Building foundations for the future: the NHS Scotland advanced practice succession planning development pathway.

PubMed

Currie, Kay; Grundy, Maggie

2011-10-01

To highlight implications for managers from the implementation of a national advanced practice succession planning development pathway within Scotland. Internationally, advanced practice posts have often developed in an ad-hoc manner, with little organizational attention to succession planning. Evaluation of a pilot national succession planning development pathway identified mechanisms which facilitate or hamper effective planning for advanced practice roles. A responsive evaluation design incorporating semi-structured questionnaires to pathway participants (n = 15) and semi-structured telephone interviews with case-site pathway participants (n = 7) and their line managers. Managers believed the development pathway was worthwhile; however, there was limited strategic planning to match individuals' development to service need. Practitioners generally perceived managers as interested in their development, although levels of practical support varied. There is concern from both managers and practitioners regarding ongoing funding for advanced practice development. The present evaluation study reiterates the need for organizational commitment to succession planning including robust service needs analysis mechanisms and adequate funding for development processes. Nurse managers are viewed as the 'gatekeepers' to opportunities for developing advanced nurse practitioners; scare resources must be targeted effectively to support succession planning through the development of selected individuals for future advanced practice posts, justified by service need. © 2011 Blackwell Publishing Ltd.

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.

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.

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.

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.

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.

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.

Advanced Video Guidance Sensor (AVGS) Development Testing

NASA Technical Reports Server (NTRS)

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

2004-01-01

NASA's Marshall Space Flight Center was the driving force behind the development of the Advanced Video Guidance Sensor, an active sensor system that provides near-range sensor data as part of an automatic rendezvous and docking system. 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 camera to detect the return from the target, and image capture electronics and a digital signal processor to convert the video information into the relative positions and attitudes. The AVGS will fly as part of the Demonstration of Autonomous Rendezvous Technologies (DART) in October, 2004. This development effort has required a great deal of testing of various sorts at every phase of development. Some of the test efforts included optical characterization of performance with the intended target, thermal vacuum testing, performance tests in long range vacuum facilities, EMI/EMC tests, and performance testing in dynamic situations. The sensor has been shown to track a target at ranges of up to 300 meters, both in vacuum and ambient conditions, to survive and operate during the thermal vacuum cycling specific to the DART mission, to handle EM1 well, and to perform well in dynamic situations.

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

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

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 barrelmore » 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).« less

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…

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.

Finite element method for optimal guidance of an advanced launch vehicle

NASA Technical Reports Server (NTRS)

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

1992-01-01

A temporal finite element based on a mixed form of Hamilton's weak principle is summarized for optimal control problems. The resulting weak Hamiltonian finite element method is extended to allow for discontinuities in the states and/or discontinuities in the system equations. An extension of the formulation to allow for control inequality constraints is also presented. The formulation does not require element quadrature, and it produces a sparse system of nonlinear algebraic equations. To evaluate its feasibility for real-time guidance applications, this approach is applied to the trajectory optimization of a four-state, two-stage model with inequality constraints for an advanced launch vehicle. Numerical results for this model are presented and compared to results from a multiple-shooting code. The results show the accuracy and computational efficiency of the finite element method.

Advanced Video Guidance Sensor and next-generation autonomous docking sensors

NASA Astrophysics Data System (ADS)

Granade, Stephen R.

2004-09-01

In recent decades, NASA's interest in spacecraft rendezvous and proximity operations has grown. Additional instrumentation is needed to improve manned docking operations' safety, as well as to enable telerobotic operation of spacecraft or completely autonomous rendezvous and docking. To address this need, Advanced Optical Systems, Inc., Orbital Sciences Corporation, and Marshall Space Flight Center have developed the Advanced Video Guidance Sensor (AVGS) under the auspices of the Demonstration of Autonomous Rendezvous Technology (DART) program. Given a cooperative target comprising several retro-reflectors, AVGS provides six-degree-of-freedom information at ranges of up to 300 meters for the DART target. It does so by imaging the target, then performing pattern recognition on the resulting image. Longer range operation is possible through different target geometries. Now that AVGS is being readied for its test flight in 2004, the question is: what next? Modifications can be made to AVGS, including different pattern recognition algorithms and changes to the retro-reflector targets, to make it more robust and accurate. AVGS could be coupled with other space-qualified sensors, such as a laser range-and-bearing finder, that would operate at longer ranges. Different target configurations, including the use of active targets, could result in significant miniaturization over the current AVGS package. We will discuss these and other possibilities for a next-generation docking sensor or sensor suite that involve AVGS.

Advanced Video Guidance Sensor and Next Generation Autonomous Docking Sensors

NASA Technical Reports Server (NTRS)

Granade, Stephen R.

2004-01-01

In recent decades, NASA's interest in spacecraft rendezvous and proximity operations has grown. Additional instrumentation is needed to improve manned docking operations' safety, as well as to enable telerobotic operation of spacecraft or completely autonomous rendezvous and docking. To address this need, Advanced Optical Systems, Inc., Orbital Sciences Corporation, and Marshall Space Flight Center have developed the Advanced Video Guidance Sensor (AVGS) under the auspices of the Demonstration of Autonomous Rendezvous Technology (DART) program. Given a cooperative target comprising several retro-reflectors, AVGS provides six-degree-of-freedom information at ranges of up to 300 meters for the DART target. It does so by imaging the target, then performing pattern recognition on the resulting image. Longer range operation is possible through different target geometries. Now that AVGS is being readied for its test flight in 2004, the question is: what next? Modifications can be made to AVGS, including different pattern recognition algorithms and changes to the retro-reflector targets, to make it more robust and accurate. AVGS could be coupled with other space-qualified sensors, such as a laser range-and-bearing finder, that would operate at longer ranges. Different target configurations, including the use of active targets, could result in significant miniaturization over the current AVGS package. We will discuss these and other possibilities for a next-generation docking sensor or sensor suite that involve AVGS.

PATIKAweb: a Web interface for analyzing biological pathways through advanced querying and visualization.

PubMed

Dogrusoz, U; Erson, E Z; Giral, E; Demir, E; Babur, O; Cetintas, A; Colak, R

2006-02-01

Patikaweb provides a Web interface for retrieving and analyzing biological pathways in the Patika database, which contains data integrated from various prominent public pathway databases. It features a user-friendly interface, dynamic visualization and automated layout, advanced graph-theoretic queries for extracting biologically important phenomena, local persistence capability and exporting facilities to various pathway exchange formats.

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.

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

DTIC Science & Technology

2017-10-01

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

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.

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.

Building shared experience to advance practical application of pathway-based toxicology: liver toxicity mode-of-action.

PubMed

Willett, Catherine; Caverly Rae, Jessica; 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

2014-01-01

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 extremely helpful. In addition, 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.

The continuum of behavior guidance.

PubMed

Nelson, Travis

2013-01-01

Behavior guidance is a continuum of techniques, basic and advanced, fundamental to the provision of quality dental care for pediatric patients. This practice must be individualized, pairing the correct method of behavior guidance with each child. To select the appropriate technique, the clinician must have a thorough understanding of each aspect of the continuum and anticipate parental expectations, child temperament, and the technical procedures necessary to complete care. By effectively using techniques within the continuum of behavior guidance, a healing relationship with the family is maintained while addressing dental disease and empowering the child to receive dental treatment throughout their lifetime. Copyright © 2013 Elsevier Inc. All rights reserved.

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...growth and metastasis via dysregulation of the PI3K/AKT2 pathway. (months 1-24) Major Goal 1: Assess how WDR26 regulates PI3K/ AKT signaling in

Conference Proceedings on Guidance and Control Techniques for Advanced Space Vehicles (37th) Held at Florence, Italy on 27-30 September 1983.

DTIC Science & Technology

1984-01-01

P AD-A14l 969 CONFERENCE PROCEEDINGS ON GUIDANCE AND CONTROL 1 TECHNIQUES FOR ADVANCED SP-.(U,) ADVISORY GROUP FOR AEROSPACE RESEARCH AND DEVELOPMENT...findings of these various planning groups relativie to the ’e for advanced controls technology, and the perceived status of the technology t. me-,t... control of large flexible spacecraft. The program has also involved experimental activities to guide Ind validate the theoretical work. The

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

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.

Axon Response to Guidance Cues Is Stimulated by Acetylcholine in Caenorhabditis elegans

PubMed Central

Xu, Yan; Ren, Xing-Cong; Quinn, Christopher C.; Wadsworth, William G.

2011-01-01

Gradients of acetylcholine can stimulate growth cone turning when applied to neurons grown in culture, and it has been suggested that acetylcholine could act as a guidance cue. However, the role acetylcholine plays in directing axon migrations in vivo is not clear. Here, we show that acetylcholine positively regulates signaling pathways that mediate axon responses to guidance cues in Caenorhabditis elegans. Mutations that disrupt acetylcholine synthesis, transportation, and secretion affect circumferential axon guidance of the AVM neuron and in these mutants exogenously supplied acetylcholine improves AVM circumferential axon guidance. These effects are not observed for the circumferential guidance of the DD and VD motor neuron axons, which are neighbors of the AVM axon. Circumferential guidance is directed by the UNC-6 (netrin) and SLT-1 (slit) extracellular cues, and exogenously supplied acetylcholine can improve AVM axon guidance in mutants when either UNC-6– or SLT-1–induced signaling is disrupted, but not when both signaling pathways are perturbed. Not in any of the mutants does exogenously supplied acetylcholine improve DD and VD axon guidance. The ability of acetylcholine to enhance AVM axon guidance only in the presence of either UNC-6 or SLT-1 indicates that acetylcholine potentiates UNC-6 and SLT-1 guidance activity, rather than acting itself as a guidance cue. Together, our results show that for specific neurons acetylcholine plays an important role in vivo as a modulator of axon responses to guidance cues. PMID:21868605

Video-Guidance Design for the DART Rendezvous Mission

NASA Technical Reports Server (NTRS)

Ruth, Michael; Tracy, Chisholm

2004-01-01

NASA's Demonstration of Autonomous Rendezvous Technology (DART) mission will validate a number of different guidance technologies, including state-differenced GPS transfers and close-approach video guidance. The video guidance for DART will employ NASA/Marshall s Advanced Video Guidance Sensor (AVGS). This paper focuses on the terminal phase of the DART mission that includes close-approach maneuvers under AVGS guidance. The closed-loop video guidance design for DART is driven by a number of competing requirements, including a need for maximizing tracking bandwidths while coping with measurement noise and the need to minimize RCS firings. A range of different strategies for attitude control and docking guidance have been considered for the DART mission, and design decisions are driven by a goal of minimizing both the design complexity and the effects of video guidance lags. The DART design employs an indirect docking approach, in which the guidance position targets are defined using relative attitude information. Flight simulation results have proven the effectiveness of the video guidance design.

Safety assessment guidance in the International Atomic Energy Agency RADWASS Program

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

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 safetymore » 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.« less

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.

Advancing the adverse outcome pathway framework - An international horizon scanning approach (presentation)

EPA Science Inventory

In preparation for a Society of Environmental Toxicology and Chemistry Pellston Workshop titled “Advancing the Adverse Outcome Pathway (AOP) Concept: An International Horizon Scanning Approach,” a horizon scanning effort was undertaken to gather input from the global ...

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. Copyright 2013, SLACK Incorporated.

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.

Glypican Is a Modulator of Netrin-Mediated Axon Guidance

PubMed Central

Blanchette, Cassandra R.; Perrat, Paola N.; Thackeray, Andrea; Bénard, Claire Y.

