale plastic models were successfully produced. Testing determined the optimal puncture site for catheter positioning. A guide catheter, base catheter, and microcatheter combination selected during testing was used intraoperatively with success, and the need for repeat angiograms to optimize image orientation was minimized. A difficult and unconventional procedure was successful in treating the aneurysms while preserving splenic function. We conclude that creation of small-caliber vascular models with 3D printing is possible. Free software and low-cost printing services make creation of these models affordable and practical. Models are useful in preoperative planning and intraoperative guidance. PMID:26027767

  2. Development of a Technical Basis and Guidance for Advanced SMR Function Allocation

    SciTech Connect

    Jacques Hugo; David Gertman; Jeffrey Joe; Ronal Farris; April Whaley; Heather Medema

    2013-09-01

    This report presents the results from three key activities for FY13 that influence the definition of new concepts of operations for advanced Small Modular Reactors (AdvSMR: a) the development of a framework for the analysis of the functional environmental, and structural attributes, b) the effect that new technologies and operational concepts would have on the way functions are allocated to humans or machines or combinations of the two, and c) the relationship between new concepts of operations, new function allocations, and human performance requirements.

  3. Association of the innate immunity and inflammation pathway with advanced prostate cancer risk.

    PubMed

    Kazma, Rémi; Mefford, Joel A; Cheng, Iona; Plummer, Sarah J; Levin, Albert M; Rybicki, Benjamin A; Casey, Graham; Witte, John S

    2012-01-01

    Prostate cancer is the most frequent and second most lethal cancer in men in the United States. Innate immunity and inflammation may increase the risk of prostate cancer. To determine the role of innate immunity and inflammation in advanced prostate cancer, we investigated the association of 320 single nucleotide polymorphisms, located in 46 genes involved in this pathway, with disease risk using 494 cases with advanced disease and 536 controls from Cleveland, Ohio. Taken together, the whole pathway was associated with advanced prostate cancer risk (P = 0.02). Two sub-pathways (intracellular antiviral molecules and extracellular pattern recognition) and four genes in these sub-pathways (TLR1, TLR6, OAS1, and OAS2) were nominally associated with advanced prostate cancer risk and harbor several SNPs nominally associated with advanced prostate cancer risk. Our results suggest that the innate immunity and inflammation pathway may play a modest role in the etiology of advanced prostate cancer through multiple small effects.

  4. Advanced Data Visualization in Astrophysics: The X3D Pathway

    NASA Astrophysics Data System (ADS)

    Vogt, Frédéric P. A.; Owen, Chris I.; Verdes-Montenegro, Lourdes; Borthakur, Sanchayeeta

    2016-02-01

    Most modern astrophysical data sets are multi-dimensional; a characteristic that can nowadays generally be conserved and exploited scientifically during the data reduction/simulation and analysis cascades. However, the same multi-dimensional data sets are systematically cropped, sliced, and/or projected to printable two-dimensional diagrams at the publication stage. In this article, we introduce the concept of the “X3D pathway” as a mean of simplifying and easing the access to data visualization and publication via three-dimensional (3D) diagrams. The X3D pathway exploits the facts that (1) the X3D 3D file format lies at the center of a product tree that includes interactive HTML documents, 3D printing, and high-end animations, and (2) all high-impact-factor and peer-reviewed journals in astrophysics are now published (some exclusively) online. We argue that the X3D standard is an ideal vector for sharing multi-dimensional data sets because it provides direct access to a range of different data visualization techniques, is fully open source, and is a well-defined standard from the International Organization for Standardization. Unlike other earlier propositions to publish multi-dimensional data sets via 3D diagrams, the X3D pathway is not tied to specific software (prone to rapid and unexpected evolution), but instead is compatible with a range of open-source software already in use by our community. The interactive HTML branch of the X3D pathway is also actively supported by leading peer-reviewed journals in the field of astrophysics. Finally, this article provides interested readers with a detailed set of practical astrophysical examples designed to act as a stepping stone toward the implementation of the X3D pathway for any other data set.

  5. Time controlled descent guidance algorithm for simulation of advanced ATC systems

    NASA Technical Reports Server (NTRS)

    Lee, H. Q.; Erzberger, H.

    1983-01-01

    Concepts and computer algorithms for generating time controlled four dimensional descent trajectories are described. The algorithms were implemented in the air traffic control simulator and used by experienced controllers in studies of advanced air traffic flow management procedures. A time controlled descent trajectory comprises a vector function of time, including position, altitude, and heading, that starts at the initial position of the aircraft and ends at touchdown. The trajectory provides a four dimensional reference path which will cause an aircraft tracking it to touchdown at a predetermined time with a minimum of fuel consumption. The problem of constructing such trajectories is divided into three subproblems involving synthesis of horizontal, vertical, and speed profiles. The horizontal profile is constructed as a sequence of turns and straight lines passing through a specified set of waypoints. The vertical profile consists of a sequence of level flight and constant descent angle segments defined by altitude waypoints. The speed profile is synthesized as a sequence of constant Mach number, constant indicated airspeed, and acceleration/deceleration legs. It is generated by integrating point mass differential equations of motion, which include the thrust and drag models of the aircraft.

  6. Research Advances on Pathways of Nickel-Induced Apoptosis

    PubMed Central

    Guo, Hongrui; Chen, Lian; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Wu, Bangyuan

    2015-01-01

    High concentrations of nickel (Ni) are harmful to humans and animals. Ni targets a number of organs and produces multiple toxic effects. Apoptosis is important in Ni-induced toxicity of the kidneys, liver, nerves, and immune system. Apoptotic pathways mediated by reactive oxygen species (ROS), mitochondria, endoplasmic reticulum (ER), Fas, and c-Myc participate in Ni-induced cell apoptosis. However, the exact mechanism of apoptosis caused by Ni is still unclear. Understanding the mechanism of Ni-induced apoptosis may help in designing measures to prevent Ni toxicity. PMID:26703593

  7. Clinical Practice Guidance for Radiotherapy Planning After Induction Chemotherapy in Locoregionally Advanced Head-and-Neck Cancer

    SciTech Connect

    Salama, Joseph K.; Haddad, Robert I.; Kies, Merril S.; Busse, Paul M.; Dong Lei; Brizel, David M.; Eisbruch, Avraham; Tishler, Roy B.; Trotti, Andy M.; Garden, Adam S.

    2009-11-01

    Purpose: The use of induction chemotherapy (IC) for locoregionally advanced head-and-neck cancer is increasing. The response to IC often causes significant alterations in tumor volume and location and shifts in normal anatomy. Proper determination of the radiotherapy (RT) targets after IC becomes challenging, especially with the use of conformal and precision RT techniques. Therefore, a consensus conference was convened to discuss issues related to RT planning and coordination of care for patients receiving IC. Methods and Materials: Ten participants with special expertise in the various aspects of integration of IC and RT for the treatment of locoregionally advanced head-and-neck cancer, including radiation oncologists, medical oncologists, and a medical physicist, participated. The individual members were assigned topics for focused, didactic presentations. Discussion was encouraged after each presentation, and recommendations were formulated. Results: Recommendations and guidelines emerged that emphasize up-front evaluation by all members of the head-and-neck management team, high-quality baseline and postinduction planning scans with the patient in the treatment position, the use of preinduction target volumes, and the use of full-dose RT, even in the face of a complete response. Conclusion: A multidisciplinary approach is strongly encouraged. Although these recommendations were provided primarily for patients treated with IC, many of these same principles apply to concurrent chemoradiotherapy without IC. A rapid response during RT is quite common, requiring the development of two or more plans in a sizeable fraction of patients, and suggesting the need for similar guidance in the rapidly evolving area of adaptive RT.

  8. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness

    PubMed Central

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R.

    2016-01-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

  9. Recent advances in neutralizing the IL-6 pathway in arthritis

    PubMed Central

    Malemud, Charles J

    2009-01-01

    Recent advances in understanding the mechanism(s) of how IL-6 trans-signaling regulates immune cell function and promotes inflammation in autoimmune arthritis are critically reviewed. Serum and/or synovial fluid (SF) IL-6 is markedly elevated in adult and juvenile rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and osteoarthritis (OA). IL-6, in concert with IL-17, determines the fate of CD4+ lymphocytes and therefore TH17 cell differentiation. IL-6 also plays a critical role in modulating B-lymphocyte activity. The recognition that IL-6 trans-signaling regulates inflammation resulted in the development of tocilizumab, a fully humanized monoclonal antibody that neutralizes the biological activity of the IL-6-receptor (IL-6R). Significant clinical benefit was demonstrated as well as reduced serum IL-6 levels with suppression of X-ray progression of disease in several clinical trials in which juvenile or adult RA patients were treated with tocilizumab monotherapy or tocilizumab plus methotrexate. However, levels of serum and/or SF IL-6 cytokine protein superfamily members, adiponectin, oncostatin M, pre-B-cell colony enhancing factor/visfatin and leukemia inhibitory factor are also elevated in RA. Additional studies will be required to determine if anti-IL-6 trans-signaling inhibition strategies with tocilizumab or recombinant soluble IL-6R reduce the level of these cytokines. PMID:27789987

  10. Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

    PubMed

    Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

    2014-06-01

    The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

  11. Biofuels Fuels Technology Pathway Options for Advanced Drop-in Biofuels Production

    SciTech Connect

    Kevin L Kenney

    2011-09-01

    Advanced drop-in hydrocarbon biofuels require biofuel alternatives for refinery products other than gasoline. Candidate biofuels must have performance characteristics equivalent to conventional petroleum-based fuels. The technology pathways for biofuel alternatives also must be plausible, sustainable (e.g., positive energy balance, environmentally benign, etc.), and demonstrate a reasonable pathway to economic viability and end-user affordability. Viable biofuels technology pathways must address feedstock production and environmental issues through to the fuel or chemical end products. Potential end products include compatible replacement fuel products (e.g., gasoline, diesel, and JP8 and JP5 jet fuel) and other petroleum products or chemicals typically produced from a barrel of crude. Considering the complexity and technology diversity of a complete biofuels supply chain, no single entity or technology provider is capable of addressing in depth all aspects of any given pathway; however, all the necessary expert entities exist. As such, we propose the assembly of a team capable of conducting an in-depth technology pathway options analysis (including sustainability indicators and complete LCA) to identify and define the domestic biofuel pathways for a Green Fleet. This team is not only capable of conducting in-depth analyses on technology pathways, but collectively they are able to trouble shoot and/or engineer solutions that would give industrial technology providers the highest potential for success. Such a team would provide the greatest possible down-side protection for high-risk advanced drop-in biofuels procurement(s).

  12. Effect of Image-Guidance Frequency on Geometric Accuracy and Setup Margins in Radiotherapy for Locally Advanced Lung Cancer

    SciTech Connect

    Higgins, Jane; Bezjak, Andrea; Hope, Andrew; Panzarella, Tony; Li, Winnie; Cho, John B.C.; Craig, Tim; Brade, Anthony; Sun, Alexander; Bissonnette, Jean-Pierre

    2011-08-01

    Purpose: To assess the relative effectiveness of five image-guidance (IG) frequencies on reducing patient positioning inaccuracies and setup margins for locally advanced lung cancer patients. Methods and Materials: Daily cone-beam computed tomography data for 100 patients (4,237 scans) were analyzed. Subsequently, four less-than-daily IG protocols were simulated using these data (no IG, first 5-day IG, weekly IG, and alternate-day IG). The frequency and magnitude of residual setup error were determined. The less-than-daily IG protocols were compared against the daily IG, the assumed reference standard. Finally, the population-based setup margins were calculated. Results: With the less-than-daily IG protocols, 20-43% of fractions incurred residual setup errors {>=}5 mm; daily IG reduced this to 6%. With the exception of the first 5-day IG, reductions in systematic error ({Sigma}) occurred as the imaging frequency increased and only daily IG provided notable random error ({sigma}) reductions ({Sigma} = 1.5-2.2 mm, {sigma} = 2.5-3.7 mm; {Sigma} = 1.8-2.6 mm, {sigma} = 2.5-3.7 mm; and {Sigma} = 0.7-1.0 mm, {sigma} = 1.7-2.0 mm for no IG, first 5-day IG, and daily IG, respectively. An overall significant difference in the mean setup error was present between the first 5-day IG and daily IG (p < .0001). The derived setup margins were 5-9 mm for less-than-daily IG and were 3-4 mm with daily IG. Conclusion: Daily cone-beam computed tomography substantially reduced the setup error and could permit setup margin reduction and lead to a reduction in normal tissue toxicity for patients undergoing conventionally fractionated lung radiotherapy. Using first 5-day cone-beam computed tomography was suboptimal for lung patients, given the inability to reduce the random error and the potential for the systematic error to increase throughout the treatment course.

  13. Advanced booster guidance studies

    NASA Technical Reports Server (NTRS)

    Cliff, Eugene M.

    1993-01-01

    This report is a summary of work done under Grant NAG1-946 for the period 19 December 1988 through 15 August 1992. Most of the technical work is described in the paper produced, including the NASA Contractor Report 4393 - 'Optimal Control Problems with Switching Points'. In the following pages we present a list of the papers along with a brief abstract. The technical work during the last months of the grant has not yet been submitted for publication so we present a summary of that work in an Appendix.

  14. Targeting EGFR and sonic hedgehog pathways for locally advanced eyelid and periocular carcinomas

    PubMed Central

    Yin, Vivian T; Merritt, Helen; Esmaeli, Bita

    2014-01-01

    For patients with metastatic or locally advanced eyelid and periocular carcinoma not amenable to surgical excision, targeted therapies have shown efficacy with better tolerability compared to cytotoxic chemotherapy. Overexpression of epithelial growth factor receptor was found in squamous cell carcinomas. Vismodegib targets the mutation in the hedgehog pathway identified in basal cell carcinoma and basal cell nevus syndrome. Targeted therapies provide a novel and potentially effective treatment alternative for patients with eyelid carcinoma not amendable for surgery, including those with metastatic, locally advanced disease, advanced age, and significant comorbidities. High cost, need for long-term treatment, and toxicity are relative limitations. PMID:25232546

  15. Pollinator Risk Assessment Guidance

    EPA Pesticide Factsheets

    This Guidance is part of a long-term strategy to advance the science of assessing the risks posed by pesticides to honey bees, giving risk managers the means to further improve pollinator protection in our regulatory decisions.

  16. The Drosophila neurogenin Tap functionally interacts with the Wnt-PCP pathway to regulate neuronal extension and guidance

    PubMed Central

    Yuan, Liqun; Hu, Shu; Okray, Zeynep; Ren, Xi; De Geest, Natalie; Claeys, Annelies; Yan, Jiekun; Bellefroid, Eric; Quan, Xiao-Jiang

    2016-01-01

    The neurogenin (Ngn) transcription factors control early neurogenesis and neurite outgrowth in mammalian cortex. In contrast to their proneural activity, their function in neurite growth is poorly understood. Drosophila has a single predicted Ngn homolog, Tap, of unknown function. Here we show that Tap is not a proneural protein in Drosophila but is required for proper axonal growth and guidance of neurons of the mushroom body, a neuropile required for associative learning and memory. Genetic and expression analyses suggest that Tap inhibits excessive axonal growth by fine regulation of the levels of the Wnt signaling adaptor protein Dishevelled. PMID:27385016

  17. Evaluation of Flying Qualities and Guidance Displays for an Advanced Tilt-Wing STOL Transport Aircraft in Final Approach and Landing

    NASA Technical Reports Server (NTRS)

    Frost, Chad R.; Franklin, James A.; Hardy, Gordon H.

    2002-01-01

    A piloted simulation was performed on the Vertical Motion Simulator at NASA Ames Research Center to evaluate flying qualities of a tilt-wing Short Take-Off and Landing (STOL) transport aircraft during final approach and landing. The experiment was conducted to assess the design s handling qualities, and to evaluate the use of flightpath-centered guidance for the precision approach and landing tasks required to perform STOL operations in instrument meteorological conditions, turbulence, and wind. Pilots rated the handling qualities to be satisfactory for all operations evaluated except those encountering extreme crosswinds and severe windshear; even in these difficult meteorological conditions, adequate handling qualities were maintained. The advanced flight control laws and guidance displays provided consistent performance and precision landings.

  18. WDR26 in Advanced Breast Cancer: A Novel Regulator of the P13K/AKT Pathway

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0539 TITLE: WDR26 in Advanced Breast Cancer : A Novel Regulator of the P13K/AKT Pathway PRINCIPAL INVESTIGATOR...5a. CONTRACT NUMBER WDR26 in Advanced Breast Cancer : A Novel Regulator of the P13K/AKT Pathway 5b. GRANT NUMBER W81XWH-14-1-0539 5c. PROGRAM...SUPPLEMENTARY NOTES 14. ABSTRACT The PI3K/AKT pathway is one of the most deregulated pathways in breast cancers (>70%), and a major contributor to tumor

  19. Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action

    PubMed Central

    Willett, Catherine; Rae, Jessica Caverly; Goyak, Katy O.; Minsavage, Gary; Westmoreland, Carl; Andersen, Melvin; Avigan, Mark; Duché, Daniel; Harris, Georgina; Hartung, Thomas; Jaeschke, Hartmut; Kleensang, Andre; Landesmann, Brigitte; Martos, Suzanne; Matevia, Marilyn; Toole, Colleen; Rowan, Andrew; Schultz, Terry; Seed, Jennifer; Senior, John; Shah, Imran; Subramanian, Kalyanasundaram; Vinken, Mathieu; Watkins, Paul

    2016-01-01

    Summary A workshop sponsored by the Human Toxicology Project Consortium (HTPC), “Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action” brought together experts from a wide range of perspectives to inform the process of pathway development and to advance two prototype pathways initially developed by the European Commission Joint Research Center (JRC): liver-specific fibrosis and steatosis. The first half of the workshop focused on the theory and practice of pathway development; the second on liver disease and the two prototype pathways. Participants agreed pathway development is extremely useful for organizing information and found that focusing the theoretical discussion on a specific AOP is helpful. It is important to include several perspectives during pathway development, including information specialists, pathologists, human health and environmental risk assessors, and chemical and product manufacturers, to ensure the biology is well captured and end use is considered. PMID:24535319

  20. Advanced Sensors and Controls for Building Applications: Market Assessment and Potential R&D Pathways

    SciTech Connect

    Brambley, Michael R.; Haves, Philip; McDonald, Sean C.; Torcellini, Paul; Hansen, David G.; Holmberg, David; Roth, Kurt

    2005-04-13

    Significant energy savings can be achieved in commercial building operation, along with increased comfort and control for occupants, through the implementation of advanced technologies. This document provides a market assessment of existing building sensors and controls and presents a range of technology pathways (R&D options) for pursuing advanced sensors and building control strategies. This paper is actually a synthesis of five other white papers: the first describes the market assessment including estimates of market potential and energy savings for sensors and control strategies currently on the market as well as a discussion of market barriers to these technologies. The other four cover technology pathways: (1) current applications and strategies for new applications, (2) sensors and controls, (3) networking, security, and protocols and standards, and (4) automated diagnostics, performance monitoring, commissioning, optimal control and tools. Each technology pathway chapter gives an overview of the technology or application. This is followed by a discussion of needs and the current status of the technology. Finally, a series of research topics is proposed.

  1. Vismodegib, a small-molecule inhibitor of the hedgehog pathway for the treatment of advanced cancers.

    PubMed

    De Smaele, Enrico; Ferretti, Elisabetta; Gulino, Alberto

    2010-06-01

    Vismodegib (GDC-0449) is a small, orally administrable molecule, belonging to the 2-arylpyridine class, which was discovered by Genentech Inc under a collaboration with Curis Inc. Vismodegib inhibits the Hedgehog (Hh) pathway, which is involved in tumorigenesis, thus providing a strong rationale for its use in the treatment of a variety of cancers. Vismodegib suppresses Hh signaling by binding to and interfering with smoothened, a membrane protein that provides positive signals to the Hh signaling pathway. Preclinical studies demonstrated the antitumor activity of vismodegib in mouse models of medulloblastoma (MB) and in xenograft models of colorectal and pancreatic cancer. Phase I clinical trials in patients with advanced basal cell carcinoma (BCC) and MB highlighted an objective response to vismodegib. Reported side effects were minor, with only one grade 4 adverse event. Vismodegib is currently undergoing phase II clinical trials for the treatment of advanced BCC, metastatic colorectal cancer, ovarian cancer, MB and other solid tumors. Because of its low toxicity and specificity for the Hh pathway, this drug has potential advantages compared with conventional chemotherapy, and may also be used in combination treatments. Clinical trials with other Hh inhibitors are also ongoing and their therapeutic potential will need to be compared with vismodegib.

  2. MAP kinase pathway gene copy alterations in NRAS/BRAF wild-type advanced melanoma.

    PubMed

    Orouji, Elias; Orouji, Azadeh; Gaiser, Timo; Larribère, Lionel; Gebhardt, Christoffer; Utikal, Jochen

    2016-05-01

    Recent therapeutic advances have improved melanoma patientś clinical outcome. Novel therapeutics targeting BRAF, NRAS and cKit mutant melanomas are widely used in clinical practice. However therapeutic options in NRAS(wild-type) /BRAF(wild-type) /cKit(wild-type) melanoma patients are limited. Our study shows that gene copy numbers of members of the MAPK signaling pathway vary in different melanoma subgroups. NRAS(wild-type) /BRAF(wild-type) melanoma metastases are characterized by significant gains of MAP2K1 (MEK1) and MAPK3 (ERK1) gene loci. These additional gene copies could lead to an activation of the MAPK signaling pathway via a gene-dosage effect. Our results suggest that downstream analyses of the pMEK and pERK expression status in NRAS(wild-type) /BRAF(wild-type) melanoma patients identify patients that could benefit from targeted therapies with MEK and ERK inhibitors.

  3. Current advances in DNA repair: regulation of enzymes and pathways involved in maintaining genomic stability.

    PubMed

    Neher, Tracy M; Turchi, John J

    2011-06-15

    Novel discoveries in the DNA repair field have lead to continuous and rapid advancement of our understanding of not only DNA repair but also DNA replication and recombination. Research in the field transcends numerous areas of biology, biochemistry, physiology, and medicine, making significant connections across these broad areas of study. From early studies conducted in bacterial systems to current analyses in eukaryotic systems and human disease, the innovative research into the mechanisms of repair machines and the consequences of ineffective DNA repair has impacted a wide scientific community. This Forum contains a select mix of primary research articles in addition to a number of timely reviews covering a subset of DNA repair pathways where recent advances and novel discoveries are improving our understanding of DNA repair, its regulation, and implications to human disease.

  4. An integrated Rotorcraft Avionics/Controls Architecture to support advanced controls and low-altitude guidance flight research

    NASA Technical Reports Server (NTRS)

    Jacobsen, Robert A.; Doane, Douglas H.; Eshow, Michelle M.; Aiken, Edwin W.; Hindson, William S.

    1992-01-01

    Salient design features of a new NASA/Army research rotorcraft--the Rotorcraft-Aircrew Systems Concepts Airborne Laboratory (RASCAL) are described. Using a UH-60A Black Hawk helicopter as a baseline vehicle, the RASCAL will be a flying laboratory capable of supporting the research requirements of major NASA and Army guidance, control, and display research programs. The paper describes the research facility requirements of these programs together with other critical constraints on the design of the research system. Research program schedules demand a phased development approach, wherein specific research capability milestones are met and flight research projects are flown throughout the complete development cycle of the RASCAL. This development approach is summarized, and selected features of the research system are described. The research system includes a real-time obstacle detection and avoidance system which will generate low-altitude guidance commands to the pilot on a wide field-of-view, color helmet-mounted display and a full-authority, programmable, fault-tolerant/fail-safe, fly-by-wire flight control system.

  5. Advancements in Orthopedic Intervention: Retrograde Drilling and Bone Grafting of Osteochondral Lesions of the Knee Using Magnetic Resonance Imaging Guidance

    SciTech Connect

    Seebauer, Christian J.; Bail, Hermann J.; Rump, Jens C. Walter, Thula Teichgraeber, Ulf K. M.

    2010-12-15

    Computer-assisted surgery is currently a novel challenge for surgeons and interventional radiologists. Magnetic resonance imaging (MRI)-guided procedures are still evolving. In this experimental study, we describe and assess an innovative passive-navigation method for MRI-guided treatment of osteochondritis dissecans of the knee. A navigation principle using a passive-navigation device was evaluated in six cadaveric knee joint specimens for potential applicability in retrograde drilling and bone grafting of osteochondral lesions using MRI guidance. Feasibility and accuracy were evaluated in an open MRI scanner (1.0 T Philips Panorama HFO MRI System). Interactive MRI navigation allowed precise drilling and bone grafting of osteochondral lesions of the knee. All lesions were hit with an accuracy of 1.86 mm in the coronal plane and 1.4 mm the sagittal plane. Targeting of all lesions was possible with a single drilling. MRI allowed excellent assessment of correct positioning of the cancellous bone cylinder during bone grafting. The navigation device and anatomic structures could be clearly identified and distinguished throughout the entire drilling procedure. MRI-assisted navigation method using a passive navigation device is feasible for the treatment of osteochondral lesions of the knee under MRI guidance and allows precise and safe drilling without exposure to ionizing radiation. This method may be a viable alternative to other navigation principles, especially for pediatric and adolescent patients. This MRI-navigated method is also potentially applicable in many other MRI-guided interventions.

  6. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    PubMed Central

    Fecher, Leslie A; Sharfman, William H

    2015-01-01

    Cutaneous basal cell carcinoma (BCC) is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449), a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA)-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. PMID:26604681

  7. Advances in targeting insulin-like growth factor signaling pathway in cancer treatment.

    PubMed

    You, Liangkun; Liu, Changyu; Tang, Hexiao; Liao, Yongde; Fu, Shengling

    2014-01-01

    Insulin-like growth factors (IGFs), along with their receptors and binding proteins, play key roles in human cell proliferation, differentiation and apoptosis. There is now substantial evidence suggesting that the IGF system is involved in the pathogenesis and progression of various malignancies. Recent studies have shown that targeting of the IGF-1 receptor (IGF-1R) signaling pathway might be a novel approach for the treatment of cancer. Presently numerous agents featuring different mechanisms of IGF targeting methods such as IGF-1R monoclonal antibodies, IGF-1R tyrosine kinase inhibitors and IGF ligand specific antibodies are being investigated in more than 170 clinical trials and appear to have potential therapeutic efficacy. However, advanced trials reiterate the importance of predictive biomarkers to guide the clinical efforts of these agents. As a result, current research strategies are emerging to identify the most suitable subpopulations of patients that might benefit from these treatments. Furthermore, newly presented toxicity and growth hormone response and implication of hybrid receptors in IGF signaling pathway pose unprecedented challenges in the design and application of anti-IGF agents. On the other hand, cross-talk in downstream signaling between IGF-1R and other tumor promoting pathways and the development of multi-target agents might encourage the IGF-1R-targeted therapies further into comprehensive treatments of cancer. With both challenges and prospects ahead, this paper reviewed the progress in this particular field.

  8. MO-DE-202-00: Image-Guided Interventions: Advances in Intraoperative Imaging, Guidance, and An Emerging Role for Medical Physics in Surgery.

    PubMed

    Siewerdsen, Jeffrey

    2016-06-01

    At least three major trends in surgical intervention have emerged over the last decade: a move toward more minimally invasive (or non-invasive) approach to the surgical target; the development of high-precision treatment delivery techniques; and the increasing role of multi-modality intraoperative imaging in support of such procedures. This symposium includes invited presentations on recent advances in each of these areas and the emerging role for medical physics research in the development and translation of high-precision interventional techniques. The four speakers are: (1) Keyvan Farahani, "Image-guided focused ultrasound surgery and therapy" (2) Jeffrey H. Siewerdsen, "Advances in image registration and reconstruction for image-guided neurosurgery" (3) Tina Kapur, "Image-guided surgery and interventions in the advanced multimodality image-guided operating (AMIGO) suite" (4) Raj Shekhar, "Multimodality image-guided interventions: Multimodality for the rest of us" Learning Objectives: 1. Understand the principles and applications of HIFU in surgical ablation. 2. Learn about recent advances in 3D-2D and 3D deformable image registration in support of surgical safety and precision. 3. Learn about recent advances in model-based 3D image reconstruction in application to intraoperative 3D imaging. 4. Understand the multi-modality imaging technologies and clinical applications investigated in the AMIGO suite. 5. Understand the emerging need and techniques to implement multi-modality image guidance in surgical applications such as neurosurgery, orthopaedic surgery, vascular surgery, and interventional radiology. Research supported by the NIH and Siemens Healthcare.; J. Siewerdsen; Grant Support - National Institutes of Health; Grant Support - Siemens Healthcare; Grant Support - Carestream Health; Advisory Board - Carestream Health; Licensing Agreement - Carestream Health; Licensing Agreement - Elekta Oncology.; T. Kapur, P41EB015898; R. Shekhar, Funding: R42CA137886 and

  9. Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment

    PubMed Central

    Polireddy, Kishore; Chen, Qi

    2016-01-01

    Pancreatic cancer is one of the most lethal cancers among all malignances, with a median overall survival of <1 year and a 5-year survival of ~5%. The dismal survival rate and prognosis are likely due to lack of early diagnosis, fulminant disease course, high metastasis rate, and disappointing treatment outcome. Pancreatic cancers harbor a variety of genetic alternations that render it difficult to treat even with targeted therapy. Recent studies revealed that pancreatic cancers are highly enriched with a cancer stem cell (CSC) population, which is resistant to chemotherapeutic drugs, and therefore escapes chemotherapy and promotes tumor recurrence. Cancer cell epithelial to mesenchymal transition (EMT) is highly associated with metastasis, generation of CSCs, and treatment resistance in pancreatic cancer. Reviewed here are the molecular biology of pancreatic cancer, the major signaling pathways regulating pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreatic cancer. PMID:27471566

  10. Advanced Glycation End Products Activate a Chymase-Dependent Angiotensin II Generating Pathway in Diabetic Complications

    PubMed Central

    Koka, Vijay; Wang, Wansheng; Huang, Xiao Ru; Kim-Mitsuyama, Shokei; Truong, Luan D.; Lan, Hui Y

    2006-01-01

    Background: Angiotensin II is a key mediator of diabetes-related vascular disease. It is now recognized that in addition to angiotensin converting enzyme (ACE), chymase is an important alternative angiotensin II generating enzyme in hypertension and diabetes. However, the mechanism of induction of chymase in diabetes remains unknown. Methods and Results: Here we report that chymase is upregulated in coronary and renal arteries in patients with diabetes by immunohistochemistry. Upregulation of vascular chymase is associated with deposition of advanced glycation end products (AGEs), increase in expression of the receptor for AGEs (RAGE), and activation of ERK1/2 MAP kinase. In vitro, AGEs can induce chymase expression and chymase-dependent angiotensin II generation in human vascular smooth muscle cells via the RAGE-ERK1/2 MAP kinase-dependent mechanism. This is confirmed by blockade of AGE-induced vascular chymase expression with a neutralizing RAGE antibody and an inhibitor to ERK1/2, and by overexpression of the dominant negative-ERK1/2. Compared to ACE, chymase contributes to the majority of angiotensin II production (more than 70%, p<0.01) in response to AGEs. Further more, AGE-induced Angiotensin II production is blocked by the anti-RAGE antibody and by inhibition of ERK1/2 MAP kinase activities. Conclusions: Advanced glycation end products, a hallmark of diabetes, induce chymase via the RAGE-ERK1/2 MAP kinase pathway. Chymase initiates an important alternative angiotensin II generating pathway in diabetes and may play a critical role in diabetic vascular disease. PMID:16520412

  11. Degradation pathways of lamotrigine under advanced treatment by direct UV photolysis, hydroxyl radicals, and ozone.

    PubMed

    Keen, Olya S; Ferrer, Imma; Michael Thurman, E; Linden, Karl G

    2014-12-01

    Lamotrigine is recently recognized as a persistent pharmaceutical in the water environment and wastewater effluents. Its degradation was studied under UV and ozone advanced oxidation treatments with reaction kinetics of lamotrigine with ozone (≈4 M(-1)s(-1)), hydroxyl radical [(2.1 ± 0.3) × 10(9)M(-1)s(-1)] and by UV photolysis with low and medium pressure mercury vapor lamps [quantum yields ≈0 and (2.7 ± 0.4)× 10(-4) respectively] determined. All constants were measured at pH 6 and at temperature ≈20°C. The results indicate that lamotrigine is slow to respond to direct photolysis or oxidation by ozone and no attenuation of the contaminant is expected in UV or ozone disinfection applications. The compound reacts rapidly with hydroxyl radicals indicating that advanced oxidation processes would be effective for its treatment. Degradation products were identified under each treatment process using accurate mass time-of-flight spectrometry and pathways of decay were proposed. The main transformation pathways in each process were: dechlorination of the benzene ring during direct photolysis; hydroxyl group addition to the benzene ring during the reaction with hydroxyl radicals; and triazine ring opening after reaction with ozone. Different products that form in each process may be to a varying degree less environmentally stable than the parent lamotrigine. In addition, a novel method of ozone quenching without addition of salts is presented. The new quenching method would allow subsequent mass spectrometry analysis without a solid phase extraction clean-up step. The method involves raising the pH of the sample to approximately 10 for a few seconds and lowering it back and is therefore limited to applications for which temporary pH change is not expected to affect the outcome of the analysis.

  12. Equivalent Activities of Repulsive Axon Guidance Receptors

    PubMed Central

    Long, Hong; Yoshikawa, Shingo

    2016-01-01

    Receptors on the growth cone at the leading edge of elongating axons play critical guidance roles by recognizing cues via their extracellular domains and transducing signals via their intracellular domains, resulting in changes in direction of growth. An important concept to have emerged in the axon guidance field is the importance of repulsion as a major guidance mechanism. Given the number and variety of different repulsive receptors, it is generally thought that there are likely to be qualitative differences in the signals they transduce. However, the nature of these possible differences is unknown. By creating chimeras using the extracellular and intracellular domains of three different Drosophila repulsive receptors, Unc5, Roundabout (Robo), and Derailed (Drl) and expressing them in defined cells within the embryonic nervous system, we examined the responses elicited by their intracellular domains systematically. Surprisingly, we found no qualitative differences in growth cone response or axon growth, suggesting that, despite their highly diverged sequences, each intracellular domain elicits repulsion via a common pathway. In terms of the signaling pathway(s) used by the repulsive receptors, mutations in the guanine nucleotide exchange factor Trio strongly enhance the repulsive activity of all three intracellular domains, suggesting that repulsion by Unc5, Robo, and Drl, and perhaps repulsion in general, involves Trio activity. SIGNIFICANCE STATEMENT A prevailing concept that has emerged in the axon guidance field is the importance of repulsion as a guidance mechanism for steering axons to their appropriate targets. Given the number and variety of different repulsive receptors, it is generally thought that there are differences in the signals that they transduce. However, this has never been tested directly. We have used the advanced genetics of Drosophila to compare directly the outputs of different repulsive receptors. Surprisingly, we found no qualitative

  13. Image Guidance

    EPA Pesticide Factsheets

    Guidance that explains the process for getting images approved in One EPA Web microsites and resource directories. includes an appendix that shows examples of what makes some images better than others, how some images convey meaning more than others

  14. Guidance publication proves timely.

    PubMed

    Baillie, Jonathan

    2011-05-01

    The importance of properly identifying, assessing, and managing risk in all areas of engineering practice, the fact that genuine innovation is almost impossible without a certain element of risk-taking, and the need to acknowledge and respond to public concerns, however much some may be ill-founded, over the risks inherent in technological and engineering advances, are highlighted in a new risk guidance document, Guidance on Risk for the Engineering Profession, published by the Engineering Council in London last month. HEJ editor Jonathan Baillie reports.

  15. Targeting notch signaling pathway in cancer: clinical development advances and challenges.

    PubMed

    Takebe, Naoko; Nguyen, Dat; Yang, Sherry X

    2014-02-01

    Notch signaling plays an important role in development and cell fate determination, and it is deregulated in human hematologic malignancies and solid tumors. This review includes a brief introduction of the relevant pathophysiology of Notch signaling pathway and primarily focuses on the clinical development of promising agents that either obstruct Notch receptor cleavages such as γ-secretase inhibitors (GSIs) or interfere with the Notch ligand-receptor interaction by monoclonal antibodies (mAbs). Antitumor activity by GSIs and mAbs administered as single agent in early phases of clinical trials has been observed in advanced or metastatic thyroid cancer, non-small cell lung cancer, intracranial tumors, sarcoma or desmoid tumors, colorectal cancer with neuroendocrine features, melanoma and ovarian cancer. A number of mechanism-based adverse events particularly gastrointestinal toxicities emerged and mitigation strategies are developed after testing multiple GSIs and Notch targeting mAbs. We also discuss pharmacodynamic biomarkers in conjunction with methods of assessment of the molecular target inhibition validation. Biomarkers of efficacy or benefit may be of importance for a successful development of this class of drugs.

  16. Mono-2-ethyhexyl phthalate advancing the progression of prostate cancer through activating the hedgehog pathway in LNCaP cells.

    PubMed

    Yong, Wang; Jiao, Chen; Jianhui, Wu; Yan, Zhao; Qi, Pan; Xiu, Wang; Zuyue, Sun; Yunhui, Zhang

    2016-04-01

    Hedgehog (Hh) pathway plays a critical role in the progression of prostate cancer (PCa), the most commonly diagnosed non-cutaneous cancer in male adults. Studies showed that di-n-butyl phthalate (DBP) could interference with the Hh pathway. Di-2-ethylhexyl phthalate (DEHP), the congener of DBP, is the major plasticizer used in plastic materials that are inevitably exposed by patients with PCa. The aim of this in vitro study was to investigate whether mono-2-ethyhexyl phthalate (MEHP, the active metabolite of DEHP) could activate the Hh pathway of LNCaP cells. Results showed that the expression of the critical gene of Hh pathway PTCH and androgen-regulated gene KLK3 was significantly decreased on 3, 6 and 9 days with Hh pathway inhibitor cyclopamine's treatment. MEHP notably up-regulated the expression of PTCH with a dose-response relationship in the presence of cyclopamine, which indicate that MEHP might target on the downstream components of Hh pathway and advance the progression of PCa through activating the Hh pathway.

  17. Advances in the understanding of the Fanconi anemia tumor suppressor pathway.

    PubMed

    Pickering, Anna; Zhang, Jun; Panneerselvam, Jayabal; Fei, Peiwen

    2013-12-01

    Extremely high cancer incidence in Fanconi anemia (FA) patients has long suggested that the FA signaling pathway is a tumor suppressor pathway. Indeed, our recent findings, for the first time, indicate that the FA pathway plays a significant role in suppressing the development of non-FA human cancer. Also our studies on FA group D2 protein (FANCD2) have, among the first, documented the crosstalks between the FA and Rad6/Rad18 (HHR6) pathways upon DNA damage. In this review, we will discuss how our studies enhance the understanding of the FA tumor suppressor pathway.

  18. Designing Automated Guidance for Concept Diagrams in Inquiry Instruction

    ERIC Educational Resources Information Center

    Ryoo, Kihyun; Linn, Marcia C.

    2016-01-01

    Advances in automated scoring technologies have the potential to support student learning during inquiry instruction by providing timely and adaptive guidance on individual students' responses. To identify which forms of automated guidance can be beneficial for inquiry learning, we compared reflective guidance to directive guidance for…

  19. Guidance and control, 1993; Annual Rocky Mountain Guidance and Control Conference, 16th, Keystone, CO, Feb. 6-10, 1993

    NASA Technical Reports Server (NTRS)

    Culp, Robert D. (Editor); Bickley, George (Editor)

    1993-01-01

    Papers from the sixteenth annual American Astronautical Society Rocky Mountain Guidance and Control Conference are presented. The topics covered include the following: advances in guidance, navigation, and control; control system videos; guidance, navigation and control embedded flight control systems; recent experiences; guidance and control storyboard displays; and applications of modern control, featuring the Hubble Space Telescope (HST) performance enhancement study.

  20. Microbial chemical factories: recent advances in pathway engineering for synthesis of value added chemicals.

    PubMed

    Dhamankar, Himanshu; Prather, Kristala L J

    2011-08-01

    The dwindling nature of petroleum and other fossil reserves has provided impetus towards microbial synthesis of fuels and value added chemicals from biomass-derived sugars as a renewable resource. Microbes have naturally evolved enzymes and pathways that can convert biomass into hundreds of unique chemical structures, a property that can be effectively exploited for their engineering into Microbial Chemical Factories (MCFs). De novo pathway engineering facilitates expansion of the repertoire of microbially synthesized compounds beyond natural products. In this review, we visit some recent successes in such novel pathway engineering and optimization, with particular emphasis on the selection and engineering of pathway enzymes and balancing of their accessory cofactors.

  1. Kinetics and pathways of ibuprofen degradation by the UV/chlorine advanced oxidation process.

    PubMed

    Xiang, Yingying; Fang, Jingyun; Shang, Chii

    2016-03-01

    The UV/chlorine advanced oxidation process (AOP), which forms reactive species such as hydroxyl radicals (HO) and reactive chlorine species (RCS) such as chlorine atoms (Cl) and Cl2(-), is being considered as an alternative to the UV/H2O2 AOP for the degradation of emerging contaminants. This study investigated the kinetics and pathways of the degradation of a recalcitrant pharmaceutical and personal care product (PPCP)-ibuprofen (IBP)-by the UV/chlorine AOP. The degradation of IBP followed the pseudo first-order kinetics. The first-order rate constant was 3.3 times higher in the UV/chlorine AOP than in the UV/H2O2 AOP for a given chemical molar dosage at pH 6. The first-order rate constant decreased from 3.1 × 10(-3) s(-1) to 5.5 × 10(-4) s(-1) with increasing pH from 6 to 9. Both HO and RCS contributed to the degradation, and the contribution of RCS increased from 22% to 30% with increasing pH from 6 to 9. The degradation was initiated by HO-induced hydroxylation and Cl-induced chlorine substitution, and sustained through decarboxylation, demethylation, chlorination and ring cleavage to form more stable products. Significant amounts of chlorinated intermediates/byproducts were formed from the UV/chlorine AOP, and four chlorinated products were newly identified. The yield of total organic chlorine (TOCl) was 31.6 μM after 90% degradation of 50 μM IBP under the experimental conditions. The known disinfection by-products (DBPs) comprised 17.4% of the TOCl. The effects of water matrix in filtered drinking water on the degradation were not significant, demonstrating the practicality of the UV/chlorine AOP for the control of some refractory PPCPs. However, the toxicity of the chlorinated products should be further assessed.

  2. NASP guidance design for vehicle autonomy

    NASA Astrophysics Data System (ADS)

    Wagner, E. A.; Li, I.; Nguyen, D. D.; Nguyen, P. L.

    1990-10-01

    Vehicle guidance for General Dynamics' NASP vehicle is planned to be self-contained onboard the vehicle, and independent of any ground support during the mission. It will include real-time onboard abort and ascent trajectory optimization capability. Although these features should be considered a natural outgrowth of research in guidance and trajectory optimization and advances in computation, facilitating full vehicle autonomy for NASP represents a significant advance relative to any flight-demonstrated guidance. Algorithms and processing requirements for autonomous NASP vehicle guidance are considered.

  3. Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma

    PubMed Central

    Dréno, Brigitte; Ascierto, Paolo Antonio; Dummer, Reinhard; Basset-Seguin, Nicole; Fife, Kate; Ernst, Scott; Licitra, Lisa; Neves, Rogerio I.; Peris, Ketty; Puig, Susana; Sokolof, Jonas; Sekulic, Aleksandar; Hauschild, Axel; Kunstfeld, Rainer

    2016-01-01

    Abnormal activation of hedgehog pathway signaling is a key driver in the pathogenesis of basal cell carcinoma (BCC). Vismodegib, a first-in-class small-molecule inhibitor of hedgehog pathway signaling, is approved by regulatory authorities for the treatment of adults who have metastatic BCC or locally advanced BCC that has recurred after surgery, or who are not candidates for surgery and who are not candidates for radiation. A second inhibitor, sonidegib, was also recently approved for the same patient group with locally advanced BCC. Adverse events (AEs) commonly observed in hedgehog pathway inhibitor (HPI)-treated patients include muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and asthenia (fatigue). These AEs are thought to be mechanistically related to inhibition of the hedgehog pathway in normal tissue. Although the severity of the majority of AEs associated with HPIs is grade 1–2, the long-term nature of these AEs can lead to decreased quality of life, treatment interruption, and in some cases discontinuation, all of which might affect clinical outcome. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to HPIs in advanced BCC are described. These observations represent the first step toward the development of mechanism-based preventive and management strategies. Knowledge of these AEs will allow health care professionals to provide appropriate counseling and supportive care interventions, all of which will contribute to improved quality of life and optimal benefit from therapy. Implications for Practice: The hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib represent a therapeutic breakthrough for patients with advanced basal cell carcinoma. However, the nature of the low-grade adverse events (AEs) commonly observed in HPI-treated patients, including muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and fatigue, can impact clinical outcomes as a result of decreased quality of life

  4. Adverse Outcome Pathways and Extrapolation Tools to Advance the Three Rs in Ecotoxicology

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for identifying and organizing predictive and causal linkages between cellular-level responses and endpoints conventionally considered in ecological risk assessment (e.g., effects on survival, growth/development, and repro...

  5. Temsirolimus in advanced leiomyosarcomas: patterns of response and correlation with the activation of the mammalian target of rapamycin pathway.

    PubMed

    Italiano, Antoine; Kind, Michèle; Stoeckle, Eberhard; Jones, Natalie; Coindre, Jean-Michel; Bui, Binh

    2011-06-01

    Preclinical data have indicated that alteration of PTEN and activation of the mammalian target of rapamycin (mTOR) pathway play a crucial role in the oncogenesis of leiomyosarcoma. The objective of this exploratory study was to assess the clinical role of mTOR inhibition in patients with advanced leiomyosarcoma refractory to standard chemotherapy. Patients with advanced leiomyosarcoma were treated with temsirolimus and consented to retrospective collection of data from their medical records and analysis of archival tumor specimens. Tumor response was determined according to the response evaluation criteria in solid tumor (RECIST) and Choi criteria. Tumors were assessed for immunohistochemical evidence of PTEN loss of expression and mTOR activation. Six patients participated in the study. According to the RECIST, three patients had stable disease and three patients had progressive disease. The three patients with RECIST stable disease had partial response according to the Choi criteria. Partial response according to the Choi criteria was associated with clinical improvement and biological signs of temsirolimus antitumor activity. The immunohistochemical status of PTEN and phosphorylated S6 ribosomal protein was not predictive of the outcome. This exploratory study indicates antitumor activity of temsirolimus in leiomyosarcoma, possibly through a mechanism involving aberration of the PTEN gene. Further investigations of the phosphoinositide 3-kinases/PTEN/Akt/mTOR pathway are needed to explore the role of mTOR inhibitors, either alone or in combination, in patients with advanced sarcoma.

  6. The Aggregate Exposure Pathway (AEP): A conceptual framework for advancing exposure science research and applications

    EPA Science Inventory

    Historically, risk assessment has relied upon toxicological data to obtain hazard-based reference levels, which are subsequently compared to exposure estimates to determine whether an unacceptable risk to public health may exist. Recent advances in analytical methods, biomarker ...

  7. Recent advances in understanding of meiosis initiation and the apomictic pathway in plants.

    PubMed

    Wang, Chung-Ju R; Tseng, Ching-Chih

    2014-01-01

    Meiosis, a specialized cell division to produce haploid cells, marks the transition from a sporophytic to a gametophytic generation in the life cycle of plants. In angiosperms, meiosis takes place in sporogenous cells that develop de novo from somatic cells in anthers or ovules. A successful transition from the mitotic cycle to the meiotic program in sporogenous cells is crucial for sexual reproduction. By contrast, when meiosis is bypassed or a mitosis-like division occurs to produce unreduced cells, followed by the development of an embryo sac, clonal seeds can be produced by apomixis, an asexual reproduction pathway found in 400 species of flowering plants. An understanding of the regulation of entry into meiosis and molecular mechanisms of apomictic pathway will provide vital insight into reproduction for plant breeding. Recent findings suggest that AM1/SWI1 may be the key gene for entry into meiosis, and increasing evidence has shown that the apomictic pathway is epigenetically controlled. However, the mechanism for the initiation of meiosis during sexual reproduction or for its omission in the apomictic pathway still remains largely unknown. Here we review the current understanding of meiosis initiation and the apomictic pathway and raised several questions that are awaiting further investigation.

  8. Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer

    PubMed Central

    Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

    2014-01-01

    Background and Purpose The psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. Experimental Approach To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. Key Results CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. Conclusions and Implications O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. PMID:24910342

  9. Advances in metabolic pathway and strain engineering paving the way for sustainable production of chemical building blocks.

    PubMed

    Chen, Yun; Nielsen, Jens

    2013-12-01

    Bio-based production of chemical building blocks from renewable resources is an attractive alternative to petroleum-based platform chemicals. Metabolic pathway and strain engineering is the key element in constructing robust microbial chemical factories within the constraints of cost effective production. Here we discuss how the development of computational algorithms, novel modules and methods, omics-based techniques combined with modeling refinement are enabling reduction in development time and thus advance the field of industrial biotechnology. We further discuss how recent technological developments contribute to the development of novel cell factories for the production of the building block chemicals: adipic acid, succinic acid and 3-hydroxypropionic acid.

  10. Chapter 3: Omics Advances of Biosynthetic Pathways of Isoprenoid Production in Microalgae

    SciTech Connect

    Paniagua-Michel, J.; Subramanian, Venkataramanan

    2017-01-01

    In this chapter, the current status of microalgal isoprenoids and the role of omics technologies, or otherwise specified, in bioproducts optimization and applications are reviewed. Emphasis is focused in the metabolic pathways of microalgae involved in the production of commercially important products, namely, hydrocarbons and biofuels, nutraceuticals, and pharmaceuticals.

  11. The Historical Evolution of Chinese Languages and Scripts. Pathways to Advanced Skills Series. Volume 8

    ERIC Educational Resources Information Center

    Youguang, Zhou

    2003-01-01

    This bilingual text by Zhou Youguang (in Chinese) with English translation by Zhang Liqing makes it easier for English speakers to gain advanced level skills in East Asian languages. It also exposes learners at or above intermediate skill levels to the vocabulary and discourses of academic disciplines and provides entries into discussions with…

  12. Project Athena: A Pathway to Advanced Literacy Development for Children of Poverty

    ERIC Educational Resources Information Center

    VanTassel-Baska, Joyce; Stambaugh, Tamra

    2006-01-01

    This article describes Project Athena, a Javits program funded by the U.S. Department of Education and developed through the Center for Gifted Education at the College of William and Mary. Project Athena seeks to find ways to help impoverished children develop advanced skills in reading comprehension, literary analysis, and persuasive writing. Its…

  13. Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project. ACT/Control/Guidance System study, volume 1

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The active control technology (ACT) control/guidance system task of the integrated application of active controls (IAAC) technology project within the NASA energy efficient transport program was documented. The air traffic environment of navigation and air traffic control systems and procedures were extrapolated. An approach to listing flight functions which will be performed by systems and crew of an ACT configured airplane of the 1990s, and a determination of function criticalities to safety of flight, are the basis of candidate integrated ACT/Control/Guidance System architecture. The system mechanizes five active control functions: pitch augmented stability, angle of attack limiting, lateral/directional augmented stability, gust load alleviation, and maneuver load control. The scope and requirements of a program for simulating the integrated ACT avionics and flight deck system, with pilot in the loop, are defined, system and crew interface elements are simulated, and mechanization is recommended. Relationships between system design and crew roles and procedures are evaluated.

  14. Oxidative stress, redox signaling pathways, and autophagy in cachectic muscles of male patients with advanced COPD and lung cancer.

    PubMed

    Puig-Vilanova, Ester; Rodriguez, Diego A; Lloreta, Josep; Ausin, Pilar; Pascual-Guardia, Sergio; Broquetas, Joan; Roca, Josep; Gea, Joaquim; Barreiro, Esther

    2015-02-01

    Muscle dysfunction and wasting are predictors of mortality in advanced COPD and malignancies. Redox imbalance and enhanced protein catabolism are underlying mechanisms in COPD. We hypothesized that the expression profile of several biological markers share similarities in patients with cachexia associated with either COPD or lung cancer (LC). In vastus lateralis of cachectic patients with either LC (n=10) or advanced COPD (n=16) and healthy controls (n=10), markers of redox balance, inflammation, proteolysis, autophagy, signaling pathways, mitochondrial function, muscle structure, and sarcomere damage were measured using laboratory and light and electron microscopy techniques. Systemic redox balance and inflammation were also determined. All subjects were clinically evaluated. Compared to controls, in both cachectic groups of patients, a similar expression profile of different biological markers was observed in their muscles: increased levels of muscle protein oxidation and ubiquitination (p<0.05, both), which positively correlated (r=0.888), redox-sensitive signaling pathways (NF-κB and FoxO) were activated (p<0.05, all), fast-twitch fiber sizes were atrophied, muscle structural abnormalities and sarcomere disruptions were significantly greater (p<0.05, both). Structural and functional protein levels were lower in muscles of both cachectic patient groups than in controls (p<0.05, all). However, levels of autophagy markers including ultrastructural autophagosome counts were increased only in muscles of cachectic COPD patients (p<0.05). Systemic oxidative stress and inflammation levels were also increased in both patient groups compared to controls (p<0.005, both). Oxidative stress and redox-sensitive signaling pathways are likely to contribute to the etiology of muscle wasting and sarcomere disruption in patients with respiratory cachexia: LC and COPD.

  15. Advanced oxidation protein products induce chondrocyte apoptosis via receptor for advanced glycation end products-mediated, redox-dependent intrinsic apoptosis pathway.

    PubMed

    Wu, Qian; Zhong, Zhao-Ming; Zhu, Si-Yuan; Liao, Cong-Rui; Pan, Ying; Zeng, Ji-Huan; Zheng, Shuai; Ding, Ruo-Ting; Lin, Qing-Song; Ye, Qing; Ye, Wen-Bin; Li, Wei; Chen, Jian-Ting

    2016-01-01

    Pro-inflammatory cytokine-induced chondrocyte apoptosis is a primary cause of cartilage destruction in the progression of rheumatoid arthritis (RA). Advanced oxidation protein products (AOPPs), a novel pro-inflammatory mediator, have been confirmed to accumulate in patients with RA. However, the effect of AOPPs accumulation on chondrocyte apoptosis and the associated cellular mechanisms remains unclear. The present study demonstrated that the plasma formation of AOPPs was enhanced in RA rats compared with normal. Then, chondrocyte were treated with AOPPs-modified rat serum albumin (AOPPs-RSA) in vitro. Exposure of chondrocyte to AOPPs activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and increased expression of NADPH oxidase subunits, which was mediated by receptor for advanced glycation end products (RAGE), but not scavenger receptor CD36. Moreover, AOPPs challenge triggered NADPH oxidase-dependent ROS generation which induced mitochondrial dysfunction and endoplasmic reticulum stress resulted in activation of caspase family that eventually lead to apoptosis. Lastly, blockade of RAGE, instead of CD36, largely attenuated these signals. Our study demonstrated first time that AOPPs induce chondrocyte apoptosis via RAGE-mediated and redox-dependent intrinsic apoptosis pathway in vitro. These data implicates that AOPPs may represent a novel pathogenic factor that contributes to RA progression. Targeting AOPPs-triggered cellular mechanisms might emerge as a promising therapeutic option for patients with RA.

  16. [Advanced biofuel-oriented engineering of fatty acid pathway: a review].

    PubMed

    Zhou, Yongjin J; Zhao, Zongbao K

    2011-09-01

    Biofuel is in high demand as an alternative energy source for petroleum and diesel. Fatty acid-based biofuel has higher energy density and better compatibility with existing infrastructures. Microbial fatty acid biosynthetic pathway is important to develop biofuel. In this article, recent progresses on the modification and reconstruction of fatty acid metabolism for the production of biofuel were reviewed, with a focus on micro-diesel, long chain fatty alcohol and alkane. Problems, solutions and directions for further development of fatty acid-based biofuel were also discussed in the respect of synthetic biology.

  17. Enhancing Endocrine Therapy for Hormone Receptor-Positive Advanced Breast Cancer: Cotargeting Signaling Pathways.

    PubMed

    Johnston, Stephen R D

    2015-10-01

    Overcoming primary or secondary endocrine resistance in breast cancer remains critical to further enhancing the benefit of existing therapies such as tamoxifen or an aromatase inhibitor (AI). Much progress has been made in understanding the molecular biology associated with secondary endocrine resistance. Cotargeting the estrogen receptor, together with various key intracellular proliferation and cell survival signaling pathways, has been explored as a strategy either to treat endocrine resistance once it develops in the second-line setting or to enhance first-line endocrine responsiveness by preventing secondary resistance from developing via blockade of specific pathways from the outset. While attempts to improve endocrine therapy by adding growth factor inhibitors have been disappointing, success resulting in new drug approvals has been seen in secondary endocrine resistance by treating patients with the mTOR antagonist everolimus in combination with the AI exemestane and, more recently, in the first-line setting, by the addition of the CDK 4/6 inhibitor palbociclib to the AI letrozole. Numerous other therapeutics are being evaluated in combination with endocrine therapies based on supportive preclinical evidence, including inhibitors of PI3K, Akt, HDAC, Src, IGFR-1, and FGFR. Appropriate clinical trial design and patient selection based on prior therapy exposure, together with predictive biomarkers derived through real-time molecular profiling, are needed to enrich future trials and maximize any additional benefit that cotargeting may bring to current endocrine therapies for estrogen receptor-positive breast cancer.

  18. Recent advances in the Suf Fe-S cluster biogenesis pathway: Beyond the Proteobacteria.

    PubMed

    Outten, F Wayne

    2015-06-01

    Fe-S clusters play critical roles in cellular function throughout all three kingdoms of life. Consequently, Fe-S cluster biogenesis systems are present in most organisms. The Suf (sulfur formation) system is the most ancient of the three characterized Fe-S cluster biogenesis pathways, which also include the Isc and Nif systems. Much of the first work on the Suf system took place in Gram-negative Proteobacteria used as model organisms. These early studies led to a wealth of biochemical, genetic, and physiological information on Suf function. From those studies we have learned that SufB functions as an Fe-S scaffold in conjunction with SufC (and in some cases SufD). SufS and SufE together mobilize sulfur for cluster assembly and SufA traffics the complete Fe-S cluster from SufB to target apo-proteins. However, recent progress on the Suf system in other organisms has opened up new avenues of research and new hypotheses about Suf function. This review focuses primarily on the most recent discoveries about the Suf pathway and where those new models may lead the field. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases.

  19. Recent advances in the Suf Fe-S cluster biogenesis pathway: Beyond the Proteobacteria

    PubMed Central

    Outten, F. Wayne

    2014-01-01

    Fe-S clusters play critical roles in cellular function throughout all three kingdoms of life. Consequently, Fe-S cluster biogenesis systems are present in most organisms. The Suf (sulfur formation) system is the most ancient of the three characterized Fe-S cluster biogenesis pathways, which also include the Isc and Nif systems. Much of the first work on the Suf system took place in Gram-negative Proteobacteria used as model organisms. These early studies led to a wealth of biochemical, genetic, and physiological information on Suf function. From those studies we have learned that SufB functions as an Fe-S scaffold in conjunction with SufC (and in some cases SufD). SufS and SufE together mobilize sulfur for cluster assembly and SufA traffics the complete Fe-S cluster from SufB to target apo-proteins. However, recent progress on the Suf system in other organisms has opened up new avenues of research and new hypotheses about Suf function. This review focuses primarily on the most recent discoveries about the Suf pathway and where those new models may lead the field. PMID:25447545

  20. [Advances in the pathway and molecular mechanism for the biodegradation of microcystins].

    PubMed

    Yan, Hai; Wang, Hua-Sheng; Liu, Xiao-Lu; Yin, Chun-Hua; Xu, Qian-Qian; Lü, Le; Ma, Wan-Biao

    2014-03-01

    With increasing discharge of wastewater containing nitrogen and phosphorus into rivers and lakes, harmful cyanobacterial blooms have become more frequent worldwide. The main harm of cyanobacterial blooms is producing and releasing a great amount of algal toxins mainly containing microcystins (MCs). Since MCs are extremely harmful to plants and animals and difficult to be removed efficiently by the traditional processing methods, how to control harmful cyanobacterial blooms and remove MCs have become an unsolved problem in the field of environmental science all over the world. This paper summarized the structure and toxicity of MCs, the MCs-biodegrading bacterial strains, the enzymes, the genes, and the biodegradation pathway and molecular mechanism of MCs. The further research subjects were also proposed. It was hoped that this review could provide a reference for restoring MCs-polluted lakes and reservoirs and ensuring drinking water safety.

  1. Combining natural and man-made DNA tracers to advance understanding of hydrologic flow pathway evolution

    NASA Astrophysics Data System (ADS)

    Dahlke, H. E.; Walter, M. T.; Lyon, S. W.; Rosqvist, G. N.

    2014-12-01

    Identifying and characterizing the sources, pathways and residence times of water and associated constituents is critical to developing improved understanding of watershed-stream connections and hydrological/ecological/biogeochemical models. To date the most robust information is obtained from integrated studies that combine natural tracers (e.g. isotopes, geochemical tracers) with controlled chemical tracer (e.g., bromide, dyes) or colloidal tracer (e.g., carboxilated microspheres, tagged clay particles, microorganisms) applications. In the presented study we explore how understanding of sources and flow pathways of water derived from natural tracer studies can be improved and expanded in space and time by simultaneously introducing man-made, synthetic DNA-based microtracers. The microtracer used were composed of polylactic acid (PLA) microspheres into which short strands of synthetic DNA and paramagnetic iron oxide nanoparticles are incorporated. Tracer experiments using both natural tracers and the DNA-based microtracers were conducted in the sub-arctic, glacierized Tarfala (21.7 km2) catchment in northern Sweden. Isotopic hydrograph separations revealed that even though storm runoff was dominated by pre-event water the event water (i.e. rainfall) contributions to streamflow increased throughout the summer season as glacial snow cover decreased. This suggests that glaciers are a major source of the rainwater fraction in streamflow. Simultaneous injections of ten unique DNA-based microtracers confirmed this hypothesis and revealed that the transit time of water traveling from the glacier surface to the stream decreased fourfold over the summer season leading to instantaneous rainwater contributions during storm events. These results highlight that integrating simultaneous tracer injections (injecting tracers at multiple places at one time) with traditional tracer methods (sampling multiple times at one place) rather than using either approach in isolation can

  2. Recent Advances in Targeting the EGFR Signaling Pathway for the Treatment of Metastatic Colorectal Cancer.

    PubMed

    Miyamoto, Yuji; Suyama, Koichi; Baba, Hideo

    2017-04-02

    Outcomes for metastatic colorectal cancer (mCRC) patients have been improved by treatment with anti-epidermal growth factor receptor (anti-EGFR) antibodies, particularly when combined with predictive biomarkers to select patients lacking RAS mutations. New technologies such as liquid biopsy and next-generation sequencing have revealed that potential mechanisms of resistance to anti-EGFR therapies act through acquired mutations of KRAS and the EGFR ectodomain. Mutations in cross-talking molecular effectors that participate in downstream EGFR signaling are also negative predictors for anti-EGFR therapy. In the current review, we describe recent advances in anti-EGFR therapy and discuss new treatment strategies to target downstream RAS-MAPK signaling in mCRC.

  3. Stability of 6:2 fluorotelomer sulfonate in advanced oxidation processes: degradation kinetics and pathway.

    PubMed

    Yang, Xiaoling; Huang, Jun; Zhang, Kunlun; Yu, Gang; Deng, Shubo; Wang, Bin

    2014-03-01

    Perfluorooctane sulfonate (PFOS), a widely used mist suppressant in hard chrome electroplating industry, has been listed in the Stockholm Convention for global ban. 6:2 Fluorotelomer sulfonate (6:2 FTS) acid and salts have been adopted as alternative products in the market, but no data about their abiotic degradation has been reported. In the present study, the degradability of 6:2 FTS potassium salt (6:2 FTS-K) was evaluated under various advanced oxidation processes, including ultraviolet (UV) irradiation, UV with hydrogen peroxide (H2O2), alkaline ozonation (O3, pH = 11), peroxone (O3/H2O2), and Fenton reagent oxidation (Fe(2+)/H2O2). UV/H2O2 was found to be the most effective approach, where the degradation of 6:2 FTS-K followed the pseudo-first-order kinetics. The intermediates were mainly shorter chain perfluoroalkyl carboxylic acid (C7 to C2), while sulfate (SO4 (2-)) and fluoride (F(-)) were found to be the final products. The high yields of SO4 (2-) and F(-) indicate that 6:2 FTS-K can be nearly completely desulfonated and defluorinated under UV/H2O2 condition. The degradation should firstly begin with the substitution of hydrogen atom by hydroxyl radicals, followed by desulfonation, carboxylation, and sequential "flake off" of CF2 unit. Compared with PFOS which is inert in most advanced oxidation processes, 6:2 FTS-K is more degradable as the alternative.

  4. Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-κB Pathway.

    PubMed

    Jin, Xian; Yao, Tongqing; Zhou, Zhong'e; Zhu, Jian; Zhang, Song; Hu, Wei; Shen, Chengxing

    2015-01-01

    Atherosclerotic lesions are accelerated in patients with diabetes. M1 (classically activated in contrast to M2 alternatively activated) macrophages play key roles in the progression of atherosclerosis. Since advanced glycation end products (AGEs) are major pathogenic factors and active inflammation inducers in diabetes mellitus, this study assessed the effects of AGEs on macrophage polarization. The present study showed that AGEs significantly promoted macrophages to express IL-6 and TNF-α. M1 macrophage markers such as iNOS and surface markers including CD11c and CD86 were significantly upregulated while M2 macrophage markers such as Arg1 and CD206 remained unchanged after AGEs stimulation. AGEs significantly increased RAGE expression in macrophages and activated NF-κB pathway, and the aforementioned effects were partly abolished by administration of anti-RAGE antibody or NF-κB inhibitor PDTC. In conclusion, our results suggest that AGEs enhance macrophage differentiation into proinflammatory M1 phenotype at least partly via RAGE/NF-κB pathway activation.

  5. Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway.

    PubMed

    Lv, Xing; Lv, Gao-Hong; Dai, Guo-Ying; Sun, Hong-Mei; Xu, Hui-Qin

    2016-11-01

    The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.

  6. Trapping and Structural Elucidation of a Very Advanced Intermediate in the Lesion-Extrusion Pathway of hOGG1

    SciTech Connect

    Lee, Seongmin; Radom, Christopher T.; Verdine, Gregory L.

    2008-07-28

    Here we present the first structure of a very advanced intermediate in the lesion-extrusion pathway of a DNA glycosylase, human 8-oxoguanine DNA glycosylase (hOGG1), and a substrate DNA containing a mutagenic lesion, 8-oxoguanine (oxoG). The structure was obtained by irradiation and flash-freezing of a disulfide-cross-linked (DXLed) complex of hOgg1 bound to DNA containing a novel photocaged derivative of oxoG. The X-ray structure reveals that, upon irradiation, the oxoG lesion has transited from the exosite to the active site pocket, but has not undergone cleavage by the enzyme. Furthermore, all but one of the specificity-determining interactions between the lesion and the enzyme are unformed in the flashed complex (FC), because active site functionality and elements of the DNA backbone are mispositioned. This structure thus provides a first glimpse into the structure of a very late-stage intermediate in the lesion-extrusion pathway -- the latest observed to date for any glycosylase -- in which the oxoG has undergone insertion into the enzyme active site following photodeprotection, but the enzyme and DNA have not yet completed the slower process of adjusting to the presence of the lesion in the active site.

  7. Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-κB Pathway

    PubMed Central

    Jin, Xian; Yao, Tongqing; Zhou, Zhong'e; Zhu, Jian; Zhang, Song; Hu, Wei; Shen, Chengxing

    2015-01-01

    Atherosclerotic lesions are accelerated in patients with diabetes. M1 (classically activated in contrast to M2 alternatively activated) macrophages play key roles in the progression of atherosclerosis. Since advanced glycation end products (AGEs) are major pathogenic factors and active inflammation inducers in diabetes mellitus, this study assessed the effects of AGEs on macrophage polarization. The present study showed that AGEs significantly promoted macrophages to express IL-6 and TNF-α. M1 macrophage markers such as iNOS and surface markers including CD11c and CD86 were significantly upregulated while M2 macrophage markers such as Arg1 and CD206 remained unchanged after AGEs stimulation. AGEs significantly increased RAGE expression in macrophages and activated NF-κB pathway, and the aforementioned effects were partly abolished by administration of anti-RAGE antibody or NF-κB inhibitor PDTC. In conclusion, our results suggest that AGEs enhance macrophage differentiation into proinflammatory M1 phenotype at least partly via RAGE/NF-κB pathway activation. PMID:26114112

  8. Systems biology and brain activity in neuronal pathways by smart device and advanced signal processing.

    PubMed

    Castellani, Gastone; Intrator, Nathan; Remondini, Daniel

    2014-01-01

    Contemporary biomedicine is producing large amount of data, especially within the fields of "omic" sciences. Nevertheless, other fields, such as neuroscience, are producing similar amount of data by using non-invasive techniques such as imaging, functional magnetic resonance and electroencephalography. Nowadays a big challenge and a new research horizon for Systems Biology is to develop methods to integrate and model this data in an unifying framework capable to disentangle this amazing complexity. In this paper we show how methods from genomic data analysis can be applied to brain data. In particular the concept of pathways, networks and multiplex are discussed. These methods can lead to a clear distinction of various regimes of brain activity. Moreover, this method could be the basis for a Systems Biology analysis of brain data and for the integration of these data in a multivariate and multidimensional framework. The feasibility of this integration is strongly dependent from the feature extraction method used. In our case we used an "alphabet" derived from a multi-resolution analysis that is capable to capture the most relevant information from these complex signals.

  9. Pathways to Advancing Aging Policy-Relevant Research in Academic Settings

    PubMed Central

    KIETZMAN, KATHRYN G.; TROY, LISA M.; GREEN, CARMEN R.; WALLACE, STEVEN P.

    2016-01-01

    Policy-level changes have a significant influence on the health and well-being of aging populations. Yet there is often a gap between scientific knowledge and policy action. Although previous research has identified barriers and facilitators to effective knowledge translation, little attention has been given to the role of academic institutions in knowledge generation. This exploratory focus group study examines barriers and pathways to developing and maintaining an aging policy-relevant research agenda in academic settings, and additional challenges associated with minority group membership in this pursuit. Participants were personally committed to conducting policy-relevant research despite institutional barriers such as fewer funding opportunities and less value attributed to their research, particularly in the context of tenure and promotion. Although many viewed their research as an opportunity to make a difference, especially for underserved older adult populations, a number of minority group participants expressed that their policy research interests were marginalized. Participants offer individual and institutional-level strategies for addressing barriers, including collaborating with community members and colleagues and engaging mentors within and outside of their academic institutions. Reframing the valuation of policy research through the diversification of funding and publishing opportunities can better support scholars engaged in aging policy-relevant research. PMID:26849290

  10. Pathways to Advancing Aging Policy-Relevant Research in Academic Settings.

    PubMed

    Kietzman, Kathryn G; Troy, Lisa M; Green, Carmen R; Wallace, Steven P

    2016-01-01

    Policy-level changes have a significant influence on the health and well-being of aging populations. Yet there is often a gap between scientific knowledge and policy action. Although previous research has identified barriers and facilitators to effective knowledge translation, little attention has been given to the role of academic institutions in knowledge generation. This exploratory focus group study examines barriers and pathways to developing and maintaining an aging policy-relevant research agenda in academic settings, and additional challenges associated with minority group membership in this pursuit. Participants were personally committed to conducting policy-relevant research despite institutional barriers such as fewer funding opportunities and less value attributed to their research, particularly in the context of tenure and promotion. Although many viewed their research as an opportunity to make a difference, especially for underserved older adult populations, a number of minority group participants expressed that their policy research interests were marginalized. Participants offer individual and institutional-level strategies for addressing barriers, including collaborating with community members and colleagues and engaging mentors within and outside of their academic institutions. Reframing the valuation of policy research through the diversification of funding and publishing opportunities can better support scholars engaged in aging policy-relevant research.

  11. Systems biology and brain activity in neuronal pathways by smart device and advanced signal processing

    PubMed Central

    Castellani, Gastone; Intrator, Nathan; Remondini, Daniel

    2014-01-01

    Contemporary biomedicine is producing large amount of data, especially within the fields of “omic” sciences. Nevertheless, other fields, such as neuroscience, are producing similar amount of data by using non-invasive techniques such as imaging, functional magnetic resonance and electroencephalography. Nowadays a big challenge and a new research horizon for Systems Biology is to develop methods to integrate and model this data in an unifying framework capable to disentangle this amazing complexity. In this paper we show how methods from genomic data analysis can be applied to brain data. In particular the concept of pathways, networks and multiplex are discussed. These methods can lead to a clear distinction of various regimes of brain activity. Moreover, this method could be the basis for a Systems Biology analysis of brain data and for the integration of these data in a multivariate and multidimensional framework. The feasibility of this integration is strongly dependent from the feature extraction method used. In our case we used an “alphabet” derived from a multi-resolution analysis that is capable to capture the most relevant information from these complex signals. PMID:25206359

  12. Advancing clinical development pathways for new CFTR modulators in cystic fibrosis.

    PubMed

    Mayer-Hamblett, Nicole; Boyle, Michael; VanDevanter, Donald

    2016-05-01

    Cystic fibrosis (CF) is a life-shortening genetic disease affecting approximately 70,000 individuals worldwide. Until recently, drug development efforts have emphasised therapies treating downstream signs and symptoms resulting from the underlying CF biological defect: reduced function of the CF transmembrane conductance regulator (CFTR) protein. The current CF drug development landscape has expanded to include therapies that enhance CFTR function by either restoring wild-type CFTR protein expression or increasing (modulating) the function of mutant CFTR proteins in cells. To date, two systemic small-molecule CFTR modulators have been evaluated in pivotal clinical trials in individuals with CF and specific mutant CFTR genotypes that have led to regulatory review and/or approval. Advances in the discovery of CFTR modulators as a promising new class of therapies have been impressive, yet work remains to develop highly effective, disease-modifying modulators for individuals of all CF genotypes. The objectives of this review are to outline the challenges and opportunities in drug development created by systemic genotype-specific CFTR modulators, highlight the advantages of sweat chloride as an established biomarker of CFTR activity to streamline early-phase development and summarise options for later phase clinical trial designs that respond to the adoption of approved genotype-specific modulators into standard of care. An optimal development framework will be needed to move the most promising therapies efficiently through the drug development pipeline and ultimately deliver efficacious and safe therapies to all individuals with CF.

  13. Advancing clinical development pathways for new CFTR modulators in cystic fibrosis

    PubMed Central

    Mayer-Hamblett, Nicole; Boyle, Michael; VanDevanter, Donald

    2016-01-01

    Cystic fibrosis (CF) is a life-shortening genetic disease affecting approximately 70 000 individuals worldwide. Until recently, drug development efforts have emphasised therapies treating downstream signs and symptoms resulting from the underlying CF biological defect: reduced function of the CF transmembrane conductance regulator (CFTR) protein. The current CF drug development landscape has expanded to include therapies that enhance CFTR function by either restoring wild-type CFTR protein expression or increasing (modulating) the function of mutant CFTR proteins in cells. To date, two systemic small-molecule CFTR modulators have been evaluated in pivotal clinical trials in individuals with CF and specific mutant CFTR genotypes that have led to regulatory review and/or approval. Advances in the discovery of CFTR modulators as a promising new class of therapies have been impressive, yet work remains to develop highly effective, disease-modifying modulators for individuals of all CF genotypes. The objectives of this review are to outline the challenges and opportunities in drug development created by systemic genotype-specific CFTR modulators, highlight the advantages of sweat chloride as an established biomarker of CFTR activity to streamline early-phase development and summarise options for later phase clinical trial designs that respond to the adoption of approved genotype-specific modulators into standard of care. An optimal development framework will be needed to move the most promising therapies efficiently through the drug development pipeline and ultimately deliver efficacious and safe therapies to all individuals with CF. PMID:26903594

  14. Degradation of diclofenac by advanced oxidation and reduction processes: kinetic studies, degradation pathways and toxicity assessments.

    PubMed

    Yu, Hui; Nie, Er; Xu, Jun; Yan, Shuwen; Cooper, William J; Song, Weihua

    2013-04-01

    Many pharmaceutical compounds and metabolites are found in surface and ground waters suggesting their ineffective removal by conventional wastewater treatment technologies. Advanced oxidation/reduction processes (AO/RPs), which utilize free radical reactions to directly degrade chemical contaminants, are alternatives to traditional water treatment. This study reports the absolute rate constants for reaction of diclofenac sodium and model compound (2, 6-dichloraniline) with the two major AO/RP radicals: the hydroxyl radical (•OH) and hydrated electron (e(aq)(-)). The bimolecular reaction rate constants (M(-1) s(-1)) for diclofenac for •OH was (9.29 ± 0.11) × 10(9), and for e(-)(aq) was (1.53 ± 0.03) ×10(9). To provide a better understanding of the decomposition of the intermediate radicals produced by hydroxyl radical reactions, transient absorption spectra are observed from 1 - 250 μs. In addition, preliminary degradation mechanisms and major products were elucidated using (60)Co γ-irradiation and LC-MS. The toxicity of products was evaluated using luminescent bacteria. These data are required for both evaluating the potential use of AO/RPs for the destruction of these compounds and for studies of their fate and transport in surface waters where radical chemistry may be important in assessing their lifetime.

  15. Degradation of ciprofloxacin in water by advanced oxidation process: kinetics study, influencing parameters and degradation pathways.

    PubMed

    Sayed, Murtaza; Ismail, M; Khan, Sanaullah; Tabassum, Safia; Khan, Hasan M

    2016-01-01

    Gamma-radiation-induced degradation of ciprofloxacin (CIP) in aqueous solution and the factors affecting the degradation process have been investigated. The results showed that CIP (4.6 mg/L) was almost completely degraded at an absorbed dose of 870 Gy. The kinetic studies of aqueous solutions containing 4.6, 10, 15 and 17.9 mg/L indicated that the decomposition of CIP by gamma irradiation followed pseudo-first-order kinetics and the decay constant (k) decreased from 5.9  ×  10(-3) to 1.6  ×  10(-3) Gy(-1) with an increase in CIP initial concentration from 4.6 to 17.9 mg/L. The effect of saturation of CIP solution with N2, N2O or air on radiation-induced degradation of CIP was also investigated. The effects of radical scavengers, such as t-BuOH and i-PrOH, showed the role of reactive radicals towards degradation of CIP in the order of OH > e(aq)- . H. The apparent second-order rate constant of [Formula: see text] with CIP was calculated to be 2.64 × 10(9) M(-1) s(-1). The effects of solution pH as well as natural water contaminants, such as [HCO3-, CO3(2-), and NO2-, on CIP degradation by gamma-irradiation were also investigated. Major degradation products, including organic acids, were identified using UPLC-MS/MS and IC, and degradation pathways have been proposed.

  16. Guidance and control, 1993; Annual Rocky Mountain Guidance and Control Conference, 16th, Keystone, CO, Feb. 6-10, 1993

    NASA Astrophysics Data System (ADS)

    Culp, Robert D.; Bickley, George

    Papers from the sixteenth annual American Astronautical Society Rocky Mountain Guidance and Control Conference are presented. The topics covered include the following: advances in guidance, navigation, and control; control system videos; guidance, navigation and control embedded flight control systems; recent experiences; guidance and control storyboard displays; and applications of modern control, featuring the Hubble Space Telescope (HST) performance enhancement study. For individual titles, see A95-80390 through A95-80436.

  17. Pathway Targeted Immunotherapy: Rationale and Evidence of Durable Clinical Responses with a Novel, EGF-directed Agent for Advanced NSCLC.

    PubMed

    Rosell, Rafael; Neninger, Elia; Nicolson, Marianne; Huber, Rudolf M; Thongprasert, Sumitra; Parikh, Purvish M; D'Hondt, Erik

    2016-11-01

    Abnormalities in the epidermal growth factor (EGF) and EGFR pathway promote progression of NSCLC. Immunization with EGF vaccine induces specific, neutralizing anti-EGF antibodies that prevent binding of the ligand to its receptor. This concept of pathway targeted immunotherapy (PTI) was validated in vitro by dose-related suppression of EGFR, Akt, and Erk1/2 phosphorylation in cell lines with different mutations. A randomized phase II trial showed improved overall survival (OS) in subgroups with advanced NSCLC showing a clear immunologic response. By per-protocol analysis of the ensuing phase IIb trial, patients receiving EGF PTI survived 3 months longer than controls (12.43 versus 9.43 months; hazard ratio = 0.77 [95% confidence interval, 0.61-0.98]). These data were confirmed in a larger trial showing an OS benefit over control of >3 months. The variable most strongly correlated with efficacy was circulating EGF at enrolment. Patients with serum EGF levels >250 pg/mL benefited most from treatment with EGF PTI. Of 188 patients tested, 94 were above this biomarker threshold. The OS benefit from active versus control treatment was 6.7 months. More than 15% of patients had responses for >5 years. Long-term survivors are seen in all EGF PTI trials. Treatment is well-tolerated, induces high anti-EGF antibody titers, reduces levels of circulating serum EGF, achieves durable responses, and significantly prolongs OS. A threshold of 250 pg/mL has been set to enrich the study population in the ongoing pivotal trial. This biomarker-guided study in an enriched population of patients with both squamous and nonsquamous stage IV NSCLC aims to replicate the favorable efficacy/tolerability balance of earlier studies.

  18. Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project. ACT/Control/Guidance System study. Volume 2: Appendices

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The integrated application of active controls (IAAC) technology to an advanced subsonic transport is reported. Supplementary technical data on the following topics are included: (1) 1990's avionics technology assessment; (2) function criticality assessment; (3) flight deck system for total control and functional features list; (4) criticality and reliability assessment of units; (5) crew procedural function task analysis; and (6) recommendations for simulation mechanization.

  19. Advances in genome-wide RNAi cellular screens: a case study using the Drosophila JAK/STAT pathway

    PubMed Central

    2012-01-01

    Background Genome-scale RNA-interference (RNAi) screens are becoming ever more common gene discovery tools. However, whilst every screen identifies interacting genes, less attention has been given to how factors such as library design and post-screening bioinformatics may be effecting the data generated. Results Here we present a new genome-wide RNAi screen of the Drosophila JAK/STAT signalling pathway undertaken in the Sheffield RNAi Screening Facility (SRSF). This screen was carried out using a second-generation, computationally optimised dsRNA library and analysed using current methods and bioinformatic tools. To examine advances in RNAi screening technology, we compare this screen to a biologically very similar screen undertaken in 2005 with a first-generation library. Both screens used the same cell line, reporters and experimental design, with the SRSF screen identifying 42 putative regulators of JAK/STAT signalling, 22 of which verified in a secondary screen and 16 verified with an independent probe design. Following reanalysis of the original screen data, comparisons of the two gene lists allows us to make estimates of false discovery rates in the SRSF data and to conduct an assessment of off-target effects (OTEs) associated with both libraries. We discuss the differences and similarities between the resulting data sets and examine the relative improvements in gene discovery protocols. Conclusions Our work represents one of the first direct comparisons between first- and second-generation libraries and shows that modern library designs together with methodological advances have had a significant influence on genome-scale RNAi screens. PMID:23006893

  20. Unified powered flight guidance

    NASA Technical Reports Server (NTRS)

    Brand, T. J.; Brown, D. W.; Higgins, J. P.

    1973-01-01

    A complete revision of the orbiter powered flight guidance scheme is presented. A unified approach to powered flight guidance was taken to accommodate all phases of exo-atmospheric orbiter powered flight, from ascent through deorbit. The guidance scheme was changed from the previous modified version of the Lambert Aim Point Maneuver Mode used in Apollo to one that employs linear tangent guidance concepts. This document replaces the previous ascent phase equation document.

  1. Molecular mechanisms of optic axon guidance

    NASA Astrophysics Data System (ADS)

    Inatani, Masaru

    2005-12-01

    Axon guidance is one of the critical processes during vertebrate central nervous system (CNS) development. The optic nerve, which contains the axons of retinal ganglion cells, has been used as a powerful model to elucidate some of the mechanisms underlying axon guidance because it is easily manipulated experimentally, and its function is well understood. Recent molecular biology studies have revealed that numerous guidance molecules control the development of the visual pathway. This review introduces the molecular mechanisms involved in each critical step during optic axon guidance. Axonal projections to the optic disc are thought to depend on adhesion molecules and inhibitory extracellular matrices such as chondroitin sulfate. The formation of the head of the optic nerve and the optic chiasm require ligand-receptor interactions between netrin-1 and the deleted in colorectal cancer receptor, and Slit proteins and Robo receptors, respectively. The gradient distributions of ephrin ligands and Eph receptors are essential for correct ipsilateral projections at the optic chiasm and the topographic mapping of axons in the superior colliculus/optic tectum. The precise gradient is regulated by transcription factors determining the retinal dorso-ventral and nasal-temporal polarities. Moreover, the axon guidance activities by Slit and semaphorin 5A require the existence of heparan sulfate, which binds to numerous guidance molecules. Recent discoveries about the molecular mechanisms underlying optic nerve guidance will facilitate progress in CNS developmental biology and axon-regeneration therapy.

  2. Advanced glycosylation end product promotes forkhead box O1 and inhibits Wnt pathway to suppress capacities of epidermal stem cells

    PubMed Central

    Zhu, Jie; Wang, Peng; Yu, Zhimin; Lai, Wei; Cao, Yi; Huang, Pinbo; Xu, Qiaodong; Yu, Menglei; Xu, Junyao; Huang, Zitong; Zeng, Bing

    2016-01-01

    Diabetes mellitus is frequently accompanied by chronic complications like delayed wound healing, which is consider to be attributed to the accumulation of advanced glycosylation end product (AGE). However, the impacts of AGE on epidermal stem cells (ESCs) are largely unknown. This study aims to address the influence and mechanism of AGE on ESCs. ESCs isolated from rats were cultured in AGE-modified bovine serum albumin and transfected with small interfering RNA to knock down AGE-specific receptor (AGER). Expression of stem cell markers integrin β1 (ITGB1) and keratin 19 (KRT19), cell viability, apoptosis and reactive oxygen species (ROS) were examined. Wnt pathway-related factors Wnt family member 1 (WNT1), WNT3A, β-catenin, v-myc avian myelocytomatosis viral oncogene homolog (MYC), cyclin D1 (CCND1) and matrix metallopeptidase 7 (MMP7) were quantified. The interaction between forkhead box O1 (FOXO1) and β-catenin was assessed by co-immunoprecipitation. Results indicated that AGE down-regulated ITGB1 and KRT19 expression, suppressed ESC viability and promoted apoptosis, and ROS level (P < 0.01), implying decreased capacities of ESCs. AGE also promoted AGER and FOXO1, while AGER knockdown had the opposite effects. Moreover, AGER knockdown elevated the level of WNT1, WNT3A, MYC, CCND1 and MMP7 that were suppressed by AGE (P < 0.01). Immunoprecipitation analysis showed that FOXO1 could compete with lymphoid enhancer binding factor 1 to interact with β-catenin, which might help to elucidate the mechanism of AGE repressing ESCs. This study helps to understand the mechanism of accumulated AGE in affecting ESC capacities, and provides potential therapeutic targets to meliorate diabetic wound healing. PMID:28078027

  3. Entry Guidance for the Reusable Launch Vehicle

    NASA Technical Reports Server (NTRS)

    Lu, Ping

    1999-01-01

    The X-33 Advanced Technology Demonstrator is a half-scale prototype developed to test the key technologies needed for a full-scale single-stage reusable launch vehicle (RLV). The X-33 is a suborbital vehicle that will be launched vertically, and land horizontally. The goals of this research were to develop an alternate entry guidance scheme for the X-33 in parallel to the actual X-33 entry guidance algorithms, provide comparative and complementary study, and identify potential new ways to improve entry guidance performance. Toward these goals, the nominal entry trajectory is defined by a piecewise linear drag-acceleration-versus-energy profile, which is in turn obtained by the solution of a semi-analytical parameter optimization problem. The closed-loop guidance is accomplished by tracking the nominal drag profile with primarily bank-angle modulation on-board. The bank-angle is commanded by a single full-envelope nonlinear trajectory control law. Near the end of the entry flight, the guidance logic is switched to heading control in order to meet strict conditions at the terminal area energy management interface. Two methods, one on ground-track control and the other on heading control, were proposed and examined for this phase of entry guidance where lateral control is emphasized. Trajectory dispersion studies were performed to evaluate the effectiveness of the entry guidance algorithms against a number of uncertainties including those in propulsion system, atmospheric properties, winds, aerodynamics, and propellant loading. Finally, a new trajectory-regulation method is introduced at the end as a promising precision entry guidance method. The guidance principle is very different and preliminary application in X-33 entry guidance simulation showed high precision that is difficult to achieve by existing methods.

  4. Downstream of guidance receptors: entering the baroque period of axon guidance signaling.

    PubMed

    Schmucker, Dietmar

    2003-09-25

    The Roundabout ("Robo") family of transmembrane proteins are the receptors and mediators of the repellent axon guidance signal Slit. However, the molecular mechanisms by which Robo signaling leads to growth cone or neuron repulsion are still poorly understood. A study by Fan et al. in this issue of Neuron expands the repertoire of Robo pathway components and stimulates a new look at axon guidance signaling in general.

  5. 78 FR 56718 - Draft Guidance for Industry on Bioanalytical Method Validation; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-13

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Bioanalytical Method Validation; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and... revising the guidance to reflect advancements in the science and technology of bioanalytical...

  6. Autonomous landing guidance program

    NASA Astrophysics Data System (ADS)

    Brown, John A.