2015-01-01

Netrin is a key axon guidance cue that orients axon growth during neural circuit formation. However, the mechanisms regulating netrin and its receptors in the extracellular milieu are largely unknown. Here we demonstrate that in Caenorhabditis elegans, LON-2/glypican, a heparan sulfate proteoglycan, modulates UNC-6/netrin signaling and may do this through interactions with the UNC-40/DCC receptor. We show that developing axons misorient in the absence of LON-2/glypican when the SLT-1/slit guidance pathway is compromised and that LON-2/glypican functions in both the attractive and repulsive UNC-6/netrin pathways. We find that the core LON-2/glypican protein, lacking its heparan sulfate chains, and secreted forms of LON-2/glypican are functional in axon guidance. We also find that LON-2/glypican functions from the epidermal substrate cells to guide axons, and we provide evidence that LON-2/glypican associates with UNC-40/DCC receptor–expressing cells. We propose that LON-2/glypican acts as a modulator of UNC-40/DCC-mediated guidance to fine-tune axonal responses to UNC-6/netrin signals during migration. PMID:26148345

76 FR 14660 - Public Comment on the Development of Final Guidance for Evaluating the Vapor Intrusion to Indoor...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-17

... Groundwater and Soils (Subsurface Vapor Intrusion Guidance) AGENCY: Environmental Protection Agency (EPA... Pathway from Contaminated Groundwater and Soil (Subsurface Vapor Intrusion Guidance). A draft of the... Evaluating Vapor Intrusion to Indoor Air Pathway from Contaminated Groundwater and Soil (Subsurface Vapor...

Rewriting the Metabolic Blueprint: Advances in Pathway Diversification in Microorganisms

PubMed Central

Hossain, Gazi Sakir; Nadarajan, Saravanan Prabhu; Zhang, Lei; Ng, Tee-Kheang; Foo, Jee Loon; Ling, Hua; Choi, Won Jae; Chang, Matthew Wook

2018-01-01

Living organisms have evolved over millions of years to fine tune their metabolism to create efficient pathways for producing metabolites necessary for their survival. Advancement in the field of synthetic biology has enabled the exploitation of these metabolic pathways for the production of desired compounds by creating microbial cell factories through metabolic engineering, thus providing sustainable routes to obtain value-added chemicals. Following the past success in metabolic engineering, there is increasing interest in diversifying natural metabolic pathways to construct non-natural biosynthesis routes, thereby creating possibilities for producing novel valuable compounds that are non-natural or without elucidated biosynthesis pathways. Thus, the range of chemicals that can be produced by biological systems can be expanded to meet the demands of industries for compounds such as plastic precursors and new antibiotics, most of which can only be obtained through chemical synthesis currently. Herein, we review and discuss novel strategies that have been developed to rewrite natural metabolic blueprints in a bid to broaden the chemical repertoire achievable in microorganisms. This review aims to provide insights on recent approaches taken to open new avenues for achieving biochemical production that are beyond currently available inventions. PMID:29483901

Rewriting the Metabolic Blueprint: Advances in Pathway Diversification in Microorganisms.

PubMed

Hossain, Gazi Sakir; Nadarajan, Saravanan Prabhu; Zhang, Lei; Ng, Tee-Kheang; Foo, Jee Loon; Ling, Hua; Choi, Won Jae; Chang, Matthew Wook

2018-01-01

Living organisms have evolved over millions of years to fine tune their metabolism to create efficient pathways for producing metabolites necessary for their survival. Advancement in the field of synthetic biology has enabled the exploitation of these metabolic pathways for the production of desired compounds by creating microbial cell factories through metabolic engineering, thus providing sustainable routes to obtain value-added chemicals. Following the past success in metabolic engineering, there is increasing interest in diversifying natural metabolic pathways to construct non-natural biosynthesis routes, thereby creating possibilities for producing novel valuable compounds that are non-natural or without elucidated biosynthesis pathways. Thus, the range of chemicals that can be produced by biological systems can be expanded to meet the demands of industries for compounds such as plastic precursors and new antibiotics, most of which can only be obtained through chemical synthesis currently. Herein, we review and discuss novel strategies that have been developed to rewrite natural metabolic blueprints in a bid to broaden the chemical repertoire achievable in microorganisms. This review aims to provide insights on recent approaches taken to open new avenues for achieving biochemical production that are beyond currently available inventions.

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.

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.

Blended Homing Guidance Law Using Fuzzy Logic

DTIC Science & Technology

1998-01-01

President, Associate Fellow AIAA + Research Scientist Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection...mixed-strategy guidance strategies discussed in References 3 and 4. According to that research , mixed strategy guidance strategies are found to be...for an advanced missile is the focus of present paper. The present research employs the missile  Copyright 1998 by Optimal Synthesis Inc. All Rights

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.

A weak Hamiltonian finite element method for optimal guidance of an advanced launch vehicle

NASA Technical Reports Server (NTRS)

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

1989-01-01

A temporal finite-element method based on a mixed form of the Hamiltonian weak principle is presented for optimal control problems. The mixed form of this principle contains both states and costates as primary variables, which are expanded in terms of nodal values and simple shape functions. Time derivatives of the states and costates do not appear in the governing variational equation; the only quantities whose time derivatives appear therein are virtual states and virtual costates. Numerical results are presented for an elementary trajectory optimization problem; they show very good agreement with the exact solution along with excellent computational efficiency and self-starting capability. The feasibility of this approach for real-time guidance applications is evaluated. A simplified model for an advanced launch vehicle application that is suitable for finite-element solution is presented.

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

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

Brambley, M. R.; Haves, P.; McDonald, S. C.

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.

Guidance concepts for time-based flight operations

NASA Technical Reports Server (NTRS)

Vicroy, Dan D.

1990-01-01

Airport congestion and the associated delays are severe in today's airspace system and are expected to increase. NASA and the FAA is investigating various methods of alleviating this problem through new technology and operational procedures. One concept for improving airspace productivity is time-based control of aircraft. Research to date has focused primarily on the development of time-based flight management systems and Air Traffic Control operational procedures. Flight operations may, however, require special onboard guidance in order to satisfy the Air Traffic Control imposed time constraints. The results are presented of a simulation study aimed at evaluating several time-based guidance concepts in terms of tracking performance, pilot workload, and subjective preference. The guidance concepts tested varied in complexity from simple digital time-error feedback to an advanced time-referenced-energy guidance scheme.

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.

NRC ARDC Guidance Support Status Report

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

Holbrook, Mark R.

This report provides a summary that reflects the progress and status of proposed regulatory design criteria for advanced non-light water reactor (LWR) designs in accordance with the Level 3 milestone M3AT-17IN2001013 in work package AT-17IN200101. These criteria have been designated as advanced reactor design criteria (ARDC) and they provide guidance to future applicants for addressing the general design criteria (GDC) that are currently applied specifically to LWR designs. This report provides a summary of Phase 2 activities related to the various tasks associated with ARDC development and the subsequent development of ARDC regulatory guidance for sodium fast reactor (SFR) andmore » modular high-temperature gas-cooled reactor (HTGR) designs. Status Report Organization: Section 2 discusses the origin of the GDC and their application to LWRs. Section 3 addresses the objective of this initiative and how it benefits the advanced non-LWR reactor vendors. Section 4 discusses the scope and structure of the initiative. Section 5 provides background on the U.S. Department of Energy (DOE) ARDC team’s original development of the proposed ARDC that were submitted to the NRC for consideration. Section 6 provides a summary of recent ARDC Phase 2 activities. Appendices A through E document the DOE ARDC team’s public comments on various sections of the NRC’s draft regulatory guide DG–1330, “Guidance for Developing Principal Design Criteria for Non-Light Water Reactors.”« less

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.

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.

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

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

Brambley, Michael R.; Haves, Philip; McDonald, Sean C.

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 othermore » 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.« less

Medulloblastoma initiation and spread: Where neurodevelopment, microenvironment and cancer cross pathways.

PubMed

Martirosian, Vahan; Chen, Thomas C; Lin, Michelle; Neman, Josh

2016-12-01

Medulloblastomas are the most common malignant pediatric brain tumors. Over the past several decades, a wide range of tumor-centric studies have identified genes and their regulators within signaling pathways that promote medulloblastoma growth. This review aims to raise awareness that transdisciplinary research between developmental neurobiology and cancer foundations can advance our current understanding of how the nervous system contributes to medulloblastomas. By leveraging current advances in neurodevelopment, microenvironment (including secreted neuropeptides), neurotransmitters, and axon guidance cues, we can uncover novel mechanisms used by the nervous system to promote medulloblastoma growth and spread. This will ultimately result in development of improved strategies for cancer prevention and treatment of pediatric patients with this devastating disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

Practical management of everolimus-related toxicities in patients with advanced solid tumors.

PubMed

Grünwald, Viktor; Weikert, Steffen; Pavel, Marianne E; Hörsch, Dieter; Lüftner, Diana; Janni, Wolfgang; Geberth, Matthias; Weber, Matthias M

2013-01-01

Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), an intracellular protein kinase downstream of the phosphatidylinositol 3-kinase/AKT pathway involved in key components of tumorigenesis, including cell growth, proliferation, and angiogenesis. In the advanced cancer setting, based on favorable results from phase III trials, everolimus is indicated for the treatment of advanced renal cell carcinoma, advanced neuroendocrine tumors of pancreatic origin, and advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Additional oncology indications for everolimus include renal angiomyolipoma with tuberous sclerosis complex and subependymal giant-cell astrocytoma. Although it is generally well tolerated, with most adverse events of mild to moderate severity and manageable, everolimus exhibits a distinct adverse event profile that warrants guidance for proper diagnostic and medical management. This guidance is particularly important given the potential for widespread long-term use of everolimus. This review will focus on the most relevant toxicities associated with mTOR inhibitors and on their management. Practical treatment recommendations are presented for stomatitis, noninfectious pneumonitis, rash, selected metabolic abnormalities, and infections. Provided these events are rapidly identified and treated, the vast majority should resolve with minimal effect on treatment outcomes and patients' quality of life. Copyright © 2013 S. Karger AG, Basel.

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…

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).

Experimental Therapy of Advanced Breast Cancer: Targeting NFAT1-MDM2-p53 Pathway.

PubMed

Qin, Jiang-Jiang; Wang, Wei; Zhang, Ruiwen

2017-01-01

Advanced breast cancer, especially advanced triple-negative breast cancer, is typically more aggressive and more difficult to treat than other breast cancer phenotypes. There is currently no curable option for breast cancer patients with advanced diseases, highlighting the urgent need for novel treatment strategies. We have recently discovered that the nuclear factor of activated T cells 1 (NFAT1) activates the murine double minute 2 (MDM2) oncogene. Both MDM2 and NFAT1 are overexpressed and constitutively activated in breast cancer, particularly in advanced breast cancer, and contribute to its initiation, progression, and metastasis. MDM2 regulates cancer cell proliferation, cell cycle progression, apoptosis, migration, and invasion through both p53-dependent and -independent mechanisms. We have proposed to target the NFAT1-MDM2-p53 pathway for the treatment of human cancers, especially breast cancer. We have recently identified NFAT1 and MDM2 dual inhibitors that have shown excellent in vitro and in vivo activities against breast cancer, including triple-negative breast cancer. Herein, we summarize recent advances made in the understanding of the oncogenic functions of MDM2 and NFAT1 in breast cancer, as well as current targeting strategies and representative inhibitors. We also propose several strategies for inhibiting the NFAT1-MDM2-p53 pathway, which could be useful for developing more specific and effective inhibitors for breast cancer therapy. Copyright © 2017. Published by Elsevier Inc.

USAF Development Of Optical Correlation Missile Guidance

NASA Astrophysics Data System (ADS)

Kaehr, Ronald; Spector, Marvin

1980-12-01

In 1965, the Advanced Development Program (ADP)-679A of the Avionics Laboratory initiated development of guidance systems for stand-off tactical missiles. Employing project engineering support from the Aeronautical Systems Division, WPAFB, the Avionics Laboratory funded multiple terminal guidance concepts and related midcourse navigation technology. Optical correlation techniques which utilize prestored reference information for autonomous target acquisition offered the best near-term opportunity for meeting mission goals. From among the systems studied and flight tested, Aimpoint* optical area guidance provided the best and most consistent performance. Funded development by the Air Force ended in 1974 with a MK-84 guided bomb drop test demonstration at White Sands Missile Range and the subsequent transfer of the tactical missile guidance development charter to the Air Force Armament Laboratory, Eglin AFB. A historical review of optical correlation development within the Avionics Laboratory is presented. Evolution of the Aimpoint system is specifically addressed. Finally, a brief discussion of trends in scene matching technology is presented.