    1996-05-01

    The Autonomous Landing Guidance program is partly funded by the US Government under the Technology Reinvestment Project. The program consortium consists of avionics and other equipment vendors, airlines and the USAF. A Sextant Avionique HUD is used to present flight symbology in cursive form as well as millimeter wave radar imagery from Lear Astronics equipment and FLIR Systems dual-channel, forward-looking, infrared imagery. All sensor imagery is presented in raster form. A future aim is to fuse all imagery data into a single presentation. Sensor testing has been accomplished in a Cessna 402 operated by the Maryland Advanced Development Laboratory. Development testing is under way in a Northwest Airlines simulator equipped with HUD and image simulation. Testing is also being carried out using United Airlines Boeing 727 and USAF C-135C (Boeing 707) test aircraft. The paper addresses the technology utilized in sensory and display systems as well as modifications made to accommodate the elements in the aircraft. Additions to the system test aircraft include global positioning systems, inertial navigation systems and extensive data collection equipment. Operational philosophy and benefits for both civil and military users are apparent. Approach procedures have been developed allowing use of Category 1 ground installations in Category 3 conditions.

  7. Functional Proteomic Analysis of Advanced Serous Ovarian Cancer using Reverse Phase Protein Array: TGFβ Pathway Signaling Indicates Response to Primary Chemotherapy

    PubMed Central

    Carey, Mark S.; Agarwal, Roshan; Gilks, Blake; Swenerton, Kenneth; Kalloger, Steve; Santos, Jennifer; Ju, Zhenlin; Lu, Yiling; Zhang, Fan; Coombes, Kevin; Miller, Dianne; Huntsman, David; Mills, Gordon B.; Hennessy, Bryan T

    2010-01-01

    Purpose: Using Reverse Phase Protein Array (RPPA) we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage high-grade serous ovarian cancer. Experimental Design: Tumor samples were obtained from forty-five patients with advanced high-grade serous cancers from the Gynecology Tumor Bank at the British Columbia Cancer Agency. Treatment consisted of platinum-based chemotherapy following debulking surgery. Protein lysates were prepared from fresh frozen tumor samples and 80 validated proteins from signaling pathways implicated in ovarian carcinogenesis were measured by RPPA. Normalization of Ca-125 by the 3rd cycle of chemotherapy was chosen as the primary outcome measure of chemotherapy response. Logistic regression was used for multivariate analysis to identify protein predictors of Ca-125 normalization, and Cox regression to test for the association between protein expression and PFS. A significance level of p ≤ 0.05 was used. Results: The mean age at diagnosis was 56.8 years. EGFR, YKL-40 and several TGFβ pathway proteins (c-Jun N-terminal kinase JNK, JNK phosphorylated at residues 183 and 185, PAI-1, Smad3, TAZ) showed significant associations with Ca-125 normalization on univariate testing. On multivariate analysis, EGFR (p < 0.02), JNK (p < 0.01), and Smad3 (p < 0.04) were significantly associated with normalization of Ca-125. Contingency table analysis of pathway-classified proteins revealed that the selection of TGFβ pathway proteins was unlikely due to false discovery (p < 0.007, Bonferroni-adjusted). Conclusion: TGFβ pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted. PMID:20460476

  8. WE-EF-BRD-03: I Want It Now!: Advances in MRI Acquisition, Reconstruction and the Use of Priors to Enable Fast Anatomic and Physiologic Imaging to Inform Guidance and Adaptation Decisions

    SciTech Connect

    Hu, Y.

    2015-06-15

    MRI-guided treatment is a growing area of medicine, particularly in radiotherapy and surgery. The exquisite soft tissue anatomic contrast offered by MRI, along with functional imaging, makes the use of MRI during therapeutic procedures very attractive. Challenging the utility of MRI in the therapy room are many issues including the physics of MRI and the impact on the environment and therapeutic instruments, the impact of the room and instruments on the MRI; safety, space, design and cost. In this session, the applications and challenges of MRI-guided treatment will be described. The session format is: Past, present and future: MRI-guided radiotherapy from 2005 to 2025: Jan Lagendijk Battling Maxwell’s equations: Physics challenges and solutions for hybrid MRI systems: Paul Keall I want it now!: Advances in MRI acquisition, reconstruction and the use of priors to enable fast anatomic and physiologic imaging to inform guidance and adaptation decisions: Yanle Hu MR in the OR: The growth and applications of MRI for interventional radiology and surgery: Rebecca Fahrig Learning Objectives: To understand the history and trajectory of MRI-guided radiotherapy To understand the challenges of integrating MR imaging systems with linear accelerators To understand the latest in fast MRI methods to enable the visualisation of anatomy and physiology on radiotherapy treatment timescales To understand the growing role and challenges of MRI for image-guided surgical procedures My disclosures are publicly available and updated at: http://sydney.edu.au/medicine/radiation-physics/about-us/disclosures.php.

  9. Ascent Guidance Comparisons

    NASA Technical Reports Server (NTRS)

    Hanson, John M.; Shrader, M. Wade; Cruzen, Craig A.

    1995-01-01

    This paper contains results from ascent guidance studies conducted at the NASA Marshall Space Flight Center. The studies include investigation of different guidance schemes for a variety of potential launch vehicles. Criteria of a successful ascent guidance scheme are low operations cost, satisfaction of load indicator constraints, and maximization of performance. Results show that open-loop designs as a function of altitude or velocity are preferable to designs that are functions of time. Optimized open-loop trajectories can increase performance while maintaining load indicators within limits. Closed-loop atmospheric schemes that involve linear tangent steering or feedback of velocity terms for trajectory modification did not yield any improvement. Early release of vacuum closed-loop guidance, including use during solid rocket booster operation, yields some improvements. Evaluation of a closed-loop optimization scheme for flying through the atmosphere shows no advantages over open-loop optimization. Dispersion study results for several potential guidance schemes and launch vehicles are included in the paper and are not a discriminator between guidance schemes. The primary cost driver is mission operations philosophy, not choice of guidance scheme. More autonomous guidance schemes can help in movement towards a philosophy that would reduce operations costs.

  10. Aiding Vertical Guidance Understanding

    NASA Technical Reports Server (NTRS)

    Feary, Michael; McCrobie, Daniel; Alkin, Martin; Sherry, Lance; Polson, Peter; Palmer, Everett; McQuinn, Noreen

    1998-01-01

    A two-part study was conducted to evaluate modern flight deck automation and interfaces. In the first part, a survey was performed to validate the existence of automation surprises with current pilots. Results indicated that pilots were often surprised by the behavior of the automation. There were several surprises that were reported more frequently than others. An experimental study was then performed to evaluate (1) the reduction of automation surprises through training specifically for the vertical guidance logic, and (2) a new display that describes the flight guidance in terms of aircraft behaviors instead of control modes. The study was performed in a simulator that was used to run a complete flight with actual airline pilots. Three groups were used to evaluate the guidance display and training. In the training, condition, participants went through a training program for vertical guidance before flying the simulation. In the display condition, participants ran through the same training program and then flew the experimental scenario with the new Guidance-Flight Mode Annunciator (G-FMA). Results showed improved pilot performance when given training specifically for the vertical guidance logic and greater improvements when given the training and the new G-FMA. Using actual behavior of the avionics to design pilot training and FMA is feasible, and when the automated vertical guidance mode of the Flight Management System is engaged, the display of the guidance mode and targets yields improved pilot performance.

  11. Shuttle entry guidance

    NASA Technical Reports Server (NTRS)

    Harpold, J. C.; Graves, C. A., Jr.

    1978-01-01

    This paper describes the design of the entry guidance for the Space Shuttle Orbiter. This guidance provides the steering commands for trajectory control from initial penetration of the earth's atmosphere until the terminal area guidance is activated at an earth-relative speed of 2500 fps. At this point, the Orbiter is at a distance of about 50 nmi from the runway threshold, and at an altitude of about 80,000 ft. The entry guidance design is based on an analytic solution of the equations of motion defining the drag acceleration profile that meets the terminal criteria of the entry flight while maintaining the flight within systems and operational constraints. Guidance commands, which are based on a control law that ensures damping of oscillatory type trajectory motion, are computed to steer the Orbiter to this drag acceleration profile.

  12. Shuttle entry guidance revisited

    NASA Astrophysics Data System (ADS)

    Mease, Kenneth D.; Kremer, Jean-Paul

    1992-08-01

    The Shuttle entry guidance concept is reviewed which is aimed at tracking a reference drag trajectory that leads to the specified range and velocity for the initiation of the terminal energy management phase. An approximate method of constructing the domain of attraction is proposed, and its validity is ascertained by simulation. An alternative guidance law yielding global exponential tracking in the absence of control saturation is derived using a feedback linearization method. It is noted that the alternative guidance law does not improve on the stability and performance of the current guidance law, for the operating domain and control capability of the Shuttle. It is suggested that the new guidance law with a larger operating domain and increased lift-to-drag capability would be superior.

  13. Shuttle entry guidance revisited

    NASA Technical Reports Server (NTRS)

    Mease, Kenneth D.; Kremer, Jean-Paul

    1992-01-01

    The Shuttle entry guidance concept is reviewed which is aimed at tracking a reference drag trajectory that leads to the specified range and velocity for the initiation of the terminal energy management phase. An approximate method of constructing the domain of attraction is proposed, and its validity is ascertained by simulation. An alternative guidance law yielding global exponential tracking in the absence of control saturation is derived using a feedback linearization method. It is noted that the alternative guidance law does not improve on the stability and performance of the current guidance law, for the operating domain and control capability of the Shuttle. It is suggested that the new guidance law with a larger operating domain and increased lift-to-drag capability would be superior.

  14. astray, a zebrafish roundabout homolog required for retinal axon guidance.

    PubMed

    Fricke, C; Lee, J S; Geiger-Rudolph, S; Bonhoeffer, F; Chien, C B

    2001-04-20

    As growing retinotectal axons navigate from the eye to the tectum, they sense guidance molecules distributed along the optic pathway. Mutations in the zebrafish astray gene severely disrupt retinal axon guidance, causing anterior-posterior pathfinding defects, excessive midline crossing, and defasciculation of the retinal projection. Eye transplantation experiments show that astray function is required in the eye. We identify astray as zebrafish robo2, a member of the Roundabout family of axon guidance receptors. Retinal ganglion cells express robo2 as they extend axons. Thus, robo2 is required for multiple axon guidance decisions during establishment of the vertebrate visual projection.

  15. 32 CFR Appendix A to Part 282 - Guidance

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Guidance A Appendix A to Part 282 National... PROCEDURES FOR SETTLING PERSONNEL AND GENERAL CLAIMS AND PROCESSING ADVANCE DECISION REQUESTS Pt. 282, App. A Appendix A to Part 282—Guidance (a) Submitting a claim. The procedures a claimant must follow to submit...

  16. Guidance of Nonlinear Nonminimum-Phase Dynamic Systems

    NASA Technical Reports Server (NTRS)

    Devasia, Santosh

    1997-01-01

    The first two years research work has advanced the inversion-based guidance theory for: (1) systems with non-hyperbolic internal dynamics; (2) systems with parameter jumps; (3) systems where a redesign of the output trajectory is desired; and (4) the generation of recovery guidance maneuvers.

  17. Federal Guidance for Radiation Protection

    EPA Pesticide Factsheets

    EPA produces federal guidance technical reports, which standardize dose and risk assessment and issues radiation protection guidance to federal agencies. This page provides links to federal guidance policy recommendations and technical reports.

  18. Advances in Guidance and Control Systems.

    DTIC Science & Technology

    1983-01-01

    PILOTAGE DES AlIONS A GRAMD MAflONWnABILITS par Oiner L.* MERCIER Office National d’Etudes et de Recherches A~rospatiales (OaRA) 92320 Chitillon...de s6v~res erreurs ou variationa. Cependant, lea objectifa de pilotage doivent Atre atteinta tout en reapectant lea aPifiCationa, de qUalit4a de vol...niveaux eat pr~sentie. Apiiqu6e au pilotage d’un avion d’arme, ce ach~.a de r6gulation permet do commander de mani~re pr~ciae des manmuvres de grande

  19. EPA Policy and Guidance

    EPA Pesticide Factsheets

    The policy establishes the principles for accessible Electronic and Information Technology (EIT) and complying with Section 508 requirements. The guidance defines EIT and the technical and functional performance criteria necessary for compliance.

  20. Aeroassist flight experiment guidance, navigation and control

    NASA Technical Reports Server (NTRS)

    Brand, Timothy J.; Engel, Albert G.

    1986-01-01

    The Aeroassist Flight Experiment scheduled for the early 1990's will demonstrate the use of a low L/D lifting brake using aerodynamic drag to return a spacecraft from a high energy to a low earth orbit. The experimental vehicle will be deployed and retrieved by the Shuttle Orbiter. This paper reviews some of the challenges, problems, and solutions encountered to date during guidance system development, with emphasis on technology advances which will benefit an operational Orbit Transfer Vehicle (OTV). Key factors to be discussed include guidance alternatives, aerodynamic modeling, navigation requirements, the impact of atmospheric uncertainties, and flight profile alternatives considered during initial planning.

  1. Advances in the development of cancer therapeutics directed against the RAS-mitogen-activated protein kinase pathway.

    PubMed

    Sebolt-Leopold, Judith S

    2008-06-15

    Among mammalian mitogen-activated protein kinase (MAPK) signaling cascades, the extracellular signal-related kinase (ERK) pathway has received the most attention in the oncology drug discovery arena. By virtue of its central role in promoting proliferation, survival, and metastasis, this pathway directly affects both the formation and progression of human tumors. The identification of non-ATP-competitive inhibitors of the MAPK kinase MAPK/ERK kinase (MEK) resulted in the first demonstration that the ERK pathway could be effectively shut down in a highly selective fashion. Subsequent discovery of the oncogenic nature of B-raf kinase led to the escalation of drug discovery efforts revolving around MEK and RAF. The emergence of multiple drug candidates targeting these downstream kinases provides us with the means for validating the importance of the RAS-RAF-MEK-ERK signaling cascade in human tumors. This article highlights the lessons learned in the clinical evaluation of MAPK pathway inhibitors as anticancer agents and the complexities surrounding optimization of their therapeutic potential in light of the challenges posed by genetic heterogeneity within patient populations.

  2. Comprehensive Guidance Programs That Work.

    ERIC Educational Resources Information Center

    Gysbers, Norman C.; And Others

    This monograph describes how the comprehensive guidance model is transforming elementary-secondary school guidance and counseling programs in schools across the country. It incorporates the ideas and experiences of 12 guidance program developers in the actual use of the comprehensive guidance model in diverse school and cultural settings. The book…

  3. HUMAN FACTORS GUIDANCE FOR CONTROL ROOM EVALUATION

    SciTech Connect

    OHARA,J.; BROWN,W.; STUBLER,W.; HIGGINS,J.; WACHTEL,J.; PERSENSKY,J.J.

    2000-07-30

    The Human-System Interface Design Review Guideline (NUREG-0700, Revision 1) was developed by the US Nuclear Regulatory Commission (NRC) to provide human factors guidance as a basis for the review of advanced human-system interface technologies. The guidance consists of three components: design review procedures, human factors engineering guidelines, and a software application to provide design review support called the ``Design Review Guideline.'' Since it was published in June 1996, Rev. 1 to NUREG-0700 has been used successfully by NRC staff, contractors and nuclear industry organizations, as well as by interested organizations outside the nuclear industry. The NRC has committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool in the face of emerging and rapidly changing technology. This paper addresses the current research to update of NUREG-0700 based on the substantial work that has taken place since the publication of Revision 1.

  4. Human Genetic Disorders of Axon Guidance

    PubMed Central

    Engle, Elizabeth C.

    2010-01-01

    This article reviews symptoms and signs of aberrant axon connectivity in humans, and summarizes major human genetic disorders that result, or have been proposed to result, from defective axon guidance. These include corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders, horizontal gaze palsy with progressive scoliosis, Kallmann syndrome, albinism, congenital fibrosis of the extraocular muscles type 1, Duane retraction syndrome, and pontine tegmental cap dysplasia. Genes mutated in these disorders can encode axon growth cone ligands and receptors, downstream signaling molecules, and axon transport motors, as well as proteins without currently recognized roles in axon guidance. Advances in neuroimaging and genetic techniques have the potential to rapidly expand this field, and it is feasible that axon guidance disorders will soon be recognized as a new and significant category of human neurodevelopmental disorders. PMID:20300212

  5. The Aggregate Exposure Pathway (AEP): A conceptual framework for advancing exposure science research and transforming risk assessment

    EPA Science Inventory

    Recent advances in analytical methods, biomarker discovery, cell-based assay development, computational tools, sensor/monitor, and omics technology have enabled new streams of exposure and toxicity data to be generated at higher volumes and speed. These new data offer the opport...

  6. Anticipatory guidance through DVD.

    PubMed

    Franz, Sandra; McMahon, Pamela M; Calongne, Laurinda; Steele-Moses, Susan K

    2014-03-01

    The major purpose of the study was to determine if a 5-minute DVD is an effective method for communicating anticipatory guidance to parents at their child's 4-month well-child visit. A total of 84 caregivers were randomly assigned to receive anticipatory guidance through standard care (written anticipatory guidance handout and free talk) or DVD (DVD format + standard care). Participants completed a brief questionnaire immediately before and after their visit. As anticipated, knowledge scores improved significantly from pre-test to post-test. There was also a significant interaction between format used for anticipatory guidance and time. Specifically, there was greater improvement in knowledge over time for parents in the DVD group as compared with the standard care group. Additionally, the mean knowledge level of those in the DVD group as compared with those in the standard care group trended toward significance. Finally, visit length was shortened by nearly 3 minutes in the DVD group, and close to 100% of all respondents, regardless of anticipatory guidance format, indicated that they were very satisfied with their visit and amount of information learned.

  7. Computer-based first-principles kinetic modeling of degradation pathways and byproduct fates in aqueous-phase advanced oxidation processes.

    PubMed

    Guo, Xin; Minakata, Daisuke; Niu, Junfeng; Crittenden, John

    2014-05-20

    In this study, a computer-based first-principles kinetic model is developed to predict the degradation mechanisms and fates of intermediates and byproducts produced during aqueous-phase advanced oxidation processes (AOPs) for various organic compounds. The model contains a rule-based pathway generator to generate the reaction pathways, a reaction rate constant estimator to estimate the reaction rate constant for each reaction generated, a mechanistic reduction module to reduce the generated mechanisms, an ordinary differential equations generator and solver to solve the generated mechanisms and calculate the concentration profiles for all species, and a toxicity estimator to estimate the toxicity of major species and calculate time-dependent profiles of relative toxicity (i.e., concentration of species divided by toxicity value). We predict concentration profiles of acetone and trichloroethylene and their intermediates and byproducts in photolysis with hydrogen peroxide (i.e., UV/H2O2) and validate with experimental observations. The predicted concentration profiles for both parent compounds are consistent with experimental data. The calculated profiles of 96-h green algae chronic toxicity show that the overall toxicity decreases during the degradation process. These generated mechanisms also provide detailed and quantitative insights into the pathways for the formation and consumption of important intermediates and byproducts produced during AOPs. Our approach is sufficiently general to be applied to a wide range of contaminants.

  8. GUIDANCE FOR EVALUATING LANDFILL GAS EMISSIONS ...

    EPA Pesticide Factsheets

    This document provides guidance to Superfund remedial project managers, on scene coordinators, facility owners, and potentially responsible parties for conducting an air pathway analysis for landfill gas (LFG) emissions under the Comprehensive Environmental Response, Compensation and Liability Act, Superfund Amendments and Reauthorization Act, and the Resource Conservation and Recovery Act. The document provides procedures and a set of tools for evaluating LFG emissions to ambient air, subsurface vapor migration due to landfill gas pressure gradients, and subsurface vapor intrusion into buildings. The air pathway analysis is used to evaluate the inhalation risks of offsite receptors as well as the hazards of both onsite and offsite methane explosions and landfill fires. information

  9. Annual Compliance Certification Guidance

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  10. Neuroglial expression of the MHCI pathway and PirB receptor is upregulated in the hippocampus with advanced aging.

    PubMed

    VanGuilder Starkey, Heather D; Van Kirk, Colleen A; Bixler, Georgina V; Imperio, Caesar G; Kale, Vijay P; Serfass, Jacob M; Farley, Julie A; Yan, Han; Warrington, Junie P; Han, Song; Mitschelen, Matthew; Sonntag, William E; Freeman, Willard M

    2012-09-01

    The hippocampus undergoes changes with aging that impact neuronal function, such as synapse loss and altered neurotransmitter release. Nearly half of the aged population also develops deficits in spatial learning and memory. To identify age-related hippocampal changes that may contribute to cognitive decline, transcriptomic analysis of synaptosome preparations from adult (12 months) and aged (28 months) Fischer 344-Brown Norway rats assessed for spatial learning and memory was performed. Bioinformatic analysis identified the MHCI pathway as significantly upregulated with aging. Age-related increases in mRNAs encoding the MHCI genes RT1-A1, RT1-A2, and RT1-A3 were confirmed by qPCR in synaptosomes and in CA1 and CA3 dissections. Elevated levels of the MHCI cofactor (B2m), antigen-loading components (Tap1, Tap2, Tapbp), and two known MHCI receptors (PirB, Klra2) were also confirmed. Protein expression of MHCI was elevated with aging in synaptosomes, CA1, and DG, while PirB protein expression was induced in both CA1 and DG. MHCI expression was localized to microglia and neuronal excitatory postsynaptic densities, and PirB was localized to neuronal somata, axons, and dendrites. Induction of the MHCI antigen processing and presentation pathway in hippocampal neurons and glia may contribute to age-related hippocampal dysfunction by increasing neuroimmune signaling or altering synaptic homeostasis.

  11. Neuroglial expression of the MHCI pathway and PirB receptor is upregulated in the hippocampus with advanced aging

    PubMed Central

    VanGuilder Starkey, Heather D.; Van Kirk, Colleen A.; Bixler, Georgina V.; Imperio, Caesar G.; Kale, Vijay P.; Serfass, Jacob M.; Farley, Julie A.; Yan, Han; Warrington, Junie P.; Han, Song; Mitschelen, Matthew; Sonntag, William E.; Freeman, Willard M.

    2012-01-01

    The hippocampus undergoes changes with aging that impact neuronal function, such as synapse loss and altered neurotransmitter release. Nearly half of the aged population also develops deficits in spatial learning and memory. To identify age-related hippocampal changes that may contribute to cognitive decline, transcriptomic analysis of synaptosome preparations from adult (12 months) and aged (28 months) Fischer 344-Brown Norway rats assessed for spatial learning and memory was performed. Bioinformatic analysis identified the MHCI pathway as significantly upregulated with aging. Age-related increases in mRNAs encoding the MHCI genes RT1-A1, RT1-A2, and RT1-A3 was confirmed by qPCR in synaptosomes and in CA1 and CA3 dissections. Elevated levels of the MHCI cofactor (B2m), antigen-loading components (Tap1, Tap2, Tapbp), and two known MHCI receptors (PirB, Klra2) were also confirmed. Protein expression of MHCI was elevated with aging in synaptosomes, CA1, and DG, while PirB protein expression was induced in both CA1 and DG. MHCI expression was localized to microglia and neuronal excitatory postsynaptic densities, and PirB localized to neuronal somata, axons and dendrites. Induction of the MHCI antigen processing and presentation pathway in hippocampal neurons and glia may contribute to age-related hippocampal dysfunction by increasing neuroimmune signaling or altering synaptic homeostasis. PMID:22562814

  12. Guidance on lobbying restrictions

    EPA Pesticide Factsheets

    The purpose of this guidance is to remind nonprofit organizations, universities, and other non-government recipients of EPA grants that, with very limited exceptions, you may not use Federal grant funds or cost-sharing funds to conduct lobbying activities.

  13. Guidelines for Guidance Services.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    The purpose of this booklet is to provide direction and assistance to school divisions as they develop responsive, effective, and accountable guidance services and programs at the school level. The guidelines presented provide a broad conceptual framework of definitions and goals and outline expectations for service standards. Models and…

  14. Foundations of Career Guidance.

    ERIC Educational Resources Information Center

    Ruff, Eldon E.

    The paper traces the evolution of career guidance from 1909 to the present. The predominant views before 1950 were almost entirely nondevelopmental, but in response to questions raised at a series of major national conferences in the 1960's and the national impact of the career education concept, the 1970's have seen a flurry of writings and…

  15. The Counseling & Guidance Curriculum.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    Counseling and guidance services are vital in any school curriculum. Counselors may themselves be dealing with students of diverse abilities and handicaps. Counselors may have to work with students affected by drug addiction, fetal alcohol syndrome, homelessness, poverty, Acquired Immune Deficiency Syndrome (AIDS) and divorce. Students may present…

  16. PIV Logon Configuration Guidance

    SciTech Connect

    Lee, Glen Alan

    2016-03-04

    This document details the configurations and enhancements implemented to support the usage of federal Personal Identity Verification (PIV) Card for logon on unclassified networks. The guidance is a reference implementation of the configurations and enhancements deployed at the Los Alamos National Laboratory (LANL) by Network and Infrastructure Engineering – Core Services (NIE-CS).

  17. Quality in Careers Guidance.

    ERIC Educational Resources Information Center

    Plant, Peter

    This paper examines quality issues in career guidance, counseling, and information services in Europe and elsewhere from a range of different perspectives related to economic, ethical, and/or effectiveness criteria. Selected examples from the European Union member states, Canada, and the United States are used to illustrate how quality is…

  18. Regulatory guidance document

    SciTech Connect

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM`s evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7.

  19. Vocational Development and Guidance.

    ERIC Educational Resources Information Center

    Tennyson, W. Wesley; And Others

    The vocational education volume considers questions of career development, the role of guidance in the school, vocational training, the relation of self-concept to vocational choice, and occupational information. Twenty-six papers deal with theories of vocational behavior, the success of vocational education programs, and testing information.…

  20. The Impact on Future Guidance Programs of Current Developments in Computer Science, Telecommunications, and Biotechnology.

    ERIC Educational Resources Information Center

    Mitchell, Lynda K.; Hardy, Philippe L.

    The purpose of this chapter is to envision how the era of technological revolution will affect the guidance, counseling, and student support programs of the future. Advances in computer science, telecommunications, and biotechnology are discussed. These advances have the potential to affect dramatically the services of guidance programs of the…

  1. Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

    PubMed Central

    Revandkar, Ajinkya; Perciato, Maria Luna; Toso, Alberto; Alajati, Abdullah; Chen, Jingjing; Gerber, Hermeto; Dimitrov, Mitko; Rinaldi, Andrea; Delaleu, Nicolas; Pasquini, Emiliano; D'Antuono, Rocco; Pinton, Sandra; Losa, Marco; Gnetti, Letizia; Arribas, Alberto; Fraering, Patrick; Bertoni, Francesco; Nepveu, Alain; Alimonti, Andrea

    2016-01-01

    Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of the therapeutic efficacy of NOTCH inhibitors in prostate cancer is lacking. Here, we provide evidence that PTEN loss in prostate tumours upregulates the expression of ADAM17, thereby activating NOTCH signalling. Using prostate conditional inactivation of both Pten and Notch1 along with preclinical trials carried out in Pten-null prostate conditional mouse models, we demonstrate that Pten-deficient prostate tumours are addicted to the NOTCH signalling. Importantly, we find that pharmacological inhibition of γ-secretase promotes growth arrest in both Pten-null and Pten/Trp53-null prostate tumours by triggering cellular senescence. Altogether, our findings describe a novel pro-tumorigenic network that links PTEN loss to ADAM17 and NOTCH signalling, thus providing the rational for the use of γ-secretase inhibitors in advanced prostate cancer patients. PMID:27941799

  2. Multimode guidance project low frequency ECM simulator: Hardware description

    NASA Astrophysics Data System (ADS)

    Kaye, H. M.

    1982-10-01

    The Multimode Guidance(MMG) Project, part of the Army/Navy Area Defense SAM Technology Prototyping Program, was established to conduct a feasibility demonstration of multimode guidance concepts. Prototype guidance units for advanced, long range missiles are being built and tested under MMG Project sponsorship. The Johns Hopkins University Applied Physics Laboratory has been designated as Government Agent for countermeasures for this project. In support of this effort, a family of computer-controlled ECM simulators is being developed for validation of contractor's multimode guidance prototype designs. The design of the Low Frequency ECM Simulator is documented in two volumes. This report, Volume A, describes the hardware design of the simulator; Volume B describes the software design. This computer-controlled simulator can simulate up to six surveillance frequency jammers in B through F bands and will be used to evaluate the performance of home-on-jamming guidance modes in multiple jammer environments.

  3. Gametophytic Pollen Tube Guidance: Attractant Peptides, Gametic Controls, and Receptors.

    PubMed

    Higashiyama, Tetsuya; Yang, Wei-Cai

    2017-01-01

    Pollen tube guidance in flowering plants is a unique and critical process for successful sexual reproduction. The pollen tube that grows from pollen, which is the male gametophyte, precisely navigates to the embryo sac, which is the female gametophyte, within the pistil. Recent advances have clarified the molecular framework of gametophytic pollen tube guidance. Multiple species-specific attractant peptides are secreted from synergid cells, the proper development and function of which are regulated by female gametes. Multiple receptor-like kinases on the pollen tube tip are involved in sensing species-specific attractant peptides. In this Update article, recent progress in our understanding of the mechanism of gametophytic pollen tube guidance is reviewed, including attraction by synergid cells, control of pollen tube guidance by female gametes, and directional growth of the pollen tube by directional cue sensing. Future directions in the study of pollen tube guidance also are discussed.

  4. Metformin Inhibits Advanced Glycation End Products-Induced Inflammatory Response in Murine Macrophages Partly through AMPK Activation and RAGE/NFκB Pathway Suppression

    PubMed Central

    Zhou, Zhong'e; Tang, Yong; Chen, Chengjun; Lu, Yi; Liu, Liang

    2016-01-01

    Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects. In conclusion, metformin inhibits AGEs-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFκB pathway suppression. PMID:27761470

  5. Metformin Inhibits Advanced Glycation End Products-Induced Inflammatory Response in Murine Macrophages Partly through AMPK Activation and RAGE/NFκB Pathway Suppression.

    PubMed

    Zhou, Zhong'e; Tang, Yong; Jin, Xian; Chen, Chengjun; Lu, Yi; Liu, Liang; Shen, Chengxing

    2016-01-01

    Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects. In conclusion, metformin inhibits AGEs-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFκB pathway suppression.

  6. Proteomic analysis reveals tanshinone IIA enhances apoptosis of advanced cervix carcinoma CaSki cells through mitochondria intrinsic and endoplasmic reticulum stress pathways.

    PubMed

    Pan, Tai-Long; Wang, Pei-Wen; Hung, Yu-Chiang; Huang, Chun-Hsun; Rau, Kun-Ming

    2013-12-01

    Cervix cancer is the second most common cancer among women worldwide, whereas paclitaxel, the first line chemotherapeutic drug used to treat cervical cancer, shows low chemosensitivity on the advanced cervical cancer cell line. Tanshinone IIA (Tan IIA) exhibited strong growth inhibitory effect on CaSki cells (IC50 = 5.51 μM) through promoting caspase cascades with concomitant upregulating the phosphorylation of p38 and JNK signaling. Comprehensive proteomics revealed the global protein changes and the network analysis implied that Tan IIA treatment would activate ER stress pathways that finally lead to apoptotic cell death. Moreover, ER stress inhibitor could alleviate Tan IIA caused cell growth inhibition and ameliorate C/EBP-homologous protein as well as apoptosis signal-regulating kinase 1 mediated cell death. The therapeutic interventions targeting the mitochondrial-related apoptosis and ER stress responses might be promising strategies to conquer paclitaxel resistance.

  7. Test Results for Entry Guidance Methods for Space Vehicles

    NASA Technical Reports Server (NTRS)

    Hanson, John M.; Jones, Robert E.

    2004-01-01

    There are a number of approaches to advanced guidance and control that have the potential for achieving the goals of significantly increasing reusable launch vehicle (or any space vehicle that enters an atmosphere) safety and reliability, and reducing the cost. This paper examines some approaches to entry guidance. An effort called Integration and Testing of Advanced Guidance and Control Technologies has recently completed a rigorous testing phase where these algorithms faced high-fidelity vehicle models and were required to perform a variety of representative tests. The algorithm developers spent substantial effort improving the algorithm performance in the testing. This paper lists the test cases used to demonstrate that the desired results are achieved, shows an automated test scoring method that greatly reduces the evaluation effort required, and displays results of the tests. Results show a significant improvement over previous guidance approaches. The two best-scoring algorithm approaches show roughly equivalent results and are ready to be applied to future vehicle concepts.

  8. Test Results for Entry Guidance Methods for Reusable Launch Vehicles

    NASA Technical Reports Server (NTRS)

    Hanson, John M.; Jones, Robert E.

    2003-01-01

    There are a number of approaches to advanced guidance and control (AG&C) that have the potential for achieving the goals of significantly increasing reusable launch vehicle (RLV) safety and reliability, and reducing the cost. This paper examines some approaches to entry guidance. An effort called Integration and Testing of Advanced Guidance and Control Technologies (ITAGCT) has recently completed a rigorous testing phase where these algorithms faced high-fidelity vehicle models and were required to perform a variety of representative tests. The algorithm developers spent substantial effort improving the algorithm performance in the testing. This paper lists the test cases used to demonstrate that the desired results are achieved, shows an automated test scoring method that greatly reduces the evaluation effort required, and displays results of the tests. Results show a significant improvement over previous guidance approaches. The two best-scoring algorithm approaches show roughly equivalent results and are ready to be applied to future reusable vehicle concepts.

  9. Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways

    PubMed Central

    Wu, Xu; Gu, Wenyu; Lu, Huan; Liu, Chengying; Yu, Biyun; Xu, Hui; Tang, Yaodong

    2016-01-01

    Obstructive sleep apnea (OSA) associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH) triggered tissue damage. Receptor for advanced glycation end product (RAGE) and its ligand high mobility group box 1 (HMGB1) are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE), the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1) normal air (NA), (2) CIH, (3) CIH+sRAGE, and (4) NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6), apoptotic (Bcl-2/Bax), and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK) signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways. PMID:27688824

  10. Suppression of antioxidant Nrf-2 and downstream pathway in H9c2 cells by advanced glycation end products (AGEs) via ERK phosphorylation.

    PubMed

    Ko, Shun-Yao; Chang, Shu-Shing; Lin, I-Hsuan; Chen, Hong-I

    2015-11-01

    Diabetic cardiomyopathy is related to oxidative stress and correlated with the presence of advanced glycation end products (AGEs). In a clinical setting, AGEs can be detected in patients presenting diabetic cardiomyopathy; however, the underlying mechanism has yet to be elucidated. In our previous study, AGEs increase cell hypertrophy via ERK phosphorylation in a process closely related to ROS production. Thus, we propose that AGEs regulate the antioxidant gene nuclear factor-erythroid 2-related factor (Nrf-2). In H9c2 cells treated with AGEs, the expression of Nrf-2 was reduced; however, ERK phosphorylation was shown to increase. Treatment with H2O2 was also shown to increase Nrf-2 and ERK phosphorylation. In cells pretreatment with ROS scavenger NAC, the effects of H2O2 were reduced; however, the effects of the AGEs remained largely unchanged. Conversely, when cells were pretreated with PD98059 (ERK inhibitor), the expression of Nrf-2 was recovered following treatment with AGEs. Our results suggest that AGEs inhibit Nrf-2 via the ERK pathway; however, this influence is partly associated with ROS. Our finding further indicated that AGEs possess both ROS-dependent and ROS-independent pathways, resulting in a reduction in Nrf-2. This report reveals an important mechanism underlying the regulation of diabetic cardiomyopathy progression by AGEs.

  11. Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus.

    PubMed

    Wald, Ori; Pappo, Orit; Safadi, Rifaat; Dagan-Berger, Michal; Beider, Katia; Wald, Hanna; Franitza, Suzanna; Weiss, Ido; Avniel, Shani; Boaz, Pal; Hanna, Jacob; Zamir, Gidi; Eid, Ahmed; Mandelboim, Ofer; Spengler, Ulrich; Galun, Eithan; Peled, Amnon

    2004-04-01

    Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is accompanied by inflammation and fibrosis eventually leading to cirrhosis. The chemokine CXCL12 is involved in chronic inflammatory conditions. The role of the CXCL12/CXCR4 pathway in HCV- and HBV-associated liver inflammation and fibrosis was therefore studied. The levels and tissue localization of CXCL12 in liver and plasma of HCV and HBV patients were tested using immunohistochemistry and ELISA. The expression and function of CXCR4 on liver-infiltrating lymphocytes (LIL) were tested by FACS and transwell migration assays. We found that CXCL12 is expressed by bile duct epithelial cells in normal liver tissue. Bile duct proliferation and liver fibrosis in chronic HCV and HBV infection result in the anatomical re-distribution of CXCL12 in the liver. Moreover, CXCL12 is up-regulated in the endothelium of neo-blood-vessels formed in active inflammatory foci and is significantly elevated, compared with controls, in the plasma of patients with advanced liver fibrosis. Complementing these observations were others indicating that over 50% of LIL express CXCR4 and, in response to CXCL12, migrated and adhered to fibronectin. These observations suggest an important role for the CXCL12/CXCR4 pathway in recruitment and retention of immune cells in the liver during chronic HCV and HBV infection.

  12. Vocational Guidance and Human Development.

    ERIC Educational Resources Information Center

    Herr, Edwin L., Ed.

    New knowledge and practices in the area of vocational guidance and human growth and development that have occurred since 1964 as well as future directions for guidance, both nationally and internationally, are covered in this second volume of a decennial volume series sponsored by the National Vocational Guidance Association to up-date the…

  13. When Instructional Guidance is Needed

    ERIC Educational Resources Information Center

    Chen, Ouhao; Kalyuga, Slava; Sweller, John

    2016-01-01

    Studying worked examples providing problem solutions to learners usually leads to better test performance than solving the equivalent problems without guidance, demonstrating the worked-example effect. The generation effect occurs when learners who generate answers without guidance learn better than those who read answers that provide guidance.…

  14. PLC/CAMK IV-NF-kappaB involved in the receptor for advanced glycation end products mediated signaling pathway in human endothelial cells.

    PubMed

    You, Jie; Peng, Wei; Lin, Xu; Huang, Qing-Ling; Lin, Jian-Yin

    2010-05-14

    Advanced glycation end products (AGEs) and their interaction with the receptor for advanced glycation end products (RAGE) play an important role in diabetic vascular complications. The current study demonstrated that AGEs significantly increased RAGE expression and the release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) in human umbilical vein endothelial cell-derived line ECV304 cells. RAGE antisense RNA partially inhibited the expression of TNF-alpha and IL-6 induced by AGEs. Oligonucleotide microarray was used to identify the genes that respond to RAGE activation. Phospholipase C beta 1 (PLC beta 1), phospholipase C beta 4 (PLC beta 4) and calcium/calmodulin-dependent protein kinase IV (CAMK IV) which associated with Ca(2+) signaling were upregulated. The rise of intracellular calcium and the NF-kappaB promoter activity induced by AGEs were suppressed by RAGE antisense RNA, PLC inhibitor U73122 and dominant negative CAMK IV, respectively. These findings suggest that PLC/CAMK IV-NF-kappaB is involved in RAGE mediated signaling pathway in human endothelial cells.

  15. Genetic variations in the transforming growth factor-beta pathway as predictors of survival in advanced non-small cell lung cancer

    PubMed Central

    Stewart, David J.; Spitz, Margaret R.; Hildebrandt, Michelle A.T.; Lu, Charles; Lin, Jie; Gu, Jian; Huang, Maosheng; Lippman, Scott M.; Wu, Xifeng

    2011-01-01

    The magnitude of benefit is variable for advanced non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy. The purpose of this study is to determine whether genetic variations in the transforming growth factor-beta (TGF-β) pathway are associated with clinical outcomes in NSCLC patients receiving first-line platinum-based chemotherapy. Five hundred and ninety-eight advanced-stage NSCLC patients who received first-line platinum-based chemotherapy with or without radiotherapy were recruited at the MD Anderson Cancer Center between 1995 and 2007. DNA from blood was genotyped for 227 single nucleotide polymorphisms (SNPs) in 23 TGF-β pathway-related genes to evaluate their associations with overall survival. In individual SNP analysis, 22 variants were significantly associated with overall survival, of which the strongest associations were found for BMP2:rs235756 [hazard ratio (HR) = 1.45; 95% confidence interval (CI), 1.11–1.90] and SMAD3:rs4776342 (HR = 1.25; 95% CI, 1.06–1.47). Fifteen and 18 genetic loci displayed treatment-specific associations for chemotherapy and chemoradiation, respectively, identifying a majority of the cases who would be predicted to respond favorably to a specific treatment regimen. BMP2:rs235753 and a haplotype in SMAD3 were associated with overall survival for both treatment modalities. Cumulative effect analysis showed that multiple risk genotypes had a significant dose-dependent effect on overall survival (Ptrend = 2.44 x 10−15). Survival tree analysis identified subgroups of patients with dramatically different median survival times of 45.39 versus 13.55 months and 18.02 versus 5.89 months for high- and low- risk populations when treated with chemoradiation and chemotherapy, respectively. These results suggest that genetic variations in the TGF-β pathway are potential predictors of overall survival in NSCLC patients treated with platinum-based chemotherapy with or without radiation. PMID:21515830

  16. Environmental guidance regulatory bulletin

    SciTech Connect

    1997-01-31

    This document describes the background on expanding public participation in the Resource Conservation and Recovery Act and DOE`s response. The bulletin also describes the changes made by the final rule to existing regulations, guidance provided by EPA in the preamble and in the revised RCRA Public Participation Manual, the relationship between public participation and environmental justice, and DOE`s recent public participation and environmental justice initiatives.

  17. The downregulation of thioredoxin accelerated Neuro2a cell apoptosis induced by advanced glycation end product via activating several pathways.

    PubMed

    Ren, Xiang; Ma, Haiying; Qiu, Yuanyuan; Liu, Bo; Qi, Hui; Li, Zeyu; Kong, Hui; Kong, Li

    2015-08-01

    Thioredoxin (Trx), a 12 kDa protein, has different functions in different cellular environments, playing important anti-oxidative and anti-apoptotic roles and regulating the expression of transcription factors. Advanced glycation end products (AGEs) are a heterogeneous group of irreversible adducts from glucose-protein condensation reactions and are considered crucial to the development of diabetic nephropathy, retinopathy, neurodegeneration and atherosclerosis. The aim of this study was to use a Trx inhibitor to investigate the effects and mechanism of Trx down-regulation on AGE-induced Neuro2a cell apoptosis. Neuro2a cells were cultured in vitro and treated with different conditions. The apoptosis and proliferation of Neuro2a cells were detected using flow cytometry, DNA-Ladder and CCK8 assays. Rho 123 was used to detect the mitochondrial membrane potential. ROS generation and caspase3 activity were detected using a DCFH-DA probe and micro-plate reader. Western blotting and real-time PCR were used to detect the expression of proteins and genes. We found that the down-regulation of thioredoxin could accelerate AGE-induced apoptosis in Neuro2a cells. A possible underlying mechanism is that the down-regulation of thioredoxin stimulated the up-regulation of ASK1, p-JNK, PTEN, and Txnip, as well as the down-regulation of p-AKT, ultimately increasing ROS levels and caspase3 activity.

  18. Precision Medicine Approach to Anaplastic Thyroid Cancer: Advances in Targeted Drug Therapy Based on Specific Signaling Pathways.

    PubMed

    Samimi, Hilda; Fallah, Parviz; Naderi Sohi, Alireza; Tavakoli, Rezvan; Naderi, Mahmood; Soleimani, Masoud; Larijani, Bagher; Haghpanah, Vahid

    2017-03-01

    Personalized medicine is a set of diagnostic, prognostic and therapeutic approaches in which medical interventions are carried out based on individual patient characteristics. As life expectancy increases in developed and developing countries, the incidence of diseases such as cancer goes up among people in the community. Cancer is a disease that the response to treatment varies from one person to another and also it is costly for individuals, families, and society. Among thyroid cancers, anaplastic thyroid carcinoma (ATC) is the most aggressive, lethal and unresponsive form of the disease. Unfortunately, current drugs are not targetable, and therefore they have restricted role in ATC treatment. Consequently, mortality of this cancer, despite advances in the field of diagnosis and treatment, is one of the most important challenges in medicine. Cellular, molecular and genetic evidences play an important role in finding more effective diagnostic and therapeutic approaches. Review of these evidences confirms the application of personalized medicine in cancer treatment including ATC. A growing body of evidence has elucidated that cellular and molecular mechanisms of cancer would pave the way for defining new biomarkers for targeted therapy, taking into account individual differences. It should be noted that this approach requires further progress in the fields of basic sciences, pharmacogenetics and drug design. An overview of the most important aspects in individualized anaplastic thyroid cancer treatment will be discussed in this review.

  19. 78 FR 56752 - Interim Staff Guidance Specific Environmental Guidance for Integral Pressurized Water Reactors...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-13

    ... COMMISSION Interim Staff Guidance Specific Environmental Guidance for Integral Pressurized Water Reactors Reviews AGENCY: Nuclear Regulatory Commission. ACTION: Draft Interim Staff Guidance; request for comment... comment on, draft Interim Staff Guidance (ISG) ESP/COL-ISG-027, ``Interim Staff Guidance...

  20. Shuttle ascent guidance and control.

    NASA Technical Reports Server (NTRS)

    Lovingood, J. A.; Blair, J. C.; Geissler, E. O.

    1972-01-01

    The requirements of a unified optimal guidance scheme are discussed, giving attention to a general formulation, aspects of self-targeting, problems of optimum guidance within the atmosphere, and a unified concept for all flight phases. Since no previous guidance scheme meets these requirements, the shuttle demands a fundamentally new approach. A new unified optimal guidance scheme, called Mascot, was developed. The capabilities of Mascot include the real-time solution of general trajectory-optimization problems and the unification of guidance for all flight phases.

  1. High-mobility group box 1 inhibits HCO3− absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway

    PubMed Central

    George, Thampi; Watts, Bruns A.

    2015-01-01

    High-mobility group box 1 (HMGB1) is a damage-associated molecule implicated in mediating kidney dysfunction in sepsis and sterile inflammatory disorders. HMGB1 is a nuclear protein released extracellularly in response to infection or injury, where it interacts with Toll-like receptor 4 (TLR4) and other receptors to mediate inflammation. Previously, we demonstrated that LPS inhibits HCO3- absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-ERK pathway (Watts BA III, George T, Sherwood ER, Good DW. Am J Physiol Cell Physiol 301: C1296–C1306, 2011). Here, we examined whether HMGB1 could inhibit HCO3- absorption through the same pathway. Adding HMGB1 to the bath decreased HCO3− absorption by 24% in isolated, perfused rat and mouse MTALs. In contrast to LPS, inhibition by HMGB1 was preserved in MTALs from TLR4−/− mice and was unaffected by ERK inhibitors. Inhibition by HMGB1 was eliminated by the receptor for advanced glycation end products (RAGE) antagonist FPS-ZM1 and by neutralizing anti-RAGE antibody. Confocal immunofluorescence showed expression of RAGE in the basolateral membrane domain. Inhibition of HCO3−absorption by HMGB1 through RAGE was additive to inhibition by LPS through TLR4 and to inhibition by Gram-positive bacterial molecules through TLR2. Bath amiloride, which selectively prevents inhibition of MTAL HCO3− absorption mediated through Na+/H+ exchanger 1 (NHE1), eliminated inhibition by HMGB1. We conclude that HMGB1 inhibits MTAL HCO3− absorption through a RAGE-dependent pathway distinct from TLR4-mediated inhibition by LPS. These studies provide new evidence that HMGB1-RAGE signaling acts directly to impair the transport function of renal tubules. They reveal a novel paradigm for sepsis-induced renal tubule dysfunction, whereby exogenous pathogen-associated molecules and endogenous damage-associated molecules act directly and independently to inhibit MTAL HCO3− absorption through different receptor

  2. A parallel genome-wide mRNA and microRNA profiling of the frontal cortex of HIV patients with and without HIV-associated dementia shows the role of axon guidance and downstream pathways in HIV-mediated neurodegeneration

    PubMed Central

    2012-01-01

    Background HIV-associated dementia (HAD) is the most common dementia type in young adults less than 40 years of age. Although the neurotoxins, oxidative/metabolic stress and impaired activity of neurotrophic factors are believed to be underlying reasons for the development of HAD, the genomic basis, which ultimately defines the virus-host interaction and leads to neurologic manifestation of HIV disease is lacking. Therefore, identifying HIV fingerprints on the host gene machinery and its regulation by microRNA holds a great promise and potential for improving our understanding of HAD pathogenesis, its diagnosis and therapy. Results A parallel profiling of mRNA and miRNA of the frontal cortex autopsies from HIV positive patients with and without dementia was performed using Illumina Human-6 BeadChip and Affymetrix version 1.0 miRNA array, respectively. The gene ontology and pathway analysis of the two data sets showed high concordance between miRNA and mRNAs, revealing significant interference with the host axon guidance and its downstream signalling pathways in HAD brains. Moreover, the differentially expressed (DE) miRNAs identified in this study, in particular miR-137, 153 and 218, based on which most correlations were built cumulatively targeted neurodegeneration related pathways, implying their future potential in diagnosis, prognosis and possible therapies for HIV-mediated and possibly other neurodegenerative diseases. Furthermore, this relationship between DE miRNAs and DE mRNAs was also reflected in correlation analysis using Bayesian networks by splitting-averaging strategy (SA-BNs), which revealed 195 statistically significant correlated miRNA-mRNA pairs according to Pearson’s correlation test (P<0.05). Conclusions Our study provides the first evidence on unambiguous support for intrinsic functional relationship between mRNA and miRNA in the context of HIV-mediated neurodegeneration, which shows that neurologic manifestation in HIV patients possibly

  3. Pathway Design Effects on Synthetic Vision Head-Up Displays

    NASA Technical Reports Server (NTRS)

    Kramer, Lynda J.; Prinzel, Lawrence J., III; Arthur, Jarvis J., III; Bailey, Randall E.

    2004-01-01

    NASA s Synthetic Vision Systems (SVS) project is developing technologies with practical applications that will eliminate low visibility conditions as a causal factor to civil aircraft accidents while replicating the operational benefits of clear day flight operations, regardless of the actual outside visibility condition. A major thrust of the SVS project involves the development/demonstration of affordable, certifiable display configurations that provide intuitive out-the-window terrain and obstacle information with advanced pathway guidance for transport aircraft. This experiment evaluated the influence of different tunnel and guidance concepts upon pilot situation awareness (SA), mental workload, and flight path tracking performance for Synthetic Vision display concepts using a Head-Up Display (HUD). Two tunnel formats (dynamic, minimal) were evaluated against a baseline condition (no tunnel) during simulated IMC approaches to Reno-Tahoe International airport. Two guidance cues (tadpole, follow-me aircraft) were also evaluated to assess their influence on the tunnel formats. Results indicated that the presence of a tunnel on an SVS HUD had no effect on flight path performance but that it did have significant effects on pilot SA and mental workload. The dynamic tunnel concept with the follow-me aircraft guidance symbol produced the lowest workload and provided the highest SA among the tunnel concepts evaluated.

  4. PSD Guidance Document

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  5. Hypervelocity Orbital Intercept Guidance

    DTIC Science & Technology

    1988-04-14

    Professor Charles E. Fosha, Jr. Terminal guidance of a hypervelocity exo-atmospheric orbital interceptor with free end-time is examined. The pursuer is...stochastic nonlinear systems with free end-time was developed by Tse and 29 Bar-Shalom [5]. This method differs from the optimal control formulation...Vol. AC-18, No. 2, April 1973, pp. 98-108. 5. Tse, E., and Y. Bar-Shalom, "Adaptive Dual Control For Stochastic Nonlinear Systems with Free End- Time

  6. PSD Increment Consumption Guidance

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  7. NSR Program Transitional Guidance

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  8. FasL expression in cardiomyocytes activates the ERK1/2 pathway, leading to dilated cardiomyopathy and advanced heart failure.

    PubMed

    Huby, Anne-Cecile; Turdi, Subat; James, Jeanne; Towbin, Jeffrey A; Purevjav, Enkhsaikhan

    2016-02-01

    Increase in the apoptotic molecule Fas ligand (FasL) in serum and cardiomyocytes has been shown to be associated with progressive dilated cardiomyopathy (DCM) and congestive heart failure (CHF) in humans. However, the underlying mechanism(s) of FasL-related deterioration of heart function remain obscure. The aim of the present study is to determine roles of myocardial FasL in the activation of alternative pathways such as extracellular-signal-regulated kinase 1/2 (ERK1/2), inflammation or fibrosis and to identify effective treatments of progressive DCM and advanced CHF. Transgenic mice with cardiomyocyte-specific overexpression of FasL were investigated and treated with an ERK1/2 inhibitor (U-0126), losartan (los), prednisolone (pred) or placebo. Morpho-histological and molecular studies were subsequently performed. FasL mice showed significantly higher mortality compared with wild-type (WT) littermates due to DCM and advanced CHF. Prominent perivascular and interstitial fibrosis, increased interleukin secretion and diffuse CD3-positive cell infiltration were evident in FasL hearts. Up-regulation of the short form of Fas-associated death domain (FADD)-like interleukin 1β-converting enzyme (FLICE) inhibitory protein (s-FLIP), RIP (receptor-interacting protein) and ERK1/2 and down-regulation of transforming growth factor beta 1 (TGFβ1) and nuclear factor-κB (NF-κB) was determined in the myocardium, whereas expression of ERK1/2, periostin (Postn) and osteopontin increased in cardiac fibroblasts. U-0126 and los increased CHF survival by 75% compared with pred and placebo groups. U-0126 had both anti-fibrotic and anti-apoptotic effects, whereas los reduced fibrosis only. Myocardial FasL expression in mice activates differential robust fibrotic, apoptotic and inflammatory responses via ERK1/2 in cardiomyocytes and cardiac fibroblasts inducing DCM and CHF. Blocking the ERK1/2 pathway prevented progression of FasL-induced DCM and CHF by reducing fibrosis, inflammation

  9. Advanced-glycation-end-product-cholesterol-aggregated-protein accelerates the proliferation of mesangial cells mediated by transforming-growth-factor-beta 1 receptors and the ERK-MAPK pathway.

    PubMed

    Hirasawa, Yasushi; Sakai, Takayuki; Ito, Masanori; Yoshimura, Hiromitsu; Feng, Yibin; Nagamatsu, Tadashi

    2011-12-15

    Hyperglycemia and hyperlipidemia are considered critical to the development of diabetic nephropathy. The aim of this study is to clarify the effect of cholesterol on advanced-glycation-end-products and the mechanisms behind the advanced-glycation-end-product-cholesterol-aggregated bovine serum albumin (BSA)-induced proliferation of mesangial cells. Mesangial cells were treated with advanced-glycation-end-product-cholesterol-aggregated-BSA, and RNA and protein were isolated. Cholesterol caused a 1.5-fold increase in fluorescent intensity and 2-fold increase in advanced-glycation-end-products in vitro. Pyridoxamine, aminoguanidine, and N-acetyl-l-cycteine suppressed the production of advanced-glycation-end-product-cholesterol-aggregated-BSA. Advanced-glycation-end-product-cholesterol-BSA was analyzed by matrix-assisted-laser-desorption/ionization-time of flight mass spectrometry, and peaks were found to shift toward a higher mass. Advanced-glycation-end-product-cholesterol-aggregated-BSA induced overexpression of the mRNA of transforming growth factor-beta1, collagen type 1, collagen type 4 and receptor for advanced-glycation-end-products, and the proliferation of mesangial cells. The injection of advanced-glycation-end-product-cholesterol-aggregated-BSA caused glomerular changes and albuminuria in non-diabetic mice. A transforming-growth-factor-beta receptor 1 kinase inhibitor or Mitogen-activated-Protein-Kinase/Extracellular-Signal-regulated-Kinase kinase (ERK) inhibitor (U-0126) suppressed the proliferation of mesangial cells induced by advanced-glycation-end-product-cholesterol-aggregated-BSA dose-dependently. U-0126 inhibited the phosphorylation of ERK1/2 in advanced-glycation-end-product-cholesterol-aggregated-BSA treated mesangial cells. These findings suggested that cholesterol promotes the formation of advanced-glycation-end-products-protein and that advanced-glycation-end-product-cholesterol-aggregated protein stimulates mesangial cells to proliferate via

  10. Taken out of Context: Piecing Together College Guidance Information in Urban High Schools

    ERIC Educational Resources Information Center

    Shamsuddin, Shomon

    2016-01-01

    Information and guidance about college is critical for students to pursue postsecondary education. However, students attending urban schools often have less information and less access to information about college pathways than their peers at wealthy suburban schools. High school counselors are a primary source of college guidance but little is…

  11. A Further Look at X-33 Entry Guidance and Beyond

    NASA Technical Reports Server (NTRS)

    Lu, Ping

    1999-01-01

    An entry guidance design developed at Iowa State University (ISU) for the X-33 advanced technology demonstrator is outlined and compared with the X-33 entry guidance algorithms developed at NASA Marshall. Both designs are based on the Space Shuttle entry guidance concept, but significant improvements have been made to enhance the performance and reduce the complexity. The ISU design was incorporated into MAVERIC, a high fidelity vehicle simulation software for the X-33, and evaluated in Monte Carlo simulations against random dispersions in propulsion system, wind and atmospheric properties, aerodynamic coefficients, interaction between propulsion and aerodynamics, and navigation data. The simulations clearly demonstrated the capability and precision of the ISU entry guidance design in successfully guiding the X-33 in some rather difficult flight scenarios. As the entry guidance development for the X-33 is completing, this report also offers some review of the strength and limitations of the current Shuttle-based entry guidance framework, and finally some potential candidates for next generation of more capable and cost-effective entry guidance designs are discussed.

  12. Effect of PKC-β Signaling Pathway on Expression of MCP-1 and VCAM-1 in Different Cell Models in Response to Advanced Glycation End Products (AGEs).

    PubMed

    Rempel, Lisienny C T; Finco, Alessandra B; Maciel, Rayana A P; Bosquetti, Bruna; Alvarenga, Larissa M; Souza, Wesley M; Pecoits-Filho, Roberto; Stinghen, Andréa E M

    2015-05-14

    Advanced glycation end products (AGEs) are compounds classified as uremic toxins in patients with chronic kidney disease that have several pro-inflammatory effects and are implicated in the development of cardiovascular diseases. To explore the mechanisms of AGEs-endothelium interactions through the receptor for AGEs (RAGE) in the PKC-β pathway, we evaluated the production of MCP-1 and VCAM-1 in human endothelial cells (HUVECs), monocytes, and a coculture of both. AGEs were prepared by albumin glycation and characterized by absorbance and electrophoresis. The effect of AGEs on cell viability was assessed with an MTT assay. The cells were also treated with AGEs with and without a PKC-β inhibitor. MCP-1 and VCAM-1 in the cell supernatants were estimated by ELISA, and RAGE was evaluated by immunocytochemistry. AGEs exposure did not affect cell viability, but AGEs induced RAGE, MCP-1, and VCAM-1 expression in HUVECs. When HUVECs or monocytes were incubated with AGEs and a PKC-β inhibitor, MCP-1 and VCAM-1 expression significantly decreased. However, in the coculture, exposure to AGEs and a PKC-β inhibitor produced no significant effect. This study demonstrates, in vitro, the regulatory mechanisms involved in MCP-1 production in three cellular models and VCAM-1 production in HUVECs, and thus mimics the endothelial dysfunction caused by AGEs in early atherosclerosis. Such mechanisms could serve as therapeutic targets to reduce the harmful effects of AGEs in patients with chronic kidney disease.

  13. Green tea epigallocatechin 3-gallate alleviates hyperglycemia and reduces advanced glycation end products via nrf2 pathway in mice with high fat diet-induced obesity.

    PubMed

    Sampath, Chethan; Rashid, Muhammed Raihan; Sang, Shengmin; Ahmedna, Mohamed

    2017-03-01

    Epigallocatechin 3-gallate (EGCG) from green tea may reduce plasma glucose and alleviate complications of diabetes by attenuating advanced glycation end products (AGEs) formation. We hypothesized that EGCG would mitigate AGEs formation via activating the nuclear factor erythroid-2-related-factor-2 (Nrf2) pathway in a mouse model of high fat diet-induced obesity. Dietary EGCG was tested in C57BL/6 mice that were placed on a high-fat diet with or without ECGC for 17 weeks and compared to a control group placed on low-fat diet for the same period. Weight gain and fasting blood glucose were measured throughout the study duration. Supplementation of high fat diet with dietary EGCG significantly reduced weight gain, plasma glucose, insulin level, liver and kidney weight. EGCG administration also decreased the levels of AGEs in both plasma and liver while inhibiting the receptor for AGE (RAGE) expression of, activating Nrf2 and enhancing GSH/GSSG ratio compared to mice on high fat diet without added EGCG. This study demonstrated that EGCG has the potential to help control hyperglycemia, reduce weight, and alleviate diabetes complications.

  14. Advanced glycation end products interfere with gastric smooth muscle contractile marker expression via the AGE/RAGE/NF-κB pathway.

    PubMed

    Yu, Ting; Zheng, Yongping; Wang, Yun; Xiong, Wenjie; Lin, Lin

    2017-02-01

    Excessive production of advanced glycation end products (AGE) has been implicated in the pathogenesis of diabetic complications. Smooth muscle (SM) phenotype transition is involved in diabetes-associated gastric motility dysfunction. We investigated whether AGE interfere with gastric antral SM contractile marker expression. Sixteen Sprague-Dawley rats were randomly divided into control and streptozotocin-induced diabetic groups. Sixteen weeks after streptozotocin administration, gastric antral SM strip contractility in the groups were measured. The gastric tissue expression of AGE was tested. Primary cultured gastric smooth muscle cells (SMCs) were used in complementary in vitro studies. In the presence and absence of AGE, SMCs were transfected with myocardin plasmid or treated with nuclear factor-κB (NF-κB) inhibitor or anti-RAGE antibody. Diabetic rats showed weakness of SM strip contractility and decreased expression of SM contractile marker genes (myosin heavy chains [MHC], α-actin, calponin) as compared with the control group. Gastric antral SM layer Nε-(carboxymethyl) lysine (CML) level, the major AGE compound, were increased in the diabetic rats. AGE downregulated SM contractile markers and myocardin expression in a concentration-dependent manner. Myocardin overexpression prevented these results. AGE treatment activated NF-κB in SMCs. The NF-κB inhibitor BAY 11-7082 and anti-RAGE antibody blocked the effects of AGE on myocardin downregulation. AGE may induce the development of gastric dysmotility by downregulating SM contractile proteins and myocardin expression via the AGE/RAGE/NF-κB pathway.

  15. GUIDANCE FOR EVALUATING LANDFILL GAS EMISSIONS FROM CLOSED OR ABANDONED FACILITIES

    EPA Science Inventory

    This document provides guidance to Superfund remedial project managers, on scene coordinators, facility owners, and potentially responsible parties for conducting an air pathway analysis for landfill gas (LFG) emissions under the Comprehensive Environmental Response, Compensation...

  16. Comprehensive Career Guidance. Career Guidance Curriculum. Staff Development K-6.

    ERIC Educational Resources Information Center

    Straub, Vicki W.; Moore, Earl J.

    One of six staff development training manuals for career guidance infusion in the elementary school curriculum (K-6), this manual focuses on the curriculum design of a comprehensive career guidance program. It is divided into the following five major sections: (1) a list of the major goals and activities covered in the manual; (2) an overview…

  17. Endangerment assessment guidance

    SciTech Connect

    Not Available

    1985-11-22

    The directive clarifies the requirement that an endangerment assessment be developed to support all administrative and judicial enforcement actions under Section 106 of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) and Section 7003 of the Resource Conservation and Recovery Act (RCRA). Before taking enforcement action under these provisions to abate the hazards or potential hazards at a site, the Environmental Protection Agency (EPA) must be able to properly document and justify its assertion that an imminent and substantial endangerment to public health or welfare or the environment may exist. The endangerment assessment provides this documentation and justification. The endangerment assessment is not necessary to support Section 104 actions. It also provides guidance on the content, timing, level of detail, format, and resources required for the preparation of endangerment assessments.

  18. Pathways Advancing Career Training Act

    THOMAS, 111th Congress

    Rep. DeLauro, Rosa L. [D-CT-3

    2009-04-23

    06/04/2009 Referred to the Subcommittee on Higher Education, Lifelong Learning, and Competitiveness. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  19. Guidance for the New Millenium?

    ERIC Educational Resources Information Center

    McLaren, David J.

    1996-01-01

    Reviews the "Guidance Arrangements" consultation document issued with "Higher Still" (proposed new Scottish upper secondary curricula). Argues that the paper ignores the full implications for educational change in Higher Still and misses the opportunity for timely modernization of school guidance. Advocates a cross-curricular…

  20. Guidance in the Secondary School

    ERIC Educational Resources Information Center

    Kumar, V. Jurist Lional

    2010-01-01

    Secondary School Students face a lot of problems in their body as well as in mind due to puberty that tends to adolescence stage. Adolescence has peculiar characters of their own. They need proper Guidance and Counselling to tackle their own problems. Guidance is described as a counselling service to assist the individual in achieving self…

  1. Restructuring Guidance and Counseling Programs.

    ERIC Educational Resources Information Center

    Snyder, Beverly A.; Daly, Timothy P.

    1993-01-01

    Briefly reviews counseling profession's call for revitalization and transformation in school counseling and guidance programs. Summarizes one school system's efforts during late 1980s and early 1990s to transform its program from services and crisis orientation into a comprehensive developmental model based on Myrick's developmental guidance and…

  2. Guidance Services in Spanish Universities

    ERIC Educational Resources Information Center

    Vidal, Javier; Diez, Gloria; Vieira, Maria J.

    2003-01-01

    Since the 80s, higher education in Spain has undergone important modifications such as greater autonomy, expansion in the number of students and the introduction of more flexible programmes. In this context, guidance services have proliferated in an unstructured way. This paper presents a description of guidance services in Spanish universities…

  3. Final OSWER Vapor Intrusion Guidance

    EPA Science Inventory

    EPA is preparing to finalize its guidance on assessing and addressing vapor intrusion, which is defined as migration of volatile constituents from contaminated media in the subsurface (soil or groundwater) into the indoor environment. In November 2002, EPA issued draft guidance o...

  4. Marxist Guidance: A Dialectic Lesson

    ERIC Educational Resources Information Center

    Drapela, Victor J.

    1971-01-01

    Based on primary sources published in the Soviet Bloc, this article compares the stated goals of Marxist guidance with actual outcomes, and identifies the foundations of guidance in the Soviet Bloc in terms of Marxist philosophy and social doctrine. Current symptoms of ideological unrest in socialist society as exemplified by the suppressed reform…

  5. GUIDANCE AWARENESS IN ELEMENTARY EDUCATION.

    ERIC Educational Resources Information Center

    MOREAU, GEORGE H., ED.

    THE PURPOSE OF THE WORKSHOP IN ELEMENTARY SCHOOL GUIDANCE WAS TWOFOLD--(1) TO SHOW HOW GUIDANCE PROCEDURES AND TECHNIQUES CENTER ABOUT AND INVOLVE THE CHILD AS HE ADAPTS TO A NEW TYPE OF SCHOOL SETTING AND LEARNING PROCESS, AND (2) TO CREATE AN AWARENESS OF THE NEED FOR ALL AREAS OF COUNSELING AT THE ELEMENTARY SCHOOL LEVEL. OF THE ELEVEN PAPERS…

  6. Automated Guidance for Student Inquiry

    ERIC Educational Resources Information Center

    Gerard, Libby F.; Ryoo, Kihyun; McElhaney, Kevin W.; Liu, Ou Lydia; Rafferty, Anna N.; Linn, Marcia C.

    2016-01-01

    In 4 classroom experiments we investigated uses for technologies that automatically score student generated essays, concept diagrams, and drawings in inquiry curricula. We used the automatic scores to assign typical and research-based guidance and studied the impact of the guidance on student progress. Seven teachers and their 897 students…

  7. Discussing Diverse Perspectives on Guidance

    ERIC Educational Resources Information Center

    Gonzalez-Mena, Janet; Shareef, Intisar

    2005-01-01

    Ideas about discipline and guidance get extremely complex when they intersect with culture and oppression. Some groups of people who are targets of racism have to protect their children from the oppressive practices of racist individuals and institutions. Their methods of guidance and discipline may be different from those of groups for whom…

  8. Analysis of the coexisting pathways for NO and N2O formation in Chernozem using the (15)N-tracer SimKIM-Advanced model.

    PubMed

    Stange, Claus Florian; Spott, Oliver; Russow, Rolf

    2013-01-01

    The nitrogen (N) cycle consists of a variety of microbial processes. These processes often occur simultaneously in soils, but respond differently to local environmental conditions due to process-specific biochemical restrictions (e.g. oxygen levels). Hence, soil nitrogen cycling (e.g. soil N gas production through nitrification and denitrification) is individually affected through these processes, resulting in the complex and highly dynamic behaviour of total soil N turnover. The development and application of methods that facilitate the quantification of individual contributions of coexisting processes is a fundamental prerequisite for (i) understanding the dynamics of soil N turnover and (ii) implementing these processes in ecosystem models. To explain the unexpected results of the triplet tracer experiment (TTE) of Russow et al. (Role of nitrite and nitric oxide in the processes of nitrification and denitrification in soil: results from (15)N tracer experiments. Soil Biol Biochem. 2009;41:785-795) the existing SimKIM model was extended to the SimKIM-Advanced model through the addition of three separate nitrite subpools associated with ammonia oxidation, oxidation of organic nitrogen (Norg), and denitrification, respectively. For the TTE, individual treatments with (15)N ammonium, (15)N nitrate, and (15)N nitrite were conducted under oxic, hypoxic, and anoxic conditions, respectively, to clarify the role of nitric oxide as a denitrification intermediate during N2O formation. Using a split nitrite pool, this analysis model explains the observed differences in the (15)N enrichments in nitric oxide (NO) and nitrous oxide (N2O) which occurred in dependence on different oxygen concentrations. The change from oxic over hypoxic to anoxic conditions only marginally increased the NO and N2O release rates (1.3-fold). The analysis using the model revealed that, under oxic and hypoxic conditions, Norg-based N2O production was the dominant pathway, contributing to 90 and 50

  9. 21 CFR 7.59 - General industry guidance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false General industry guidance. 7.59 Section 7.59 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENFORCEMENT..., but there are several steps a prudent firm can take in advance to minimize this disruptive...

  10. 21 CFR 7.59 - General industry guidance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false General industry guidance. 7.59 Section 7.59 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENFORCEMENT..., but there are several steps a prudent firm can take in advance to minimize this disruptive...

  11. The Consequences of Fading Instructional Guidance on Delayed Performance: The Case of Financial Services Training

    ERIC Educational Resources Information Center

    Kissane, Mark; Kalyuga, Slava; Chandler, Paul; Sweller, John

    2008-01-01

    Empirical studies within a cognitive load framework have determined that for novice learners, worked examples provide appropriate levels of instructional guidance. As learners advance in specific subject domains, worked examples should be gradually replaced by practice problems with limited guidance. This study compared performance, both…

  12. Advanced glycation end-products induce skeletal muscle atrophy and dysfunction in diabetic mice via a RAGE-mediated, AMPK-down-regulated, Akt pathway.

    PubMed

    Chiu, Chen-Yuan; Yang, Rong-Sen; Sheu, Meei-Ling; Chan, Ding-Cheng; Yang, Ting-Hua; Tsai, Keh-Sung; Chiang, Chih-Kang; Liu, Shing-Hwa

    2016-02-01

    Diabetic myopathy, a less studied complication of diabetes, exhibits the clinical observations characterized by a less muscle mass, muscle weakness and a reduced physical functional capacity. Accumulation of advanced glycation end-products (AGEs), known to play a role in diabetic complications, has been identified in ageing human skeletal muscles. However, the role of AGEs in diabetic myopathy remains unclear. Here, we investigated the effects of AGEs on myogenic differentiation and muscle atrophy in vivo and in vitro. We also evaluated the therapeutic potential of alagebrium chloride (Ala-Cl), an inhibitor of AGEs. Muscle fibre atrophy and immunoreactivity for AGEs, Atrogin-1 (a muscle atrophy marker) and phosphorylated AMP-activated protein kinase (AMPK) expressions were markedly increased in human skeletal muscles from patients with diabetes as compared with control subjects. Moreover, in diabetic mice we found increased blood AGEs, less muscle mass, lower muscular endurance, atrophic muscle size and poor regenerative capacity, and increased levels of muscle AGE and receptor for AGE (RAGE), Atrogin-1 and phosphorylated AMPK, which could be significantly ameliorated by Ala-Cl. Furthermore, in vitro, AGEs (in a dose-dependent manner) reduced myotube diameters (myotube atrophy) and induced Atrogin-1 protein expression in myotubes differentiated from both mouse myoblasts and primary human skeletal muscle-derived progenitor cells. AGEs exerted a negative regulation of myogenesis of mouse and human myoblasts. Ala-Cl significantly inhibited the effects of AGEs on myotube atrophy and myogenesis. We further demonstrated that AGEs induced muscle atrophy/myogenesis impairment via a RAGE-mediated AMPK-down-regulation of the Akt signalling pathway. Our findings support that AGEs play an important role in diabetic myopathy, and that an inhibitor of AGEs may offer a therapeutic strategy for managing the dysfunction of muscle due to diabetes or ageing.

  13. Receptor for advanced glycation end product blockade enhances the chemotherapeutic effect of cisplatin in tongue squamous cell carcinoma by reducing autophagy and modulating the Wnt pathway.

    PubMed

    Zhao, Ziming; Wang, Hongyu; Zhang, Liao; Mei, Xifan; Hu, Jing; Huang, Keqiang

    2017-02-01

    Tongue squamous cell carcinoma (TSCC) is one of the most severe types of cancer with poor outcomes. Cisplatin is used widely to treat cancer cells, but many patients develop acquired drug resistance. The receptor for advanced glycation end products (RAGE) is expressed widely in TSCC and associated with drug-induced chemotherapy resistance. However, the effect of RAGE and cisplatin on Tca-8113 cells remains unknown. We assayed the combined use of RAGE blockade and cisplatin effect on Tca-8113 cells' viability by MTT and apoptosis rate of Tca-8113 cells on RAGE blockade+cisplatin treatment; cisplatin alone; or RAGE blockade alone by flow cytometry. We observed the expressions of autophagy-related proteins beclin1, LC3II, p62; Wnt signaling-related proteins β-catenin, GSK3β, WNT5A, ROR-2; and apoptosis-related protein cleaved caspase-3, bcl-2-associated X proteins using western blot. We determined WNT5A and beclin1 expression on Tca-8113 cells by immunofluorescence. We further observed autophagy vacuoles by monodansylcadaverine staining. We found that RAGE blockade and cisplatin significantly decreased cell viability and increased the cell apoptosis rate compared with cisplatin alone. Furthermore, RAGE blockade suppressed the canonical Wnt pathway proteins β-catenin and GSK-3β, but upregulated noncanonical WNT5A and receptor ROR-2. We show that RAGE blockade suppressed the levels of autophagy-related protein LC3II/I, beclin1, accelerated degradation of autophagy for the increasing p62 expression, and increased cell apoptosis for the increasing expressions of cleaved caspase-3 and bcl-2-associated X proteins. We observed the location of WNT5A and beclin1 expressions on cells by immunofluorescence and their trends were consistent with western blotting. Taken together, our findings suggested that RAGE blockade+cisplatin improved chemotherapeutic effects by reducing autophagy and regulating Wnt/β-catenin to suppress the progression of TSCC.

  14. RH Packaging Program Guidance

    SciTech Connect

    Washington TRU Solutions LLC

    2008-01-12

    The purpose of this program guidance document is to provide the technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package (also known as the "RH-TRU 72-B cask") and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the C of C shall govern. The C of C states: "...each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application." It further states: "...each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application." Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M&O) Contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations (CFR) §71.8, "Deliberate Misconduct." Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the U.S. Department of Energy (DOE) Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required.In accordance with 10 CFR Part 71, "Packaging and Transportation of Radioactive Material," certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21, "Reporting of Defects and Noncompliance," regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a

  15. Cask system design guidance for robotic handling

    SciTech Connect

    Griesmeyer, J.M.; Drotning, W.D.; Morimoto, A.K.; Bennett, P.C.

    1990-10-01

    Remote automated cask handling has the potential to reduce both the occupational exposure and the time required to process a nuclear waste transport cask at a handling facility. The ongoing Advanced Handling Technologies Project (AHTP) at Sandia National Laboratories is described. AHTP was initiated to explore the use of advanced robotic systems to perform cask handling operations at handling facilities for radioactive waste, and to provide guidance to cask designers regarding the impact of robotic handling on cask design. The proof-of-concept robotic systems developed in AHTP are intended to extrapolate from currently available commercial systems to the systems that will be available by the time that a repository would be open for operation. The project investigates those cask handling operations that would be performed at a nuclear waste repository facility during cask receiving and handling. The ongoing AHTP indicates that design guidance, rather than design specification, is appropriate, since the requirements for robotic handling do not place severe restrictions on cask design but rather focus on attention to detail and design for limited dexterity. The cask system design features that facilitate robotic handling operations are discussed, and results obtained from AHTP design and operation experience are summarized. The application of these design considerations is illustrated by discussion of the robot systems and their operation on cask feature mock-ups used in the AHTP project. 11 refs., 11 figs.

  16. Pandemic influenza guidance for corporations.

    PubMed

    2011-06-01

    The purpose of this guidance document is to assist members of the American College of Occupational and Environmental Medicine (ACOEM), and the organizations for which they work, in managing the impact of a pandemic of influenza or other contagious respiratory disease on patients, employees, and business. This guidance document outlines actions to take before and during an influenza pandemic on the basis of two main strategies: (1) reducing the spread of the virus within facilities; and (2) providing medical care and medical surveillance to client/patient populations. Facilities in which ACOEM members serve include government agencies and the military, universities, and corporations, which generally have multiple locations/sites and their own medical staff, with members responsible for medical care and disease control. This guidance is for organizations with outpatient occupational medicine services, to be used as appropriate. Medical centers should also use guidance that addresses additional employee and external patient care needs.1–3 The ACOEM fully supports implementation of occupational influenza programs that conform with guidance from the Centers for Disease Control and Prevention (CDC), with other guidance from the US Department of Health and Human Services (DHHS), and Occupational Safety and Health Administration (OSHA) regulations and guidance.

  17. General RMP Guidance - Appendix D: OSHA Guidance on PSM

    EPA Pesticide Factsheets

    OSHA's Process Safety Management (PSM) Guidance on providing complete and accurate written information concerning process chemicals, process technology, and process equipment; including process hazard analysis and material safety data sheets.

  18. Uprated fine guidance sensor study

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Future orbital observatories will require star trackers of extremely high precision. These sensors must maintain high pointing accuracy and pointing stability simultaneously with a low light level signal from a guide star. To establish the fine guidance sensing requirements and to evaluate candidate fine guidance sensing concepts, the Space Telescope Optical Telescope Assembly was used as the reference optical system. The requirements review was separated into three areas: Optical Telescope Assembly (OTA), Fine Guidance Sensing and astrometry. The results show that the detectors should be installed directly onto the focal surface presented by the optics. This would maximize throughput and minimize point stability error by not incoporating any additional optical elements.

  19. Ascent Guidance for a Winged Boost Vehicle. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Corvin, Michael Alexander

    1988-01-01

    The objective of the advanced ascent guidance study was to investigate guidance concepts which could contribute to increased autonomy during ascent operations in a winged boost vehicle such as the proposed Shuttle II. The guidance scheme was required to yield near a full-optimal ascent in the presence of vehicle system and environmental dispersions. The study included consideration of trajectory shaping issues, trajectory design, closed loop and predictive adaptive guidance techniques and control of dynamic pressure by throttling. An extensive ascent vehicle simulation capability was developed for use in the study.

  20. Safety assessment guidance in the International Atomic Energy Agency RADWASS Program

    SciTech Connect

    Vovk, I.F.; Seitz, R.R.

    1995-12-31

    The IAEA RADWASS programme is aimed at establishing a coherent and comprehensive set of principles and standards for the safe management of waste and formulating the guidelines necessary for their application. A large portion of this programme has been devoted to safety assessments for various waste management activities. Five Safety Guides are planned to be developed to provide general guidance to enable operators and regulators to develop necessary framework for safety assessment process in accordance with international recommendations. They cover predisposal, near surface disposal, geological disposal, uranium/thorium mining and milling waste, and decommissioning and environmental restoration. The Guide on safety assessment for near surface disposal is at the most advanced stage of preparation. This draft Safety Guide contains guidance on description of the disposal system, development of a conceptual model, identification and description of relevant scenarios and pathways, consequence analysis, presentation of results and confidence building. The set of RADWASS publications is currently undergoing in-depth review to ensure a harmonized approach throughout the Safety Series.

  1. Guidance signalling regulates leading edge behaviour during collective cell migration of cardiac cells in Drosophila.

    PubMed

    Raza, Qanber; Jacobs, J Roger

    2016-11-15

    Collective cell migration is the coordinated movement of cells, which organize tissues during morphogenesis, repair and some cancers. The motile cell membrane of the advancing front in collective cell migration is termed the Leading Edge. The embryonic development of the vertebrate and Drosophila hearts are both characterized by the coordinated medial migration of a bilateral cluster of mesodermal cells. In Drosophila, the cardioblasts form cohesive bilateral rows that migrate collectively as a unit towards the dorsal midline to form the dorsal vessel. We have characterized the collective cell migration of cardioblasts as an in vivo quantitative model to study the behaviour of the Leading Edge. We investigated whether guidance signalling through Slit and Netrin pathways plays a role in cell migration during heart development. Through time-lapse imaging and quantitative assessment of migratory behaviour of the cardioblasts in loss-of-function mutants, we demonstrate that both Slit and Netrin mediated signals are autonomously and concomitantly required to maximize migration velocity, filopodial and lamellipodial activities. Additionally, we show that another Slit and Netrin receptor, Dscam1, the role of which during heart development was previously unknown, is required for both normal migration of cardioblasts and luminal expansion. Leading edge behaviour analysis revealed a dosage dependent genetic interaction between Slit and Netrin receptors suggesting that downstream signalling through these receptors converge on a common output that increases leading edge activity of the cardioblasts. Finally, we found that guidance signalling maintains the balance between epithelial and mesenchymal characteristics of the migrating cardioblasts.

  2. RH Packaging Program Guidance

    SciTech Connect

    Washington TRU Solutions, LLC

    2003-08-25

    The purpose of this program guidance document is to provide technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the SARP and/or C of C shall govern. The C of C states: ''...each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, ''Operating Procedures,'' of the application.'' It further states: ''...each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, ''Acceptance Tests and Maintenance Program of the Application.'' Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M&O) contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC approved, users need to be familiar with 10 CFR {section} 71.11, ''Deliberate Misconduct.'' Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the Carlsbad Field Office (CBFO) shall be notified immediately. CBFO will evaluate the issue and notify the NRC if required. This document details the instructions to be followed to operate, maintain, and test the RH-TRU 72-B packaging. This Program Guidance standardizes instructions for all users. Users shall follow these instructions. Following these instructions assures that operations are safe and meet the requirements of the SARP. This document is available on the Internet at: ttp://www.ws/library/t2omi/t2omi.htm. Users are responsible for ensuring they are using the current revision and change notices. Sites may prepare their own document using the word

  3. SPLC Sustainable Purchasing Guidance Profile

    EPA Pesticide Factsheets

    To help you find the resource that is right for your organization, EPA conducted a scan of the landscape and developed summary profiles of some of the leading sources of sustainable purchasing guidance around the globe.

  4. Guidance Documents for Marine Fuel

    EPA Pesticide Factsheets

    The following guidance documents apply to marine fuel used in ocean-going vessels. All vessels that operate in the North American Emission Control Area (ECA) must generally use fuel with 1,000 ppm sulfur or less.

  5. Chesapeake Bay Program Grant Guidance

    EPA Pesticide Factsheets

    Grant Guidance and appendices for the Chesapeake Bay Program that describes how the U.S. Environmental Protection Agency’s (EPA) Region 3’s Chesapeake Bay Program Office (CBPO) administers grant and cooperative agreement funds.

  6. Inert Ingredients Overview and Guidance

    EPA Pesticide Factsheets

    This Web page provides information on inert ingredients approved for use in pesticide products and the guidance documents that are available to assist in obtaining approval for a new inert ingredient.

  7. Enforcement Response Policies and Guidance

    EPA Pesticide Factsheets

    EPA's Enforcement Response Policies relating to violations or noncompliance with the environmental statutes and regulations. The listing is not inclusive of all policy and guidance that may be relied upon in developing enforcement actions.

  8. BASINS User Information and Guidance

    EPA Pesticide Factsheets

    This page provides links to guidance on how to use BASINS, including the User’s Manual, tutorials and training, technical notes, case studies, and publications that highlight the use of BASINS in various watershed analyses.

  9. In Respect to the Cognitive Load Theory: Adjusting Instructional Guidance with Student Expertise.

    PubMed

    Schilling, Jim

    2017-01-01

    The amount of guidance supplied by educators to students in allied health programs is a factor in student learning. According to the cognitive load theory of learning, without adequate instructional support, novice learners will be overwhelmed and unable to store information, while unnecessary guidance supplied to advanced students will cause extraneous cognitive load on the working memory system. Adjusting instructional guidance for students according to their level of expertise to minimize extraneous cognitive load and optimize working memory storage capacity will enhance learning effectiveness. Novice students presented with complex subject matter require significant guidance during the initial stages, using strategies such as worked examples. As students comprehend information, instructional guidance needs to gradually fade to avoid elevated extraneous cognitive load from the expertise reversal effect. An instructional strategy that utilizes a systemic (fixed) or adjustable (adaptive) tapering of guidance to students in allied health programs depending on their expertise will optimize learning capability.

  10. Controls and guidance research

    NASA Technical Reports Server (NTRS)

    Homaifar, Abdollah; Dunn, Derome; Song, Yong-Duan; Lai, Steven H.-Y.

    1992-01-01

    The objectives of the control group are concentrated on research and education. The control problem of the hypersonic space vehicle represents an important and challenging issue in aerospace engineering. The work described in this report is part of our effort in developing advanced control strategies for such a system. In order to achieve the objectives stated in the NASA-CORE proposal, the tasks were divided among the group based upon their educational expertise. Within the educational component we are offering a Linear Systems and Control course for students in electrical and mechanical engineering. Also, we are proposing a new course in Digital Control Systems with a corresponding laboratory.

  11. Resources for Guidance Program Improvement. Volume 2.

    ERIC Educational Resources Information Center

    Frenza, Mary C., Comp.; and Others

    This guide, for guidance personnel and teachers, is designed to provide ready access to current, practical programs, activities, and references for improving guidance programs. The resources are organized in four sections representing areas of basic concern for guidance personnel. Section 1 presents selected portions of guidance programs from…

  12. Resources for Guidance Program Improvement. Volume I.

    ERIC Educational Resources Information Center

    Walz, Garry R., Comp.; And Others

    Designed for use by counselors, guidance directors, school administrators, school board members, and anyone interested in the improvement of school guidance programs, this resource book provides a collection of over 100 guidance program models and individual guidance practices. The format consists of references (bibliographic information with…

  13. microRNAs in axon guidance

    PubMed Central

    Iyer, Archana N.; Bellon, Anaïs; Baudet, Marie-Laure

    2014-01-01

    Brain wiring is a highly intricate process in which trillions of neuronal connections are established. Its initial phase is particularly crucial in establishing the general framework of neuronal circuits. During this early step, differentiating neurons extend axons, which reach their target by navigating through a complex environment with extreme precision. Research in the past 20 years has unraveled a vast and complex array of chemotropic cues that guide the leading tip of axons, the growth cone, throughout its journey. Tight regulation of these cues, and of their receptors and signaling pathways, is necessary for the high degree of accuracy required during circuit formation. However, little is known about the nature of regulatory molecules or mechanisms fine-tuning axonal cue response. Here we review recent, and somewhat fragmented, research on the possibility that microRNAs (miRNAs) could be key fine-tuning regulatory molecules in axon guidance. miRNAs appear to shape long-range axon guidance, fasciculation and targeting. We also present several lines of evidence suggesting that miRNAs could have a compartmentalized and differential action at the cell soma, and within axons and growth cones. PMID:24672429

  14. Guidance and control 1989; Proceedings of the Annual Rocky Mountain Guidance and Control Conference, Keystone, CO, Feb. 4-8, 1989

    NASA Astrophysics Data System (ADS)

    Culp, Robert D.; Lewis, Robert A.

    1989-05-01

    Papers are presented on advances in guidance, navigation, and control; guidance and control storyboard displays; attitude referenced pointing systems; guidance, navigation, and control for specialized missions; and recent experiences. Other topics of importance to support the application of guidance and control to the space community include concept design and performance test of a magnetically suspended single-gimbal control moment gyro; design, fabrication and test of a prototype double gimbal control moment gyroscope for the NASA Space Station; the Circumstellar Imaging Telescope Image Motion Compensation System providing ultra-precise control on the Space Station platform; pinpointing landing concepts for the Mars Rover Sample Return mission; and space missile guidance and control simulation and flight testing.

  15. Application of a Fully Numerical Guidance to Mars Aerocapture

    NASA Technical Reports Server (NTRS)

    Matz, Daniel A.; Lu, Ping; Mendeck, Gavin F.; Sostaric, Ronald R.

    2017-01-01

    An advanced guidance algorithm, Fully Numerical Predictor-corrector Aerocapture Guidance (FNPAG), has been developed to perform aerocapture maneuvers in an optimal manner. It is a model-based, numerical guidance that benefits from requiring few adjustments across a variety of different hypersonic vehicle lift-to-drag ratios, ballistic co-efficients, and atmospheric entry conditions. In this paper, FNPAG is first applied to the Mars Rigid Vehicle (MRV) mid lift-to-drag ratio concept. Then the study is generalized to a design map of potential Mars aerocapture missions and vehicles, ranging from the scale and requirements of recent robotic to potential human and precursor missions. The design map results show the versatility of FNPAG and provide insight for the design of Mars aerocapture vehicles and atmospheric entry conditions to achieve desired performance.