Advancing the adverse outcome pathway framework and its ...

EPA Pesticide Factsheets

Regulatory agencies worldwide are confronted with the challenging task of assessing the risks of thousands of chemicals to protect both human health and the environment. Traditional toxicity testing largely relies on apical endpoints from whole animal studies, which, in addition to ethical concerns, is costly and time prohibitive. As a result, the utility of mechanism-based in silico, in vitro, and in vivo approaches to support chemical safety evaluations have increasingly been explored. An approach that has gained traction for capturing available knowledge describing the linkage between mechanistic data and apical toxicity endpoints, required for regulatory assessments, is the adverse outcome pathway (AOP) framework. A number of international workshops and expert meetings have been held over the past years focusing on the AOP framework and its applications to chemical risk assessment. Although, these interactions have illustrated the necessity of expert guidance in moving the science of AOPs and their applications forward, there is also the recognition that a broader survey of the scientific community could be useful in guiding future initiatives in the AOP arena. To that end, a Horizon Scanning exercise was conducted to solicit questions from the global scientific community concerning the challenges or limitations that must be addressed in order to realize the full potential of the AOP framework in research and regulatory decision making. Over a 4 month ques

Image-based global registration system for bronchoscopy guidance

NASA Astrophysics Data System (ADS)

Khare, Rahul; Higgins, William E.

2011-03-01

Previous studies have shown that bronchoscopy guidance systems improve accuracy and reduce skill variation among physicians during bronchoscopy. In the past, we presented an image-based bronchoscopy guidance system that has been extensively validated in live bronchoscopic procedures. However, this system cannot actively recover from adverse events, such as patient coughing or dynamic airway collapses. After such events, the bronchoscope position is recovered only by moving back to a previously seen and easily identifiable bifurcation such as the main carina. Furthermore, the system requires an attending technician to closely follow the physician's movement of the bronchoscope to avoid misguidance. Also, when the physician is forced to advance the bronchoscope across multiple bifurcations, the system is not able to detect faulty maneuvers. We propose two system-level solutions. The first solution is a system-level guidance strategy that incorporates a global-registration algorithm to provide the physician with updated navigational and guidance information during bronchoscopy. The system can handle general navigation to a region of interest (ROI), as well as adverse events, and it requires minimal commands so that it can be directly controlled by the physician. The second solution visualizes the global picture of all the bifurcations and their relative orientations in advance and suggests the maneuvers needed by the bronchoscope to approach the ROI. Guided bronchoscopy results using human airway-tree phantoms demonstrate the potential of the two solutions.

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.

EphrinB3/EphA4-mediated guidance of ascending and descending spinal tracts.

PubMed

Paixão, Sónia; Balijepalli, Aarathi; Serradj, Najet; Niu, Jingwen; Luo, Wenqin; Martin, John H; Klein, Rüdiger

2013-12-18

The spinal cord contains many descending and ascending longitudinal tracts whose development appears to be controlled by distinct guidance systems. We identified a population of dorsal spinal neurons marked by coexpression of the transcription factor Zic2 and the guidance receptor EphA4. Zic2+;EphA4+ neurons are surrounded by mechanosensory terminals, suggesting innervation by mechanoreceptor afferents. Their axons form an ipsilateral ascending pathway that develops during embryogenesis and projects within the ventral aspect of the dorsal funiculus, the same location as the descending corticospinal tract (CST), which develops postnatally. Interestingly, the same guidance mechanism, namely, ephrinB3-induced EphA4 forward signaling, is required for the guidance of both ascending and descending axon tracts. Our analysis of conditional EphA4 mutant mice also revealed that the development of the dorsal funiculus occurs independently of EphA4 expression in descending CST axons and is linked to the distribution of Zic2+;EphA4+ spinal neurons and the formation of the ascending pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

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...

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.

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

Guidance and Control Aspects of Tactical Air-Launched Missiles

DTIC Science & Technology

1980-10-01

information; - Continuously stimulating advances in the aerospace sciences relevant to strengthening the common defence pusture; -- Improving the co...Symposium on Precision Delivery Systems was held at Eglin Air Force Base , Florida. USA. Many important advances in guidance sensor technology, control system...paper concentrates primarily or the US Army Missile Command’s technology base for development of the precision pointing and tracking or fire control

Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure.

PubMed

Balacescu, Ovidiu; Balacescu, Loredana; Tudoran, Oana; Todor, Nicolae; Rus, Meda; Buiga, Rares; Susman, Sergiu; Fetica, Bogdan; Pop, Laura; Maja, Laura; Visan, Simona; Ordeanu, Claudia; Berindan-Neagoe, Ioana; Nagy, Viorica

2014-04-08

Advanced squamous cervical cancer, one of the most commonly diagnosed cancers in women, still remains a major problem in oncology due to treatment failure and distant metastasis. Antitumor therapy failure is due to both intrinsic and acquired resistance; intrinsic resistance is often decisive for treatment response. In this study, we investigated the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer. Twenty-one patients with locally advanced squamous cell carcinoma were enrolled in this study. Primary biopsies harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient's 6 months clinical response. Ingenuity Pathway Analysis was used to investigate the altered molecular function and canonical pathways between the responding and non-responding patients. The microarray results were validated by qRT-PCR and immunohistochemistry. An additional set of 24 formalin-fixed paraffin-embedded cervical cancer samples was used for independent validation of the proteins of interest. A 2859-gene signature was identified to distinguish between responder and non-responder patients. 'DNA Replication, Recombination and Repair' represented one of the most important mechanisms activated in non-responsive cervical tumors, and the 'Role of BRCA1 in DNA Damage Response' was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262). Immunohistological staining confirmed increased expression of BRCA1, BRIP1, FANCD2 and RAD51 in non-responsive compared with responsive advanced squamous cervical cancer, both in the initial set of 21 cervical cancer samples and the second set of 24 samples. Our findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information about the

An Innovate Robotic Endoscope Guidance System for Transnasal Sinus and Skull Base Surgery: Proof of Concept.

PubMed

Friedrich, D T; Sommer, F; Scheithauer, M O; Greve, J; Hoffmann, T K; Schuler, P J

2017-12-01

Objective  Advanced transnasal sinus and skull base surgery remains a challenging discipline for head and neck surgeons. Restricted access and space for instrumentation can impede advanced interventions. Thus, we present the combination of an innovative robotic endoscope guidance system and a specific endoscope with adjustable viewing angle to facilitate transnasal surgery in a human cadaver model. Materials and Methods  The applicability of the robotic endoscope guidance system with custom foot pedal controller was tested for advanced transnasal surgery on a fresh frozen human cadaver head. Visualization was enabled using a commercially available endoscope with adjustable viewing angle (15-90 degrees). Results  Visualization and instrumentation of all paranasal sinuses, including the anterior and middle skull base, were feasible with the presented setup. Controlling the robotic endoscope guidance system was effectively precise, and the adjustable endoscope lens extended the view in the surgical field without the common change of fixed viewing angle endoscopes. Conclusion  The combination of a robotic endoscope guidance system and an advanced endoscope with adjustable viewing angle enables bimanual surgery in transnasal interventions of the paranasal sinuses and the anterior skull base in a human cadaver model. The adjustable lens allows for the abandonment of fixed-angle endoscopes, saving time and resources, without reducing the quality of imaging.

Perspectives on driver preferences for dynamic route guidance systems

DOT National Transportation Integrated Search

1997-01-01

Insights about the design of route guidance systems based on the needs and desires of drivers who are familiar with the travel network are provided. Results from the ADVANCE Intelligent Transportation System operational test, in which more than 100 d...

Application of image guidance in pituitary surgery

PubMed Central

de Lara, Danielle; Filho, Leo F. S. Ditzel; Prevedello, Daniel M.; Otto, Bradley A.; Carrau, Ricardo L.

2012-01-01

Background: Surgical treatment of pituitary pathologies has evolved along the years, adding safety and decreasing morbidity related to the procedure. Advances in the field of radiology, coupled with stereotactic technology and computer modeling, have culminated in the contemporary and widespread use of image guidance systems, as we know them today. Image guidance navigation has become a frequently used technology that provides continuous three-dimensional information for the accurate performance of neurosurgical procedures. We present a discussion about the application of image guidance in pituitary surgeries. Methods: Major indications for image guidance neuronavigation application in pituitary surgery are presented and demonstrated with illustrative cases. Limitations of this technology are also presented. Results: Patients presenting a history of previous transsphenoidal surgeries, anatomical variances of the sphenoid sinus, tumors with a close relation to the internal carotid arteries, and extrasellar tumors are the most important indications for image guidance in pituitary surgeries. The high cost of the equipment, increased time of surgery due to setup time, and registration and the need of specific training for the operating room personnel could be pointed as limitations of this technology. Conclusion: Intraoperative image guidance systems provide real-time images, increasing surgical accuracy and enabling safe, minimally invasive interventions. However, the use of intraoperative navigation is not a replacement for surgical experience and a systematic knowledge of regional anatomy. It must be recognized as a tool by which the neurosurgeon can reduce the risk associated with surgical approach and treatment of pituitary pathologies. PMID:22826819

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…

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…

Factors influencing behavior guidance: a survey of practicing pediatric dentists.

PubMed

Juntgen, Laura M; Sanders, Brian J; Walker, Laquia A; Jones, James E; Weddell, James A; Tomlin, Angela M; Eckert, George; Maupome, Gerardo

2013-01-01

The purpose of this study was to identify factors influencing behavior guidance technique utilization among practicing pediatric dentists and explore potential barriers to the incorporation of previously unused techniques. The data for this study were obtained from a web-based survey containing 15 multiple choice questions concerning the practitioners' past, current, and anticipated future behavior guidance technique utilization. Most respondents received hands-on training in 10 of the American Academy of Pediatric Dentistry behavior guidance techniques. The type of training was associated with the practitioners' level of comfort using a given technique upon graduation and with the current frequency of technique utilization. Residency type impacted hands-on behavior guidance training, with 39 percent of respondents reporting no intravenous sedation training. The type of practice was associated with the frequency of behavior guidance technique utilization, as was graduation decade. Currently practicing dentists cited legal concerns, parental acceptance to change, and limited resources as perceived obstacles in the incorporation of new techniques. Behavior guidance technique selection and utilization among practicing pediatric dentists was influenced by multiple factors, including advanced education training, residency type, graduation decade, and practice type. Obstacles to the incorporation of previously unused techniques appear to be multifactorial.

Expanded Guidance for NASA Systems Engineering. Volume 1: Systems Engineering Practices

NASA Technical Reports Server (NTRS)

Hirshorn, Steven R.

2016-01-01

This document is intended to provide general guidance and information on systems engineering that will be useful to the NASA community. It provides a generic description of Systems Engineering (SE) as it should be applied throughout NASA. A goal of the expanded guidance is to increase awareness and consistency across the Agency and advance the practice of SE. This guidance provides perspectives relevant to NASA and data particular to NASA. This expanded guidance should be used as a companion for implementing NPR 7123.1, Systems Engineering Processes and Requirements, the Rev 2 version of SP-6105, and the Center-specific handbooks and directives developed for implementing systems engineering at NASA. It provides a companion reference book for the various systems engineering-related training being offered under NASA's auspices.

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.

Care pathways for organ donation after brain death: guidance from available literature?