  16. HFE Process Guidance and Standards for potential application to updating NRC guidance

    SciTech Connect

    Jacques Hugo; J. J. Persensky

    2012-07-01

    The U.S. Nuclear Regulatory Commission (NRC) reviews and evaluates the human factors engineering (HFE) programs of applicants for nuclear power plant construction permits, operating licenses, standard design certifications, and combined operating licenses. The purpose of these safety reviews is to help ensure that personnel performance and reliability are appropriately supported. Detailed design review procedures and guidance for the evaluations is provided in three key documents: the Standard Review Plan (NUREG-0800), the HFE Program Review Model (NUREG-0711), and the Human-System Interface Design Review Guidelines (NUREG-0700). These documents were last revised in 2007, 2004 and 2002, respectively. The NRC is committed to the periodic update and improvement of these guidance documents to ensure that they remain state-of-the-art design evaluation tools. Thus, the NRC has initiated a project with BNL to update the NRC guidance to remain current with recent research on human performance, advances in HFE methods and tools, and new technology. INL supported Brookhaven National Lab (BNL) to update the detailed HFE review criteria contained in NUREG-0711 and NUREG-0700 based on (1) feedback obtained from end users, (2) the results of NRC research and development efforts supporting the NRC staff’s HFE safety reviews, and (3) other material the project staff identify as applicable to the update effort. INL submitted comments on development plans and sections of NUREGs 0800, 0711, and 0700. The contractor prepared the report attached here as the deliverable for this work.

  17. Supplementary Guidance for Conducting Health Risk ...

    EPA Pesticide Factsheets

    This document is a supplement to the EPA Guidelines for the Health Risk Assessment of Chemical Mixtures of 1986. The 1986 Guidelines represent the Agency's science policy and are a procedural guide for evaluating data on the health risks from exposures to chemical mixtures. The emphasis is on dose response and risk characterization. The principles and concepts put forth in the Guidelines remain in effect. However, where the Guidelines describe broad principles and include few specific procedures, the present guidance is a supplement that is intended to provide more detail on these principles and their applications.After an overview of the background and scope, this supplementary guidance puts forth the risk assessment paradigm for mixtures. This paradigm begins with problem formulation, then briefly discusses hazard identification, dose-response assessment, exposure, and risk characterization. The document is organized according to the type of data available. Procedures are described for assessment using data on the mixture of concern, data on a toxicologically similar mixture, and data on the mixture component chemicals. The state of the science varies dramatically for these three approaches. The whole-mixture procedures are most advanced for assessing carcinogenic risk, mainly because of the long use of in vitro mutagenicity tests to indicate carcinogenic potency. In vitro test procedures for noncancer endpoints are still in the pionee

  18. Ultrasound guidance for vascular access.

    PubMed

    Abboud, Paul-André C; Kendall, John L

    2004-08-01

    The evidence that supports the general application of US guidance for venous access in the ED has reached a critical mass. The increasing familiarity of emergency physicians with US and the recent focus on patient safety and clinical outcomes has intensified attention on the capacity for US to improve patient care in the ED. US guidance can increase the safety and efficiency of venous access procedures and offers improved outcomes. The potential for these improvements is compelling, especially among certain types of ED patients such as those with difficult or complicated access. Varying levels of evidence support the use of US guidance over the traditional landmark approach for venous access in adult and pediatric populations and for central and peripheral veins. Many different techniques may be applied, depending on the clinical situation and equipment available.

  19. Autonomous Guidance, Navigation and Control

    NASA Technical Reports Server (NTRS)

    Bordano, A. J.; Mcswain, G. G.; Fernandes, S. T.

    1991-01-01

    The NASA Autonomous Guidance, Navigation and Control (GN&C) Bridging program is reviewed to demonstrate the program plan and GN&C systems for the Space Shuttle. The ascent CN&C system is described in terms of elements such as the general-purpose digital computers, sensors for the navigation subsystem, the guidance-system software, and the flight-control subsystem. Balloon-based and lidar wind soundings are used for operations assessment on the day of launch, and the guidance software is based on dedicated units for atmospheric powered flight, vacuum powered flight, and abort-specific situations. Optimization of the flight trajectories is discussed, and flight-control responses are illustrated for wavelengths of 500-6000 m. Alternate sensors are used for load relief, and adaptive GN&C systems based on alternate gain synthesis are used for systems failures.

  20. Information architecture. Volume 3: Guidance

    SciTech Connect

    1997-04-01

    The purpose of this document, as presented in Volume 1, The Foundations, is to assist the Department of Energy (DOE) in developing and promulgating information architecture guidance. This guidance is aimed at increasing the development of information architecture as a Departmentwide management best practice. This document describes departmental information architecture principles and minimum design characteristics for systems and infrastructures within the DOE Information Architecture Conceptual Model, and establishes a Departmentwide standards-based architecture program. The publication of this document fulfills the commitment to address guiding principles, promote standard architectural practices, and provide technical guidance. This document guides the transition from the baseline or defacto Departmental architecture through approved information management program plans and budgets to the future vision architecture. This document also represents another major step toward establishing a well-organized, logical foundation for the DOE information architecture.

  1. Guidance automation for nap-of-the-earth flight

    NASA Technical Reports Server (NTRS)

    Denton, Richard V.; Pekelsma, Nick; Hagen, Mine; Mcgee, Leonard

    1986-01-01

    Low-Altitude/Nap-of-the-Earth (NOE) rotorcraft flight in adverse weather has been identified as a major technology void by both military and civil agencies because of its direct relationship to the needs of the military's new scout-attack helicopter and to various civilian applications including Emergency Medical Services (EMS). As part of NASA's Aircraft Automation Program, Ames Research Center has identified as a major goal the automating and advancing of applicable terrain following/terrain avoidance/obstacle avoidance (TF/TA/OA) guidance technologies to a level where NOE rotorcraft flight can be demonstrated in an advanced simulator and, later, in fully automatic flight. Areas of emphasis to date for achieving automatic guidance include real-time sensor blending and the real-time computation of NOE guidance commands. The present paper reports on the guidance command generation. The applicability of TF/TA techniques to the NOE problem is described, and simulation results are presented that suggest that automatic NOE can indeed be accomplished.

  2. Optical technologies for intraoperative neurosurgical guidance

    PubMed Central

    Valdés, Pablo A.; Roberts, David W.; Lu, Fa-Ke; Golby, Alexandra

    2016-01-01

    Biomedical optics is a broadly interdisciplinary field at the interface of optical engineering, biophysics, computer science, medicine, biology, and chemistry, helping us understand light–tissue interactions to create applications with diagnostic and therapeutic value in medicine. Implementation of biomedical optics tools and principles has had a notable scientific and clinical resurgence in recent years in the neurosurgical community. This is in great part due to work in fluorescence-guided surgery of brain tumors leading to reports of significant improvement in maximizing the rates of gross-total resection. Multiple additional optical technologies have been implemented clinically, including diffuse reflectance spectroscopy and imaging, optical coherence tomography, Raman spectroscopy and imaging, and advanced quantitative methods, including quantitative fluorescence and lifetime imaging. Here we present a clinically relevant and technologically informed overview and discussion of some of the major clinical implementations of optical technologies as intraoperative guidance tools in neurosurgery. PMID:26926066

  3. Enhancements to an Atmospheric Ascent Guidance Algorithm

    NASA Technical Reports Server (NTRS)

    Dukeman, Greg A.

    2003-01-01

    Enhancements to an advanced ascent guidance algorithm for rocket-powered launch vehicles are described. A general method has been developed for conveniently and efficiently handling the common case of (asymmetric) launch vehicles with unbalanced thrust and aerodynamic moments. The new part of this development concerns the treatment of endo-atmospheric flight. An alternative method for handing the transversality conditions has been developed that eliminates the need for a priori elimination of the constant multipliers that adjoin the terminal state constraints to the performance index. As a result, new constraints can be formulated and implemented with relative ease. The problem of burn-coast-burn trajectory optimization is treated using a modified multiple shooting technique.

  4. Recent Events in Guidance, Navigation and Control

    NASA Technical Reports Server (NTRS)

    Polites, Michael E.; Bullman, Jack (Technical Monitor)

    2001-01-01

    This article summarizes recent events in Guidance, Navigation, and Control (GN&C) in space, weapons and missiles, and aircraft. The section on space includes recent developments with the following NASA spacecraft and space vehicles: Near Earth Asteroid Rendezvous, Deep Space 1, Microwave Anisotropy Probe, Earth Observer-1, Compton Gamma Ray Observatory, the International Space Station, X-38, and X-40A. The section on weapons and missiles includes recent developments with the following missiles: Joint Air-to-Surface Standoff Missile, Storm Shadow/Scalp EG precision standoff missile, Hellfire missile, AIM-120C Advanced medium-range air-to-air missile, Derby missile, Arrow 2, and the Standard Missile SM-3. The section on aircraft includes recent developments with the following aircraft: Joint Strike Fighter, X-31, V-22, Couger/SUDer Puma Mk. 2, Predator B 001, and the Unmanned Combat Air Vehicle.

  5. Optical technologies for intraoperative neurosurgical guidance.

    PubMed

    Valdés, Pablo A; Roberts, David W; Lu, Fa-Ke; Golby, Alexandra

    2016-03-01

    Biomedical optics is a broadly interdisciplinary field at the interface of optical engineering, biophysics, computer science, medicine, biology, and chemistry, helping us understand light-tissue interactions to create applications with diagnostic and therapeutic value in medicine. Implementation of biomedical optics tools and principles has had a notable scientific and clinical resurgence in recent years in the neurosurgical community. This is in great part due to work in fluorescence-guided surgery of brain tumors leading to reports of significant improvement in maximizing the rates of gross-total resection. Multiple additional optical technologies have been implemented clinically, including diffuse reflectance spectroscopy and imaging, optical coherence tomography, Raman spectroscopy and imaging, and advanced quantitative methods, including quantitative fluorescence and lifetime imaging. Here we present a clinically relevant and technologically informed overview and discussion of some of the major clinical implementations of optical technologies as intraoperative guidance tools in neurosurgery.

  6. Guidance for state attainment plans

    SciTech Connect

    Strait, R.

    1994-06-01

    Title I of the Clean Air act Amendments of 1990 significantly changed requirements for regulatory agencies to prepare state implementation plans that demonstrate attainment of the ozone National Ambient Air Quality Standards. State agencies now are required to submit plans that show how they will meet the standards by their attainment date. EPA has published a series of guidance documents to assist states in preparing their plans. In addition, the agency is developing software to assist states in projecting emissions and tracking reductions. This article summarizes the guidance documents and software program.

  7. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    SciTech Connect

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-06-06

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.

  8. Guidance Manual for Conducting Screening Level Ecological Risk Assessments at the INEL

    SciTech Connect

    R. L. VanHorn; N. L. Hampton; R. C. Morris

    1995-06-01

    This document presents reference material for conducting screening level ecological risk assessments (SLERAs)for the waste area groups (WAGs) at the Idaho National Engineering Laboratory. Included in this document are discussions of the objectives of and processes for conducting SLERAs. The Environmental Protection Agency ecological risk assessment framework is closely followed. Guidance for site characterization, stressor characterization, ecological effects, pathways of contaminant migration, the conceptual site model, assessment endpoints, measurement endpoints, analysis guidance, and risk characterization are included.

  9. Reading Guidance: Death and Grief.

    ERIC Educational Resources Information Center

    Smith, Alice Gullen

    1989-01-01

    Gives guidelines for the librarian using reading guidance (similar to bibliotherapy). Provides a nine-item annotated bibliography of novels for children and adolescents on the subject of death and grief. Appends an embryo list of categories suitable for content analysis of any file librarians might wish to keep on books suitable for use in this…

  10. THE STRESSOR IDENTIFICATION GUIDANCE DOCUMENT

    EPA Science Inventory

    THE STRESSOR IDENTIFICATION GUIDANCE DOCUMENT

    Susan M. Cormier, ORD/NRMRL, Susan B. Norton, ORD/NCEA, Glenn W. Suter, II ORD/NCEA, William Swietlik, OW lOST

    Science Question(s):

    MYP Science Question: How can multiple and possibly related causes of biological ...

  11. Atmospheric guidance techniques and performance

    NASA Technical Reports Server (NTRS)

    Harpold, J. C.; Gavert, D. E.

    1982-01-01

    The Orbiter entry guidance system controls the Space Shuttle Orbiter from the initial atmospheric penetration point to the point at which an earth relative velocity of 2500 feet/second is reached. At the latter point, control of the Orbiter is transferred to the terminal area energy management system. The entry guidance system is based on the concept that the range to be flown during entry is a unique function of the drag deceleration profile flown throughout the entry. The range prediction during entry is based on analytic equations which are simple drag deceleration functions of earth relative velocity above Mach 10.5 and energy with respect to the earth below Mach 10.5. Flight through the entry corridor is accomplished by linking these simple drag deceleration functions together in series in order to define a drag deceleration reference profile. The results of the first three Space Shuttle missions have not only verified the entry guidance concept but have also demonstrated the stability of the guidance system.

  12. Theater As A Guidance Technique

    ERIC Educational Resources Information Center

    Wolpert, William

    1973-01-01

    Guidance-drama activity provides (a) crisp definitions of selected issues; (b) potent modeling from the characters in the play, the students actively engaged in the play, and the students involved in the discussions that follow the play; and (c) a technique for peer-led discussions on sensitive issues. This article gives precise definition to the…

  13. Guidance: Interim Municipal Settlement Policy

    EPA Pesticide Factsheets

    Interim guidance and fact sheets regarding settlements involving municipalities or municipal waste under Section 122 CERCLA as amended by SARA. Interim policy sets forth the criteria by which EPA generally determines whether to exercise enforcement discretion to pursue MSW generators and transporters as PRPs.

  14. Abortion Information: A Guidance Viewpoint

    ERIC Educational Resources Information Center

    Wolleat, Patricia L.

    1975-01-01

    A number of questions relating to providing abortion information to teenagers can be raised from legal, ethical and philosophical standpoints. The purpose of this article is to examine abortion information-giving from the perspective of counseling and guidance theory and practice. (Author)

  15. Imaging Futuristic Career Guidance Goals.

    ERIC Educational Resources Information Center

    Miller, Juliet V.; and Others

    This module is directed toward guidance personnel in school (k-adult) and agency settings such as counselors, teachers, students and administrators. It is also designed for students in pre-service education programs who are familiar with career development theories and information. The Module assumes that the participant is not familiar with the…

  16. Imaging Futuristic Career Guidance Programs.

    ERIC Educational Resources Information Center

    Miller, Juliet V; And Others

    This Module is directed toward guidance personnel in school (K-adult) and agency settings such as counselors, teachers, students and administrators. It is also designed for students in pre-service education programs who have had previous exposure to career development theories and to sources of educational-occupational information. The Module…

  17. Developing Local Lifelong Guidance Strategies.

    ERIC Educational Resources Information Center

    Watts, A. G.; Hawthorn, Ruth; Hoffbrand, Jill; Jackson, Heather; Spurling, Andrea

    1997-01-01

    Outlines the background, rationale, methodology, and outcomes of developing local lifelong guidance strategies in four geographic areas. Analyzes the main components of the strategies developed and addresses a number of issues relating to the process of strategy development. Explores implications for parallel work in other localities. (RJM)

  18. Research Bulletin: Bayesian Guidance Technology.

    ERIC Educational Resources Information Center

    Novick, Melvin R.; Jackson, Paul H.

    This paper presents a discussion of the use of educational tests in guidance services as seen in the light of modern developments in statistical theory and computer technology, and of the increasing demands for such services. A focus and vocabulary for this discussion is found in Turnbull's recent article on "Relevance in Testing." Following an…

  19. Elementary Guidance Program. Navajo Area.

    ERIC Educational Resources Information Center

    Bureau of Indian Affairs (Dept. of Interior), Window Rock, AZ.

    A program designed to assist guidance staff in working with Navajo elementary school students, particularly boarding school students, is presented in this booklet with emphasis directed toward meeting both individual and group needs in the areas of home living, student activities, and counseling. The first section gives 14 separate functions of…

  20. Consensus standard requirements and guidance

    SciTech Connect

    Putman, V.L.

    1995-12-01

    This report presents information from the ANS Criticality Alarm System Workshop relating to the consensus standard requirements and guidance. Topics presented include: definition; nomenclature; requirements and recommendations; purpose of criticality alarms; design criteria; signal characteristics; reliability, dependability and durability; tests; and emergency preparedness and planning.

  1. Child Development, Care, and Guidance.

    ERIC Educational Resources Information Center

    Texas Education Agency, Austin. Dept. of Occupational Education and Technology.

    This teacher's guide on child development, care, and guidance is one of seven subject area guides developed for use in consumer and homemaking education in secondary schools in Texas. The guide is correlated with the "Conceptual Framework for Consumer and Homemaking Education in Texas." Content is based on the competencies needed by…

  2. DOE Waste Treatability Group Guidance

    SciTech Connect

    Kirkpatrick, T.D.

    1995-01-01

    This guidance presents a method and definitions for aggregating U.S. Department of Energy (DOE) waste into streams and treatability groups based on characteristic parameters that influence waste management technology needs. Adaptable to all DOE waste types (i.e., radioactive waste, hazardous waste, mixed waste, sanitary waste), the guidance establishes categories and definitions that reflect variations within the radiological, matrix (e.g., bulk physical/chemical form), and regulated contaminant characteristics of DOE waste. Beginning at the waste container level, the guidance presents a logical approach to implementing the characteristic parameter categories as part of the basis for defining waste streams and as the sole basis for assigning streams to treatability groups. Implementation of this guidance at each DOE site will facilitate the development of technically defined, site-specific waste stream data sets to support waste management planning and reporting activities. Consistent implementation at all of the sites will enable aggregation of the site-specific waste stream data sets into comparable national data sets to support these activities at a DOE complex-wide level.

  3. Guidance for Supporting School Counselors

    ERIC Educational Resources Information Center

    Light, Carolyn

    2005-01-01

    School counselors need the assistance of principals and other administrators to improve guidance and school counseling services in schools. Principals and other administrators are the leaders in education, and it is important that they know how to create the best school counseling programs possible. This article provides 12 suggestions that can…

  4. Educational Guidance and Curriculum Change.

    ERIC Educational Resources Information Center

    Oakeshott, Martin

    A project conducted by Britain's Further Education Unit: (1) identified and evaluated strategies used by Educational Guidance Services for Adults (EGSAs) to feed back to providers of learning opportunities the unmet needs of adult clients with particular reference to the unemployed and unwaged; (2) identified and evaluated mechanisms used by…

  5. Guidance strategies for microburst escape

    NASA Astrophysics Data System (ADS)

    Dogan, Atilla

    This study compares three escape guidance laws for microburst encounters during final landing approach: Altitude-Guidance, Dive-Guidance, and Pitch-Guidance from the point of view of safety. It also introduces Modified Altitude- and Dive-Guidance laws. In this study, we use a full, 6-DOF, nonlinear, rigid-body aircraft model, including the effects of windshear and wind vorticity, and a model of microburst with turbulence. We also model the effect of stall prevention on the escape path. We first construct a new safety metric that quantifies the aircraft upward force capability in a microburst encounter. In the absence of turbulence, the safety factor is analytically proven to be a decreasing function of altitude. This suggests that descending to a low altitude may improve safety in the sense that the aircraft will have more upward force capability to maintain its altitude. In the presence of stochastic turbulence, the safety factor is treated as a random variable and its probability distribution function is analytically approximated as a function of altitude. This approximation reveals that the probability of safety factor being less than a given value has a minimum, i.e. safety increases as the altitude decreases up to a certain altitude, then starts decreasing. In the dissertation, two different approaches are used for comparison. (1) In a sample analysis approach, typical samples of the time histories of various variables are analyzed. Additionally, an animation of an aircraft escaping a microburst is produced and the behavior of the aircraft along with its inertial velocity and airspeed vectors are studied. (2) In a statistical approach, the probability distribution of the minimum altitude is estimated by the Monte Carlo Method when the statistical properties of the microburst parameters are known. Both approaches suggest that, within the modeling assumptions of this dissertation, and in the absence of human factors, altitude and dive guidance with low commanded

  6. The Advanced Course in Professional Selling

    ERIC Educational Resources Information Center

    Loe, Terry; Inks, Scott

    2014-01-01

    More universities are incorporating sales content into their curriculums, and although the introductory courses in professional sales have much common ground and guidance from numerous professional selling texts, instructors teaching the advanced selling course lack the guidance provided by common academic tools and materials. The resulting…

  7. Advances in targeting co-inhibitory and co-stimulatory pathways in transplantation settings: the Yin to the Yang of cancer immunotherapy.

    PubMed

    Kean, Leslie S; Turka, Laurence A; Blazar, Bruce R

    2017-03-01

    In the past decade, the power of harnessing T-cell co-signaling pathways has become increasingly understood to have significant clinical importance. In cancer immunotherapy, the field has concentrated on two related modalities: First, targeting cancer antigens through highly activated chimeric antigen T cells (CAR-Ts) and second, re-animating endogenous quiescent T cells through checkpoint blockade. In each of these strategies, the therapeutic goal is to re-ignite T-cell immunity, in order to eradicate tumors. In transplantation, there is also great interest in targeting T-cell co-signaling, but with the opposite goal: in this field, we seek the Yin to cancer immunotherapy's Yang, and focus on manipulating T-cell co-signaling to induce tolerance rather than activation. In this review, we discuss the major T-cell signaling pathways that are being investigated for tolerance induction, detailing preclinical studies and the path to the clinic for many of these molecules. These include blockade of co-stimulation pathways and agonism of coinhibitory pathways, in order to achieve the delicate state of balance that is transplant tolerance: a state which guarantees lifelong transplant acceptance without ongoing immunosuppression, and with preservation of protective immune responses. In the context of the clinical translation of immune tolerance strategies, we discuss the significant challenge that is embodied by the fact that targeted pathway modulators may have opposing effects on tolerance based on their impact on effector vs regulatory T-cell biology. Achieving this delicate balance holds the key to the major challenge of transplantation: lifelong control of alloreactivity while maintaining an otherwise intact immune system.

  8. Gametophytic Pollen Tube Guidance: Attractant Peptides, Gametic Controls, and Receptors1[OPEN

    PubMed Central

    2017-01-01

    Pollen tube guidance in flowering plants is a unique and critical process for successful sexual reproduction. The pollen tube that grows from pollen, which is the male gametophyte, precisely navigates to the embryo sac, which is the female gametophyte, within the pistil. Recent advances have clarified the molecular framework of gametophytic pollen tube guidance. Multiple species-specific attractant peptides are secreted from synergid cells, the proper development and function of which are regulated by female gametes. Multiple receptor-like kinases on the pollen tube tip are involved in sensing species-specific attractant peptides. In this Update article, recent progress in our understanding of the mechanism of gametophytic pollen tube guidance is reviewed, including attraction by synergid cells, control of pollen tube guidance by female gametes, and directional growth of the pollen tube by directional cue sensing. Future directions in the study of pollen tube guidance also are discussed. PMID:27920159

  9. Pathways toward high-performance perovskite solar cells: review of recent advances in organo-metal halide perovskites for photovoltaic applications

    NASA Astrophysics Data System (ADS)

    Song, Zhaoning; Watthage, Suneth C.; Phillips, Adam B.; Heben, Michael J.

    2016-04-01

    Organo-metal halide perovskite-based solar cells have been the focus of intense research over the past five years, and power conversion efficiencies have rapidly been improved from 3.8 to >21%. This article reviews major advances in perovskite solar cells that have contributed to the recent efficiency enhancements, including the evolution of device architecture, the development of material deposition processes, and the advanced device engineering techniques aiming to improve control over morphology, crystallinity, composition, and the interface properties of the perovskite thin films. The challenges and future directions for perovskite solar cell research and development are also discussed.

  10. Guidance: CERCLA Section 106 Judicial Actions

    EPA Pesticide Factsheets

    This guidance provides criteria for consideration in selecting and initiating Section 106 judicial actions. The guidance also identifies and discusses issues that should be considered in preparation of a Section 106 referral.

  11. A guidance concept for hypersonic aerospacecrafts

    NASA Astrophysics Data System (ADS)

    Ishimoto, Shinji

    In this paper a guidance concept for hypersonic re-entry flights is presented. The method uses a closed-form guidance technique based on a drag acceleration reference profile. A guidance law for range control is developed. It employs a physical relation between vehicle energy and range instead of a prediction-correction technique used for Shuttle entry guidance. Simulation results show that the algorithm provides good performance.

  12. Boston and New England: Advancing the Revolution in Geographic Education in a Region of Change. Pathways in Geography Series, Title No. 21.

    ERIC Educational Resources Information Center

    Pikora, Theodore S., Ed.; Young, Stephen S., Ed.

    This collection of essays offers ideas, observations, maps, photographs, and descriptions of Boston (Massachusetts) and New England. The 13 essays in the collection include: (1) "An Introduction to New England and Boston: Advancing the Revolution in Geographic Education in a Region of Change" (Theodore S. Pikora; Stephen S. Young); (2)…

  13. 78 FR 35940 - Guidance for Industry on Codevelopment of Two or More New Investigational Drugs for Use in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-14

    ... treat a disease or condition. Recent scientific advances have increased our understanding of the pathophysiological processes that underlie many complex diseases, such as cancer, cardiovascular disease, and... disease or condition. The guidance provides recommendations and advice on how to address...

  14. [Advances of PD-1/PD-L1 signaling pathway in immune escape and treatment for 
non-small cell lung cancer].

    PubMed

    Lin, Cheng; Chen, Xiong; Liu, Jingnan; Huang, Yufang; Ou-Yang, Xuenong

    2014-10-20

    Lung cancer is the leading cause of cancer-related mortality worldwide. Despiting the great progress on target agents, majority of people who do not harbor a mutation could not get benefit from them. Immunotherapy, through stimulating the body's immune system to improve the antitumor immunity effect, has been a new therapeutic method for non-small cell lung cancer (NSCLC). Study had been reported that immune checkpoint molecules, including programmed death-1 (PD-1)/PD-ligand (L) 1 axis, are closedly related with cancer generation and development, and play a key role on clinical significance of NSCLC. Activation of PD-1/PD-L1 pathway contributes to tumor immune escape, and block PD-1/PD-L1 pathway can enhance endogenous antimuor immunity. Currently increasing clinical trials suggested that immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 monoclonal antibodies turned out to be beneficial and safe in NSCLC. Here, we provide a review on the progress of PD-1/PD-L1 pathway and immune checkpoint inhibitors in NSCLC.

  15. Quality Assurance in University Guidance Services

    ERIC Educational Resources Information Center

    Simon, Alexandra

    2014-01-01

    In Europe there is no common quality assurance framework for the delivery of guidance in higher education. Using a case study approach in four university career guidance services in England, France and Spain, this article aims to study how quality is implemented in university career guidance services in terms of strategy, standards and models,…

  16. Space Shuttle ascent guidance, navigation, and control

    NASA Technical Reports Server (NTRS)

    Mchenry, R. L.; Long, A. D.; Cockrell, B. F.; Thibodeau, J. R., III; Brand, T. J.

    1979-01-01

    The factors leading to the particular design of the Shuttle guidance, navigation and control software are discussed. The derivation of explicit guidance equations satisfying a wide range of different maneuver constraints and steering equations that create attitude steering errors from the guidance solutions is presented, as are navigation equations, and equations for identifying faulty instruments from sets of redundant instrument measurements.

  17. Providing Career Guidance for Young Women.

    ERIC Educational Resources Information Center

    Colby, Pamela G.

    This module is directed at personnel working or planning to work in the areas of guidance, counseling, placement and follow-through in junior and senior high school settings, grades 7-12. The module topic is career guidance for young women of junior and senior high school age, aand the focus will be on providing nonbiased career guidance which…

  18. 75 FR 76079 - Sound Incentive Compensation Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

    ... Office of Thrift Supervision Sound Incentive Compensation Guidance AGENCY: Office of Thrift Supervision... collection. Title of Proposal: Sound Incentive Compensation Guidance. OMB Number: 1550-0129. Form Number: N/A... principles and the guidance are consistent with the Principles for Sound Compensation Practices adopted...

  19. 75 FR 22679 - Sound Incentive Compensation Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... Office of Thrift Supervision Sound Incentive Compensation Guidance AGENCY: Office of Thrift Supervision... collection. Title of Proposal: Sound Incentive Compensation Guidance. OMB Number: 1550-0NEW. Form Number: N/A... principles and the guidance are consistent with the Principles for Sound Compensation Practices adopted...

  20. 75 FR 53023 - Sound Incentive Compensation Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-30

    ... Office of Thrift Supervision Sound Incentive Compensation Guidance AGENCY: Office of Thrift Supervision... collection. Title of Proposal: Sound Incentive Compensation Guidance. OMB Number: 1550-0129. Form Number: N/A... principles and the guidance are consistent with the Principles for Sound Compensation Practices adopted...

  1. The expectation of applying IR guidance in medium range air-to-air missiles

    NASA Astrophysics Data System (ADS)

    Li, Lijuan; Liu, Ke

    2016-10-01

    IR guidance has been widely used in near range dogfight air-to-air missiles while radar guidance is dominant in medium and long range air-to-air missiles. With the development of stealth airplanes and advanced electronic countermeasures, radar missiles have met with great challenges. In this article, the advantages and potential problems of applying IR guidance in medium range air-to-air missiles are analyzed. Approaches are put forward to solve the key technologies including depressing aerodynamic heating, increasing missiles' sensitivity and acquiring target after launch. IR medium range air-to-air missiles are predicted to play important role in modern battle field.

  2. A new modular guidance system for the Southern African Large Telescope

    NASA Astrophysics Data System (ADS)

    Brink, Janus D.; Strydom, Ockert J.; Hulme, Stephen N.; Koeslag, Anthony R.; Maartens, Deneys S.; Wilkinson, Martin; Lochner, Wouter; Browne, Keith; Wiid, Eben P.; van den Berg, Raoul

    2016-07-01

    Following successful commissioning of the SALT Fiber Instrument Feed guidance system, the concept was developed further to re-design the guidance probe currently supporting observations with the Robert Stobie Spectrograph. Major advances of the new system include a compact, modular and line-replaceable design, high optical efficiency, a doubleprobe positioning system allowing both translation and rotation guidance corrections as well as closed-loop focus feedback. The mechanical and optical designs, the control system architecture and performance aspects of the system are presented. The probe`s integration with the greater telescope software control system is also discussed.

  3. Reentry guidance for Space Shuttle

    NASA Technical Reports Server (NTRS)

    Causey, W.; Sohoni, V.

    1973-01-01

    An explicit guidance scheme is outlined which provides the appropriate energy management in order for the shuttle orbiter to reach any location within the required footprint. Considering the orbiter as entering the earth's atmosphere, expressions for the downrange, crossrange, and the time of the termination of the entry phase as functions of the control variables are developed. Performing an order-of-magnitude analysis of the terms in these expressions, only dominant terms are retained. Analytical expressions for the elements of the sensitivity matrix which represents the partial derivatives of the desired range with respect to control variables are formulated. Using the Gauss-Jordan inversion technique, the required change in guidance commands as a function of the deviations in the downrange and crossrange are explicitly computed.

  4. Teleautonomous guidance for mobile robots

    NASA Technical Reports Server (NTRS)

    Borenstein, J.; Koren, Y.

    1990-01-01

    Teleautonomous guidance (TG), a technique for the remote guidance of fast mobile robots, has been developed and implemented. With TG, the mobile robot follows the general direction prescribed by an operator. However, if the robot encounters an obstacle, it autonomously avoids collision with that obstacle while trying to match the prescribed direction as closely as possible. This type of shared control is completely transparent and transfers control between teleoperation and autonomous obstacle avoidance gradually. TG allows the operator to steer vehicles and robots at high speeds and in cluttered environments, even without visual contact. TG is based on the virtual force field (VFF) method, which was developed earlier for autonomous obstacle avoidance. The VFF method is especially suited to the accommodation of inaccurate sensor data (such as that produced by ultrasonic sensors) and sensor fusion, and allows the mobile robot to travel quickly without stopping for obstacles.

  5. Optical guidance vidicon test program

    NASA Technical Reports Server (NTRS)

    Eiseman, A. R.; Stanton, R. H.; Voge, C. C.

    1976-01-01

    A laboratory and field test program was conducted to quantify the optical navigation parameters of the Mariner vidicons. A scene simulator and a camera were designed and built for vidicon tests under a wide variety of conditions. Laboratory tests characterized error sources important to the optical navigation process and field tests verified star sensitivity and characterized comet optical guidance parameters. The equipment, tests and data reduction techniques used are described. Key test results are listed. A substantial increase in the understanding of the use of selenium vidicons as detectors for spacecraft optical guidance was achieved, indicating a reduction in residual offset errors by a factor of two to four to the single pixel level.

  6. 2011 Army Strategic Planning Guidance

    DTIC Science & Technology

    2011-03-25

    TESI ) of 22,000 Soldiers, the Army’s total force by the end of the mid-term period is programmed to be 520K (AC). We will achieve a more...dwell ratios, extending TESI authority to adequately man deploying units and sustain the All-Volunteer Force, right-sizing the generating force, and... TESI Temporary End-Strength Increase WMD Weapons of Mass Destruction 2011 ARMY STRATEGIC PLANNING GUIDANCE Page 19 2011

  7. Mars Science Laboratory Entry Guidance

    NASA Technical Reports Server (NTRS)

    Mendeck, Gavin F.

    2011-01-01

    The Mars Science Laboratory will be the first Mars mission to attempt a guided entry with the objective of safely delivering the entry vehicle to a survivable parachute deploy state within 12.5 km of the pre-designated parachute deploy coordinates. The Entry Terminal Point Controller guidance algorithm is derived from the final phase Apollo Command Module guidance and, like Apollo, modulates the bank angle to control range based on deviations in range, altitude rate, and drag acceleration from a reference trajectory. For application to Mars landers which must make use of the tenuous Martian atmosphere, it is critical to balance the lift of the vehicle to minimize the range while still ensuring a safe deploy altitude. An overview of the process to generate optimized guidance settings is presented, discussing improvements made over the last nine years. Performance tradeoffs between ellipse size and deploy altitude will be presented, along with imposed constraints of entry acceleration and heating. Performance sensitivities to the bank reversal deadbands, heading alignment, attitude initialization error, and entry delivery errors are presented.

  8. BENCHMARK DOSE TECHNICAL GUIDANCE DOCUMENT ...

    EPA Pesticide Factsheets

    The U.S. EPA conducts risk assessments for an array of health effects that may result from exposure to environmental agents, and that require an analysis of the relationship between exposure and health-related outcomes. The dose-response assessment is essentially a two-step process, the first being the definition of a point of departure (POD), and the second extrapolation from the POD to low environmentally-relevant exposure levels. The benchmark dose (BMD) approach provides a more quantitative alternative to the first step in the dose-response assessment than the current NOAEL/LOAEL process for noncancer health effects, and is similar to that for determining the POD proposed for cancer endpoints. As the Agency moves toward harmonization of approaches for human health risk assessment, the dichotomy between cancer and noncancer health effects is being replaced by consideration of mode of action and whether the effects of concern are likely to be linear or nonlinear at low doses. Thus, the purpose of this project is to provide guidance for the Agency and the outside community on the application of the BMD approach in determining the POD for all types of health effects data, whether a linear or nonlinear low dose extrapolation is used. A guidance document is being developed under the auspices of EPA's Risk Assessment Forum. The purpose of this project is to provide guidance for the Agency and the outside community on the application of the benchmark dose (BMD) appr

  9. Where does axon guidance lead us?

    PubMed Central

    Stoeckli, Esther

    2017-01-01

    During neural circuit formation, axons need to navigate to their target cells in a complex, constantly changing environment. Although we most likely have identified most axon guidance cues and their receptors, we still cannot explain the molecular background of pathfinding for any subpopulation of axons. We lack mechanistic insight into the regulation of interactions between guidance receptors and their ligands. Recent developments in the field of axon guidance suggest that the regulation of surface expression of guidance receptors comprises transcriptional, translational, and post-translational mechanisms, such as trafficking of vesicles with specific cargos, protein-protein interactions, and specific proteolysis of guidance receptors. Not only axon guidance molecules but also the regulatory mechanisms that control their spatial and temporal expression are involved in synaptogenesis and synaptic plasticity. Therefore, it is not surprising that genes associated with axon guidance are frequently found in genetic and genomic studies of neurodevelopmental disorders. PMID:28163913

  10. The nature of protein folding pathways

    PubMed Central

    Englander, S. Walter; Mayne, Leland

    2014-01-01

    How do proteins fold, and why do they fold in that way? This Perspective integrates earlier and more recent advances over the 50-y history of the protein folding problem, emphasizing unambiguously clear structural information. Experimental results show that, contrary to prior belief, proteins are multistate rather than two-state objects. They are composed of separately cooperative foldon building blocks that can be seen to repeatedly unfold and refold as units even under native conditions. Similarly, foldons are lost as units when proteins are destabilized to produce partially unfolded equilibrium molten globules. In kinetic folding, the inherently cooperative nature of foldons predisposes the thermally driven amino acid-level search to form an initial foldon and subsequent foldons in later assisted searches. The small size of foldon units, ∼20 residues, resolves the Levinthal time-scale search problem. These microscopic-level search processes can be identified with the disordered multitrack search envisioned in the “new view” model for protein folding. Emergent macroscopic foldon–foldon interactions then collectively provide the structural guidance and free energy bias for the ordered addition of foldons in a stepwise pathway that sequentially builds the native protein. These conclusions reconcile the seemingly opposed new view and defined pathway models; the two models account for different stages of the protein folding process. Additionally, these observations answer the “how” and the “why” questions. The protein folding pathway depends on the same foldon units and foldon–foldon interactions that construct the native structure. PMID:25326421

  11. A Study into Advanced Guidance Laws Using Computational Methods

    DTIC Science & Technology

    2011-12-01

    computing aerodynamic forces % and moments. Except where noted, all dimensions in % MKS system. % Inputs...9] R. L. Shaw, Fighter Combat: Tactics and Maneuvering. Annapolis, MD: Naval Institute Press, 1988. [10] U. S. Shukla and P. R. Mahapatra

  12. Advanced Alarm Systems: Revision of Guidance and Its Technical Basis

    DTIC Science & Technology

    2000-11-01

    bulletins and information notices; inspection and investigative reports; licensee event reports; and Commission papers and their attachments. NRC...List System CANDU Canadian Deuterium Uranium CE Combustion Engineering CPIAS Critical Parameter Indication and Alarm System CRT cathode ray tube...strategy for CANDU plants, Davey et al., (1995) noted that warning of conditions potentially leading to upsets is enhanced by including rate and margin

  13. Advanced in Guidance and Control Systems and Technology.

    DTIC Science & Technology

    1987-07-01

    an autopilot was needed to keep an aircraft on a predetermined course. The system developed here in the United Kingdom at the Royal Aircraft...aircraft autopilots should be based on pneumatic and magnetic amplifiers: early guided weapons used vacuum tubes but power and mass constraints set severe...delivery purposes are supplied by the SD-IRU. The autopilot func- tions are supported by the following signals: - Radar altitude h - Inertial altitude h

  14. Optimal guidance law development for an advanced launch system

    NASA Technical Reports Server (NTRS)

    Calise, Anthony J.; Hodges, Dewey H.; Leung, Martin S.; Bless, Robert R.

    1991-01-01

    The proposed investigation on a Matched Asymptotic Expansion (MAE) method was carried out. It was concluded that the method of MAE is not applicable to launch vehicle ascent trajectory optimization due to a lack of a suitable stretched variable. More work was done on the earlier regular perturbation approach using a piecewise analytic zeroth order solution to generate a more accurate approximation. In the meantime, a singular perturbation approach using manifold theory is also under current investigation. Work on a general computational environment based on the use of MACSYMA and the weak Hamiltonian finite element method continued during this period. This methodology is capable of the solution of a large class of optimal control problems.

  15. Optimal guidance law development for an advanced launch system

    NASA Technical Reports Server (NTRS)

    Calise, Anthony J.; Hodges, Dewey H.

    1990-01-01

    A regular perturbation analysis is presented. Closed-loop simulations were performed with a first order correction including all of the atmospheric terms. In addition, a method was developed for independently checking the accuracy of the analysis and the rather extensive programming required to implement the complete first order correction with all of the aerodynamic effects included. This amounted to developing an equivalent Hamiltonian computed from the first order analysis. A second order correction was also completed for the neglected spherical Earth and back-pressure effects. Finally, an analysis was begun on a method for dealing with control inequality constraints. The results on including higher order corrections do show some improvement for this application; however, it is not known at this stage if significant improvement will result when the aerodynamic forces are included. The weak formulation for solving optimal problems was extended in order to account for state inequality constraints. The formulation was tested on three example problems and numerical results were compared to the exact solutions. Development of a general purpose computational environment for the solution of a large class of optimal control problems is under way. An example, along with the necessary input and the output, is given.

  16. Opioid-induced constipation: advances and clinical guidance

    PubMed Central

    Nelson, Alfred D.; Camilleri, Michael

    2016-01-01

    Currently opioids are the most frequently used medications for chronic noncancer pain. Opioid-induced constipation is the most common adverse effect associated with prolonged use of opioids, having a major impact on quality of life. There is an increasing need to treat opioid-induced constipation. With the recent approval of medications for the treatment of opioid-induced constipation, there are several therapeutic approaches. This review addresses the clinical presentation and diagnosis of opioid-induced constipation, barriers to its diagnosis, effects of opioids in the gastrointestinal tract, differential tolerance to opiates in different gastrointestinal organs, medications approved and in development for the treatment of opioid-induced constipation, and a proposed clinical management algorithm for treating opioid-induced constipation in patients with noncancer pain. PMID:26977281

  17. Image-Guidance for Stereotactic Body Radiation Therapy

    SciTech Connect

    Fuss, Martin . E-mail: fussm@ohsu.edu; Boda-Heggemann, Judit; Papanikolau, Nikos; Salter, Bill J.

    2007-07-01

    The term stereotactic body radiation therapy (SBRT) describes a recently introduced external beam radiation paradigm by which small lesions outside the brain are treated under stereotactic conditions, in a single or few fractions of high-dose radiation delivery. Similar to the treatment planning and delivery process for cranial radiosurgery, the emphasis is on sparing of adjacent normal tissues through the creation of steep dose gradients. Thus, advanced methods for assuring an accurate relationship between the target volume position and radiation beam geometry, immediately prior to radiation delivery, must be implemented. Such methods can employ imaging techniques such as planar (e.g., x-ray) or volumetric (e.g., computed tomography [CT]) approaches and are commonly summarized under the general term image-guided radiation therapy (IGRT). This review summarizes clinical experience with volumetric and ultrasound based image-guidance for SBRT. Additionally, challenges and potential limitations of pre-treatment image-guidance are presented and discussed.

  18. Precision optical navigation guidance system

    NASA Astrophysics Data System (ADS)

    Starodubov, D.; McCormick, K.; Nolan, P.; Johnson, D.; Dellosa, M.; Volfson, L.; Fallahpour, A.; Willner, A.

    2016-05-01

    We present the new precision optical navigation guidance system approach that provides continuous, high quality range and bearing data to fixed wing aircraft during landing approach to an aircraft carrier. The system uses infrared optical communications to measure range between ship and aircraft with accuracy and precision better than 1 meter at ranges more than 7.5 km. The innovative receiver design measures bearing from aircraft to ship with accuracy and precision better than 0.5 mRad. The system provides real-time range and bearing updates to multiple aircraft at rates up to several kHz, and duplex data transmission between ship and aircraft.

  19. Orthobiologic Interventions Using Ultrasound Guidance.

    PubMed

    Malanga, Gerard; Abdelshahed, Dena; Jayaram, Prathap

    2016-08-01

    The application of regenerative therapies for the treatment of musculoskeletal conditions has emerged over the last decade with recent acceleration. These include prolotherapy, platelet-rich plasma, and mesenchymal stem cell therapy. These strategies augment the body's innate physiology to heal pathologic processes. This article presents an overview of platelet-rich plasma and mesenchymal stem cell therapy for the treatment of musculoskeletal injuries. A brief literature review is included, as are techniques for the use of ultrasound guidance to assist with these procedures.

  20. Advanced glycation end-products impair Na⁺/K⁺-ATPase activity in diabetic cardiomyopathy: role of the adenosine monophosphate-activated protein kinase/sirtuin 1 pathway.