PubMed

Hoste, Pieter; Vanhaecht, Kris; Ferdinande, Patrick; Rogiers, Xavier; Eeckloo, Kristof; Blot, Stijn; Hoste, Eric; Vogelaers, Dirk; Vandewoude, Koenraad

2016-10-01

A discussion of the literature concerning the impact of care pathways in the complex and by definition multidisciplinary process of organ donation following brain death. Enhancing the quality and safety of organs for transplantation has become a central concern for governmental and professional organizations. At the local hospital level, a donor coordinator can use a range of interventions to improve the donation and procurement process. Care pathways have been proven to represent an effective intervention in several settings for optimizing processes and outcomes. A discussion paper. A systematic review of the Medline, CINAHL, EMBASE and The Cochrane Library databases was conducted for articles published until June 2015, using the keywords donation after brain death and care pathways. Each paper was reviewed to investigate the effects of existing care pathways for donation after brain death. An additional search for unpublished information was conducted. Although literature supports care pathways as an effective intervention in several settings, few studies have explored its use and effectiveness for complex care processes such as donation after brain death. Nurses should be aware of their role in the donation process. Care pathways have the potential to support them, but their effectiveness has been insufficiently explored. Further research should focus on the development and standardization of the clinical content of a care pathway for donation after brain death and the identification of quality indicators. These should be used in a prospective effectiveness assessment of the proposed pathway. © 2016 John Wiley & Sons Ltd.

Meninges-derived cues control axon guidance.

PubMed

Suter, Tracey A C S; DeLoughery, Zachary J; Jaworski, Alexander

2017-10-01

The axons of developing neurons travel long distances along stereotyped pathways under the direction of extracellular cues sensed by the axonal growth cone. Guidance cues are either secreted proteins that diffuse freely or bind the extracellular matrix, or membrane-anchored proteins. Different populations of axons express distinct sets of receptors for guidance cues, which results in differential responses to specific ligands. The full repertoire of axon guidance cues and receptors and the identity of the tissues producing these cues remain to be elucidated. The meninges are connective tissue layers enveloping the vertebrate brain and spinal cord that serve to protect the central nervous system (CNS). The meninges also instruct nervous system development by regulating the generation and migration of neural progenitors, but it has not been determined whether they help guide axons to their targets. Here, we investigate a possible role for the meninges in neuronal wiring. Using mouse neural tissue explants, we show that developing spinal cord meninges produce secreted attractive and repulsive cues that can guide multiple types of axons in vitro. We find that motor and sensory neurons, which project axons across the CNS-peripheral nervous system (PNS) boundary, are attracted by meninges. Conversely, axons of both ipsi- and contralaterally projecting dorsal spinal cord interneurons are repelled by meninges. The responses of these axonal populations to the meninges are consistent with their trajectories relative to meninges in vivo, suggesting that meningeal guidance factors contribute to nervous system wiring and control which axons are able to traverse the CNS-PNS boundary. Copyright © 2017 Elsevier Inc. All rights reserved.

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…

Development of STOLAND, a versatile navigation, guidance and control system

NASA Technical Reports Server (NTRS)

Young, L. S.; Hansen, Q. M.; Rouse, W. E.; Osder, S. S.

1972-01-01

STOLAND has been developed to perform navigation, guidance, control, and flight management experiments in advanced V/STOL aircraft. The experiments have broad requirements and have dictated that STOLAND be capable of providing performance that would be realistic and equivalent to a wide range of current and future avionics systems. An integrated digital concept using modern avionics components was selected as the simplest approach to maximizing versatility and growth potential. Unique flexibility has been obtained by use of a single, general-purpose digital computer for all navigation, guidance, control, and displays computation.

Drosophila melanogaster Hedgehog cooperates with Frazzled to guide axons through a non-canonical signalling pathway.

PubMed

Ricolo, Delia; Butí, Elisenda; Araújo, Sofia J

2015-08-01

We report that the morphogen Hedgehog (Hh) is an axonal chemoattractant in the midline of Drosophila melanogaster embryos. Hh is present in the ventral nerve cord during axonal guidance and overexpression of hh in the midline causes ectopic midline crossing of FasII-positive axonal tracts. In addition, we show that Hh influences axonal guidance via a non-canonical signalling pathway dependent on Ptc. Our results reveal that the Hh pathway cooperates with the Netrin/Frazzled pathway to guide axons through the midline in invertebrates. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

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

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

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 tomore » 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.« less

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

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

Dissecting Nck/Dock signaling pathways in Drosophila visual system.

PubMed

Rao, Yong

2005-01-01

The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell) axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility.

Dissecting Nck/Dock Signaling Pathways in Drosophila Visual System

PubMed Central

2005-01-01

The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell) axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility. PMID:15951852

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.

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. 2010 Elsevier Inc. All rights reserved.

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.

Neural guidance molecules regulate vascular remodeling and vessel navigation.

PubMed

Eichmann, Anne; Makinen, Taija; Alitalo, Kari

2005-05-01

The development of the embryonic blood vascular and lymphatic systems requires the coordinated action of several transcription factors and growth factors that target endothelial and periendothelial cells. However, according to recent studies, the precise "wiring" of the vascular system does not occur without an ordered series of guidance decisions involving several molecules initially discovered for axons in the nervous system, including ephrins, netrins, slits, and semaphorins. Here, we summarize the new advances in our understanding of the roles of these axonal pathfinding molecules in vascular remodeling and vessel guidance, indicating that neuronal axons and vessel sprouts use common molecular mechanisms for navigation in the body.

Axon guidance molecules in vascular patterning.

PubMed

Adams, Ralf H; Eichmann, Anne

2010-05-01

Endothelial cells (ECs) form extensive, highly branched and hierarchically organized tubular networks in vertebrates to ensure the proper distribution of molecular and cellular cargo in the vertebrate body. The growth of this vascular system during development, tissue repair or in disease conditions involves the sprouting, migration and proliferation of endothelial cells in a process termed angiogenesis. Surprisingly, specialized ECs, so-called tip cells, which lead and guide endothelial sprouts, share many feature with another guidance structure, the axonal growth cone. Tip cells are motile, invasive and extend numerous filopodial protrusions sensing growth factors, extracellular matrix and other attractive or repulsive cues in their tissue environment. Axonal growth cones and endothelial tip cells also respond to signals belonging to the same molecular families, such as Slits and Roundabouts, Netrins and UNC5 receptors, Semaphorins, Plexins and Neuropilins, and Eph receptors and ephrin ligands. Here we summarize fundamental principles of angiogenic growth, the selection and function of tip cells and the underlying regulation by guidance cues, the Notch pathway and vascular endothelial growth factor signaling.

Advanced Instrumentation, Information, and Control Systems Technologies Pathway: FY 2016 External Review

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

Thomas, Kenneth David; Hallbert, Bruce Perry

2016-11-01

This report describes an External Review conducted by the LWRS Program Advanced Instrumentation, Information, and Control (II&C) Systems Technologies Pathway to solicit feedback on the topics and results of the ongoing II&C research program. This review was held in conjunction with the Nuclear Energy Institute (NEI) Digital I&C Working Group meeting that was held at Idaho National Laboratory (INL) on August 9-10, 2016. Given the opportunity to visit INL and see the pathway research projects, NEI agreed that the Working Group would serve as the External Review panel for the purpose of obtaining expert input on the value and timingmore » of the research projects. This consisted of demonstrations in the Human Systems Simulation Laboratory followed by presentations on the II&C research program in general as well as the five technology development areas. Following the meeting, the presentations were sent to each of the attendees so they could review them in more detail and refer to them in completing the feedback form. Follow-up activities were conducted with the attendees following the meeting to obtain the completed feedback forms. A total of 13 forms were returned. The feedback forms were reviewed by the pathway to compile the data and comments received, which are documented in the report. In all, the feedback provided by the External Review participants is taken to be a strong endorsement of the types of projects being conducted by the pathway, the value they hold for the nuclear plants, and the general timing of need. The feedback aligns well with the priorities, levels of efforts allocated for the research projects, and project schedules. The feedback also represents realistic observations on the practicality of some aspects of implementing these technologies. In some cases, the participants provided thoughtful challenges to certain assumptions in the formulation of the technologies or in deployment plans. These deserve further review and revision of plans if

The Pathways to Advancement Project: How States Can Expand Postsecondary Educational Opportunities for Working Adults. Issue Brief

ERIC Educational Resources Information Center

Mazzeo, Christopher; Strawn, Julie; Roberts, Brandon

2009-01-01

The Pathways to Advancement initiative was launched by the National Governors Association Center for Best Practices (NGA Center) to help governors and their policy advisors examine options and develop strategies for expanding working adults' access to and completion of postsecondary education. In September 2003, the NGA Center issued a request for…

Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila.

PubMed

Hing, H; Xiao, J; Harden, N; Lim, L; Zipursky, S L

1999-06-25

The SH2/SH3 adaptor protein Dock has been proposed to transduce signals from guidance receptors to the actin cytoskeleton in Drosophila photoreceptor (R cell) growth cones. Here, we demonstrate that Drosophila p21-activated kinase (Pak) is required in a Dock pathway regulating R cell axon guidance and targeting. Dock and Pak colocalize to R cell axons and growth cones, physically interact, and their loss-of-function phenotypes are indistinguishable. Normal patterns of R cell connectivity require Pak's kinase activity and binding sites for both Dock and Cdc42/Rac. A membrane-tethered form of Pak (Pak(myr) acts as a dominant gain-of-function protein. Retinal expression of Pak(myr) rescues the R cell connectivity phenotype in dock mutants. These data establish Pak as a critical regulator of axon guidance and a downstream effector of Dock in vivo.

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.

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

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

Salama, Joseph K., E-mail: jsalama@radonc.uchicago.ed; Haddad, Robert I.; Kies, Merril 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,more » 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.« less

The eClinical Care Pathway Framework: a novel structure for creation of online complex clinical care pathways and its application in the management of sexually transmitted infections.

PubMed

Gibbs, Jo; Sutcliffe, Lorna J; Gkatzidou, Voula; Hone, Kate; Ashcroft, Richard E; Harding-Esch, Emma M; Lowndes, Catherine M; Sadiq, S Tariq; Sonnenberg, Pam; Estcourt, Claudia S

2016-07-22

Despite considerable international eHealth impetus, there is no guidance on the development of online clinical care pathways. Advances in diagnostics now enable self-testing with home diagnosis, to which comprehensive online clinical care could be linked, facilitating completely self-directed, remote care. We describe a new framework for developing complex online clinical care pathways and its application to clinical management of people with genital chlamydia infection, the commonest sexually transmitted infection (STI) in England. Using the existing evidence-base, guidelines and examples from contemporary clinical practice, we developed the eClinical Care Pathway Framework, a nine-step iterative process. Step 1: define the aims of the online pathway; Step 2: define the functional units; Step 3: draft the clinical consultation; Step 4: expert review; Step 5: cognitive testing; Step 6: user-centred interface testing; Step 7: specification development; Step 8: software testing, usability testing and further comprehension testing; Step 9: piloting. We then applied the Framework to create a chlamydia online clinical care pathway (Online Chlamydia Pathway). Use of the Framework elucidated content and structure of the care pathway and identified the need for significant changes in sequences of care (Traditional: history, diagnosis, information versus Online: diagnosis, information, history) and prescribing safety assessment. The Framework met the needs of complex STI management and enabled development of a multi-faceted, fully-automated consultation. The Framework provides a comprehensive structure on which complex online care pathways such as those needed for STI management, which involve clinical services, public health surveillance functions and third party (sexual partner) management, can be developed to meet national clinical and public health standards. The Online Chlamydia Pathway's standardised method of collecting data on demographics and sexual behaviour, with

Drosophila Neurexin IV Interacts with Roundabout and is Required for Repulsive Midline Axon Guidance

PubMed Central

Banerjee, Swati; Blauth, Kevin; Peters, Kimberly; Rogers, Stephen L.; Fanning, Alan S.; Bhat, Manzoor A.

2010-01-01

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 that 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. PMID:20410118

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.

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)

Whole genome survey of coding SNPs reveals a reproducible pathway determinant of Parkinson disease

PubMed Central

Srinivasan, Balaji S; Doostzadeh, Jaleh; Absalan, Farnaz; Mohandessi, Sharareh; Jalili, Roxana; Bigdeli, Saharnaz; Wang, Justin; Mahadevan, Jaydev; Lee, Caroline LG; Davis, Ronald W; William Langston, J; Ronaghi, Mostafa

2009-01-01

It is quickly becoming apparent that situating human variation in a pathway context is crucial to understanding its phenotypic significance. Toward this end, we have developed a general method for finding pathways associated with traits that control for pathway size. We have applied this method to a new whole genome survey of coding SNP variation in 187 patients afflicted with Parkinson disease (PD) and 187 controls. We show that our dataset provides an independent replication of the axon guidance association recently reported by Lesnick et al. [PLoS Genet 2007;3:e98], and also indicates that variation in the ubiquitin-mediated proteolysis and T-cell receptor signaling pathways may predict PD susceptibility. Given this result, it is reasonable to hypothesize that pathway associations are more replicable than individual SNP associations in whole genome association studies. However, this hypothesis is complicated by a detailed comparison of our dataset to the second recent PD association study by Fung et al. [Lancet Neurol 2006;5:911–916]. Surprisingly, we find that the axon guidance pathway does not rank at the very top of the Fung dataset after controlling for pathway size. More generally, in comparing the studies, we find that SNP frequencies replicate well despite technologically different assays, but that both SNP and pathway associations are globally uncorrelated across studies. We thus have a situation in which an association between axon guidance pathway variation and PD has been found in 2 out of 3 studies. We conclude by relating this seeming inconsistency to the molecular heterogeneity of PD, and suggest future analyses that may resolve such discrepancies. PMID:18853455

Navigational Guidance and Ablation Planning Tools for Interventional Radiology.

PubMed

Sánchez, Yadiel; Anvari, Arash; Samir, Anthony E; Arellano, Ronald S; Prabhakar, Anand M; Uppot, Raul N

Image-guided biopsy and ablation relies on successful identification and targeting of lesions. Currently, image-guided procedures are routinely performed under ultrasound, fluoroscopy, magnetic resonance imaging, or computed tomography (CT) guidance. However, these modalities have their limitations including inadequate visibility of the lesion, lesion or organ or patient motion, compatibility of instruments in an magnetic resonance imaging field, and, for CT and fluoroscopy cases, radiation exposure. Recent advances in technology have resulted in the development of a new generation of navigational guidance tools that can aid in targeting lesions for biopsy or ablations. These navigational guidance tools have evolved from simple hand-held trajectory guidance tools, to electronic needle visualization, to image fusion, to the development of a body global positioning system, to growth in cone-beam CT, and to ablation volume planning. These navigational systems are promising technologies that not only have the potential to improve lesion targeting (thereby increasing diagnostic yield of a biopsy or increasing success of tumor ablation) but also have the potential to decrease radiation exposure to the patient and staff, decrease procedure time, decrease the sedation requirements, and improve patient safety. The purpose of this article is to describe the challenges in current standard image-guided techniques, provide a definition and overview for these next-generation navigational devices, and describe the current limitations of these, still evolving, next-generation navigational guidance tools. Copyright © 2017 Elsevier Inc. All rights reserved.

Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

PubMed

Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

2017-06-01

Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RP<0.01 were defined as critical pathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RP<0.01, and the top 10 pathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing

Implementing Guided Pathways: Early Insights from the AACC Pathways Colleges

ERIC Educational Resources Information Center

Jenkins, Davis; Lahr, Hana; Fink, John

2017-01-01

Across the United States, a growing number of colleges are redesigning their programs and student support services according to the "guided pathways" model. Central to this approach are efforts to clarify pathways to program completion, career advancement, and further education. Equally essential are efforts to help students explore…

One Chance to Get it Right: understanding the new guidance for care of the dying person.

PubMed

Sykes, Nigel

2015-09-01

Following criticism of the Liverpool Care of the Dying Pathway (LCP), widely used to guide care of dying people in British health-care settings, the UK Government set up an independent review which in 2013 recommended that use of the LCP be discontinued. In response, the Leadership Alliance for the Care of Dying People, a coalition of a wide range of stakeholders, recently published guidance entitled One Chance to Get it Right. This guidance contains five Priorities of Care for the dying person that are intended to guide clinical staff and will inform Care Quality Commission inspections of health-care providers. This article summarizes the background to One Chance to Get it Right and the guidance it contains. One Chance to Get it Right, More Care, Less Pathway and related guidance documents. The need to improve the standard of end-of-life care in every clinical setting. The value of a pathway-based approach to end-of-life care in a context where well-implemented programmes of staff education in the subject are lacking. Public concern with, and scrutiny of, the quality of dying in the UK health-care system, particularly in hospitals but also the ability of patients to die well at home where that is their place of choice. Effective methods of teaching end of life care to all clinical staff; the effect upon families of caring for a dying relative at home; the optimum type, quantity and source of external support to informal carers that is perceived by them as adequate and enables the ill person to die well in in their own home; fuller understanding of the physiology of dying. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

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

NONE

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: Keyvan Farahani, “Image-guided focused ultrasound surgery and therapy” Jeffrey H. Siewerdsen, “Advances in image registration and reconstruction for image-guidedmore » neurosurgery” Tina Kapur, “Image-guided surgery and interventions in the advanced multimodality image-guided operating (AMIGO) suite” Raj Shekhar, “Multimodality image-guided interventions: Multimodality for the rest of us” Learning Objectives: Understand the principles and applications of HIFU in surgical ablation. Learn about recent advances in 3D–2D and 3D deformable image registration in support of surgical safety and precision. Learn about recent advances in model-based 3D image reconstruction in application to intraoperative 3D imaging. Understand the multi-modality imaging technologies and clinical applications investigated in the AMIGO suite. 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 R41

Understanding chemotherapy treatment pathways of advanced colorectal cancer patients to inform an economic evaluation in the United Kingdom

PubMed Central

Shabaruddin, F H; Elliott, R A; Valle, J W; Newman, W G; Payne, K

2010-01-01

Background: Accurate description of current practice within advanced colorectal cancer (CRC) specialties were needed to inform an economic evaluation of the UGT1A1 pharmacogenetic test for irinotecan in the United Kingdom. Methods: The study was based on a literature review and elicitation of expert opinion. The expert panel comprised 44 consultant oncologists in NHS Hospital Trusts across England. Results: Ten first-line, 10 second-line and 12 third-line chemotherapy regimens were reported, reflecting wide variations in treatment pathways. Predominant pathways emerged with: first-line treatment with oxaliplatin-based regimens, second-line treatment with irinotecan-based regimens and third-line treatment with mitomycin-based regimens. Experts estimated the frequency of febrile neutropaenia 8.4% (95% CI: 6.7–10.0), septic neutropaenia 4.7% (95% CI: 3.4–6.0) and severe diarrhoea 13.1% (95% CI: 10.8–15.5). Approaches for the clinical management of neutropaenia within the NHS were described. Conclusions: This study identified wide variations in the clinical management of advanced CRC patients. Descriptions of current treatment pathways are necessary for economic evaluations. Variations in clinical practice must be reflected in the model to ensure the findings from an economic evaluation of UGT1A1 testing are sufficient to inform policy regarding the cost-effective use of NHS resources. PMID:20661248

Dysregulated Pathway Identification of Alzheimer's Disease Based on Internal Correlation Analysis of Genes and Pathways.

PubMed

Kong, Wei; Mou, Xiaoyang; Di, Benteng; Deng, Jin; Zhong, Ruxing; Wang, Shuaiqun

2017-11-20

Dysregulated pathway identification is an important task which can gain insight into the underlying biological processes of disease. Current pathway-identification methods focus on a set of co-expression genes and single pathways and ignore the correlation between genes and pathways. The method proposed in this study, takes into account the internal correlations not only between genes but also pathways to identifying dysregulated pathways related to Alzheimer's disease (AD), the most common form of dementia. In order to find the significantly differential genes for AD, mutual information (MI) is used to measure interdependencies between genes other than expression valves. Then, by integrating the topology information from KEGG, the significant pathways involved in the feature genes are identified. Next, the distance correlation (DC) is applied to measure the pairwise pathway crosstalks since DC has the advantage of detecting nonlinear correlations when compared to Pearson correlation. Finally, the pathway pairs with significantly different correlations between normal and AD samples are known as dysregulated pathways. The molecular biology analysis demonstrated that many dysregulated pathways related to AD pathogenesis have been discovered successfully by the internal correlation detection. Furthermore, the insights of the dysregulated pathways in the development and deterioration of AD will help to find new effective target genes and provide important theoretical guidance for drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Correlation of parenting style and pediatric behavior guidance strategies in the dental setting: preliminary findings.

PubMed

Aminabadi, Naser Asl; Farahani, Ramin Mostofi Zadeh

2008-04-01

The aim of this study was to investigate the influence of parenting style on the choice of proper behavior guidance strategies in pedodontics. Seventy-two children aged between 4 and 6 years (mean 5.12 years) with carious primary mandibular molars were selected. The Primary Caregivers' Practices Report (PCPR) was used to quantify authoritarian, permissive and authoritative aspects of the caregivers' parenting style. After inferior alveolar nerve block, carious lesions were removed and the teeth were restored using amalgam. The children's behavior during operation was assessed according to the sound, eye, and motor (SEM) scale. Communicative guidance, advance behavior guidance, parental separation, and deferred treatment were used for behavior management. The dominant authoritative score was observed in 50% of parents, permissive in 37.5%, and authoritarian in 12.5%. The mean SEM score in children belonging to authoritative parents was significantly lower than in children of permissive and of authoritarian parents (p<0.05). Communicative guidance was necessary for all patients regardless of parenting style. Advanced behavior guidance (protective stabilization) was applied in 16.7% of cases in the authoritative category and in 100% in the permissive and authoritarian categories. The use of restrictive devices (7.4%) and sedation (3.7%) was limited to the permissive category. Parental separation (40.7%) and deferred treatment (3.7%) were performed only in the permissive category. This study provides preliminary evidence that a child's reaction to restorative dental procedures is influenced by the nature of the caregiver's parenting style.

Multiple cytoskeletal pathways and PI3K signaling mediate CDC-42-induced neuronal protrusion in C. elegans.

PubMed

Alan, Jamie K; Struckhoff, Eric C; Lundquist, Erik A

2013-01-01

Rho GTPases are key regulators of cellular protrusion and are involved in many developmental events including axon guidance during nervous system development. Rho GTPase pathways display functional redundancy in developmental events, including axon guidance. Therefore, their roles can often be masked when using simple loss-of-function genetic approaches. As a complement to loss-of-function genetics, we constructed a constitutively activated CDC-42(G12V) expressed in C. elegans neurons. CDC-42(G12V) drove the formation of ectopic lamellipodial and filopodial protrusions in the PDE neurons, which resembled protrusions normally found on migrating growth cones of axons. We then used a candidate gene approach to identify molecules that mediate CDC-42(G12V)-induced ectopic protrusions by determining if loss of function of the genes could suppress CDC-42(G12V). Using this approach, we identified 3 cytoskeletal pathways previously implicated in axon guidance, the Arp2/3 complex, UNC-115/abLIM, and UNC-43/Ena. We also identified the Nck-interacting kinase MIG-15/NIK and p21-activated kinases (PAKs), also implicated in axon guidance. Finally, PI3K signaling was required, specifically the Rictor/mTORC2 branch but not the mTORC1 branch that has been implicated in other aspects of PI3K signaling including stress and aging. Our results indicate that multiple pathways can mediate CDC-42-induced neuronal protrusions that might be relevant to growth cone protrusions during axon pathfinding. Each of these pathways involves Rac GTPases, which might serve to integrate the pathways and coordinate the multiple CDC-42 pathways. These pathways might be relevant to developmental events such as axon pathfinding as well as disease states such as metastatic melanoma.