    PubMed

    Yuan, Qiong; Zhou, Qian-Yi; Liu, Du; Yu, Lun; Zhan, Lin; Li, Xiao-Jing; Peng, Hong-Yan; Zhang, Xiu-Ling; Yuan, Xin-Chu

    2014-02-01

    Decreased Na(+) /K(+) -ATPase activity, and both sirtuin 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) have been reported to be involved in the development of diabetic cardiomyopathy (DCM). The present study aimed to investigate the advanced glycation end-products (AGE) that impair Na(+) /K(+) -ATPase stability by regulating the AMPK/SIRT1 pathway during progression of DCM. To study type 1 diabetic mellitus (T1DM), a disease model in rats was established by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg), and neonatal rat cardiomyocytes were also cultured. Heart function was detected by Doppler, and SIRT1 and AMPK protein expression were detected by immunohistochemistry and western blotting. Na(+) /K(+) -ATPase activity was also monitored. Using in vivo rat models of DCM, we showed that Na(+) /K(+) -ATPase activity decreased when both AMPK and SIRT1 expression were downregulated. In vitro, AGE impaired Na(+) /K(+) -ATPase activity and decreased the AMPK and SIRT1 expression. Sirtuin 1 overexpression increased Na(+) /K(+) -ATPase activity. 5-aminoimidazole-4-carboxamide-3-ribonucleoside (AICAR) upregulated SIRT1 expression and increased Na(+) /K(+) -ATPase activity, which could be partially abolished by splitomicin. Our results suggest that the dysfunction of DCM is related to AGE-induced Na(+) /K(+) -ATPase activity impairment through a mechanism involving the AMPK/SIRT1 pathway.

  1. Distinct protein domains and expression patterns confer divergent axon guidance functions for Drosophila Robo receptors.

    PubMed

    Spitzweck, Bettina; Brankatschk, Marko; Dickson, Barry J

    2010-02-05

    The orthogonal array of axon pathways in the Drosophila CNS is constructed in part under the control of three Robo family axon guidance receptors: Robo1, Robo2 and Robo3. Each of these receptors is responsible for a distinct set of guidance decisions. To determine the molecular basis for these functional specializations, we used homologous recombination to create a series of 9 "robo swap" alleles: expressing each of the three Robo receptors from each of the three robo loci. We demonstrate that the lateral positioning of longitudinal axon pathways relies primarily on differences in gene regulation, not distinct combinations of Robo proteins as previously thought. In contrast, specific features of the Robo1 and Robo2 proteins contribute to their distinct functions in commissure formation. These specializations allow Robo1 to prevent crossing and Robo2 to promote crossing. These data demonstrate how diversification of expression and structure within a single family of guidance receptors can shape complex patterns of neuronal wiring.

  2. Aerocapture Guidance Algorithm Comparison Campaign

    NASA Technical Reports Server (NTRS)

    Rousseau, Stephane; Perot, Etienne; Graves, Claude; Masciarelli, James P.; Queen, Eric

    2002-01-01

    The aerocapture is a promising technique for the future human interplanetary missions. The Mars Sample Return was initially based on an insertion by aerocapture. A CNES orbiter Mars Premier was developed to demonstrate this concept. Mainly due to budget constraints, the aerocapture was cancelled for the French orbiter. A lot of studies were achieved during the three last years to develop and test different guidance algorithms (APC, EC, TPC, NPC). This work was shared between CNES and NASA, with a fruitful joint working group. To finish this study an evaluation campaign has been performed to test the different algorithms. The objective was to assess the robustness, accuracy, capability to limit the load, and the complexity of each algorithm. A simulation campaign has been specified and performed by CNES, with a similar activity on the NASA side to confirm the CNES results. This evaluation has demonstrated that the numerical guidance principal is not competitive compared to the analytical concepts. All the other algorithms are well adapted to guaranty the success of the aerocapture. The TPC appears to be the more robust, the APC the more accurate, and the EC appears to be a good compromise.

  3. Flight Guidance System Requirements Specification

    NASA Technical Reports Server (NTRS)

    Miller, Steven P.; Tribble, Alan C.; Carlson, Timothy M.; Danielson, Eric J.

    2003-01-01

    This report describes a requirements specification written in the RSML-e language for the mode logic of a Flight Guidance System of a typical regional jet aircraft. This model was created as one of the first steps in a five-year project sponsored by the NASA Langley Research Center, Rockwell Collins Inc., and the Critical Systems Research Group of the University of Minnesota to develop new methods and tools to improve the safety of avionics designs. This model will be used to demonstrate the application of a variety of methods and techniques, including safety analysis of system and subsystem requirements, verification of key properties using theorem provers and model checkers, identification of potential sources mode confusion in system designs, partitioning of applications based on the criticality of system hazards, and autogeneration of avionics quality code. While this model is representative of the mode logic of a typical regional jet aircraft, it does not describe an actual or planned product. Several aspects of a full Flight Guidance System, such as recovery from failed sensors, have been omitted, and no claims are made regarding the accuracy or completeness of this specification.

  4. Energy angular momentum closed-loop guidance

    NASA Astrophysics Data System (ADS)

    Patera, Russell P.

    2015-03-01

    A novel guidance algorithm for launch vehicle ascent to the desired mission orbit is proposed. The algorithm uses total specific energy and orbital angular momentum as new state vector parameters. These parameters are ideally suited for the ascent guidance task, since the guidance algorithm steers the launch vehicle along a pre-flight optimal trajectory in energy angular momentum space. The guidance algorithm targets apogee, perigee, inclination and right ascension of ascending node. Computational complexities are avoided by eliminating time in the guidance computation and replacing it with angular momentum magnitude. As a result, vehicle acceleration, mass, thrust, length of motor burns, and staging times are also eliminated from the pitch plane guidance calculations. The algorithm does not involve launch vehicle or target state propagation, which results in minimal computational effort. Proof of concept of the new algorithm is presented using several numerical examples that illustrate performance results.

  5. Collective cell migration: guidance principles and hierarchies.

    PubMed

    Haeger, Anna; Wolf, Katarina; Zegers, Mirjam M; Friedl, Peter

    2015-09-01

    Collective cell migration results from the establishment and maintenance of collective polarization, mechanocoupling, and cytoskeletal kinetics. The guidance of collective cell migration depends on a reciprocal process between cell-intrinsic multicellular organization with leader-follower cell behavior and results in mechanosensory integration of extracellular guidance cues. Important guidance mechanisms include chemotaxis, haptotaxis, durotaxis, and strain-induced mechanosensing to move cell groups along interfaces and paths of least resistance. Additional guidance mechanisms steering cell groups during specialized conditions comprise electrotaxis and passive drift. To form higher-order cell and tissue structures during morphogenesis and cancer invasion, these guidance principles act in parallel and are integrated for collective adaptation to and shaping of varying tissue environments. We review mechanochemical and electrical inputs and multiparameter signal integration underlying collective guidance, decision making, and outcome.

  6. Updating the Wnt pathways

    PubMed Central

    Yu, Jia; Virshup, David M.

    2014-01-01

    In the three decades since the discovery of the Wnt1 proto-oncogene in virus-induced mouse mammary tumours, our understanding of the signalling pathways that are regulated by the Wnt proteins has progressively expanded. Wnts are involved in an complex signalling network that governs multiple biological processes and cross-talk with multiple additional signalling cascades, including the Notch, FGF (fibroblast growth factor), SHH (Sonic hedgehog), EGF (epidermal growth factor) and Hippo pathways. The Wnt signalling pathway also illustrates the link between abnormal regulation of the developmental processes and disease manifestation. Here we provide an overview of Wnt-regulated signalling cascades and highlight recent advances. We focus on new findings regarding the dedicated Wnt production and secretion pathway with potential therapeutic targets that might be beneficial for patients with Wnt-related diseases. PMID:25208913

  7. A phase I pilot study of the insulin-like growth factor 1 receptor pathway modulator AXL1717 in combination with gemcitabine HCl and carboplatin in previously untreated, locally advanced, or metastatic non-small cell lung cancer.

    PubMed

    Holgersson, Georg; Bergström, Stefan; Harmenberg, Johan; Ringbom, Magnus; Klockare, Maria; Jerling, Markus; Ekman, Simon; Lundström, Kristina Lamberg; Koyi, Hirsh; Brandén, Eva; Larsson, Olle; Bergqvist, Michael

    2015-04-01

    AXL1717 is an orally bioavailable IGF-1R pathway modulator that has been shown to have anti-tumoral effects. The objectives of the present study were to define maximum tolerated dose and the recommended phase II dose (RPTD) of AXL1717 in combination with gemcitabine HCl and carboplatin in non-small cell lung cancer (NSCLC). Patients with previously untreated, locally advanced, or metastatic NSCLC (squamous cell cancer or adenocarcinoma) in good performance status and with preserved major organ functions were enrolled in the study. The study was an open-label phase I study with planned cohorts of three patients per dose level of AXL1717 (215, 290, and 390 mg BID). In total, 12 patients were enrolled in the study, and of these, two were prematurely excluded. AXL1717 was administered at one dose level, 215 mg BID. A total number of 81 unique adverse events were reported. Bone marrow toxicity was reported in 10 out of 12 patients, and this organ class showed the largest number of related events. AXL1717 in combination with gemcitabine HCl and carboplatin is a possible treatment approach in previously untreated, locally advanced, or metastatic non-small cell lung cancer. However, due to the bone marrow toxicity profile shown in the present study, further dose increases of AXL1717 above 215 mg BID will probably not be feasible. Therefore, 215 mg BID constitutes maximum tolerated dose and RPTD.

  8. Biodegradation pathway of an anionic surfactant (Igepon TC-42) during recycling waste water through plant hydroponics for advanced life support during long-duration space missions

    NASA Astrophysics Data System (ADS)

    Levine, L. H.; Kagie, H. R.; Garland, J. L.

    The degradation of an anionic surfactant (Igepon TC-42) was investigated as part of an integrated study of direct recycling of human hygiene water through hydroponic plant growth systems. Several chemical approaches were developed to characterize the degradation of Igepon and to measure the accumulation of intermediates such as fatty acids and methyl taurine. Igepon was rapidly degraded as indicated by the reduction of methylene blue active substances (MBAS) and component fatty acids. The Igepon degradation rate continued to increase over a period of several weeks following repeated daily exposure to 18 μg/l Igepon. The accumulation of free fatty acids and methyl taurine was also observed during decomposition of Igepon. The concentration of methyl taurine was below detection limit (0.2 nmol/ml) during the slow phase of Igepon degradation, and increased to 1-2 nmol/ml during the phase of rapid degradation. These findings support a degradation pathway involving initial hydrolysis of amide to release fatty acids and methyl taurine, and subsequent degradation of these intermediates.

  9. Biodegradation pathway of an anionic surfactant (Igepon TC-42) during recycling waste water through plant hydroponics for advanced life support during long-duration space missions.

    PubMed

    Levine, L H; Kagie, H R; Garland, J L

    2003-01-01

    The degradation of an anionic surfactant (Igepon TC-42) was investigated as part of an integrated study of direct recycling of human hygiene water through hydroponic plant growth systems. Several chemical approaches were developed to characterize the degradation of Igepon and to measure the accumulation of intermediates such as fatty acids and methyl taurine. Igepon was rapidly degraded as indicated by the reduction of methylene blue active substances (MBAS) and component fatty acids. The Igepon degradation rate continued to increase over a period of several weeks following repeated daily exposure to 18 micrograms/l Igepon. The accumulation of free fatty acids and methyl taurine was also observed during decomposition of Igepon. The concentration of methyl taurine was below detection limit (0.2 nmol/ml) during the slow phase of Igepon degradation, and increased to 1-2 nmol/ml during the phase of rapid degradation. These findings support a degradation pathway involving initial hydrolysis of amide to release fatty acids and methyl taurine, and subsequent degradation of these intermediates.

  10. Biodegradation pathway of an anionic surfactant (Igepon TC-42) during recycling waste water through plant hydroponics for advanced life support during long-duration space missions

    NASA Technical Reports Server (NTRS)

    Levine, L. H.; Kagie, H. R.; Garland, J. L.

    2003-01-01

    The degradation of an anionic surfactant (Igepon TC-42) was investigated as part of an integrated study of direct recycling of human hygiene water through hydroponic plant growth systems. Several chemical approaches were developed to characterize the degradation of Igepon and to measure the accumulation of intermediates such as fatty acids and methyl taurine. Igepon was rapidly degraded as indicated by the reduction of methylene blue active substances (MBAS) and component fatty acids. The Igepon degradation rate continued to increase over a period of several weeks following repeated daily exposure to 18 micrograms/l Igepon. The accumulation of free fatty acids and methyl taurine was also observed during decomposition of Igepon. The concentration of methyl taurine was below detection limit (0.2 nmol/ml) during the slow phase of Igepon degradation, and increased to 1-2 nmol/ml during the phase of rapid degradation. These findings support a degradation pathway involving initial hydrolysis of amide to release fatty acids and methyl taurine, and subsequent degradation of these intermediates. Published by Elsevier Science Ltd on behalf of COSPAR.

  11. Simulation of low thrust guidance problems

    NASA Technical Reports Server (NTRS)

    Dawkins, G. S.; Long, D.

    1974-01-01

    The determination of optimal rocket control profiles and the guidance procedures used to approximate these profiles have received much attention. Simple guidance procedures have sufficed for the Apollo flights. A modified version of the linear tangent guidance law is developed which can be used for a low-thrust orbital maneuvering system such as the space shuttle. The modification allows the estimation of gravity over long thrusting arcs which is necessary for low thrust systems.

  12. Comparative effectiveness of combined therapy inhibiting EGFR and VEGF pathways in patients with advanced non-small-cell lung cancer: a meta-analysis of 16 phase II/III randomized trials

    PubMed Central

    Cai, Shangli; Wu, Tongwei; Yan, Guangyue; Cheng, Sijin; Cui, Kang; Xi, Ying; Qi, Xiaolong; Zhang, Jie; Ma, Wang

    2017-01-01

    Background & Aims Combined therapy inhibiting EGFR and VEGF pathways is becoming a promising therapy in the treatment of advanced non-small-cell lung cancer (NSCLC), however, with controversy. The study aims to compare the efficacy of combined inhibition therapy versus control therapy (including placebo, single EGFR inhibition and single VEGF inhibition) in patients with advanced NSCLC. Materials and Methods An adequate literature search in EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was conducted. Phase II or III randomized controlled trials (RCTs) that compared effectiveness between combined inhibition therapy and control therapy in patients with advanced NSCLC were eligible. The endpoint was overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Results Sixteen phase II or III RCTs involving a total of 7,109 patients were included. The results indicated that the combined inhibition therapy significantly increased the ORR (OR = 1.59, 95% CI = 1.36-1.87, p<0.00001; I2 = 36%) when compared to control therapy. In the subgroup analysis, the combined inhibition therapy clearly increased the ORR (OR = 2.04, 95% CI = 1.60-2.60, p<0.00001; I2 = 0%) and improved the PFS (HR = 0.78, 95% CI = 0.71-0.85, p<0.00001;I2 = 0%) when compared with the placebo, and similar results was detected when compared with the single EGFR inhibition in terms of ORR (OR = 1.39, 95% CI = 1.12-1.74, p = 0.003; I2 = 30%) and PFS (HR = 0.73, 95% CI = 0.67-0.81, p<0.0001; I2 = 50%). No obvious difference was found between the combined inhibition therapy and single VEGF inhibition in term of ORR, however, combined inhibition therapy significantly decreased the PFS when compared to the single VEGF inhibition therapy (HR = 1.70, 95% CI = 1.34-2.17, p<0.0001; I2 = 50%). Besides, no significant difference was observed between the combined inhibition therapy

  13. New perspectives in cyclic AMP-mediated axon growth and guidance: The emerging epoch of Epac.

    PubMed

    Peace, Andrew G; Shewan, Derryck A

    2011-03-10

    In the search for a cure to brain and spinal cord injury much has been learned about the inhibitory environment of the central nervous system (CNS), and yet a clinical therapy remains elusive. In recent years great advances have been made in understanding intracellular molecular mechanisms that transduce cell surface receptor-mediated signals that neurons receive from their environment. Many of these signalling pathways share common mechanisms, which presents the possibility that manipulating activities of key cell signalling molecules such as those regulated by 3'-5'-cyclic adenosine monophosphate (cAMP) might allow axons to simultaneously overcome the inhibitory effects of a number of extracellular ligands. The identification of Epac, a novel direct intracellular target for cAMP, has opened up a new avenue of research that is beginning to explain how cAMP can mediate a range of neuronal functions including distinct axon growth and guidance decisions. With current research tools that allow more specific activation of proteins or knock-down of their expression, as well as quantitation of protein activities in live cells, it is already becoming clear that Epac plays highly important roles in the development and function of the nervous system. Here, we focus on emerging evidence that Epac mediates cAMP-regulated axon growth and chemoattraction, and thus represents a novel target for overcoming axon growth inhibition and promoting CNS regeneration.

  14. Virtual Ultrasound Guidance for Inexperienced Operators

    NASA Technical Reports Server (NTRS)

    Caine, Timothy; Martin, Davis

    2012-01-01

    Medical ultrasound or echocardiographic studies are highly operator-dependent and generally require lengthy training and internship to perfect. To obtain quality echocardiographic images in remote environments, such as on-orbit, remote guidance of studies has been employed. This technique involves minimal training for the user, coupled with remote guidance from an expert. When real-time communication or expert guidance is not available, a more autonomous system of guiding an inexperienced operator through an ultrasound study is needed. One example would be missions beyond low Earth orbit, in which the time delay inherent with communication will make remote guidance impractical.

  15. Comparison of EGFR signaling pathway somatic DNA mutations derived from peripheral blood and corresponding tumor tissue of patients with advanced non-small-cell lung cancer using liquidchip technology.

    PubMed

    Zhang, Hui; Liu, Deruo; Li, Shanqing; Zheng, Yongqing; Yang, Xinjie; Li, Xi; Zhang, Quan; Qin, Na; Lu, Jialin; Ren-Heidenreich, Lifen; Yang, Huiyi; Wu, Yuhua; Zhang, Xinyong; Nong, Jingying; Sun, Yifen; Zhang, Shucai

    2013-11-01

    Somatic DNA mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway are known to predict responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers. We evaluated a sensitive liquidchip platform for detecting EGFR, KRAS (alias Ki-ras), proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations in plasma samples, which were highly correlated with matched tumor tissues from 86 patients with advanced non-small-cell lung cancers. Either EGFR exon 19 or 21 mutations were detected in 36 patients: 23 of whom had identical mutations in both their blood and tissue samples; whereas mutations in the remaining 13 were found only in their tumor samples. These EGFR mutations occurred at a significantly higher frequency in females, never-smokers, and in patients with adenocarcinomas (P ≤ 0.001). The EGFR exon 20 T790M mutation was detected in only one of the paired samples [100% (95% CI, 96% to 100%) agreement]. For KRAS, proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations, the overall agreements were 97% (95% CI, 90% to 99%), 98% (95% CI, 92% to 99%), and 97% (95% CI, 90% to 99%), respectively, and these were not associated with age, sex, smoking history, or histopathologic type. In conclusion, mutations detected in plasma correlated strongly with mutation profiles in each respective tumor sample, suggesting that this liquidchip platform may offer a rapid and noninvasive method for predicting tumor responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers.

  16. Evaluation of Guidance Control Accuracy during Rendezvous Docking Experiment of ETS-VII

    NASA Astrophysics Data System (ADS)

    Kawano, Isao; Mokuno, Masaaki; Suzuki, Takashi; Koyama, Hiroshi; Kunugi, Makoto

    ETS-VII is a test satellite to perform in-orbit demonstration of autonomous rendezvous docking (RVD) technology, which will be necessary for advanced space activities in the early 21st century. ETS-VII performed three RVD experiment flights, and verified all technical items. Three types of guidance and control method were used in three approach phases; C-W guidance law in relative approach phase, reference trajectory guidance law in final approach phase, and relative 6 degree of freedom control in docking phase respectively. We present ETS-VII RVD guidance and control system, and evaluation of its on-orbit performance in this paper. Its performance was better than requirement in each phases.

  17. Argonne Liquid-Metal Advanced Burner Reactor : components and in-vessel system thermal-hydraulic research and testing experience - pathway forward.

    SciTech Connect

    Kasza, K.; Grandy, C.; Chang, Y.; Khalil, H.; Nuclear Engineering Division

    2007-06-30

    This white paper provides an overview and status report of the thermal-hydraulic nuclear research and development, both experimental and computational, conducted predominantly at Argonne National Laboratory. Argonne from the early 1970s through the early 1990s was the Department of Energy's (DOE's) lead lab for thermal-hydraulic development of Liquid Metal Reactors (LMRs). During the 1970s and into the mid-1980s, Argonne conducted thermal-hydraulic studies and experiments on individual reactor components supporting the Experimental Breeder Reactor-II (EBR-II), Fast Flux Test Facility (FFTF), and the Clinch River Breeder Reactor (CRBR). From the mid-1980s and into the early 1990s, Argonne conducted studies on phenomena related to forced- and natural-convection thermal buoyancy in complete in-vessel models of the General Electric (GE) Prototype Reactor Inherently Safe Module (PRISM) and Rockwell International (RI) Sodium Advanced Fast Reactor (SAFR). These two reactor initiatives involved Argonne working closely with U.S. industry and DOE. This paper describes the very important impact of thermal hydraulics dominated by thermal buoyancy forces on reactor global operation and on the behavior/performance of individual components during postulated off-normal accident events with low flow. Utilizing Argonne's LMR expertise and design knowledge is vital to the further development of safe, reliable, and high-performance LMRs. Argonne believes there remains an important need for continued research and development on thermal-hydraulic design in support of DOE's and the international community's renewed thrust for developing and demonstrating the Global Nuclear Energy Partnership (GNEP) reactor(s) and the associated Argonne Liquid Metal-Advanced Burner Reactor (LM-ABR). This white paper highlights that further understanding is needed regarding reactor design under coolant low-flow events. These safety-related events are associated with the transition from normal high

  18. Federal Guidance Report No. 8: Guidance for the Control of Radiation Hazards in Uranium Mining

    EPA Pesticide Factsheets

    This report contains background material used in the development of guidance concerning radiation protection in the mining of uranium ore, and seeks to provide guidance for long-term radiation protection in uranium mining.

  19. Vehicle health management for guidance, navigation and control systems

    NASA Technical Reports Server (NTRS)

    Radke, Kathleen; Frazzini, Ron; Bursch, Paul; Wald, Jerry; Brown, Don

    1993-01-01

    The objective of the program was to architect a vehicle health management (VHM) system for space systems avionics that assures system readiness for launch vehicles and for space-based dormant vehicles. The platforms which were studied and considered for application of VHM for guidance, navigation and control (GN&C) included the Advanced Manned Launch System (AMLS), the Horizontal Landing-20/Personnel Launch System (HL-20/PLS), the Assured Crew Return Vehicle (ACRV) and the Extended Duration Orbiter (EDO). This set was selected because dormancy and/or availability requirements are driving the designs of these future systems.

  20. Micro guidance and control synthesis: New components, architectures, and capabilities

    NASA Technical Reports Server (NTRS)

    Mettler, Edward; Hadaegh, Fred Y.

    1993-01-01

    New GN&C (guidance, navigation and control) system capabilities are shown to arise from component innovations that involve the synergistic use of microminiature sensors and actuators, microelectronics, and fiber optics. Micro-GN&C system and component concepts are defined that include micro-actuated adaptive optics, micromachined inertial sensors, fiber-optic data nets and light-power transmission, and VLSI microcomputers. The thesis is advanced that these micro-miniaturization products are capable of having a revolutionary impact on space missions and systems, and that GN&C is the pathfinder micro-technology application that can bring that about.

  1. Longwall Guidance and Control Development

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The longwall guidance and control (G&C) system was evaluated to determine which systems and subsystems lent themselves to automatic control in the mining of coal. The upper coal/shale interface was identified as the reference for a vertical G&C system, with two sensors (the natural backgound and the sensitized pick) being used to locate and track this boundary. In order to insure a relatively smooth recession surface (roof and floor of the excavated seam), a last and present cut measuring instrument (acoustic sensor) was used. Potentiometers were used to measure elevations of the shearer arms. The intergration of these components comprised the vertical control system (pitch control). Yaw and roll control were incorporated into a face alignment system which was designed to keep the coal face normal to its external boundaries. Numerous tests, in the laboratory and in the field, have confirmed the feasibility of automatic horizon control, as well as determining the face alignment.

  2. Orion Cislunar Guidance and Navigation

    NASA Technical Reports Server (NTRS)

    D'Souza, Christopher; Crain, Timothy; Clark, Fred C.

    2007-01-01

    The Orion vehicle is being designed to provide nominal crew transport to the lunar transportation stack in low Earth orbit, crew abort prior during transit to the moon, and crew return to Earth once lunar orbit is achieved. Design of guidance and navigation algorithms to perform maneuvers in support of these functions is dependent on the support provided by navigation infrastructure, the performance of the onboard GN&C system, and the choice of trajectory maneuver methodology for outbound and return mission phases. This paper documents the preliminary integrated analyses performed by members of the Orion Orbit GN&C System team investigating the navigation update accuracy of a modern equivalent to the Apollo era ground tracking network and the expected onboard dispersion and navigation errors during a lunar mission using a linear covariance error analysis technique.

  3. Aerocapture - Guidance, navigation, and control

    NASA Astrophysics Data System (ADS)

    Mease, K. D.; Weidner, R. J.; Kechichian, J. A.; Wood, L. J.; Cruz, M. I.

    1982-08-01

    Aerocapture is a concept for inserting a spacecraft into orbit about a target planet. The energy required for orbit insertion is obtained from natural resources present at or near the target body, thereby reducing the amount of propellant which must be carried onboard. Specifically, the transfer from a hyperbolic flyby trajectory to a desired bound orbit is effected by aerodynamic lift and drag forces acting on the spacecraft during controlled flight through the atmosphere of either the target planet or a nearby satellite. A survey is provided of the trajectory guidance, navigation, and control aspects of aerocapture, and a summary is given of the results of a number of preliminary studies concerning certain of these aspects. The investigation has additional significance in connection with the current interest in aeroassisted orbital transfer vehicles, which may be used in conjunction with the Space Shuttle.

  4. Aerocapture - Guidance, navigation, and control

    NASA Technical Reports Server (NTRS)

    Mease, K. D.; Weidner, R. J.; Kechichian, J. A.; Wood, L. J.; Cruz, M. I.

    1982-01-01

    Aerocapture is a concept for inserting a spacecraft into orbit about a target planet. The energy required for orbit insertion is obtained from natural resources present at or near the target body, thereby reducing the amount of propellant which must be carried onboard. Specifically, the transfer from a hyperbolic flyby trajectory to a desired bound orbit is effected by aerodynamic lift and drag forces acting on the spacecraft during controlled flight through the atmosphere of either the target planet or a nearby satellite. A survey is provided of the trajectory guidance, navigation, and control aspects of aerocapture, and a summary is given of the results of a number of preliminary studies concerning certain of these aspects. The investigation has additional significance in connection with the current interest in aeroassisted orbital transfer vehicles, which may be used in conjunction with the Space Shuttle.

  5. Endangerment assessment guidance. Final report

    SciTech Connect

    Not Available

    1985-10-21

    The directive clarifies the requirement that an endangerment assessment be developed to support all administrative and judicial enforcement actions under Section 106 of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) and Section 7003 of the Resource Conservation and Recovery Act (RCRA). Before taking enforcement action under these provisions to abate the hazards or potential hazards at a site, the Environmental Protection Agency (EPA) must be able to properly document and justify its assertion that an imminent and substantial endangerment to public health or welfare or the environment may exist. The endangerment assessment provides the documentation and justification. The endangerment assessment is not necessary to support Section 104 actions. It also provides guidance on the content, timing, level of detail, format, and resources required for the preparation of endangerment assessments.

  6. Guidance, Navigation, and Control Program

    NASA Technical Reports Server (NTRS)

    Hinkel, Heather; Tamblyn, Scott; Jackson, William L.; Foster, Chris; Brazzel, Jack; Manning, Thomas R.; Clark, Fred; Spehar, Pete; Barrett, Jim D.; Milenkovic, Zoran

    2011-01-01

    The Rendezvous and Proximity Operations Program (RPOP) is real-time guidance, navigation, and control (GN&C) domain piloting-aid software that provides 3D Orbiter graphics and runs on the Space Shuttle's Criticality-3 Payload and General Support Computer (PGSC) in the crew cockpit. This software provides the crew with Situational Awareness during the rendezvous and proximity operations phases of flight. RPOP can be configured from flight to flight, accounting for mission-specific flight scenarios and target vehicles, via initialization load (I-load) data files. The software provides real-time, automated, closed-loop guidance recommendations and the capability to integrate the crew s manual backup techniques. The software can bring all relative navigation sensor data, including the Orbiter's GPC (general purpose computer) data, into one central application to provide comprehensive situational awareness of the rendezvous and proximity operations trajectory. RPOP also can separately maintain trajectory estimates (past, current, and predicted) based on certain data types and co-plot them, in order to show how the various navigation solutions compare. RPOP s best estimate of the relative trajectory is determined by a relative Kalman filter processing data provided by the sensor suite s most accurate sensor, the trajectory control sensor (TCS). Integrated with the Kalman filter is an algorithm that identifies the reflector that the TCS is tracking. Because RPOP runs on PC laptop computers, the development and certification lifecycles are more agile, flexible, and cheaper than those that govern the Orbiter FSW (flight software) that runs in the GPC. New releases of RPOP can be turned around on a 3- to 6-month template, from new Change Request (CR) to certification, depending on the complexity of the changes.

  7. 78 FR 48175 - Retrospective Review of Draft Guidance Documents Issued Before 2010; Withdrawal of Guidances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-07

    ... to the pharmaceutical industry. In most cases, FDA has developed other guidances and resources to... guidances: 1. ``Manufacturing, Processing, or Holding Active Pharmaceutical Ingredients''--issued April 1998... guidances (number 19 through 22), contact the Office of Pharmaceutical Science in CDER. 23. ``Qualifying...

  8. A soluble receptor for advanced glycation end-products inhibits myocardial apoptosis induced by ischemia/reperfusion via the JAK2/STAT3 pathway.

    PubMed

    Jiang, Xue; Guo, Cai-xia; Zeng, Xiang-jun; Li, Hui-hua; Chen, Bu-xing; Du, Feng-he

    2015-08-01

    /2 inhibitor PD98059. These results suggest that sRAGE protects cardiomyocytes from apoptosis induced by I/R in vitro and in vivo by activating the JAK2/STAT3 signaling pathway.

  9. Atmospheric Ascent Guidance for Rocket-Powered Launch Vehicles

    NASA Technical Reports Server (NTRS)

    Dukeman, Greg A.

    2002-01-01

    An advanced ascent guidance algorithm for rocket- powered launch vehicles is developed. This algorithm cyclically solves the calculus-of-variations two-point boundary-value problem starting at vertical rise completion through main engine cutoff. This is different from traditional ascent guidance algorithms which operate in a simple open-loop mode until high dynamic pressure (including the critical max-Q) portion of the trajectory is over, at which time guidance operates under the assumption of negligible aerodynamic acceleration (i.e., vacuum dynamics). The initial costate guess is corrected based on errors in the terminal state constraints and the transversality conditions. Judicious approximations are made to reduce the order and complexity of the state/costate system. Results comparing guided launch vehicle trajectories with POST open-loop trajectories are given verifying the basic formulation of the algorithm. Multiple shooting is shown to be a very effective numerical technique for this application. In particular, just one intermediate shooting point, in addition to the initial shooting point, is sufficient to significantly reduce sensitivity to the guessed initial costates. Simulation results from a high-fidelity trajectory simulation are given for the case of launch to sub-orbital cutoff conditions as well as launch to orbit conditions. An abort to downrange landing site formulation of the algorithm is presented.

  10. Advanced oxidation protein products decrease the expression of calcium transport channels in small intestinal epithelium via the p44/42 MAPK signaling pathway.

    PubMed

    Wu, Peiqun; Xie, Fang; Xue, Minmin; Xu, Xiaoping; He, Shuying; Lin, Minyi; Bai, Lan

    2015-05-01

    Advanced oxidation protein products (AOPPs), novel protein markers of oxidative damage, accumulate in the plasma of patients with inflammatory bowel disease (IBD). Osteoporosis, which is closely related to the regulation of intestinal calcium transport channels (CTCs), is a prevalent extraintestinal complication of IBD and is associated with oxidative stress. However, the underlying mechanisms are unknown. The present study aimed to verify whether AOPPs inhibit CTCs in the small intestinal epithelium and to identify the underlying mechanisms that may contribute to IBD-associated osteoporosis. Normal Sprague-Dawley rats were treated with AOPP-modified rat serum albumin. The calcium ion level in serum was not significantly altered, while the duodenal expression of CTCs (e.g. transient receptor potential vanilloid [TRPV6], calbindin-D9k [CaBP-D9k], plasma membrane Ca(2+)-ATPase 1 [PMCA1], and Na(+)/Ca(2+) exchanger 1 [NCX1]) were decreased. In contrast, the levels of the related hormones that regulate calcium absorption including parathyroid hormone (PTH), 25-(OH)D₃, and 1,25-(OH)₂D₃ were increased, although the trend toward an increase in PTH levels was not significant. In order to further investigate the effects of AOPP exposure, we also evaluated the expression of CTCs (including the voltage-dependent L-type calcium channel [CaV1.3], TRPV6, CaBP-D9k, PMCA1, and NCX1) in cultured human colorectal adenocarcinoma cells (Caco-2). The expression levels of total CTC protein and mRNA, except for CaV1.3, were significantly down-regulated in a concentration- and time-dependent manner. Moreover, phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) was observed in vivo and in vitro. The p44/42 inhibitor U0126 reversed the down-regulation of CTCs induced by AOPPs in the Caco-2 monolayer. Our results indicate that AOPPs down-regulate the expression of CTCs through p44/42 MAPK signaling mechanisms in the small intestinal epithelium. These data provide new

  11. Getting Closer: Workplace Guidance for Lifelong Learning

    ERIC Educational Resources Information Center

    Plant, Peter; Turner, Bob

    2005-01-01

    The purposes of this article are twofold. First, it considers the policy links between guidance and lifelong learning, highlighting in particular the implications of findings from a recent study by the Organisation for Economic Co-operation and Development (OECD). Secondly, it critically compares two approaches to workplace guidance about…

  12. Social Benefits of Career Guidance. NICEC Briefing.

    ERIC Educational Resources Information Center

    Killeen, John; Watts, Tony; Kidd, Jenny

    Social benefits can be thought of as aggregates of individual benefits, though with possible "snowball" effects. Potential social benefits of career guidance fall into the following two main categories: reducing social exclusion and enhancing social development. Guidance is a way of making the structure of society work, by linking…

  13. Elementary School Guidance Work Conference. Conference Report.

    ERIC Educational Resources Information Center

    Herr, Edwin L.; Hershberger, James K.

    In October, 1967, 100 invited participants representing all aspects of guidance, education, school administration, counselor education, psychology, and interested government agencies in Pennsylvania met for three days to listen, think, discuss, and hopefully develop some recommendations for those who want a better program of elementary guidance.…

  14. Foundations for Policy in Guidance and Counseling.

    ERIC Educational Resources Information Center

    Herr, Edwin L., Ed.; Pinson, Nancy M., Ed.

    This book provides educators, counselors, policy makers, and community members with information about the state of the art of federal and state policy in guidance and counseling. The two chapters in part 1, Overview, are: "Foundations for Policy in Guidance and Counseling: An Introduction", by Edwin L. Herr and Nancy M. Pinson; and "A Counselor…

  15. Career Guidance and Public Mental Health

    ERIC Educational Resources Information Center

    Robertson, Peter J.

    2013-01-01

    Career guidance may have the potential to promote public health by contributing positively to both the prevention of mental health conditions and to population level well-being. The policy implications of this possibility have received little attention. Career guidance agencies are well placed to reach key target groups. Producing persuasive…

  16. Guidance trajectories for aeroassisted orbital transfer

    NASA Technical Reports Server (NTRS)

    Miele, A.

    1990-01-01

    Research on aerobraking guidance schemes is presented. The intent is to produce aerobraking guidance trajectories exhibiting many of the desirable characteristics of optimal aerobraking trajectories. Both one-control schemes and two-control schemes are studied. The research is in the interest of aeroassisted flight experiment vehicles (AFE) and aeroassisted orbital transfer (AOT) vehicles.

  17. Guidance in Adult and Continuing Education.

    ERIC Educational Resources Information Center

    McNamara, Gerry

    The provision of guidance in adult and continuing education in Ireland was examined. First, policy in Ireland regarding guidance for adults in education is discussed in the context of the proposals adopted by the European Union (EU) Commission and EU Member States pursuant to the EU Year of Lifelong Learning in 1996. Recent literature on career…

  18. 48 CFR 427.104 - General guidance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false General guidance. 427.104 Section 427.104 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS General 427.104 General guidance. As used in FAR part 27, the...

  19. 48 CFR 27.102 - General guidance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false General guidance. 27.102 Section 27.102 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS General 27.102 General guidance. (a) The Government encourages...

  20. 48 CFR 27.102 - General guidance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false General guidance. 27.102 Section 27.102 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS General 27.102 General guidance. (a) The Government encourages...

  1. 48 CFR 27.102 - General guidance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false General guidance. 27.102 Section 27.102 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS General 27.102 General guidance. (a) The Government encourages...

  2. 21 CFR 312.145 - Guidance documents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Guidance documents. 312.145 Section 312.145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Miscellaneous § 312.145 Guidance documents. (a) FDA...

  3. Guidance for performing preliminary assessments under CERCLA

    SciTech Connect

    1991-09-01

    EPA headquarters and a national site assessment workgroup produced this guidance for Regional, State, and contractor staff who manage or perform preliminary assessments (PAs). EPA has focused this guidance on the types of sites and site conditions most commonly encountered. The PA approach described in this guidance is generally applicable to a wide variety of sites. However, because of the variability among sites, the amount of information available, and the level of investigative effort required, it is not possible to provide guidance that is equally applicable to all sites. PA investigators should recognize this and be aware that variation from this guidance may be necessary for some sites, particularly for PAs performed at Federal facilities, PAs conducted under EPA`s Environmental Priorities Initiative (EPI), and PAs at sites that have previously been extensively investigated by EPA or others. The purpose of this guidance is to provide instructions for conducting a PA and reporting results. This guidance discusses the information required to evaluate a site and how to obtain it, how to score a site, and reporting requirements. This document also provides guidelines and instruction on PA evaluation, scoring, and the use of standard PA scoresheets. The overall goal of this guidance is to assist PA investigators in conducting high-quality assessments that result in correct site screening or further action recommendations on a nationally consistent basis.

  4. 77 FR 48591 - State Rail Plan Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ... Federal Railroad Administration State Rail Plan Guidance AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Request for Public Comment on Proposed State Rail Plan Guidance..., submission, and acceptance of State rail plans. State rail plans are documents that are required...

  5. Gifted Child Development and Guidance Study.

    ERIC Educational Resources Information Center

    Virginia Beach City Public Schools, VA.

    The Gifted Child Development and Guidance Program of Virginia Beach City (Virginia) Public Schools was developed to interest gifted college-bound students in a vocational class in child development and guidance that might lead to further career interest in child-related professions. This report briefly describes program promotion; student…

  6. 78 FR 67442 - Congestion Mitigation and Air Quality Improvement Program Interim Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-12

    ... Federal Highway Administration Congestion Mitigation and Air Quality Improvement Program Interim Guidance... Mitigation and Air Quality Improvement (CMAQ) Program (Interim Guidance). The Interim Guidance revises CMAQ....gov/environment/air_quality/cmaq/policy_and_guidance/2008_guidance/ guidance/. DATES: This...

  7. Pollen tube guidance by attractant molecules: LUREs.

    PubMed

    Okuda, Satohiro; Higashiyama, Tetsuya

    2010-01-01

    Sexual reproduction in flowering plants requires pollen-tube guidance, which is thought to be mediated by chemoattractants derived from target ovules. To date, however, no convincing evidence has been reported of a particular molecule being the true attractant. Emerging data indicate that two synergid cells, which are on either side of the egg cell, emit a diffusible, species-specific signal to attract the pollen tube at the last step of pollen-tube guidance. Recently, it was demonstrated that LUREs (LURE1 and LURE2), cysteine-rich polypeptides secreted from the synergid cell, are the key molecules in pollen-tube guidance. In this review, we summarize the mechanism of pollen-tube guidance, with special focus on gametophytic guidance and the attractants.

  8. Approach guidance for outer planet pioneer missions

    NASA Technical Reports Server (NTRS)

    Bejczy, A. K.

    1975-01-01

    Onboard optical approach guidance measurements for spin-stabilized Pioneer-type spacecraft are discussed. Approach guidance measurement accuracy requirements are outlined. The application concept and operation principle of the V-slit star tracker are discussed within the context of approach guidance measurements and measurables. It is shown that the accuracy of onboard optical approach guidance measurements is inherently coupled to the stability characteristics of the spacecraft spin axis. Geometrical and physical measurement parameters are presented for Pioneer entry probe missions to Uranus via Jupiter or Saturn flyby. The impact of these parameters on both sensor instrumentation and measurement system design is discussed. The need for sensing extended objects is shown. The feasibility of implementing an onboard approach guidance measurement system for Pioneer-type spacecraft is indicated. Two Pioneer 10 onboard measurement experiments performed in May-June 1974 are described.

  9. Appropriation from a Script Theory of Guidance Perspective: A Response to Pierre Tchounikine

    ERIC Educational Resources Information Center

    Stegmann, Karsten; Kollar, Ingo; Weinberger, Armin; Fischer, Frank

    2016-01-01

    In a recent paper, Pierre Tchounikine has suggested to advance the Script Theory of Guidance (SToG) by addressing the question how learners appropriate collaboration scripts presented to them in learning environments. Tchounikine's main criticism addresses SToG's "internal script configuration principle." This principle states that in…

  10. Draxin, an axon guidance protein, affects chick trunk neural crest migration.

    PubMed

    Su, Yuhong; Naser, Iftekhar B; Islam, Shahidul M; Zhang, Sanbing; Ahmed, Giasuddin; Chen, Sandy; Shinmyo, Yohei; Kawakami, Minoru; Yamamura, Ken-ichi; Tanaka, Hideaki

    2009-12-01

    The neural crest is a multipotent population of migratory cells that arises in the central nervous system and subsequently migrates along defined stereotypic pathways. In the present work, we analyzed the role of a repulsive axon guidance protein, draxin, in the migration of neural crest cells. Draxin is expressed in the roof plate of the chick trunk spinal cord and around the early migration pathway of neural crest cells. Draxin modulates chick neural crest cell migration in vitro by reducing the polarization of these cells. When exposed to draxin, the velocity of migrating neural crest cells was reduced, and the cells changed direction so frequently that the net migration distance was also reduced. Overexpression of draxin also caused some early migrating neural crest cells to change direction to the dorsolateral pathway in the chick trunk region, presumably due to draxin's inhibitory activity. These results demonstrate that draxin, an axon guidance protein, can also affect trunk neural crest migration in the chick embryo.

  11. Peptide Sharing Between Influenza A H1N1 Hemagglutinin and Human Axon Guidance Proteins

    PubMed Central

    Kanduc, Darja

    2014-01-01

    Epidemiologic data suggest that maternal microbial infections may cause fetal neurodevelopmental disorders, potentially increasing susceptibility to heavy psychopathologies such as schizophrenia, schizophreniform disorder, autism, pervasive developmental disorders, bipolar disorders, psychosis, epilepsy, language and speech disorders, and cognitive impairment in adult offspring. However, the molecular pathomechanisms underlying such a relationship are not clear. Here we analyze the potential role of the maternal immune response to viral infection in determining fetal brain injuries that increase the risk of neurological disorders in the adult. We use influenza infection as a disease model and human axon guidance pathway, a key process in the formation of neural network during midgestation, as a potential fetal target of immune insults. Specifically, we examined influenza A H1N1 hemagglutinin (HA), an antigenic viral protein, for amino acid sequence similarity to a random library of 188 axon guidance proteins. We obtain the results that (1) contrary to any theoretical expectations, 45 viral pentapeptide matches are distributed throughout a subset of 36 guidance molecules; (2) in 24 guidance proteins, the peptide sharing with HA antigen involves already experimentally validated influenza HA epitopes; and (3) most of the axon guidance vs HA peptide overlap is conserved among influenza A viral strains and subsets. Taken together, our data indicate that immune cross-reactivity between influenza HA and axon guidance molecules is possible and may well represent a pathologic mechanism capable of determining neurodevelopmental disruption in the fetus. PMID:23378012

  12. Advanced oxidation protein products induce intestine epithelial cell death through a redox-dependent, c-jun N-terminal kinase and poly (ADP-ribose) polymerase-1-mediated pathway.