Multiple cytoskeletal pathways and PI3K signaling mediate CDC-42-induced neuronal protrusion in C. elegans

PubMed Central

Alan, Jamie K; Struckhoff, Eric C; Lundquist, Erik A

2013-01-01

Rho GTPases are key regulators of cellular protrusion and are involved in many developmental events including axon guidance during nervous system development. Rho GTPase pathways display functional redundancy in developmental events, including axon guidance. Therefore, their roles can often be masked when using simple loss-of-function genetic approaches. As a complement to loss-of-function genetics, we constructed a constitutively activated CDC-42(G12V) expressed in C. elegans neurons. CDC-42(G12V) drove the formation of ectopic lamellipodial and filopodial protrusions in the PDE neurons, which resembled protrusions normally found on migrating growth cones of axons. We then used a candidate gene approach to identify molecules that mediate CDC-42(G12V)-induced ectopic protrusions by determining if loss of function of the genes could suppress CDC-42(G12V). Using this approach, we identified 3 cytoskeletal pathways previously implicated in axon guidance, the Arp2/3 complex, UNC-115/abLIM, and UNC-43/Ena. We also identified the Nck-interacting kinase MIG-15/NIK and p21-activated kinases (PAKs), also implicated in axon guidance. Finally, PI3K signaling was required, specifically the Rictor/mTORC2 branch but not the mTORC1 branch that has been implicated in other aspects of PI3K signaling including stress and aging. Our results indicate that multiple pathways can mediate CDC-42-induced neuronal protrusions that might be relevant to growth cone protrusions during axon pathfinding. Each of these pathways involves Rac GTPases, which might serve to integrate the pathways and coordinate the multiple CDC-42 pathways. These pathways might be relevant to developmental events such as axon pathfinding as well as disease states such as metastatic melanoma. PMID:24149939

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

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.

The Rejection and Modification of Past Values: The Effect on the Adolescent's Developing Philosophy (A Concern for Guidance Personnel).

ERIC Educational Resources Information Center

Spowart, Andrew C.

School guidance and counseling programs have been quite effective in providing vocational guidance and counseling for mental health, but the effectiveness of these programs in the future is cause for concern as rapid scientific and technological advances influence youth's creation of ideas and values. Adults today have experienced such rapid…

The Assay Guidance Manual: Quantitative Biology and Pharmacology in Preclinical Drug Discovery.

PubMed

Coussens, Nathan P; Sittampalam, G Sitta; Guha, Rajarshi; Brimacombe, Kyle; Grossman, Abigail; Chung, Thomas D Y; Weidner, Jeffrey R; Riss, Terry; Trask, O Joseph; Auld, Douglas; Dahlin, Jayme L; Devanaryan, Viswanath; Foley, Timothy L; McGee, James; Kahl, Steven D; Kales, Stephen C; Arkin, Michelle; Baell, Jonathan; Bejcek, Bruce; Gal-Edd, Neely; Glicksman, Marcie; Haas, Joseph V; Iversen, Philip W; Hoeppner, Marilu; Lathrop, Stacy; Sayers, Eric; Liu, Hanguan; Trawick, Bart; McVey, Julie; Lemmon, Vance P; Li, Zhuyin; McManus, Owen; Minor, Lisa; Napper, Andrew; Wildey, Mary Jo; Pacifici, Robert; Chin, William W; Xia, Menghang; Xu, Xin; Lal-Nag, Madhu; Hall, Matthew D; Michael, Sam; Inglese, James; Simeonov, Anton; Austin, Christopher P

2018-06-07

The Assay Guidance Manual (AGM) is an eBook of best-practices for the design, development, and implementation of robust assays for early drug discovery. Initiated by pharmaceutical company scientists, the manual provides guidance for designing a "testing funnel" of assays to identify genuine hits using high-throughput screening (HTS) and advancing them through pre-clinical development. Combined with a workshop/tutorial component, the overall goal of the AGM is to provide a valuable resource for training translational scientists. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

"Old drugs" for the treatment of rheumatoid arthritis: will the cholinergic anti-inflammatory pathway and anti-nociceptive pathway work?

PubMed

Pan, Xiaohua; Yu, Xiaowei; Qin, Ling; Zhang, Peng

2010-12-01

Based on the newly discovered cholinergic anti-inflammatory pathway, on the anti-nociceptive pathway and on our preliminary research, we raise a new strategy for the treatment of rheumatoid arthritis (RA) which mainly focuses on the application of old drugs that can activate both of the above mentioned pathways. It has been reported that nicotinic receptor agonists used for the treatment of neurological diseases were expected to be applied to the therapy of inflammatory diseases (RA). Therefore, it is promising that old drugs available in clinics may exert new functions for the treatment of RA, which may greatly reduce the expense of such treatment, once applied. These currently-used old drugs should be considered as another new resource in exploring anti-rheumatic agents under the guidance of the newly discovered cholinergic anti-inflammatory pathway and the anti-nociceptive pathway.

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

PubMed

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

2014-10-01

The psychoactive cannabinoid Δ(9) -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. 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. 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. 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. © 2014 The British Pharmacological Society.

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

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…

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

PubMed

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.

Apollo lunar descent guidance

NASA Technical Reports Server (NTRS)

Klumpp, A. R.

1974-01-01

Apollo lunar-descent guidance transfers the Lunar Module from a near-circular orbit to touchdown, traversing a 17 deg central angle and a 15 km altitude in 11 min. A group of interactive programs in an onboard computer guide the descent, controlling altitude and the descent propulsion system throttle. A ground-based program pre-computes guidance targets. The concepts involved in this guidance are described. Explicit and implicit guidance are discussed, guidance equations are derived, and the earlier Apollo explicit equation is shown to be an inferior special case of the later implicit equation. Interactive guidance, by which the two-man crew selects a landing site in favorable terrain and directs the trajectory there, is discussed. Interactive terminal-descent guidance enables the crew to control the essentially vertical descent rate in order to land in minimum time with safe contact speed. The altitude maneuver routine uses concepts that make gimbal lock inherently impossible.

Pathway concepts experiment for head-down synthetic vision displays

NASA Astrophysics Data System (ADS)

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

2004-08-01

Eight 757 commercial airline captains flew 22 approaches using the Reno Sparks 16R Visual Arrival under simulated Category I conditions. Approaches were flown using a head-down synthetic vision display to evaluate four tunnel ("minimal", "box", "dynamic pathway", "dynamic crow's feet") and three guidance ("ball", "tadpole", "follow-me aircraft") concepts and compare their efficacy to a baseline condition (i.e., no tunnel, ball guidance). The results showed that the tunnel concepts significantly improved pilot performance and situation awareness and lowered workload compared to the baseline condition. The dynamic crow's feet tunnel and follow-me aircraft guidance concepts were found to be the best candidates for future synthetic vision head-down displays. These results are discussed with implications for synthetic vision display design and future research.

Apollo LM guidance computer software for the final lunar descent.

NASA Technical Reports Server (NTRS)

Eyles, D.

1973-01-01

In all manned lunar landings to date, the lunar module Commander has taken partial manual control of the spacecraft during the final stage of the descent, below roughly 500 ft altitude. This report describes programs developed at the Charles Stark Draper Laboratory, MIT, for use in the LM's guidance computer during the final descent. At this time computational demands on the on-board computer are at a maximum, and particularly close interaction with the crew is necessary. The emphasis is on the design of the computer software rather than on justification of the particular guidance algorithms employed. After the computer and the mission have been introduced, the current configuration of the final landing programs and an advanced version developed experimentally by the author are described.

Computed intraoperative navigation guidance--a preliminary report on a new technique.

PubMed

Enislidis, G; Wagner, A; Ploder, O; Ewers, R

1997-08-01

To assess the value of a computer-assisted three-dimensional guidance system (Virtual Patient System) in maxillofacial operations. Laboratory and open clinical study. Teaching Hospital, Austria. 6 patients undergoing various procedures including removal of foreign body (n=3) and biopsy, maxillary advancement, and insertion of implants (n=1 each). Storage of computed tomographic (CT) pictures on an optical disc, and imposition of intraoperative video images on to these. The resulting display is shown to the surgeon on a micromonitor in his head-up display for guidance during the operations. To improve orientation during complex or minimally invasive maxillofacial procedures and to make such operations easier and less traumatic. Successful transferral of computed navigation technology into an operation room environment and positive evaluation of the method by the surgeons involved. Computer-assisted three-dimensional guidance systems have the potential for making complex or minimally invasive procedures easier to do, thereby reducing postoperative morbidity.

Human performance evaluation of a pathway HMD

NASA Astrophysics Data System (ADS)

Lorenz, Bernd; Tobben, Helmut; Schmerwitz, Sven

2005-05-01

Head-up displays (HUD) and helmet (or head)-mounted displays (HMD) aim at reducing the pilot's visual scanning cost in support of concurrent monitoring of both instrument information (near domain) and the outside environment (far domain). An HMD used in combination with a head tracker enables the assessment of the pilot"s head direction in real time allowing symbologies to remain spatially linked to elements of the outside environment. The paper examines the potential added benefits of improved flight path tracking to be expected by displaying symbologies of a virtual 3D perspective pathway plus predictor information on an HMD. Results of a high-fidelity flight-simulation experiment are reported that involved a series of curved approaches supported with such a pathway HMD. The study used a monocular retinal-scanning HMD and involved 18 pilots. Dependent human performance data were derived from flight path tracking measures, subjective measures of mental workload and situation awareness and pilot reactions in response to an unexpected rare event in the outside scene (intruding aircraft on the active runway for the intended landing). Comparison with a standard head-down ILS baseline condition revealed a mix of performance costs and benefits, which is consistent with most of the human factors literature on the general use of HUDs and of HUDs used in combination with pathway guidance: The pathway HMD promoted substantially better flight path tracking but caused also a delayed response to the unexpected event. This effect points to some disadvantages of HUDs referred to as 'attention capture', which may become exaggerated by the additional use of pathway guidance symbology.

Advanced integrated enhanced vision systems

NASA Astrophysics Data System (ADS)

Kerr, J. R.; Luk, Chiu H.; Hammerstrom, Dan; Pavel, Misha

2003-09-01

In anticipation of its ultimate role in transport, business and rotary wing aircraft, we clarify the role of Enhanced Vision Systems (EVS): how the output data will be utilized, appropriate architecture for total avionics integration, pilot and control interfaces, and operational utilization. Ground-map (database) correlation is critical, and we suggest that "synthetic vision" is simply a subset of the monitor/guidance interface issue. The core of integrated EVS is its sensor processor. In order to approximate optimal, Bayesian multi-sensor fusion and ground correlation functionality in real time, we are developing a neural net approach utilizing human visual pathway and self-organizing, associative-engine processing. In addition to EVS/SVS imagery, outputs will include sensor-based navigation and attitude signals as well as hazard detection. A system architecture is described, encompassing an all-weather sensor suite; advanced processing technology; intertial, GPS and other avionics inputs; and pilot and machine interfaces. Issues of total-system accuracy and integrity are addressed, as well as flight operational aspects relating to both civil certification and military applications in IMC.

Pathways Post-Participation Outcomes: Preliminary Findings. Carnegie Math Pathways Research Brief

ERIC Educational Resources Information Center

Norman, Jon

2017-01-01

The Carnegie Foundation for the Advancement of Teaching's Math Pathways seek to improve outcomes for community college students who take remedial math courses. The Pathways include two comprehensive instructional systems--Statway® and Quantaway® and are described in this report. They are designed to support students to achieve the necessary math…

Ecological compensation: From general guidance and expertise to specific proposals for road developments

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

Villarroya, Ana, E-mail: avillarroya@alumni.unav.es; Persson, Jesper, E-mail: jesper.persson@slu.se; Puig, Jordi, E-mail: jpbaguer@unav.es

The main scientific bibliography addressing the rationale behind ecological compensation is reviewed in order to examine general guidelines. This contains interesting general guidance on how to implement compensation, and provides the basis for future developments in compensation practice. On this basis, we propose a further step in compensation practice, advancing compensation proposals or rules for specific kinds of projects and contexts, focusing on road projects in the Spanish Environmental Impact Assessment (EIA). Three main residual impacts of roads are identified which usually remain uncompensated for: the loss of natural and semi-natural land use, the increase in emissions resulting from anymore » new road, and the fragmentation, severance or barrier effect on the landscape and its wildlife. To counteract these, four proposals, or “rules”, are advanced: conservation of natural and semi-natural land use area, conservation of dominant plant species physiognomy, compensation for emissions, and the rule of positive defragmentation. -- Highlights: • Ecological compensation theory does not specify guidelines for types of projects. • EIA practitioners lack valuable specific guidance on how to implement compensation. • Specific guidance for road project ecological compensation is proposed. • Compensation proposals should have in mind present-day compensation practice level. • Specific ways to compensate for habitat loss, emissions, and fragmentation are shown.« less

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.

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.

Federal Guidance Report No. 15: External Exposure to Radionuclides in Air, Water and Soil

EPA Pesticide Factsheets

FGR 15 updates the 1993 Federal Guidance Report No. 12 (FGR 12), External Exposure to Radionuclides in Air, Water, and Soil. FGR 15 incorporates advances in radiation protection science regarding how organ/tissue doses change with age and sex.

Flight evaluation of a computer aided low-altitude helicopter flight guidance system

NASA Technical Reports Server (NTRS)

Swenson, Harry N.; Jones, Raymond D.; Clark, Raymond

1993-01-01

The Flight Systems Development branch of the U.S. Army's Avionics Research and Development Activity (AVRADA) and NASA Ames Research Center developed for flight testing a Computer Aided Low-Altitude Helicopter Flight (CALAHF) guidance system. The system includes a trajectory-generation algorithm which uses 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 precision navigation information to determine a trajectory between mission waypoints that seeks valleys to minimize threat exposure. This system was developed and evaluated through extensive use of piloted simulation and has demonstrated a 'pilot centered' concept of automated and integrated navigation and terrain mission planning flight guidance. This system has shown a significant improvement in pilot situational awareness, and mission effectiveness as well as a decrease in training and proficiency time required for a near terrain, nighttime, adverse weather system.

LCIA framework and cross-cutting issues guidance within the UNEP/SETAC Life Cycle Initiative

EPA Science Inventory

Increasing needs for decision support and advances in scientific knowledge within life cycle assessment (LCA) led to substantial efforts to provide global guidance on environmental life cycle impact assessment (LCIA) indicators under the auspices of the UNEP-SETAC Life Cycle Init...

[Advance in flavonoids biosynthetic pathway and synthetic biology].

PubMed

Zou, Li-Qiu; Wang, Cai-Xia; Kuang, Xue-Jun; Li, Ying; Sun, Chao

2016-11-01

Flavonoids are the valuable components in medicinal plants, which possess a variety of pharmacological activities, including anti-tumor, antioxidant and anti-inflammatory activities. There is an unambiguous understanding about flavonoids biosynthetic pathway, that is,2S-flavanones including naringenin and pinocembrin are the skeleton of other flavonoids and they can transform to other flavonoids through branched metabolic pathway. Elucidation of the flavonoids biosynthetic pathway lays a solid foundation for their synthetic biology. A few flavonoids have been produced in Escherichia coli or yeast with synthetic biological technologies, such as naringenin, pinocembrin and fisetin. Synthetic biology will provide a new way to get valuable flavonoids and promote the research and development of flavonoid drugs and health products, making flavonoids play more important roles in human diet and health. Copyright© by the Chinese Pharmaceutical Association.

Image Guidance Technologies for Interventional Pain Procedures: Ultrasound, Fluoroscopy, and CT.

PubMed

Wang, Dajie

2018-01-26

Chronic pain is a common medical condition. Patients who suffer uncontrolled chronic pain may require interventions including spinal injections and various nerve blocks. Interventional procedures have evolved and improved over time since epidural injection was first introduced for low back pain and sciatica in 1901. One of the major contributors in the improvement of these interventions is the advancement of imaging guidance technologies. The utilization of image guidance has dramatically improved the accuracy and safety of these interventions. The first image guidance technology adopted by pain specialists was fluoroscopy. This was followed by CT and ultrasound. Fluoroscopy can be used to visualize bony structures of the spine. It is still the most commonly used guidance technology in spinal injections. In the recent years, ultrasound guidance has been increasingly adopted by interventionists to perform various injections. Because its ability to visualize soft tissue, vessels, and nerves, this guidance technology appears to be a better option than fluoroscopy for interventions including SGB and celiac plexus blocks, when visualization of the vessels may prevent intravascular injection. The current evidence indicates the efficacies of these interventions are similar between ultrasound guidance and fluoroscopy guidance for SGB and celiac plexus blocks. For facet injections and interlaminar epidural steroid injections, it is important to visualize bony structures in order to perform these procedures accurately and safely. It is worth noting that facet joint injections can be done under ultrasound guidance with equivalent efficacy to fluoroscopic guidance. However, obese patients may present challenge for ultrasound guidance due to its poor visualization of deep anatomical structures. Regarding transforaminal epidural steroid injections, there are limited evidence to support that ultrasound guidance technology has equivalent efficacy and less complications comparing

Performance of an Advanced MOS System in the 1996-97 National Collegiate Weather Forecasting Contest.

NASA Astrophysics Data System (ADS)

Vislocky, Robert L.; Fritsch, J. Michael

1997-12-01

A prototype advanced model output statistics (MOS) forecast system that was entered in the 1996-97 National Collegiate Weather Forecast Contest is described and its performance compared to that of widely available objective guidance and to contest participants. The prototype system uses an optimal blend of aviation (AVN) and nested grid model (NGM) MOS forecasts, explicit output from the NGM and Eta guidance, and the latest surface weather observations from the forecast site. The forecasts are totally objective and can be generated quickly on a personal computer. Other "objective" forms of guidance tracked in the contest are 1) the consensus forecast (i.e., the average of the forecasts from all of the human participants), 2) the combination of NGM raw output (for precipitation forecasts) and NGM MOS guidance (for temperature forecasts), and 3) the combination of Eta Model raw output (for precipitation forecasts) and AVN MOS guidance (for temperature forecasts).Results show that the advanced MOS system finished in 20th place out of 737 original entrants, or better than approximately 97% of the human forecasters who entered the contest. Moreover, the advanced MOS system was slightly better than consensus (23d place). The fact that an objective forecast system finished ahead of consensus is a significant accomplishment since consensus is traditionally a very formidable "opponent" in forecast competitions. Equally significant is that the advanced MOS system was superior to the traditional guidance products available from the National Centers for Environmental Prediction (NCEP). Specifically, the combination of NGM raw output and NGM MOS guidance finished in 175th place, and the combination of Eta Model raw output and AVN MOS guidance finished in 266th place. The latter result is most intriguing since the proposed elimination of all NGM products would likely result in a serious degradation of objective products disseminated by NCEP, unless they are replaced with equal

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…

Pathway Concepts Experiment for Head-Down Synthetic Vision Displays

NASA Technical Reports Server (NTRS)

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

2004-01-01

Eight 757 commercial airline captains flew 22 approaches using the Reno Sparks 16R Visual Arrival under simulated Category I conditions. Approaches were flown using a head-down synthetic vision display to evaluate four tunnel ("minimal", "box", "dynamic pathway", "dynamic crow s feet") and three guidance ("ball", "tadpole", "follow-me aircraft") concepts and compare their efficacy to a baseline condition (i.e., no tunnel, ball guidance). The results showed that the tunnel concepts significantly improved pilot performance and situation awareness and lowered workload compared to the baseline condition. The dynamic crow s feet tunnel and follow-me aircraft guidance concepts were found to be the best candidates for future synthetic vision head-down displays. These results are discussed with implications for synthetic vision display design and future research.

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.

An integrated analysis of genes and functional pathways for aggression in human and rodent models.

PubMed

Zhang-James, Yanli; Fernàndez-Castillo, Noèlia; Hess, Jonathan L; Malki, Karim; Glatt, Stephen J; Cormand, Bru; Faraone, Stephen V

2018-06-01

Human genome-wide association studies (GWAS), transcriptome analyses of animal models, and candidate gene studies have advanced our understanding of the genetic architecture of aggressive behaviors. However, each of these methods presents unique limitations. To generate a more confident and comprehensive view of the complex genetics underlying aggression, we undertook an integrated, cross-species approach. We focused on human and rodent models to derive eight gene lists from three main categories of genetic evidence: two sets of genes identified in GWAS studies, four sets implicated by transcriptome-wide studies of rodent models, and two sets of genes with causal evidence from online Mendelian inheritance in man (OMIM) and knockout (KO) mice reports. These gene sets were evaluated for overlap and pathway enrichment to extract their similarities and differences. We identified enriched common pathways such as the G-protein coupled receptor (GPCR) signaling pathway, axon guidance, reelin signaling in neurons, and ERK/MAPK signaling. Also, individual genes were ranked based on their cumulative weights to quantify their importance as risk factors for aggressive behavior, which resulted in 40 top-ranked and highly interconnected genes. The results of our cross-species and integrated approach provide insights into the genetic etiology of aggression.

Study on the Reduced Traffic Congestion Method Based on Dynamic Guidance Information

NASA Astrophysics Data System (ADS)

Li, Shu-Bin; Wang, Guang-Min; Wang, Tao; Ren, Hua-Ling; Zhang, Lin

2018-05-01

This paper studies how to generate the reasonable information of travelers’ decision in real network. This problem is very complex because the travelers’ decision is constrained by different human behavior. The network conditions can be predicted by using the advanced dynamic OD (Origin-Destination, OD) estimation techniques. Based on the improved mesoscopic traffic model, the predictable dynamic traffic guidance information can be obtained accurately. A consistency algorithm is designed to investigate the travelers’ decision by simulating the dynamic response to guidance information. The simulation results show that the proposed method can provide the best guidance information. Further, a case study is conducted to verify the theoretical results and to draw managerial insights into the potential of dynamic guidance strategy in improving traffic performance. Supported by National Natural Science Foundation of China under Grant Nos. 71471104, 71771019, 71571109, and 71471167; The University Science and Technology Program Funding Projects of Shandong Province under Grant No. J17KA211; The Project of Public Security Department of Shandong Province under Grant No. GATHT2015-236; The Major Social and Livelihood Special Project of Jinan under Grant No. 20150905

MRI-guidance in percutaneous core decompression of osteonecrosis of the femoral head.

PubMed

Kerimaa, Pekka; Väänänen, Matti; Ojala, Risto; Hyvönen, Pekka; Lehenkari, Petri; Tervonen, Osmo; Blanco Sequeiros, Roberto

2016-04-01

The purpose of this study was to evaluate the usefulness of MRI-guidance for core decompression of avascular necrosis of the femoral head. Twelve MRI-guided core decompressions were performed on patients with different stages of avascular necrosis of the femoral head. The patients were asked to evaluate their pain and their ability to function before and after the procedure and imaging findings were reviewed respectively. Technical success in reaching the target was 100 % without complications. Mean duration of the procedure itself was 54 min. All patients with ARCO stage 1 osteonecrosis experienced clinical benefit and pathological MRI findings were seen to diminish. Patients with more advanced disease gained less, if any, benefit and total hip arthroplasty was eventually performed on four patients. MRI-guidance seems technically feasible, accurate and safe for core decompression of avascular necrosis of the femoral head. Patients with early stage osteonecrosis may benefit from the procedure. • MRI is a useful guidance method for minimally invasive musculoskeletal interventions. • Bone drilling seems beneficial at early stages of avascular necrosis. • MRI-guidance is safe and accurate for bone drilling.

Drosophila photoreceptor axon guidance and targeting requires the dreadlocks SH2/SH3 adapter protein.

PubMed

Garrity, P A; Rao, Y; Salecker, I; McGlade, J; Pawson, T; Zipursky, S L

1996-05-31

Mutations in the Drosophila gene dreadlocks (dock) disrupt photoreceptor cell (R cell) axon guidance and targeting. Genetic mosaic analysis and cell-type-specific expression of dock transgenes demonstrate dock is required in R cells for proper innervation. Dock protein contains one SH2 and three SH3 domains, implicating it in tyrosine kinase signaling, and is highly related to the human proto-oncogene Nck. Dock expression is detected in R cell growth cones in the target region. We propose Dock transmits signals in the growth cone in response to guidance and targeting cues. These findings provide an important step for dissection of signaling pathways regulating growth cone motility.

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.

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Sporophytic control of pollen tube growth and guidance in grasses.