    PubMed

    Xie, F; Sun, S; Xu, A; Zheng, S; Xue, M; Wu, P; Zeng, J H; Bai, L

    2014-01-16

    Advanced oxidation protein products (AOPPs), a novel protein marker of oxidative damage, have been confirmed to accumulate in patients with inflammatory bowel disease (IBD), as well as those with diabetes and chronic kidney disease. However, the role of AOPPs in the intestinal epithelium remains unclear. This study was designed to investigate whether AOPPs have an effect on intestinal epithelial cell (IEC) death and intestinal injury. Immortalized rat intestinal epithelial (IEC-6) cells and normal Sprague Dawley rats were treated with AOPP-albumin prepared by incubation of rat serum albumin (RSA) with hypochlorous acid. Epithelial cell death, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit activity, reactive oxygen species (ROS) generation, apoptosis-related protein expression, and c-jun N-terminal kinase (JNK) phosphorylation were detected both in vivo and in vitro. In addition, we measured AOPPs deposition and IEC death in 23 subjects with Crohn's disease (CD). Extracellular AOPP-RSA accumulation induced apoptosis in IEC-6 cultures. The triggering effect of AOPPs was mainly mediated by a redox-dependent pathway, including NADPH oxidase-derived ROS generation, JNK phosphorylation, and poly (ADP-ribose) polymerase-1 (PARP-1) activation. Chronic AOPP-RSA administration to normal rats resulted in AOPPs deposition in the villous epithelial cells and in inflammatory cells in the lamina propria. These changes were companied with IEC death, inflammatory cellular infiltration, and intestinal injury. Both cell death and intestinal injury were ameliorated by chronic treatment with apocynin. Furthermore, AOPPs deposition was also observed in IECs and inflammatory cells in the lamina propria of patients with CD. The high immunoreactive score of AOPPs showed increased apoptosis. Our results demonstrate that AOPPs trigger IEC death and intestinal tissue injury via a redox-mediated pathway. These data suggest that AOPPs may represent a novel pathogenic factor

  13. Space shuttle guidance, navigation, and control design equations. Volume 3: Guidance

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Space shuttle guidance, navigation, and control design equations are presented. The space-shuttle mission includes three relatively distinct guidance phases which are discussed; atmospheric boost, which is characterized by an adaptive guidance law; extra-atmospheric activities; and re-entry activities, where aerodynamic surfaces are the principal effectors. Guidance tasks include pre-maneuver targeting and powered flight guidance, where powered flight is defined to include the application of aerodynamic forces as well as thruster forces. A flow chart which follows guidance activities throughout the mission from the pre-launch phase through touchdown is presented. The main guidance programs and subroutines used in each phase of a typical rendezvous mission are listed. Detailed software requirements are also presented.

  14. Guidance, Navigation, and Control Considerations for Nuclear Thermal Propulsion

    NASA Technical Reports Server (NTRS)

    Houts, Michael G.; Mitchell, Doyce P.; Kim, Tony

    2015-01-01

    The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation NTP system could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of a first generation NTP in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NTP project could also help enable high performance fission power systems and Nuclear Electric Propulsion (NEP). Guidance, navigation, and control of NTP may have some unique but manageable characteristics.

  15. ADGS-2100 Adaptive Display and Guidance System Window Manager Analysis

    NASA Technical Reports Server (NTRS)

    Whalen, Mike W.; Innis, John D.; Miller, Steven P.; Wagner, Lucas G.

    2006-01-01

    Recent advances in modeling languages have made it feasible to formally specify and analyze the behavior of large system components. Synchronous data flow languages, such as Lustre, SCR, and RSML-e are particularly well suited to this task, and commercial versions of these tools such as SCADE and Simulink are growing in popularity among designers of safety critical systems, largely due to their ability to automatically generate code from the models. At the same time, advances in formal analysis tools have made it practical to formally verify important properties of these models to ensure that design defects are identified and corrected early in the lifecycle. This report describes how these tools have been applied to the ADGS-2100 Adaptive Display and Guidance Window Manager being developed by Rockwell Collins Inc. This work demonstrates how formal methods can be easily and cost-efficiently used to remove defects early in the design cycle.

  16. 78 FR 54949 - Major Project Financial Plan Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-06

    ... TRANSPORTATION Federal Highway Administration Major Project Financial Plan Guidance AGENCY: Federal Highway... Major Project Financial Plan Guidance outlining the procedures the FHWA will follow when reviewing and approving Financial Plans. The proposed Major Project Financial Plan Guidance incorporates changes...

  17. The Development of Vocational Guidance in the USSR.

    ERIC Educational Resources Information Center

    Kostin, L. A.

    1986-01-01

    The author defines the scope and importance of vocational guidance in the Soviet Union. He states that such guidance is primarily for youth. He discusses the institutional framework of vocational guidance programs and new developments in the Soviet Union. (CH)

  18. 76 FR 411 - Regulatory Guidance Concerning Electronic Signatures and Documents

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ... Federal Motor Carrier Safety Administration Regulatory Guidance Concerning Electronic Signatures and... guidance. SUMMARY: FMCSA issues regulatory guidance concerning the use of electronic signatures and... information regarding FMCSA's acceptance of electronic signature on documents required by the Federal...

  19. Numerical Skip-Entry Guidance

    NASA Technical Reports Server (NTRS)

    Tigges, Michael; Crull, Timothy; Rea, Jeremy; Johnson, Wyatt

    2006-01-01

    This paper assesses a preliminary guidance and targeting strategy for accomplishing Skip-Entry (SE) flight during a lunar return-capsule entry flight. One of the primary benefits of flying a SE trajectory is to provide the crew with continuous Continental United States (CONUS) landing site access throughout the lunar month. Without a SE capability, the capsule must land either in water or at one of several distributed land sites in the Southern Hemisphere for a significant portion of a lunar month using a landing and recovery scenario similar to that employed during the Apollo program. With a SE trajectory, the capsule can land either in water at a site in proximity to CONUS or at one of several distributed landing sites within CONUS, thereby simplifying the operational requirements for crew retrieval and vehicle recovery, and possibly enabling a high degree of vehicle reusability. Note that a SE capability does not require that the vehicle land on land. A SE capability enables a longer-range flight than a direct-entry flight, which permits the vehicle to land at a much greater distance from the Entry Interface (EI) point. This does not exclude using this approach to push the landing point to a water location in proximity of CONUS and utilizing water or airborne recovery forces.

  20. Optofluidic control of axonal guidance

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Ordonez, Simon; Black, Bryan; Mohanty, Samarendra K.

    2013-03-01

    Significant efforts are being made for control on axonal guidance due to its importance in nerve regeneration and in the formation of functional neuronal circuitry in-vitro. These include several physical (topographic modification, optical force, and electric field), chemical (surface functionalization cues) and hybrid (electro-chemical, photochemical etc) methods. Here, we report comparison of the effect of linear flow versus microfluidic flow produced by an opticallydriven micromotor in guiding retinal ganglion axons. A circularly polarized laser tweezers was used to hold, position and spin birefringent calcite particle near growth cone, which in turn resulted in microfluidic flow. The flow rate and resulting shear-force on axons could be controlled by a varying the power of the laser tweezers beam. The calcite particles were placed separately in one chamber and single particle was transported through microfluidic channel to another chamber containing the retina explant. In presence of flow, the turning of axons was found to strongly correlate with the direction of flow. Turning angle as high as 90° was achieved. Optofluidic-manipulation can be applied to other types of mammalian neurons and also can be extended to stimulate mechano-sensing neurons.

  1. Core needle biopsy guidance based on EMOCT imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Iftimia, Nicusor V.; Park, Jesung; Maguluri, Gopi

    2016-03-01

    We present a novel method, based on encoder mapping OCT imaging, for real-time guidance of core biopsy procedures. This method provides real-time feedback to the interventional radiologist, such that he/she can reorient the needle during the biopsy and sample the most representative area of the suspicious mass that is being investigated. This aspect is very important for tailoring therapy to the specific cancer based on biomarker analysis, which will become one of the next big advances in our search for the optimal cancer therapy. To enable individualized treatment, the genetic constitution and the DNA repair status in the affected areas is needed for each patient. Thus, representative sampling of the tumor is needed for analyzing various biomarkers, which are used as a tool to personalize cancer therapy. The encoder-based OCT enables samping of large size masses and provides full control on the imaging probe, which is passed through the bore of the biopsy guidance needle. The OCT image is built gradually, based on the feedback of an optical encoder which senses the incremental movement of the needle with a few microns resolution. Tissue mapping is independent of the needle speed, while it is advanced through the tissue. The OCT frame is analyzed in real-time and tissue cellularity is reported in a very simple manner (pie chart). Our preliminary study on a rabbit model of cancer has demonstrated the capability of this technology for accurately differentiating between viable cancer and heterogeneous or necrotic tissue.

  2. Optimal guidance law in quantum mechanics

    SciTech Connect

    Yang, Ciann-Dong Cheng, Lieh-Lieh

    2013-11-15

    Following de Broglie’s idea of a pilot wave, this paper treats quantum mechanics as a problem of stochastic optimal guidance law design. The guidance scenario considered in the quantum world is that an electron is the flight vehicle to be guided and its accompanying pilot wave is the guidance law to be designed so as to guide the electron to a random target driven by the Wiener process, while minimizing a cost-to-go function. After solving the stochastic optimal guidance problem by differential dynamic programming, we point out that the optimal pilot wave guiding the particle’s motion is just the wavefunction Ψ(t,x), a solution to the Schrödinger equation; meanwhile, the closed-loop guidance system forms a complex state–space dynamics for Ψ(t,x), from which quantum operators emerge naturally. Quantum trajectories under the action of the optimal guidance law are solved and their statistical distribution is shown to coincide with the prediction of the probability density function Ψ{sup ∗}Ψ. -- Highlights: •Treating quantum mechanics as a pursuit-evasion game. •Reveal an interesting analogy between guided flight motion and guided quantum motion. •Solve optimal quantum guidance problem by dynamic programming. •Gives a formal proof of de Broglie–Bohm’s idea of a pilot wave. •The optimal pilot wave is shown to be a wavefunction solved from Schrödinger equation.

  3. Advanced Glycation End Products Affect Osteoblast Proliferation and Function by Modulating Autophagy Via the Receptor of Advanced Glycation End Products/Raf Protein/Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase/Extracellular Signal-regulated Kinase (RAGE/Raf/MEK/ERK) Pathway.

    PubMed

    Meng, Hong-Zheng; Zhang, Wei-Lin; Liu, Fei; Yang, Mao-Wei

    2015-11-20

    The interaction between advanced glycation end products (AGEs) and receptor of AGEs (RAGE) is associated with the development and progression of diabetes-associated osteoporosis, but the mechanisms involved are still poorly understood. In this study, we found that AGE-modified bovine serum albumin (AGE-BSA) induced a biphasic effect on the viability of hFOB1.19 cells; cell proliferation was stimulated after exposure to low dose AGE-BSA, but cell apoptosis was stimulated after exposure to high dose AGE-BSA. The low dose AGE-BSA facilitates proliferation of hFOB1.19 cells by concomitantly promoting autophagy, RAGE production, and the Raf/MEK/ERK signaling pathway activation. Furthermore, we investigated the effects of AGE-BSA on the function of hFOB1.19 cells. Interestingly, the results suggest that the short term effects of low dose AGE-BSA increase osteogenic function and decrease osteoclastogenic function, which are likely mediated by autophagy and the RAGE/Raf/MEK/ERK signal pathway. In contrast, with increased treatment time, the opposite effects were observed. Collectively, AGE-BSA had a biphasic effect on the viability of hFOB1.19 cells in vitro, which was determined by the concentration of AGE-BSA and treatment time. A low concentration of AGE-BSA activated the Raf/MEK/ERK signal pathway through the interaction with RAGE, induced autophagy, and regulated the proliferation and function of hFOB1.19 cells.

  4. 76 FR 43690 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... Administration (FDA) is announcing the availability of the guidance entitled ``Class II Special Controls Guidance Document: Electrocardiograph Electrodes.'' The special controls identify the following risks to health... Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph...

  5. 76 FR 29251 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls; Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-20

    ...; Class II Special Controls; Guidance Document: Topical Oxygen Chamber for Extremities; Availability... Drug Administration Staff; Class II Special Controls Guidance Documents: Topical Oxygen Chamber for... Guidance Document: Topical Oxygen Chamber for Extremities'' to the Division of Small...

  6. SU-E-J-185: A Systematic Review of Breathing Guidance in Radiation Oncology and Radiology

    SciTech Connect

    Pollock, S; Keall, P; Keall, R

    2015-06-15

    Purpose: The advent of image-guided radiation therapy (IGRT) has led to dramatic improvements in the accuracy of treatment delivery in radiotherapy. Such advancements have highlighted the deleterious impact tumor motion can have on both image quality and radiation treatment delivery. One approach to reducing tumor motion is the use of breathing guidance systems during imaging and treatment. A review of such research had not yet been performed, it was therefore our aim to perform a systematic review of breathing guidance interventions within the fields of radiation oncology and radiology. Methods: Results of online database searches were filtered in accordance to a set of eligibility criteria. The search, filtration, and analysis of articles were conducted in accordance with the PRISMAStatement reporting standard (Preferred Reporting Items for Systematic reviews and Meta-Analyses) utilizing the PICOS approach (Participants, Intervention, Comparison, Outcome, Study design). Participants: Cancer patients, healthy volunteers. Intervention: Biofeedback breathing guidance systems. Comparison: No breathing guidance of the same breathing type. Outcome: Regularity of breathing signal and anatomic/tumor motion, medical image quality, radiation treatment margins and coverage, medical imaging and radiation treatment times. Study design: Quantitative and controlled prospective or retrospective trials. Results: The systematic search yielded a total of 479 articles, which were filtered down to 27 relevant articles in accordance to the eligibility criteria. The vast majority of investigated outcomes were significantly positively impacted by the use of breathing guidance; however, this was dependent upon the nature of the breathing guidance system and study design. In 25/27 studies significant improvements from the use of breathing guidance were observed. Conclusion: The results found here indicate that further clinical studies are warranted which quantify more comprehensively the

  7. The Title V guidance notebook

    SciTech Connect

    Powell, R.D.; McCutchen, G.D.

    1998-12-31

    In October 1997, the Air and Waste Management Association (A and WMA) made available a notebook consisting of documents pertaining to implementation of the operating permits program required by title V of the Clean Air Act and the Environmental Protection Agency`s (EPA) part 70 operating permits regulations. The documents include guidance memos/letters, questions/answers, several specialty documents, and related Federal Register notices that have been produced by EPA since inception of the program with the Clean Air Act amendments of 1990. The notebook contents were made available by EPA and the project was carried out under an EPA contract to A and WMA. The work was performed by RTP Environmental Associates Inc. of Raleigh, North Carolina. The notebook contains more than 75 documents; all the materials EPA believes relevant to implementation of the part 70 program by States, local agencies, territories, and Indian tribes. The documents that comprise the notebook are organized by subject matter and each is given a reference number for purposes of referring to the document. The part 70 operating permits regulations are annotated with document reference numbers to indicate where a document relates to a specific section of the regulations. In addition, documents are indexed four ways; by date, by author, alphabetically by title, and by reference number. Abstracts of each document are included in the notebook to allow the user to determine if the document is of interest. The notebook user, therefore, should be able to readily locate documents and be aware of all materials that affect any area of interest the user may have. The notebook will periodically be updated to add any new materials generated since the last update. The notebook should also be of interest to sources who must obtain a part 70 operating permit and to the general public interested in following implementation of the program. Notebooks may be purchased from A and WMA.

  8. The SLIT-ROBO pathway: a regulator of cell function with implications for the reproductive system.

    PubMed

    Dickinson, Rachel E; Duncan, W Colin

    2010-04-01

    The secreted SLIT glycoproteins and their Roundabout (ROBO) receptors were originally identified as important axon guidance molecules. They function as a repulsive cue with an evolutionarily conserved role in preventing axons from migrating to inappropriate locations during the assembly of the nervous system. In addition the SLIT-ROBO interaction is involved in the regulation of cell migration, cell death and angiogenesis and, as such, has a pivotal role during the development of other tissues such as the lung, kidney, liver and breast. The cellular functions that the SLIT/ROBO pathway controls during tissue morphogenesis are processes that are dysregulated during cancer development. Therefore inactivation of certain SLITs and ROBOs is associated with advanced tumour formation and progression in disparate tissues. Recent research has indicated that the SLIT/ROBO pathway could also have important functions in the reproductive system. The fetal ovary expresses most members of the SLIT and ROBO families. The SLITs and ROBOs also appear to be regulated by steroid hormones and regulate physiological cell functions in adult reproductive tissues such as the ovary and endometrium. Furthermore several SLITs and ROBOs are aberrantly expressed during the development of ovarian, endometrial, cervical and prostate cancer. This review will examine the roles this pathway could have in the development, physiology and pathology of the reproductive system and highlight areas for future research that could further dissect the influence of the SLIT/ROBO pathway in reproduction.

  9. Responsible Purchasing Network - Sustainable Purchasing Guidance Profile

    EPA Pesticide Factsheets

    To help you find the resource that is right for your organization, EPA conducted a scan of the landscape and developed summary profiles of some of the leading sources of sustainable purchasing guidance around the globe.

  10. European Union Sustainable Purchasing Guidance Profile

    EPA Pesticide Factsheets

    To help you find the resource that is right for your organization, EPA conducted a scan of the landscape and developed summary profiles of some of the leading sources of sustainable purchasing guidance around the globe.

  11. Surface Water Treatment Rules State Implementation Guidance

    EPA Pesticide Factsheets

    These documents provide guidance to states, tribes and U.S. EPA Regions exercising primary enforcement responsibility under the Safe Drinking Water Act. The documents contain EPA’s recommendations for implementation of the Surface Water Treatment Rules.

  12. Safe abortion: WHO technical and policy guidance.

    PubMed

    Cook, R J; Dickens, B M; Horga, M

    2004-07-01

    In 2003, the World Health Organization published its well referenced handbook Safe Abortion: Technical and Policy Guidance for Health Systems to address the estimated almost 20 million induced abortions each year that are unsafe, imposing a burden of approximately 67 thousand deaths annually. It is a global injustice that 95% of unsafe abortions occur in developing countries. The focus of guidance is on abortion procedures that are lawful within the countries in which they occur, noting that in almost all countries, the law permits abortion to save a woman's life. The guidance treats unsafe abortion as a public health challenge, and responds to the problem through strategies concerning improved clinical care for women undergoing procedures, and the appropriate placement of necessary services. Legal and policy considerations are explored, and annexes present guidance to further reading, international consensus documents on safe abortion, and on manual vacuum aspiration and post-abortion contraception.

  13. Optimal guidance for the space shuttle transition.

    NASA Technical Reports Server (NTRS)

    Stengel, R. F.

    1972-01-01

    A guidance method for the space shuttle's transition from hypersonic entry to subsonic cruising flight is presented. The method evolves from a numerical trajectory optimization technique in which kinetic energy and total energy (per unit weight) replace velocity and time in the dynamic equations. This allows the open end-time problem to be transformed to one of fixed terminal energy. In its ultimate form, 'E-Guidance' obtains energy balance (including dynamic-pressure-rate damping) and path length control by angle-of-attack modulation and cross-range control by roll angle modulation. The guidance functions also form the basis for a pilot display of instantaneous maneuver limits and destination. Numerical results illustrate the E-Guidance concept and the optimal trajectories on which it is based.

  14. Optimal guidance for the space shuttle transition

    NASA Technical Reports Server (NTRS)

    Stengel, R. F.

    1974-01-01

    A guidance method for the space shuttle's transition from hypersonic entry to subsonic cruising flight is presented. The method evolves from a numerical trajectory optimization technique in which kinetic energy and total energy (per unit weight) replace velocity and time in the dynamic equations. This allows the open end-time problem to be transformed to one of fixed terminal energy. In its ultimate form, E-Guidance obtains energy balance (including dynamic-pressure-rate damping) and path length control by angle-of-attack modulation and cross-range control by roll angle modulation. The guidance functions also form the basis for a pilot display of instantaneous maneuver limits and destination. Numerical results illustrate the E-Guidance concept and the optimal trajectories on which it is based.

  15. Optimal guidance for the space shuttle transition

    NASA Technical Reports Server (NTRS)

    Stengel, R. F.

    1972-01-01

    A guidance method for the space shuttle's transition from hypersonic entry to subsonic cruising flight is presented. The method evolves from a numerical trajectory optimization technique in which kinetic energy and total energy (per unit weight) replace velocity and time in the dynamic equations. This allows the open end-time problem to be transformed to one of fixed terminal energy. In its ultimate form, E-Guidance obtains energy balance (including dynamic-pressure-rate damping) and path length control by angle-of-attack modulation and cross-range control by roll angle modulation. The guidance functions also form the basis for a pilot display of instantaneous maneuver limits and destination. Numerical results illustrate the E-Guidance concept and the optimal trajectories on which it is based.

  16. General RMP Guidance - Table of Contents

    EPA Pesticide Factsheets

    The Risk Management Programs for Chemical Accident Prevention (40 CFR Part 68) guidance is in chapters; each covering topics such as applicability of the rule, and requirements for reporting five-year accident history and offsite consequence analysis.

  17. Delta launch vehicle inertial guidance system (DIGS)

    NASA Technical Reports Server (NTRS)

    Duck, K. I.

    1973-01-01

    The Delta inertial guidance system, part of the Delta launch vehicle improvement effort, has been flown on three launches and was found to perform as expected for a variety of mission profiles and vehicle configurations.

  18. RMP Guidance for Warehouses - Table of Contents

    EPA Pesticide Factsheets

    This Risk Management Program (40 CFR Part 68) Guidance is organized into chapters, each covering a topic such as applicability of the rule, requirements for the five-year accident history and offsite consequence analysis, and emergency response.

  19. Beam envelope matching for beam guidance systems

    SciTech Connect

    Brown, K.L.

    1980-08-01

    Ray optics and phase ellipse optics are developed as tools for designing charged particle beam guidance systems. Specific examples of basic optical systems and of phase ellipse matching are presented as illustrations of these mathematical techniques.

  20. Practice Greenhealth Sustainable Purchasing Guidance Profile

    EPA Pesticide Factsheets

    To help you find the resource that is right for your organization, EPA conducted a scan of the landscape and developed summary profiles of some of the leading sources of sustainable purchasing guidance around the globe.

  1. Guidance for Developing TMDLs in California

    EPA Pesticide Factsheets

    This document provides guidance to the State of California concerning its responsibility under section 303(d) of the Clean Water Act concerning the development of TMDLs for water quality-limited segments listed under section 303(d).

  2. Beyond Black: An Alternative to Ethnocentric Guidance

    ERIC Educational Resources Information Center

    Goldman, Robert C.

    1977-01-01

    This article is a clarification of the author's personal philosophy in the guidance and counseling of youth and adults, and clarification of commonalities that form the raison d'etre of all student personnel services. (Author)

  3. The Industrial User Permitting Guidance Manual

    EPA Pesticide Factsheets

    Provides guidance for control authorities to effectively develop and issue control mechanisms to IUs discharging to the POTW and covers developing and implementing control mechanisms for both SIUs and non-SIUs.

  4. Guidance: Treatment of Insurers Under Superfund

    EPA Pesticide Factsheets

    Guidance provides EPA Regional offices with the appropriate procedures to follow in issuing notice letters, developing referrals, and tracking CERCLA enforcement cases that may include insurers as third party defendants.

  5. POTW Sludge Sampling and Analysis Guidance Document

    EPA Pesticide Factsheets

    In view of the variability of municipal sludge quality,appropriate procedures must be followed to collect and analyze samples that accurately represent each POTW's sludge quality.This manual was developed to provide that guidance to POTW operators, engin

  6. A Comparison of Two Skip Entry Guidance Algorithms

    NASA Technical Reports Server (NTRS)

    Rea, Jeremy R.; Putnam, Zachary R.

    2007-01-01

    The Orion capsule vehicle will have a Lift-to-Drag ratio (L/D) of 0.3-0.35. For an Apollo-like direct entry into the Earth's atmosphere from a lunar return trajectory, this L/D will give the vehicle a maximum range of about 2500 nm and a maximum crossrange of 216 nm. In order to y longer ranges, the vehicle lift must be used to loft the trajectory such that the aerodynamic forces are decreased. A Skip-Trajectory results if the vehicle leaves the sensible atmosphere and a second entry occurs downrange of the atmospheric exit point. The Orion capsule is required to have landing site access (either on land or in water) inside the Continental United States (CONUS) for lunar returns anytime during the lunar month. This requirement means the vehicle must be capable of flying ranges of at least 5500 nm. For the L/D of the vehicle, this is only possible with the use of a guided Skip-Trajectory. A skip entry guidance algorithm is necessary to achieve this requirement. Two skip entry guidance algorithms have been developed: the Numerical Skip Entry Guidance (NSEG) algorithm was developed at NASA/JSC and PredGuid was developed at Draper Laboratory. A comparison of these two algorithms will be presented in this paper. Each algorithm has been implemented in a high-fidelity, 6 degree-of-freedom simulation called the Advanced NASA Technology Architecture for Exploration Studies (ANTARES). NASA and Draper engineers have completed several monte carlo analyses in order to compare the performance of each algorithm in various stress states. Each algorithm has been tested for entry-to-target ranges to include direct entries and skip entries of varying length. Dispersions have been included on the initial entry interface state, vehicle mass properties, vehicle aerodynamics, atmosphere, and Reaction Control System (RCS). Performance criteria include miss distance to the target, RCS fuel usage, maximum g-loads and heat rates for the first and second entry, total heat load, and control

  7. Soil screening guidance: User`s guide

    SciTech Connect

    1996-04-01

    The Soil Screening Guidance is a tool that the U.S. Environmental Protection Agency (EPA) developed to help standardize and accelerate the evaluation and cleanup of contaminated soils at sites on the National Priorities List (NPL) with future residential land use. This guidance provides a methodology for environmental science/engineering professionals to calculate risk-based, site-specific, soil screening levels (SSLs) for contaminants in soil that may be used to identify areas needing further investigation at NPL sites.

  8. Optogenetics Advances in Primate Visual Pathway.

    PubMed

    Jazayeri, Mehrdad; Remington, Evan

    2016-04-06

    In this issue of Neuron, Klein et al. (2016) used cell-type-specific optogenetics and electrical microstimulation to characterize the koniocellular geniculocortical projections in nonhuman primates. Their work offers a powerful platform for refining our understanding of the mechanisms of visual information processing in the lateral geniculate nucleus and primary visual cortex.

  9. General RMP Guidance - Appendix E: Supplemental Risk Management Program Guidance for Ammonia Refrigeration Facilities

    EPA Pesticide Factsheets

    Additional information for food processors, food distributors, refrigerated warehouses, and any other facility with ammonia refrigeration system. Includes guidance on exemptions, threshold quantity, offsite consequence analysis.

  10. Constituent Aspects of Workplace Guidance in Secondary VET

    ERIC Educational Resources Information Center

    Swager, Robert; Klarus, Ruud; van Merriënboer, Jeroen J. G.; Nieuwenhuis, Loek F. M.

    2015-01-01

    Purpose: This paper aims to present an integrated model of workplace guidance to enhance awareness of what constitutes good guidance, to improve workplace guidance practices in vocational education and training. Design/methodology/approach: To identify constituent aspects of workplace guidance, a systematic search of Web of Science was conducted,…

  11. The Development of a Lifelong Guidance System in Hungary

    ERIC Educational Resources Information Center

    Watts, A. G.; Borbely-Pecze, Bors Tibor

    2011-01-01

    The development of a lifelong guidance system in Hungary Systematic work is currently being undertaken in Hungary to develop a lifelong guidance system, in line with principles outlined by leading international organisations. The origins of career guidance in Hungary, and the nature of the current career guidance system, are outlined. The main…

  12. GUILD: GUidance for Information about Linking Data sets†.

    PubMed

    Gilbert, Ruth; Lafferty, Rosemary; Hagger-Johnson, Gareth; Harron, Katie; Zhang, Li-Chun; Smith, Peter; Dibben, Chris; Goldstein, Harvey

    2017-03-28

    Record linkage of administrative and survey data is increasingly used to generate evidence to inform policy and services. Although a powerful and efficient way of generating new information from existing data sets, errors related to data processing before, during and after linkage can bias results. However, researchers and users of linked data rarely have access to information that can be used to assess these biases or take them into account in analyses. As linked administrative data are increasingly used to provide evidence to guide policy and services, linkage error, which disproportionately affects disadvantaged groups, can undermine evidence for public health. We convened a group of researchers and experts from government data providers to develop guidance about the information that needs to be made available about the data linkage process, by data providers, data linkers, analysts and the researchers who write reports. The guidance goes beyond recommendations for information to be included in research reports. Our aim is to raise awareness of information that may be required at each step of the linkage pathway to improve the transparency, reproducibility, and accuracy of linkage processes, and the validity of analyses and interpretation of results.

  13. Drosophila neurexin IV interacts with Roundabout and is required for repulsive midline axon guidance.

    PubMed

    Banerjee, Swati; Blauth, Kevin; Peters, Kimberly; Rogers, Stephen L; Fanning, Alan S; Bhat, Manzoor A

    2010-04-21

    Slit/Roundabout (Robo) signaling controls midline repulsive axon guidance. However, proteins that interact with Slit/Robo at the cell surface remain largely uncharacterized. Here, we report that the Drosophila transmembrane septate junction-specific protein Neurexin IV (Nrx IV) functions in midline repulsive axon guidance. Nrx IV is expressed in the neurons of the developing ventral nerve cord, and nrx IV mutants show crossing and circling of ipsilateral axons and fused commissures. Interestingly, the axon guidance defects observed in nrx IV mutants seem independent of its other binding partners, such as Contactin and Neuroglian and the midline glia protein Wrapper, which interacts in trans with Nrx IV. nrx IV mutants show diffuse Robo localization, and dose-dependent genetic interactions between nrx IV/robo and nrx IV/slit indicate that they function in a common pathway. In vivo biochemical studies reveal that Nrx IV associates with Robo, Slit, and Syndecan, and interactions between Robo and Slit, or Nrx IV and Slit, are affected in nrx IV and robo mutants, respectively. Coexpression of Nrx IV and Robo in mammalian cells confirms that these proteins retain the ability to interact in a heterologous system. Furthermore, we demonstrate that the extracellular region of Nrx IV is sufficient to rescue Robo localization and axon guidance phenotypes in nrx IV mutants. Together, our studies establish that Nrx IV is essential for proper Robo localization and identify Nrx IV as a novel interacting partner of the Slit/Robo signaling pathway.

  14. Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila

    PubMed Central

    Cate, Marie-Sophie; Gajendra, Sangeetha; Alsbury, Samantha; Raabe, Thomas; Tear, Guy; Mitchell, Kevin J.

    2016-01-01

    The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule-binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance. PMID:26893348

  15. Functional diversity of Robo receptor immunoglobulin domains promotes distinct axon guidance decisions.

    PubMed

    Evans, Timothy A; Bashaw, Greg J

    2010-03-23

    Recognition molecules of the immunoglobulin (Ig) superfamily control axon guidance in the developing nervous system. Ig-like domains are among the most widely represented protein domains in the human genome, and the number of Ig superfamily proteins is strongly correlated with cellular complexity. In Drosophila, three Roundabout (Robo) Ig superfamily receptors respond to their common Slit ligand to regulate axon guidance at the midline: Robo and Robo2 mediate midline repulsion, Robo2 and Robo3 control longitudinal pathway selection, and Robo2 can promote midline crossing. How these closely related receptors mediate distinct guidance functions is not understood. We report that the differential functions of Robo2 and Robo3 are specified by their ectodomains and do not reflect differences in cytoplasmic signaling. Functional modularity of Robo2's ectodomain facilitates multiple guidance decisions: Ig1 and Ig3 of Robo2 confer lateral positioning activity, whereas Ig2 confers promidline crossing activity. Robo2's distinct functions are not dependent on greater Slit affinity but are instead due in part to differences in multimerization and receptor-ligand stoichiometry conferred by Robo2's Ig domains. Together, our findings suggest that diverse responses to the Slit guidance cue are imparted by intrinsic structural differences encoded in the extracellular Ig domains of the Robo receptors.

  16. Development of a Shuttle Infrared Telescope Facility /SIRTF/ fine guidance sensor

    NASA Technical Reports Server (NTRS)

    Salomon, P. M.; Glavich, T. A.; Goss, W. C.; Lorell, K. R.

    1981-01-01

    Fine guidance technology development for the Shuttle Infrared Telescope Facility (SIRTF) centers upon the use of a single multiple-star-tracking sensor to provide the position information necessary to produce three-axis attitude control signals for precision payload pointing. The effort described in this paper is concerned with the development of a fine guidance sensor that employs a high-density charge-coupled imaging device for producing position information signals by using star fields. Multiple star position information produces three-axis position error signals that are used to update inertial reference gyros. The sensor employs advanced position interpolation algorithms to enhance field-of-view resolution and to correct for optical aberrations inherent in spatially chopped star images resulting from the telescope's movable secondary mirror. Operation of the sensor is under the control of a high-performance microcomputer that provides both autonomy and flexibility in a guidance application.

  17. Behavior guidance techniques in Pediatric Dentistry: attitudes of parents of children with disabilities and without disabilities.

    PubMed

    de Castro, Alessandra Maia; de Oliveira, Fabiana Sodré; de Paiva Novaes, Myrian Stella; Araújo Ferreira, Danielly Cunha

    2013-01-01

    This study compared the parental acceptance of pediatric behavior guidance techniques (BGT). Forty parents of children without disabilities (Group A) and another 40 parents of children with disabilities (Group B) were selected. Each BGT was explained by a single examiner and it was presented together with a photograph album. After that parents evaluated the acceptance in: totally unacceptable, somewhat acceptable, acceptable, and totally acceptable. Results indicated that in Group A, the BGT based on communicative guidance was accepted by most participants. In Group B, just one mother considered totally unacceptable the voice control method and other two, tell-show-do. For both groups, the general anesthesia was the less accepted BGT. There was statistically significant difference in acceptance for protective stabilization with a restrictive device in Group B. Children's parents with and without disabilities accepted behavioral guidance techniques, but basic techniques showed higher rates of acceptance than advanced techniques.

  18. Planning a career as a children's nurse: the availability of career guidance during the nurse diploma course.

    PubMed

    Cox, Susanne J; Robinson, Sarah; Murrells, Trevor

    2003-12-01

    The recruitment and retention of registered children's nurses is paramount to the implementation of the national service framework for children's services. In recent years there have been increased career opportunities for children's nurses and a diversity of career pathways. Career guidance has a potential contribution to make to the effective management of nurses' careers. This article presents findings on child health diplomates' experiences of career guidance during the nurse diploma course. Findings indicate a substantial unmet demand for career guidance. The implications of the findings for child health nurses' careers are discussed and considered in relation to two key questions: should efforts be directed towards ensuring greater provision of career guidance, and if so, by whom?

  19. Signaling pathways affecting skeletal health.

    PubMed

    Marie, Pierre J

    2012-09-01

    Skeletal health is dependent on the balance between bone resorption and formation during bone remodeling. Multiple signaling pathways play essential roles in the maintenance of skeletal integrity by positively or negatively regulating bone cells. During the last years, significant advances have been made in our understanding of the essential signaling pathways that regulate bone cell commitment, differentiation and survival. New signaling anabolic pathways triggered by parathyroid hormone, local growth factors, Wnt signaling, and calcium sensing receptor have been identified. Novel signals induced by interactions between bone cells-matrix (integrins), osteoblasts/osteocytes (cadherins, connexins), and osteoblasts/osteoclast (ephrins, Wnt-RhoA, semaphorins) have been discovered. Recent studies revealed the key pathways (MAPK, PI3K/Akt) that critically control bone cells and skeletal mass. This review summarizes the most recent knowledge on the major signaling pathways that control bone cells, and their potential impact on the development of therapeutic strategies to improve human bone health.

  20. Launch flexibility using NLP guidance and remote wind sensing

    NASA Technical Reports Server (NTRS)

    Cramer, Evin J.; Bradt, Jerre E.; Hardtla, John W.

    1990-01-01

    This paper examines the use of lidar wind measurements in the implementation of a guidance strategy for a nonlinear programming (NLP) launch guidance algorithm. The NLP algorithm uses B-spline command function representation for flexibility in the design of the guidance steering commands. Using this algorithm, the guidance system solves a two-point boundary value problem at each guidance update. The specification of different boundary value problems at each guidance update provides flexibility that can be used in the design of the guidance strategy. The algorithm can use lidar wind measurements for on pad guidance retargeting and for load limiting guidance steering commands. Examples presented in the paper use simulated wind updates to correct wind induced final orbit errors and to adjust the guidance steering commands to limit the product of the dynamic pressure and angle-of-attack for launch vehicle load alleviation.

  1. Lumbar Catheter Placement Using Paramedian Approach Under Fluoroscopic Guidance

    PubMed Central

    Qureshi, Adnan I.; Khan, Asif A.; Malik, Ahmed A.; Afzal, Mohammad Rauf; Herial, Nabeel A.; Qureshi, Mushtaq H.; Suri, M. Fareed K.

    2016-01-01

    Background Lumbar catheter placement under fluoroscopic guidance may reduce the rate of technical failures and associated complications seen with insertion guided by manually palpable landmarks. Methods We reviewed our experience with 43 attempted lumbar catheter placements using paramedian approach under fluoroscopic guidance and ascertained rates of technical success, and clinical events. Results Among the 43 patients, 18, 1, and 1 patients were on aspirin (with dipyrimadole in 2), clopidogrel, and combination of both, respectively. Lumbar catheter placement was successful in 42 of 43 attempted placements. Floroscopic guidance was critical in three patients; one patient had severe cerebrospinal fluid (CSF) depletion (empty thecal sac phenomenon) following pituitary surgery leading to no cerebrospinal fluid return despite correct placement confirmation under fluoroscopy. Two patients had spinal needle placement at the junction between epidural and cerebrospinal fluid spaces (junctional position) leading to cerebrospinal fluid return but inability to introduce the lumbar catheter. After confirmation of position by the injection of contrast or radiographic landmarks the needle was advanced by indenting the subcutaneous tissue or reinserting at a spinal level above the first insertion. The lumbar catheter remained in position over a mean period (±standard deviation) of 4.1(±2.3) days. Improvement in hydrocephalus was seen in two patients with intracranial mass lesions. One patient developed cerebrospinal fluid leakage through the insertion track following removal of catheter and required skin suturing at the site of insertion. Conclusions We observed a high technical success rate with low rate of complications even in patients with intracranial mass lesions, those on ongoing antiplatelet medications or in whom insertion would not be possible guided by manually palpable landmarks. PMID:26958156

  2. Raising the Profile of Career Guidance: Educational and Vocational Guidance Practitioner

    ERIC Educational Resources Information Center

    Hiebert, Bryan

    2009-01-01

    In 2007 the International Association for Educational and Vocational Guidance (IAEVG) launched the Educational and Vocational Guidance Practitioner credential (EVGP) as one means of formally acknowledging the knowledge, skills, and personal attributes that practitioners need in order to provide quality career development services to clients. This…

  3. 78 FR 37231 - Guidance for Industry; Guidance on Abbreviated New Drug Applications: Stability Testing of Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry; Guidance on Abbreviated New Drug Applications: Stability Testing of Drug Substances and Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing...

  4. Radiation Protection Guidance for Diagnostic and Interventional X-Ray Procedures; Federal Guidance Report No. 14

    EPA Science Inventory

    Federal Guidance Report No. 14 provides federal facilities that use diagnostic and interventional x-ray equipment with updated recommendations for keeping doses as low as reasonably achievable without compromising the quality of patient care, This guidance is an update of Federal...

  5. Measuring Integrated Socioemotional Guidance at School: Factor Structure and Reliability of the Socioemotional Guidance Questionnaire (SEG-Q)

    ERIC Educational Resources Information Center

    Jacobs, Karen; Struyf, Elke

    2013-01-01

    Socioemotional guidance of students has recently become an integral part of education, however no instrument exists to measure integrated socioemotional guidance. This study therefore examines the factor structure and reliability of the Socioemotional Guidance Questionnaire. Psychometric properties of the Socioemotional Guidance Questionnaire and…

  6. VMT forecasting and tracking guidance, Section 187

    SciTech Connect

    Not Available

    1992-01-01

    The guidance is required by Section 187 (a) of the Clean Air Act Amendments of 1990. It offers the Environmental Protection Agency's (EPA's) recommendations on how to forecast and track vehicle miles traveled (VMT) in Moderate and Serious carbon monoxide (CO) non-attainment areas with design values greater than 12.7 ppm at the time of classification. The purpose of the guidance is to help states prepare State Implementation Plan (SIP) revisions that EPA can readily propose to approve as meeting the requirements of the Clean Air Act Amendments. If a state adheres to the guidance, EPA will propose approval of its SIP. A state intending to depart from the guidance, however, should show that the alternative approach it proposes is technically sound and adequate to meet the requirements of the Clean Air Act Amendments. EPA will review SIP submittals from such states on a case-by-case basis to determine whether they do in fact comply with the Clean Air Act Amendment requirements. States are encouraged to obtain EPA approval before using methods other than those specified in the guidance, in order to avoid later problems.

  7. Safety of magnetic fusion facilities: Guidance

    SciTech Connect

    1996-05-01

    This document provides guidance for the implementation of the requirements identified in DOE-STD-6002-96, Safety of Magnetic Fusion Facilities: Requirements. This guidance is intended for the managers, designers, operators, and other personnel with safety responsibilities for facilities designated as magnetic fusion facilities. While the requirements in DOE-STD-6002-96 are generally applicable to a wide range of fusion facilities, this Standard, DOE-STD-6003-96, is concerned mainly with the implementation of those requirements in large facilities such as the International Thermonuclear Experimental Reactor (ITER). Using a risk-based prioritization, the concepts presented here may also be applied to other magnetic fusion facilities. This Standard is oriented toward regulation in the Department of Energy (DOE) environment as opposed to regulation by other regulatory agencies. As the need for guidance involving other types of fusion facilities or other regulatory environments emerges, additional guidance volumes should be prepared. The concepts, processes, and recommendations set forth here are for guidance only. They will contribute to safety at magnetic fusion facilities.

  8. Fine Guidance Sensing for Coronagraphic Observatories

    NASA Technical Reports Server (NTRS)

    Brugarolas, Paul; Alexander, James W.; Trauger, John T.; Moody, Dwight C.

    2011-01-01

    Three options have been developed for Fine Guidance Sensing (FGS) for coronagraphic observatories using a Fine Guidance Camera within a coronagraphic instrument. Coronagraphic observatories require very fine precision pointing in order to image faint objects at very small distances from a target star. The Fine Guidance Camera measures the direction to the target star. The first option, referred to as Spot, was to collect all of the light reflected from a coronagraph occulter onto a focal plane, producing an Airy-type point spread function (PSF). This would allow almost all of the starlight from the central star to be used for centroiding. The second approach, referred to as Punctured Disk, collects the light that bypasses a central obscuration, producing a PSF with a punctured central disk. The final approach, referred to as Lyot, collects light after passing through the occulter at the Lyot stop. The study includes generation of representative images for each option by the science team, followed by an engineering evaluation of a centroiding or a photometric algorithm for each option. After the alignment of the coronagraph to the fine guidance system, a "nulling" point on the FGS focal point is determined by calibration. This alignment is implemented by a fine alignment mechanism that is part of the fine guidance camera selection mirror. If the star images meet the modeling assumptions, and the star "centroid" can be driven to that nulling point, the contrast for the coronagraph will be maximized.

  9. Guidance Trade-off for Aerocapture Missions

    NASA Astrophysics Data System (ADS)

    Vernis, P.; Gelly, G.; Ferreira, E.; da Costa, R.; Ortega, G.

    In the very late 90's, EADS-ST began home funded studies on aerocapture problems. The objectives of these studies were at that time to prepare a possible cooperation within the NASA/Cnes MSR-Orbiter program by investigating this new orbital insertion technique studying different algorithmic solutions from a guidance point of view. According to these preliminary studies, EADS-ST was retained in 2002 by ESA to study insertion techniques such as aerocapture, aero-gravity assist or aerobraking techniques within the frame of Technological Research Program able to bring solutions to Aurora program. In the frame of the ATPE (Aeroassist Technologies for Planetary Exploration) TRP program, EADS-ST, led by Astrium-Gmbh (now part of EADS-ST), developed and implemented an efficient and simple guidance scheme able to cope with mission requirements for aerocapture on Mars, Venus or the Earth: the Feedback Trajectory Control, or FTC. The development of this guidance scheme was made according to a preliminary trade-off analysis using different guidance schemes. Among those ones was an original predictor-corrector guidance scheme, already analyzed within the frame of the MSR-O mission. But, the FTC algoritm was prefered because of its good results and high simplicity. This paper presents an upgrade of the original Apoapsis Predictor, or AP, with the improvement of its robustness woth respect to off-nomonal flight conditions and its process simplification. A new trade-off analysis is then detailed on a Mars Sample return mission.

  10. Breathing guidance in radiation oncology and radiology: A systematic review of patient and healthy volunteer studies

    SciTech Connect

    Pollock, Sean Keall, Paul; Keall, Robyn

    2015-09-15

    Purpose: The advent of image-guided radiation therapy has led to dramatic improvements in the accuracy of treatment delivery in radiotherapy. Such advancements have highlighted the deleterious impact tumor motion can have on both image quality and radiation treatment delivery. One approach to reducing tumor motion irregularities is the use of breathing guidance systems during imaging and treatment. These systems aim to facilitate regular respiratory motion which in turn improves image quality and radiation treatment accuracy. A review of such research has yet to be performed; it was therefore their aim to perform a systematic review of breathing guidance interventions within the fields of radiation oncology and radiology. Methods: From August 1–14, 2014, the following online databases were searched: Medline, Embase, PubMed, and Web of Science. Results of these searches were filtered in accordance to a set of eligibility criteria. The search, filtration, and analysis of articles were conducted in accordance with preferred reporting items for systematic reviews and meta-analyses. Reference lists of included articles, and repeat authors of included articles, were hand-searched. Results: The systematic search yielded a total of 480 articles, which were filtered down to 27 relevant articles in accordance to the eligibility criteria. These 27 articles detailed the intervention of breathing guidance strategies in controlled studies assessing its impact on such outcomes as breathing regularity, image quality, target coverage, and treatment margins, recruiting either healthy adult volunteers or patients with thoracic or abdominal lesions. In 21/27 studies, significant (p < 0.05) improvements from the use of breathing guidance were observed. Conclusions: There is a trend toward the number of breathing guidance studies increasing with time, indicating a growing clinical interest. The results found here indicate that further clinical studies are warranted that quantify the

  11. Sperm guidance to the egg finds calcium at the helm.

    PubMed

    Sugiyama, Hitoshi; Chandler, Douglas E

    2014-05-01

    Sperm respond to multiple cues during guidance to the egg including chemical attractants, temperature, and fluid flow. Of these, sperm chemotaxis has been studied most extensively-over 100 years-but only recently has it started to be understood at the molecular level. The long gestation in this understanding has largely been due to technical limitations that include the detection of calcium signal dynamics in a relatively small structure-the flagellum, measurement of actual chemoattractant gradients, the fact that only subpopulations of sperm respond at any given time, and the diversity in swimming behaviors that sperm exhibit from different species. Today, measurements of flagellar calcium signals on a fast time scale, discovery of the ion channels and organelles that may regulate these signals, and better understanding and quantitation of sperm swimming behaviors involved have given more certainty to our understanding of sperm directional swimming and its control by characteristic, calcium-directed asymmetric flagellar bends. Future research will need to apply these technical advances to other forms of sperm guidance such as thermotaxis and rheotaxis as well as gaining an understanding of how the flagellar apparatus is controlled by calcium.

  12. Advancing molecular-guided surgery through probe development and testing in a moderate cost evaluation pipeline

    NASA Astrophysics Data System (ADS)

    Pogue, Brian W.; Paulsen, Keith D.; Hull, Sally M.; Samkoe, Kimberley S.; Gunn, Jason; Hoopes, Jack; Roberts, David W.; Strong, Theresa V.; Draney, Daniel; Feldwisch, Joachim

    2015-03-01

    Molecular guided oncology surgery has the potential to transform the way decisions about resection are done, and can be critically important in areas such as neurosurgery where the margins of tumor relative to critical normal tissues are not readily apparent from visual or palpable guidance. Yet there are major financial barriers to advancing agents into clinical trials with commercial backing. We observe that development of these agents in the standard biological therapeutic paradigm is not viable, due to the high up front financial investment needed and the limitations in the revenue models of contrast agents for imaging. The hypothesized solution to this problem is to develop small molecular biologicals tagged with an established fluorescent reporter, through the chemical agent approval pathway, targeting a phase 0 trials initially, such that the initial startup phase can be completely funded by a single NIH grant. In this way, fast trials can be completed to de-risk the development pipeline, and advance the idea of fluorescence-guided surgery (FGS) reporters into human testing. As with biological therapies the potential successes of each agent are still moderate, but this process will allow the field to advance in a more stable and productive manner, rather than relying upon isolated molecules developed at high cost and risk. The pathway proposed and tested here uses peptide synthesis of an epidermal growth factor receptor (EGFR)-binding Affibody molecules, uniquely conjugated to IRDye 800CW, developed and tested in academic and industrial laboratories with well-established records for GMP production, fill and finish, toxicity testing, and early phase clinical trials with image guidance.

  13. A CASE STUDY DEMONSTRATING GUIDANCE FOR EVALUATING LANDFILL GAS EMISSIONS FROM CLOSED OR ABANDONED FACILITIES--SOUTH KINGSTOWN, RHODE ISLAND

    EPA Science Inventory

    The report describes a case study that applies EPA/600/R-05/123a, the guidance for conducting air pathway analyses of landfill gas emissions that are of interest to superfund remedial project managers, on-scene coordinators, facility owners, and potentially responsible parties. T...

  14. Simulation evaluation of a low-altitude helicopter flight guidance system adapted for a helmet-mounted display

    NASA Technical Reports Server (NTRS)

    Swenson, Harry N.; Zelenka, Richard E.; Hardy, Gordon H.; Dearing, Munro G.

    1992-01-01

    A computer aiding concept for low-altitude helicopter flight was developed and evaluated in a real-time piloted simulation. The concept included an optimal control trajectory-generation algorithm based upon dynamic programming and a helmet-mounted display (HMD) presentation of a pathway-in-the-sky, a phantom aircraft, and flight-path vector/predictor guidance symbology. The trajectory-generation algorithm uses knowledge of the global mission requirements, a digital terrain map, aircraft performance capabilities, and advanced navigation information to determine a trajectory between mission way points that seeks valleys to minimize threat exposure. The pilot evaluation was conducted at NASA ARC moving base Vertical Motion Simulator (VMS) by pilots representing NASA, the U.S. Army, the Air Force, and the helicopter industry. The pilots manually tracked the trajectory generated by the algorithm utilizing the HMD symbology. The pilots were able to satisfactorily perform the tracking tasks while maintaining a high degree of awareness of the outside world.

  15. SRNL ALL-PATHWAYS APPLICATION

    SciTech Connect

    Koffman, L; Elmer Wilhite, E; Leonard Collard, L

    2007-05-29

    The Environmental Analysis and Performance Modeling group of Savannah River National Laboratory (SRNL) performs performance assessments of the Savannah River Site (SRS) low-level waste facilities to meet the requirements of DOE Order 435.1. One of the performance objectives in the DOE Order is that the radiological dose to representative members of the public shall not exceed 25 mrem in a year total effective dose equivalent from all exposure pathways, excluding radon. Analysis to meet this performance objective is generally referred to as all-pathways analysis. SRNL performs detailed transient groundwater transport analysis for the waste disposal units, which has been used as input for the groundwater part of all-pathways analysis. The desire to better integrate all-pathways analysis with the groundwater transport analysis lead to the development of a software application named the SRNL All-Pathways Application. Another requirement of DOE Order 435.1 is to assess the impact of nuclear waste disposal on water resources, which SRS has interpreted for groundwater protection as meeting the EPA regulations for radionuclides in drinking water. EPA specifies four separate criteria as part of their implementation guidance for radionuclides, which are specified as maximum contaminant levels (MCL). (1) Beta/gamma emitters have a combined dose limit of 4 mrem/year. (2) Alpha emitters have a combined concentration limit of 15 pCi/L (called gross alpha), excluding uranium and radon, but including radium-226. (3) Combined radium-226 and radium-228 have a concentration limit of 5 pCi/L. (4) Isotopes of uranium have a combined concentration limit of 30 {micro}g/L. The All-Pathways Application was designed to be an easy-to-use software application that utilizes transient concentration results from groundwater transport analysis to (1) calculate the groundwater part of all-pathways dose and to (2) evaluate the four EPA criteria for groundwater protection.

  16. The handling of causality in SEA guidance

    SciTech Connect

    Perdicoulis, A. . E-mail: tasso@utad.pt; Hanusch, M. . E-mail: marie.hanusch@ufz.de; Kasperidus, H.D. . E-mail: hans.kasperidus@ufz.de; Weiland, U. . E-mail: ulrike.weiland@ufz.de

    2007-03-15

    Causality, or the relation of cause and effect, is a fundamental notion in science, planning, and management. It is also a fundamental notion in impact assessment, as it relates action proposals with environmental impacts. Building on recent research about causality in impact assessment, this article turns to Strategic Environmental Assessment (SEA) and examines eleven guidance documents to see whether and how they handle causality. The findings of this research, in line with results from similar research in EIA, indicate a weak handling of causality with regards to instruction, obligation, and theoretical support. The recommendations are to investigate the reasons for the observed trend, as there is no evidence in the guidance documents themselves, and to have the fundamental premise of causality in impact assessment safeguarded in future SEA guidance.

  17. VTOL shipboard letdown guidance system analysis

    NASA Technical Reports Server (NTRS)

    Phatak, A. V.; Karmali, M. S.

    1983-01-01

    Alternative letdown guidance strategies are examined for landing of a VTOL aircraft onboard a small aviation ship under adverse environmental conditions. Off line computer simulation of shipboard landing task is utilized for assessing the relative merits of the proposed guidance schemes. The touchdown performance of a nominal constant rate of descent (CROD) letdown strategy serves as a benchmark for ranking the performance of the alternative letdown schemes. Analysis of ship motion time histories indicates the existence of an alternating sequence of quiescent and rough motions called lulls and swells. A real time algorithms lull/swell classification based upon ship motion pattern features is developed. The classification algorithm is used to command a go/no go signal to indicate the initiation and termination of an acceptable landing window. Simulation results show that such a go/no go pattern based letdown guidance strategy improves touchdown performance.

  18. Development of mining guidance and control systems

    NASA Technical Reports Server (NTRS)

    1979-01-01

    New fundamental interface sensor concepts were identified and investigated including tabulation of the physical and performance characteristics of two new interface detector concepts: - natural background radiation and magnetic spin resonance. Studies of guidance and control techniques for the longwall miner identified three basic systems for use in automated/remote controlled longwall mining. The following projects were initiated: system study which will more completely define the longwall guidance and control system design concepts; integration of the various control functions (vertical, yaw, and roll); and hardware technical requirements.

  19. Ascent guidance algorithm using lidar wind measurements

    NASA Technical Reports Server (NTRS)

    Cramer, Evin J.; Bradt, Jerre E.; Hardtla, John W.

    1990-01-01

    The formulation of a general nonlinear programming guidance algorithm that incorporates wind measurements in the computation of ascent guidance steering commands is discussed. A nonlinear programming (NLP) algorithm that is designed to solve a very general problem has the potential to address the diversity demanded by future launch systems. Using B-splines for the command functional form allows the NLP algorithm to adjust the shape of the command profile to achieve optimal performance. The algorithm flexibility is demonstrated by simulation of ascent with dynamic loading constraints through a set of random wind profiles with and without wind sensing capability.

  20. CNES Approaching Guidance Experiment within FFIORD

    NASA Technical Reports Server (NTRS)

    Berges, Jean-Claude; Cayeux, Philippe; Gaudel-Vacaresse, Angelique; Meyssignac, Benoit

    2007-01-01

    This article outlines the relative orbit control (guidance algorithm and its preliminary performance tests evaluation) that will be tested by the CNES Team on FFIORD (Formation Flying In Orbit Ranging Demonstration) onboard PRISMA mission. After a brief summary of the PRISMA mission context, the paper provides a full description of the rendezvous function involved in the approaching guidance experiment. This FFIORD onboard function is detailed in terms of on-board algorithmic method (basic algorithm and enhanced alternative), sensibility analysis used to construct maneuver plans and preliminary tests results.

  1. Overcoming Consumer Inertia to Dietary Guidance12

    PubMed Central

    Webb, Densie; Byrd-Bredbenner, Carol

    2015-01-01

    Despite 35 y of dietary guidance, there has been no substantial shift in consumer compliance. Consumers report that they seek information on nutrition and healthy eating, but most are not paying attention to dietary recommendations. For guidance to be effective, it must be realistic. Even with increasingly detailed nutrition information and evidence that diet affects health outcomes, convenience and taste remain the strongest determinants of food choices. It is up to health educators to clear up confusion and give consumers control with nutrition messages that are realistic, positive, easy to understand, and actionable without an expectation that consumers will surrender foods they love. PMID:26178023

  2. Overcoming consumer inertia to dietary guidance.

    PubMed

    Webb, Densie; Byrd-Bredbenner, Carol

    2015-07-01

    Despite 35 y of dietary guidance, there has been no substantial shift in consumer compliance. Consumers report that they seek information on nutrition and healthy eating, but most are not paying attention to dietary recommendations. For guidance to be effective, it must be realistic. Even with increasingly detailed nutrition information and evidence that diet affects health outcomes, convenience and taste remain the strongest determinants of food choices. It is up to health educators to clear up confusion and give consumers control with nutrition messages that are realistic, positive, easy to understand, and actionable without an expectation that consumers will surrender foods they love.

  3. Finite-time intercept-angle guidance

    NASA Astrophysics Data System (ADS)

    Lu, Kunfeng; Xia, Yuanqing; Yu, Chunmei; Chen, Rongfang

    2015-02-01

    In this paper, new nonsingular terminal sliding mode control guidance laws (NTSMCGLs) to unknown maneuvering target intercept are proposed and their finite-time convergences are proved. A novel nonsingular terminal sliding mode surface based on a predefined angle is designed to improve intercept performance and avoid singularity problem. The presented guidance law requires no information on maneuvering target that is estimated and compensated by extended state observer (ESO), and it can be used in practical systems where the target can evade freely. Also, undesired chattering is restrained effectively by real-time estimation and compensation of ESO. Simulation results show that the NTSMCGLs can achieve exact interception.

  4. Aerospace plane guidance using geometric control theory

    NASA Technical Reports Server (NTRS)

    Van Buren, Mark A.; Mease, Kenneth D.

    1990-01-01

    A reduced-order method employing decomposition, based on time-scale separation, of the 4-D state space in a 2-D slow manifold and a family of 2-D fast manifolds is shown to provide an excellent approximation to the full-order minimum-fuel ascent trajectory. Near-optimal guidance is obtained by tracking the reduced-order trajectory. The tracking problem is solved as regulation problems on the family of fast manifolds, using the exact linearization methodology from nonlinear geometric control theory. The validity of the overall guidance approach is indicated by simulation.

  5. Virtual Ultrasound Guidance for Inexperienced Operators

    NASA Technical Reports Server (NTRS)

    Caine, Timothy; Martin, David

    2012-01-01

    Medical ultrasound or echocardiographic studies are highly operator-dependent and generally require lengthy training and internship to perfect. To obtain quality echocardiographic images in remote environments, such as on-orbit, remote guidance of studies has been employed. This technique involves minimal training for the user, coupled with remote guidance from an expert. When real-time communication or expert guidance is not available, a more autonomous system of guiding an inexperienced operator through an ultrasound study is needed. One example would be missions beyond low Earth orbit in which the time delay inherent with communication will make remote guidance impractical. The Virtual Ultrasound Guidance system is a combination of hardware and software. The hardware portion includes, but is not limited to, video glasses that allow hands-free, full-screen viewing. The glasses also allow the operator a substantial field of view below the glasses to view and operate the ultrasound system. The software is a comprehensive video program designed to guide an inexperienced operator through a detailed ultrasound or echocardiographic study without extensive training or guidance from the ground. The program contains a detailed description using video and audio to demonstrate equipment controls, ergonomics of scanning, study protocol, and scanning guidance, including recovery from sub-optimal images. The components used in the initial validation of the system include an Apple iPod Classic third-generation as the video source, and Myvue video glasses. Initially, the program prompts the operator to power-up the ultrasound and position the patient. The operator would put on the video glasses and attach them to the video source. After turning on both devices and the ultrasound system, the audio-video guidance would then instruct on patient positioning and scanning techniques. A detailed scanning protocol follows with descriptions and reference video of each view along with

  6. Guidance accuracy considerations for realtime GPS interferometry

    NASA Technical Reports Server (NTRS)

    Braasch, Michael S.; Van Graas, Frank

    1991-01-01

    During April and May of 1991, the Avionics Engineering Center at Ohio University completed the first set of realtime flight tests of a GPS interferometric attitude and heading determination system. This technique has myriad applications for aircraft and spacecraft guidance and control. However, before these applications can be further developed, a number of guidance accuracy issues must be considered. Among these are: signal derogation due to multipath and shadowing, effects of structural flexures, and system robustness during loss of phase lock. This paper addresses these issues with special emphasis on the information content of the GPS signal, and characterization and mitigation of multipath encountered while in flight.

  7. Advanced glycation end products upregulate lysyl oxidase and endothelin-1 in human aortic endothelial cells via parallel activation of ERK1/2-NF-κB and JNK-AP-1 signaling pathways.

    PubMed

    Adamopoulos, Christos; Piperi, Christina; Gargalionis, Antonios N; Dalagiorgou, Georgia; Spilioti, Eliana; Korkolopoulou, Penelope; Diamanti-Kandarakis, Evanthia; Papavassiliou, Athanasios G

    2016-04-01

    Endothelial dysfunction involves deregulation of the key extracellular matrix (ECM) enzyme lysyl oxidase (LOX) and the vasoconstrictor protein, endothelin-1 (ET-1), whose gene expression can be modulated by the transcriptional activators nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1). Advanced glycation end products (AGEs) present an aggravating factor of endothelial dysfunction which upon engagement to their receptor RAGE induce upregulation of mitogen-activated protein kinases (MAPKs), leading to NF-κB and AP-1 potentiation. We hypothesized that AGEs could induce NF-κΒ- and AP-1-dependent regulation of LOX and ET-1 expression via the AGE/RAGE/MAPK signaling axis. Western blot, real-time qRT-PCR, FACS analysis and electrophoretic mobility-shift assays were employed in human aortic endothelial cells (HAECs) following treatment with AGE-bovine serum albumin (AGE-BSA) to investigate the signaling pathway towards this hypothesis. Furthermore, immunohistochemical analysis of AGEs, RAGE, LOX and ET-1 expression was conducted in aortic endothelium of a rat experimental model exposed to high- or low-AGE content diet. HAECs exposed to AGE-BSA for various time points exhibited upregulation of LOX and ET-1 mRNA levels in a dose- and time-dependent manner. Exposure of HAECs to AGE-BSA also showed specific elevation of phospho(p)-ERK1/2 and p-JNK levels in a dose- and time-dependent fashion. AGE administration significantly increased NF-κΒ- and AP-1-binding activity to both LOX and ET-1 cognate promoter regions. Moreover, LOX and ET-1 overexpression in rat aortic endothelium upon high-AGE content diet confirmed the functional interrelation of these molecules. Our findings demonstrate that AGEs trigger NF-κΒ- and AP-1-mediated upregulation of LOX and ET-1 via the AGE/RAGE/MAPK signaling cascade in human endothelial cells, thus contributing to distorted endothelial homeostasis by impairing endothelial barrier function, altering ECM biomechanical properties

  8. Slit/Robo pathway: a promising therapeutic target for cancer.

    PubMed

    Gara, Rishi K; Kumari, Sonam; Ganju, Aditya; Yallapu, Murali M; Jaggi, Meena; Chauhan, Subhash C

    2015-01-01

    Axon guidance molecules, slit glycoprotein (Slit) and Roundabout receptor (Robo), have implications in the regulation of physiological processes. Recent studies indicate that Slit and Robo also have important roles in tumorigenesis, cancer progression and metastasis. The Slit/Robo pathway can be considered a master regulator for multiple oncogenic signaling pathways. Herein, we provide a comprehensive review on the role of these molecules and their associated signaling pathways in cancer progression and metastasis. Overall, the current available data suggest that the Slit/Robo pathway could be a promising target for development of anticancer drugs.

  9. Apollo experience report guidance and control systems: Primary guidance, navigation, and control system development

    NASA Technical Reports Server (NTRS)

    Holley, M. D.; Swingle, W. L.; Bachman, S. L.; Leblanc, C. J.; Howard, H. T.; Biggs, H. M.

    1976-01-01

    The primary guidance, navigation, and control systems for both the lunar module and the command module are described. Development of the Apollo primary guidance systems is traced from adaptation of the Polaris Mark II system through evolution from Block I to Block II configurations; the discussion includes design concepts used, test and qualification programs performed, and major problems encountered. The major subsystems (inertial, computer, and optical) are covered. Separate sections on the inertial components (gyroscopes and accelerometers) are presented because these components represent a major contribution to the success of the primary guidance, navigation, and control system.

  10. Guidance for the knowledge and skills required for antimicrobial stewardship leaders.

    PubMed

    Cosgrove, Sara E; Hermsen, Elizabeth D; Rybak, Michael J; File, Thomas M; Parker, Sarah K; Barlam, Tamar F

    2014-12-01

    Antimicrobial stewardship programs are increasingly recognized as critical in optimizing the use of antimicrobials. Consequently, more physicians, pharmacists, and other healthcare providers are developing and implementing such programs in a variety of healthcare settings. The purpose of this guidance document is to outline the knowledge and skills that are needed to lead an antimicrobial stewardship program. It was developed by antimicrobial stewardship experts from organizations that are engaged in advancing the field of antimicrobial stewardship.

  11. NASA Office of Aeronautics and Space Technology Summer Workshop. Volume 3: Navigation, guidance and control panel

    NASA Technical Reports Server (NTRS)

    1975-01-01

    User technology requirements are identified in relation to needed technology advancement for future space missions in the areas of navigation, guidance, and control. Emphasis is placed on: reduction of mission support cost by 50% through autonomous operation, a ten-fold increase in mission output through improved pointing and control, and a hundred-fold increase in human productivity in space through large-scale teleoperator applications.

  12. Guidance Program Evaluation: What's Out There?

    ERIC Educational Resources Information Center

    Miller, Juliet V.; Grisdale, George A.

    1975-01-01

    This article reviews a number of guidance evaluation materials and programs presently in use in terms of Stufflebeam's CIPP model. Some materials were simple evaluation instruments; others were as comprehensive as process guides for the planning, development, and application of a complete systems approach evaluation. (Author)

  13. Computer-Based Vocational Guidance Systems.

    ERIC Educational Resources Information Center

    Gallagher, James J., Ed.

    Job and educational opportunities are increasing dramatically. School guidance counselors can no longer cope adequately with the available information, nor can they help all students to see the complex range of alternative life styles. Computers are now programed to give students information. They can also provide for students' decision-making…

  14. Computer Applications in Guidance and Counseling.

    ERIC Educational Resources Information Center

    Havens, Robert I.

    The purpose of this discussion is to acquaint pupil personnel workers with some of the applications of computer based information processing systems for pupil services and also to consider some of the legal and ethical concerns relative to data processing in counseling and guidance. Some of the uses discussed are: (1) scheduling; (2) student…

  15. Decisions & Values. Intermediate Level. Career Guidance.

    ERIC Educational Resources Information Center

    Cooper, Irene

    Materials contained in this career guidance unit are designed to aid ten- and eleven-year-old students in becoming effective problem solvers, and to bring to attention the relationship between an individual's values and decisions. Skill in using a simplified problem solving technique introduced in the primary grades (Decision Making, Levels…

  16. Guidance for an aeroassisted orbital transfer vehicle

    NASA Technical Reports Server (NTRS)

    Hall, Kenneth R.

    1988-01-01

    The use of atmospheric drag for slowing satellite in high energy, high apogee orbits to a lower energy, lower apogee orbit about the Earth is investigated. The high energy orbit is assumed to intercept the Earth's atmosphere. Guidance for the atmospheric phase of the trajectory may be done using the aerodynamic forces generated by the passage through the atmosphere. This research was concerned with the investigation of several methods of guidance during the atmospheric phase to cause a significant reduction in the final velocity as the vehicle leaves the atmosphere. In addition, the velocity direction was controlled to exit to a desired target orbit. Lastly excess aerodynamic lift was used to effect a plane change between the entry orbit plane and the exit orbit plane to achieve a desired orbit plane. The guidance methods were applied to a 3 degree-of-freedom simulation which included an oblate Earth gravity model and a rotating atmosphere. Simulation results were compared on the basis of speed of computation of the guidance parameters and amount of added velocity necessary to achieve the desired orbit.

  17. 21 CFR 314.445 - Guidance documents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Miscellaneous Provisions § 314.445 Guidance... directed to the Office of Training and Communications, Division of Drug Information, Center for...

  18. Epilepsy in the Classroom: Guidance for Educators.

    ERIC Educational Resources Information Center

    Lassner, Lee M.

    This paper for educators, school psychologists, and counselors attempts to provide guidance for meeting the needs of students with epilepsy. Stressed throughout the paper are ways to provide for the child's special needs while fostering his/her self esteem and full participation in classroom activities. The paper addresses the following topics:…

  19. Assessing Enterprise Capability: Guidance for Schools

    ERIC Educational Resources Information Center

    National Foundation for Educational Research, 2007

    2007-01-01

    This document offers guidance to schools on how assessment can support enterprise education. It presents the interim findings from research carried out by the National Foundation for Educational Research (NFER) for the Department for Education and Skills (DfES) in secondary schools in England. Enterprise capability is the key outcome of enterprise…

  20. Online guidance updates using neural networks

    NASA Astrophysics Data System (ADS)

    Filici, Cristian; Sánchez Peña, Ricardo S.

    2010-02-01

    The aim of this article is to present a method for the online guidance update for a launcher ascent trajectory that is based on the utilization of a neural network approximator. Generation of training patterns and selection of the input and output spaces of the neural network are presented, and implementation issues are discussed. The method is illustrated by a 2-dimensional launcher simulation.

  1. Money, Money, Money: A Developmental Guidance Approach.

    ERIC Educational Resources Information Center

    Allan, John; Klassen, Garry

    1992-01-01

    Describes developmental guidance unit on topic of money for grades six and seven. Describes class discussion format used to conduct two sessions helping students explore, understand, and develop coping skills regarding money issues. Notes that students worried about money, understood why people overspend, and developed ways of earning and saving…

  2. Career Guidance Policy: An International Review

    ERIC Educational Resources Information Center

    Watts, A. G.

    2005-01-01

    The Organization for Economic Co-operation and Development, the World Bank, and the European Commission have conducted reviews of the career guidance policies and practices in 37 countries. The 37 country studies, together with the 3 synthesis reports and a number of other commissioned papers, constitute the largest database on career guidance…

  3. A Workable Program of Career Guidance

    ERIC Educational Resources Information Center

    Hunt, Myrtle E.

    1974-01-01

    Seven observations made by a career education team (a counselor, an occupational specialist, and classroom teachers) provided the basis for establishing career guidance goals. The goals were devoloped around the accepted elements of career education and implemented in a teacher-counselor shared accountability effort in Florida's Pinellas County.…

  4. Guidance for Industry: Food Producers, Processors, and ...

    Center for Food Safety and Applied Nutrition (CFSAN)

    ... สองฉบับประกอบคําแนะนําเรื่องความปลอดภัย ของอาหารชื่อ "Food Producers, Processors, and Transporters: Food security preventive measures guidance ...

  5. Athletics Guidance Aims for Level Field

    ERIC Educational Resources Information Center

    Samuels, Christina A.

    2013-01-01

    A document from the U.S. Department of Education intended to clarify schools' responsibility to make sure students with disabilities have access to extracurricular sports has drawn sharply different opinions. Disability-rights advocates welcome the guidance, while critics say federal officials are pushing requirements that could place new…

  6. 2008 Rapanos Guidance and Related Documents

    EPA Pesticide Factsheets

    This memo provides guidance to EPA regions and Corps districts implementing the Supreme Court's decision in the consolidated cases Rapanos v. US and Carabell v. US which address the jurisdiction over waters of the U.S. under the Clean Water Act.

  7. 78 FR 53792 - Draft Guidance for Reciprocity

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-30

    ... COMMISSION Draft Guidance for Reciprocity AGENCY: Nuclear Regulatory Commission. ACTION: Draft NUREG; request... for reciprocity. The NRC is requesting public comment on draft NUREG-1556, Volume 19, Revision 1... (Reciprocity).'' The document has been updated from the previous revision to include safety culture,...

  8. Guidance and Control strategies for aerospace vehicles

    NASA Technical Reports Server (NTRS)

    Hibey, J. L.; Naidu, D. S.; Charalambous, C. D.

    1989-01-01

    A neighboring optimal guidance scheme was devised for a nonlinear dynamic system with stochastic inputs and perfect measurements as applicable to fuel optimal control of an aeroassisted orbital transfer vehicle. For the deterministic nonlinear dynamic system describing the atmospheric maneuver, a nominal trajectory was determined. Then, a neighboring, optimal guidance scheme was obtained for open loop and closed loop control configurations. Taking modelling uncertainties into account, a linear, stochastic, neighboring optimal guidance scheme was devised. Finally, the optimal trajectory was approximated as the sum of the deterministic nominal trajectory and the stochastic neighboring optimal solution. Numerical results are presented for a typical vehicle. A fuel-optimal control problem in aeroassisted noncoplanar orbital transfer is also addressed. The equations of motion for the atmospheric maneuver are nonlinear and the optimal (nominal) trajectory and control are obtained. In order to follow the nominal trajectory under actual conditions, a neighboring optimum guidance scheme is designed using linear quadratic regulator theory for onboard real-time implementation. One of the state variables is used as the independent variable in reference to the time. The weighting matrices in the performance index are chosen by a combination of a heuristic method and an optimal modal approach. The necessary feedback control law is obtained in order to minimize the deviations from the nominal conditions.

  9. "Telling Tales": Using Narrative in Career Guidance

    ERIC Educational Resources Information Center

    Reid, Hazel; West, Linden

    2011-01-01

    In this article the authors argue for the importance of narrative-based approaches in career guidance work in an uncertain, unpredictable world. This requires a paradigmatic shift in thinking that can be too difficult, at present, for some practitioners. The article reports on the first phase of a collaborative project with a group of…

  10. Stressor Identification Guidance Document | Science Inventory ...

    EPA Pesticide Factsheets

    EPA has made availabile the Stressor Identification Guidance Document (EPA 822-B-00-025) published under the authority of Section 304(a)(2) of the Clean Water Act (CWA). This technical guidance document is designed to assist water quality managers in identifying unknown causes of biological impairments in any type of water body. Section 101(a) of the Clean Water Act states that it is the objective of the Act to restore and maintain the chemical, physical and biological integrity of the Nation's waters. To achieve this objective, numerous States and Tribes are using biological assessments and biocriteria to help protect the Nation's waters. Using these tools, State and Tribal water quality experts are finding water bodies where the fish, invertebrate, algae or plant communities (or other aquatic life) have been detrimentally impacted by different singular or multiple causes. In many cases, the cause, or causes, of these biological impairments have not yet been identified. The Stressor Identification Guidance Document provides a logical, scientific process by which State, Tribal, and other water quality experts can evaluate available information to identify the stressor(s) causing the biological impairments. The process has three main steps: (1) List candidate causes of impairment, (2) analyze the evidence, and (3) characterize the causes. When evidence is adequate, using this guidance, investigators should be able to successfully identify the likely cause, or ca

  11. 21 CFR 316.50 - Guidance documents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Products Development will maintain and make publicly available a list of guidance documents that apply to... Federal Register. A request for a copy of the list should be directed to the Office of Orphan Products Development (HF-35), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857....

  12. From the Church to the Guidance Department.

    ERIC Educational Resources Information Center

    Fraser, Bruce W.

    1979-01-01

    The religious instituations seem to be experiencing an exodus of young people from active participation, but those who leave are not rejecting life, they are simply looking for answers from different sources. Guidance counselors have opportunities to assist the young people who come to them in several ways. (Author)

  13. Guidance for performing site inspections under CERCLA

    SciTech Connect

    Not Available

    1992-09-01

    This guidance presents EPA`s site inspection (SI) strategy. The strategy discusses procedural guidelines to investigate potential Superfund (CERCLA) sites for evaluation pursuant to the Hazard Ranking System (HRS), revised in accordance with the Superfund Amendments and Reauthorization Act of 1986. The HRS is the primary means by which EPA evaluates sites for superfund`s National Priorities List (NPL).

  14. Hypermedia Authoring with Writing Process Guidance

    ERIC Educational Resources Information Center

    Chang, Kuo-En; Sung, Yao-Ting; Zheng, Jie-Wen

    2007-01-01

    A writing process of five stages, setting the topic and goals, planning the outline, organising the structure, building the content, and reviewing, is proposed to guide hypermedia authoring. To explore the effects of the system designed with writing-process guidance, this study enrolled 108 seventh graders at a junior high school as experimental…

  15. The Spanish Family Guidance Center of Miami.

    ERIC Educational Resources Information Center

    Hispanic Research Center: Research Bulletin, 1979

    1979-01-01

    Two major programs of the Spanish Family Guidance Center, a facility that addresses the mental health needs of Hispanics in the Greater Miami (Florida) area, are described in this report. One program, the Spanish Drug Rehabilitation Project (completed in 1977), compared a series of activities including: (1) research on the characteristics of…

  16. Designing Schoolwide Programs. Non-Regulatory Guidance

    ERIC Educational Resources Information Center

    US Department of Education, 2006

    2006-01-01

    This guidance offers a renewed vision for the use of the schoolwide program, both as a reform strategy and as a means of realizing the high standards for student achievement envisioned by the No Child Left Behind Act of 2001 (NCLB). It is intended to be used as a companion document to the statute and regulations, as well as a technical assistance…

  17. Advisory List of Instructional Media Guidance.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Public Instruction, Raleigh.

    A bibliography of materials relevant to the competency-based guidance curriculum of the North Carolina State Department of Public Instruction is presented in this document. Books for students, books for teacher/counselor use, filmstrips (sound), and videocassettes are listed. Grade ranges are provided for each item, although use of the materials…

  18. Self-Awareness. Level One. Career Guidance.

    ERIC Educational Resources Information Center

    Fiendach, Nancy; And Others

    Materials contained in this career guidance unit are designed to develop in five-and six-year-old children an awareness of their senses and the related body organs, likenesses and differences, and self-control. The nineteen activities included in the unit vary in length from twenty to sixty minutes; the entire unit requires approximately ten hours…

  19. MR imaging guidance for minimally invasive procedures

    NASA Astrophysics Data System (ADS)

    Wong, Terence Z.; Kettenbach, Joachim; Silverman, Stuart G.; Schwartz, Richard B.; Morrison, Paul R.; Kacher, Daniel F.; Jolesz, Ferenc A.

    1998-04-01

    Image guidance is one of the major challenges common to all minimally invasive procedures including biopsy, thermal ablation, endoscopy, and laparoscopy. This is essential for (1) identifying the target lesion, (2) planning the minimally invasive approach, and (3) monitoring the therapy as it progresses. MRI is an ideal imaging modality for this purpose, providing high soft tissue contrast and multiplanar imaging, capability with no ionizing radiation. An interventional/surgical MRI suite has been developed at Brigham and Women's Hospital which provides multiplanar imaging guidance during surgery, biopsy, and thermal ablation procedures. The 0.5T MRI system (General Electric Signa SP) features open vertical access, allowing intraoperative imaging to be performed. An integrated navigational system permits near real-time control of imaging planes, and provides interactive guidance for positioning various diagnostic and therapeutic probes. MR imaging can also be used to monitor cryotherapy as well as high temperature thermal ablation procedures sing RF, laser, microwave, or focused ultrasound. Design features of the interventional MRI system will be discussed, and techniques will be described for interactive image acquisition and tracking of interventional instruments. Applications for interactive and near-real-time imaging will be presented as well as examples of specific procedures performed using MRI guidance.

  20. Career Guidance and Counseling: Recent Legislation.

    ERIC Educational Resources Information Center

    Cunanan, Esmeralda S.; Maddy-Bernstein, Carolyn

    1995-01-01

    The Perkins Act of 1990 and the School to Work Opportunities Act (STWOA) of 1994 both contain explicit provisions regarding career guidance and counseling provisions for special populations. The Perkins Act sets the direction for state and local agencies as they develop vocational and applied education programs to equip youth and adults with the…

  1. Effective Child Guidance: An Educator's Guidebook.

    ERIC Educational Resources Information Center

    Hill, Brent Mathews

    This guidebook is designed to assist educators in becoming more effective child guidance leaders within the school system. Sections discuss the following areas: (1) indicators of current emotional problems; (2) children's common emotional problems, including fears, separation and loss, misbehavior motivations, aggressiveness, stealing, lying,…

  2. Next Steps: Water Technology Advances (Research)

    EPA Science Inventory

    This project will focus on contaminants and their impact on health, adequate removal of contaminants from various water systems, and water and resource recovery within treatment systems. It will develop the next generation of technological advances to provide guidance in support ...

  3. RMP Guidance for Chemical Distributors - Appendix D: OSHA Guidance on PSM

    EPA Pesticide Factsheets

    Guidance on the Process Safety Management standard says information (including MSDS) about chemicals, including process intermediates, must enable accurate assessment of fire/explosion characteristics, reactivity hazards, and corrosing/erosion effects.

  4. An application of extremal field guidance in statistical low thrust guidance analysis

    NASA Technical Reports Server (NTRS)

    Jacobson, R. A.

    1980-01-01

    The subject of this paper is the application of extremal field guidance to the covariance analysis of low thrust retargeting guidance. The general procedure for low thrust navigation analysis is briefly reviewed. The basic equations of trajectory optimization and extremal field guidance are presented with emphasis on the low thrust problem. The adopted formulation includes thruster on-off times as control variables and accounts for the effects of model parameter variations. A method of solution of the guidance equations is outlined; and the application of the solution in a covariance analysis, including a procedure for the treatment of model parameter variations as either biases or first order Gauss-Markov stochastic processes, is discussed.

  5. Guidance: Using RCRA's Results-Based Approaches and Tailored Oversight Guidance when Performing Superfund Oversight

    EPA Pesticide Factsheets

    Memorandum providing additional information in support of Superfund's administrative reform on PRP oversight. Superfund program managers should consider RCRA's Results-Based Guidance when developing oversight plans with PRPs.

  6. Guidance and control 1991; Proceedings of the Annual Rocky Mountain Guidance and Control Conference, Keystone, CO, Feb. 2-6, 1991

    NASA Astrophysics Data System (ADS)

    Culp, Robert D.; McQuerry, James P.

    1991-07-01

    The present conference on guidance and control encompasses advances in guidance, navigation, and control, storyboard displays, approaches to space-borne pointing control, international space programs, recent experiences with systems, and issues regarding navigation in the low-earth-orbit space environment. Specific issues addressed include a scalable architecture for an operational spaceborne autonavigation system, the mitigation of multipath error in GPS-based attitude determination, microgravity flight testing of a laboratory robot, and the application of neural networks. Other issues addressed include image navigation with second-generation Meteosat, Magellan star-scanner experiences, high-precision control systems for telescopes and interferometers, gravitational effects on low-earth orbiters, experimental verification of nanometer-level optical pathlengths, and a flight telerobotic servicer prototype simulator. (For individual items see A93-15577 to A93-15613)

  7. A Formal Investigation of the Organization of Guidance Behavior: Implications for Humans and Autonomous Guidance

    NASA Astrophysics Data System (ADS)

    Kong, Zhaodan

    Guidance behavior generated either by artificial agents or humans has been actively studied in the fields of both robotics and cognitive science. The goals of these two fields are different. The former is the automatic generation of appropriate or even optimal behavior, while the latter is the understanding of the underlying mechanism. Their challenges, though, are closely related, the most important one being the lack of a unified, formal and grounded framework where the guidance behavior can be modeled and studied. This dissertation presents such a framework. In this framework, guidance behavior is analyzed as the closed-loop dynamics of the whole agent-environment system. The resulting dynamics give rise to interaction patterns. The central points of this dissertation are that: first of all, these patterns, which can be explained in terms of symmetries that are inherent to the guidance behavior, provide building blocks for the organization of behavior; second, the existence of these patterns and humans' organization of their guidance behavior based on these patterns are the reasons that humans can generate successful behavior in spite of all the complexities involved in the planning and control. This dissertation first gives an overview of the challenges existing in both scientific endeavors, such as human and animal spatial behavior study, and engineering endeavors, such as autonomous guidance system design. It then lays out the foundation for our formal framework, which states that guidance behavior should be interpreted as the collection of the closed-loop dynamics resulting from the agent's interaction with the environment. The following, illustrated by examples of three different UAVs, shows that the study of the closed-loop dynamics should not be done without the consideration of vehicle dynamics, as is the common practice in some of the studies in both autonomous guidance and human behavior analysis. The framework, the core concepts of which are

  8. Flu Vaccine Guidance for Patients with Immune Deficiency

    MedlinePlus

    ... Guidance for Patients with Immune Deficiency Share | Flu Vaccine Guidance for Patients with Immune Deficiency This article ... should patients with immune deficiency be given the vaccine? Immune deficient patients have a decreased resistance to ...

  9. 75 FR 48973 - Draft Guidance for Industry: Prevention of Salmonella

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry: Prevention of Salmonella... availability of a draft guidance entitled ``Prevention of Salmonella Enteritidis in Shell Eggs During... ``Prevention of Salmonella Enteritidis in Shell Eggs During Production, Storage, and Transportation''...

  10. Technical Guidance for Assessing Environmental Justice in Regulatory Analysis

    EPA Science Inventory

    The Technical Guidance for Assessing Environmental Justice in Regulatory Analysis (also referred to as the Environmental Justice Technical Guidance or EJTG) is intended for use by Agency analysts, including risk assessors, economists, and other analytic staff that conduct analyse...

  11. State and Tribal Indoor Radon Grants Program Guidance and Handbook

    EPA Pesticide Factsheets

    This guidance is intended to reconcile all legal, policy, and programmatic changes that have affected the SIRG program over the past decade and to provide new clarity, consistency and organization to the guidance.

  12. FY2015 Advanced Combustion Engine Annual Progress Report

    SciTech Connect

    Singh, Gurpreet; Gravel, Roland M.; Howden, Kenneth C.; Breton, Leo

    2016-03-25

    The Advanced Combustion Engine research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for many cutting-edge automotive technologies under development. Research focuses on addressing critical barriers to commercializing higher efficiency, very low emissions advanced internal combustion engines for passenger and commercial vehicles.

  13. FY2014 Advanced Combustion Engine Annual Progress Report

    SciTech Connect

    2015-03-01

    The Advanced Combustion Engine research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for many cutting-edge automotive technologies under development. Research focuses on addressing critical barriers to commercializing higher efficiency, very low emissions advanced internal combustion engines for passenger and commercial vehicles.

  14. Wnt5a Regulates Midbrain Dopaminergic Axon Growth and Guidance

    PubMed Central

    Blakely, Brette D.; Bye, Christopher R.; Fernando, Chathurini V.; Horne, Malcolm K.; Macheda, Maria L.; Stacker, Steven A.; Arenas, Ernest; Parish, Clare L.

    2011-01-01

    During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM) the cues that guide dopaminergic (DA) axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway). Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in Wnt5a−/− mice, where fasciculation of the medial forebrain bundle (MFB) as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance. PMID:21483795

  15. Managing Student Behavior during Large Group Guidance: What Works Best?

    ERIC Educational Resources Information Center

    Quarto, Christopher J.

    2007-01-01

    Participants provided information pertaining to managing non-task-related behavior of students during large group guidance lessons. In particular, school counselors were asked often how often they provide large group guidance, the frequency of which students exhibit off-task and/or disruptive behavior during guidance lessons, and techniques they…

  16. Aptitudes of Guidance Counselors. Technical Report 1986-2.

    ERIC Educational Resources Information Center

    Tal, Joseph

    To identify the aptitude profile of successful guidance counselors, tests were administered to 49 guidance counselors (14 male, 35 female) ranging in age from 29 to 62 (Mean age 42) and having an average of 9.5 years experience. The findings indicated that guidance counselors as a group scored near or above the Johnson O'Connor Research…

  17. Guidance Concept for a Mars Ascent Vehicle First Stage

    NASA Technical Reports Server (NTRS)

    Queen, Eric M.

    2000-01-01

    This paper presents a guidance concept for use on the first stage of a Mars Ascent Vehicle (MAV). The guidance is based on a calculus of variations approach similar to that used for the final phase of the Apollo Earth return guidance. A three degree-of-freedom (3DOF) Monte Carlo simulation is used to evaluate performance and robustness of the algorithm.

  18. GUIDANCE GUIDELINES. A HANDBOOK FOR SECONDARY SCHOOL COUNSELORS.

    ERIC Educational Resources Information Center

    EHLERS, DOROTHY; AND OTHERS

    DIRECTIONAL PROCEDURES AND TECHNIQUES FOR ADMINISTERING THE OVERALL PROGRAM OF SECONDARY SCHOOL GUIDANCE ARE PRESENTED. THE MAJOR EMPHASIS OF THIS GUIDANCE PROGRAM IS UPON OCCUPATIONAL, EDUCATIONAL, AND SOCIAL ADJUSTMENT OF ALL THE PUPILS. SERVICES OF THE GUIDANCE PROGRAM ARE DESCRIBED AT LENGTH. THE KEY IS COUNSELING, OF INDIVIDUALS OR GROUPS.…

  19. Needs Assessment for Guidance and Counselling in Kenya.

    ERIC Educational Resources Information Center

    Tumuti, Sammy

    Formal guidance and counseling in Kenya is recognized more than ever. The development of effective guidance and counseling programs will be guided by needs assessment. This study used data from a larger study on guidance and counseling needs assessment of primary school pupils of Gachika Sub-location, Nyeri Town, and Nairobi City. Differences in…

  20. Simulated Administration of a Regular Guidance Operation (SARGO).

    ERIC Educational Resources Information Center

    Fredrickson, Ronald H.; Popken, Charles F.

    Simulated Administration of a Regular Guidance Operation (SARGO) is a program for the training of directors of guidance and pupil personnel services. The objective of SARGO is to prepare directors of guidance services to: (1) prepare a written description of a pupil personnel program; (2) interact with a school administrator to clarify role…