PubMed

Lausser, Andreas; Dresselhaus, Thomas

2010-04-01

Pollen tube growth and guidance in the female tissues of flowering plants is a long-studied and anatomically well-described process. A large number of gene products and chemical compounds involved have been identified in the last 20 years, and some underlying molecular mechanisms including self-incompatibility in the Brassicaceae, Solanaceae and Papaveraceae are now well understood. However, the largest part of the pollen tube pathway inside the transmitting tract towards the ovule harbouring the female gametophyte still requires intensive investigations. Especially in the economically most import plant family, the Poaceae or grasses, progamic pollen tube development is barely understood. Using maize as a model, we propose to divide pollen tube germination, growth and guidance towards the female gametophyte into five distinct phases. The model is adapted from Arabidopsis thaliana, taking anatomical differences and novel genetic and cellular studies into consideration. With the exception of Phase V, all phases seem to be under sporophytic control in grasses.

A New Era of Image Guidance with Magnetic Resonance-guided Radiation Therapy for Abdominal and Thoracic Malignancies

PubMed Central

Paliwal, Bhudatt; Hill, Patrick; Bayouth, John E; Geurts, Mark W; Baschnagel, Andrew M; Bradley, Kristin A; Harari, Paul M; Rosenberg, Stephen; Brower, Jeffrey V; Wojcieszynski, Andrzej P; Hullett, Craig; Bayliss, R A; Labby, Zacariah E; Bassetti, Michael F

2018-01-01

Magnetic resonance-guided radiation therapy (MRgRT) offers advantages for image guidance for radiotherapy treatments as compared to conventional computed tomography (CT)-based modalities. The superior soft tissue contrast of magnetic resonance (MR) enables an improved visualization of the gross tumor and adjacent normal tissues in the treatment of abdominal and thoracic malignancies. Online adaptive capabilities, coupled with advanced motion management of real-time tracking of the tumor, directly allow for high-precision inter-/intrafraction localization. The primary aim of this case series is to describe MR-based interventions for localizing targets not well-visualized with conventional image-guided technologies. The abdominal and thoracic sites of the lung, kidney, liver, and gastric targets are described to illustrate the technological advancement of MR-guidance in radiotherapy. PMID:29872602

Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells

PubMed Central

Pannella, Micaela; Caliceti, Cristiana; Fortini, Francesca; Aquila, Giorgio; Sega, Francesco Vieceli Dalla; Pannuti, Antonio; Fortini, Cinzia; Morelli, Marco Bruno; Fucili, Alessandro; Francolini, Gloria; Voltan, Rebecca; Secchiero, Paola; Dinelli, GiovannI; Leoncini, Emanuela; Ferracin, Manuela; Hrelia, Silvana; Miele, Lucio; Rizzo, Paola

2017-01-01

It is unknown whether components present in heart failure (HF) patients' serum provide an angiogenic stimulus. We sought to determine whether serum from HF patients affects angiogenesis and its major modulator, the Notch pathway, in human umbilical vein endothelial cells (HUVECs). In cells treated with serum from healthy subjects or from patients at different HF stage we determined: (1) Sprouting angiogenesis, by measuring cells network (closed tubes) in collagen gel. (2) Protein levels of Notch receptors 1, 2, 4, and ligands Jagged1, Delta-like4. We found a higher number of closed tubes in HUVECs treated with advanced HF patients serum in comparison with cells treated with serum from mild HF patients or controls. Furthermore, as indicated by the reduction of the active form of Notch4 (N4IC) and of Jagged1, advanced HF patients serum inhibited Notch signalling in HUVECs in comparison with mild HF patients' serum and controls. The circulating levels of NT-proBNP (N-terminal of the pro-hormone brain natriuretic peptide), a marker for the detection and evalutation of HF, were positively correlated with the number of closed tubes (r = 0.485) and negatively with Notch4IC and Jagged1 levels in sera-treated cells (r = −0.526 and r = −0.604, respectively). In conclusion, we found that sera from advanced HF patients promote sprouting angiogenesis and dysregulate Notch signaling in HUVECs. Our study provides in vitro evidence of an angiogenic stimulus arising during HF progression and suggests a role for the Notch pathway in it. PMID:26987674

HHS guidance on synthetic DNA is the right step.

PubMed

Gronvall, Gigi Kwik

2010-12-01

Synthetic biology has advanced to the point where some pathogens can be manufactured from scratch. This technical leap has beneficent implications for medical research and vaccine design, but it also raises concerns that the technology could be used to produce a deadly pathogen for nefarious use. Addressing these concerns, the Department of Health and Human Services (HHS) released their Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA on October 13, 2010. They took the right approach: The oversight framework for gene synthesis companies included in this guidance is adaptable to new technical developments and changing risks, it can be implemented immediately, it can be readily adopted by other countries, and it will cost little. Though there have been some calls to increase the regulatory controls on synthetic biology, these should be resisted. For now, at least, the oversight is appropriate to the risks.

Career Pathways in School-to-Work Systems. Resource Bulletin.

ERIC Educational Resources Information Center

National School-to-Work Opportunities Office, Washington, DC.

Many students in today's high schools choose courses and work experiences in an unplanned, aimless manner that often results in limited career options and undeveloped potential. Innovative educators across the nation have responded by restructuring schools around career pathways, which are integrated, multiyear sequences of career guidance,…

A Context-Aware-Based Audio Guidance System for Blind People Using a Multimodal Profile Model

PubMed Central

Lin, Qing; Han, Youngjoon

2014-01-01

A wearable guidance system is designed to provide context-dependent guidance messages to blind people while they traverse local pathways. The system is composed of three parts: moving scene analysis, walking context estimation and audio message delivery. The combination of a downward-pointing laser scanner and a camera is used to solve the challenging problem of moving scene analysis. By integrating laser data profiles and image edge profiles, a multimodal profile model is constructed to estimate jointly the ground plane, object locations and object types, by using a Bayesian network. The outputs of the moving scene analysis are further employed to estimate the walking context, which is defined as a fuzzy safety level that is inferred through a fuzzy logic model. Depending on the estimated walking context, the audio messages that best suit the current context are delivered to the user in a flexible manner. The proposed system is tested under various local pathway scenes, and the results confirm its efficiency in assisting blind people to attain autonomous mobility. PMID:25302812

FY2016 Advanced Combustion Engine Annual Progress Report

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

None, None

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.

FY2014 Advanced Combustion Engine Annual Progress Report

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

None

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.

FY2015 Advanced Combustion Engine Annual Progress Report

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

Singh, Gurpreet; Gravel, Roland M.; Howden, Kenneth C.

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.

Combined blockade of vascular endothelial growth factor and programmed death 1 pathways in advanced kidney cancer.

PubMed

Einstein, David J; McDermott, David F

2017-06-01

Targeted and immune-based therapies have improved outcomes in advanced kidney cancer, yet novel strategies are needed to extend the duration of these benefits and expand them to more patients. Combined inhibition of vascular endothelial growth factor (VEGF) and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathways with therapeutic agents already in clinical use may offer such a strategy. Here, we describe the development and clinical evaluation of VEGF inhibitors and, separately, PD-1/PD-L1 inhibitors. We present preclinical evidence of interaction between these pathways and the rationale for combined blockade. Beyond well-known effects on pathologic angiogenesis, VEGF blockade also may decrease immune tolerance and enhance PD-1/PD-L1 blockade. We conclude with the results of several early trials of combined VEGF and PD-1/PD-L1 blockade, which demonstrate encouraging antitumor activity, and we pose questions for future study.

Repulsive Guidance Molecules (RGMs) and Neogenin in Bone Morphogenetic Protein (BMP) signaling

PubMed Central

Tian, Chenxi; Liu, Jun

2015-01-01

Summary Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta (TGFβ) superfamily. BMPs mediate a highly conserved signal transduction cascade through the type I and type II serine/threonine kinase receptors and intracellular Smad proteins. The BMP pathway regulates multiple developmental and homeostatic processes. Mutations in this pathway can cause various diseases in humans, such as skeletal disorders, cardiovascular diseases and various cancers. Multiple levels of regulation, including extracellular regulation, help to ensure proper spatiotemporal control of BMP signaling in the right cellular context. The family of repulsive guidance molecules (RGMs) and the type I trans-membrane protein neogenin, a paralog of DCC (Deleted in Colorectal Cancer), have been implicated in modulating the BMP pathway. In this review, we discuss the properties and functions of RGM proteins and neogenin, focusing on their roles in the modulation of BMP signal transduction. PMID:23740870

The MADD-3 LAMMER Kinase Interacts with a p38 MAP Kinase Pathway to Regulate the Display of the EVA-1 Guidance Receptor in Caenorhabditis elegans.

PubMed

D'Souza, Serena A; Rajendran, Luckshika; Bagg, Rachel; Barbier, Louis; van Pel, Derek M; Moshiri, Houtan; Roy, Peter J

2016-04-01

The proper display of transmembrane receptors on the leading edge of migrating cells and cell extensions is essential for their response to guidance cues. We previously discovered that MADD-4, which is an ADAMTSL secreted by motor neurons in Caenorhabditis elegans, interacts with an UNC-40/EVA-1 co-receptor complex on muscles to attract plasma membrane extensions called muscle arms. In nematodes, the muscle arm termini harbor the post-synaptic elements of the neuromuscular junction. Through a forward genetic screen for mutants with disrupted muscle arm extension, we discovered that a LAMMER kinase, which we call MADD-3, is required for the proper display of the EVA-1 receptor on the muscle's plasma membrane. Without MADD-3, EVA-1 levels decrease concomitantly with a reduction of the late-endosomal marker RAB-7. Through a genetic suppressor screen, we found that the levels of EVA-1 and RAB-7 can be restored in madd-3 mutants by eliminating the function of a p38 MAP kinase pathway. We also found that EVA-1 and RAB-7 will accumulate in madd-3 mutants upon disrupting CUP-5, which is a mucolipin ortholog required for proper lysosome function. Together, our data suggests that the MADD-3 LAMMER kinase antagonizes the p38-mediated endosomal trafficking of EVA-1 to the lysosome. In this way, MADD-3 ensures that sufficient levels of EVA-1 are present to guide muscle arm extension towards the source of the MADD-4 guidance cue.

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.

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.

GUILD: GUidance for Information about Linking Data sets†

PubMed Central

Gilbert, Ruth; Lafferty, Rosemary; Hagger-Johnson, Gareth; Zhang, Li-Chun; Smith, Peter; Dibben, Chris; Goldstein, Harvey

2018-01-01

Abstract 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. PMID:28369581

NSRD-10: Leak Path Factor Guidance Using MELCOR

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

Louie, David; Humphries, Larry L.

Estimates of the source term from a U.S. Department of Energy (DOE) nuclear facility requires that the analysts know how to apply the simulation tools used, such as the MELCOR code, particularly for a complicated facility that may include an air ventilation system and other active systems that can influence the environmental pathway of the materials released. DOE has designated MELCOR 1.8.5, an unsupported version, as a DOE ToolBox code in its Central Registry, which includes a leak-path-factor guidance report written in 2004 that did not include experimental validation data. To continue to use this MELCOR version requires additional verificationmore » and validations, which may not be feasible from a project cost standpoint. Instead, the recent MELCOR should be used. Without any developer support and lack of experimental data validation, it is difficult to convince regulators that the calculated source term from the DOE facility is accurate and defensible. This research replaces the obsolete version in the 2004 DOE leak path factor guidance report by using MELCOR 2.1 (the latest version of MELCOR with continuing modeling development and user support) and by including applicable experimental data from the reactor safety arena and from applicable experimental data used in the DOE-HDBK-3010. This research provides best practice values used in MELCOR 2.1 specifically for the leak path determination. With these enhancements, the revised leak-path-guidance report should provide confidence to the DOE safety analyst who would be using MELCOR as a source-term determination tool for mitigated accident evaluations.« less

der(11)t(11;17): a distinct cytogenetic pathway of advanced stage neuroblastoma (NBL) - detected by spectral karyotyping (SKY).

PubMed

Stark, Batia; Jeison, Marta; Glaser-Gabay, Leticia; Bar-Am, Irit; Mardoukh, Jacques; Ash, Shifra; Atias, Dina; Stein, Jerry; Zaizov, Rina; Yaniv, Isaac

2003-07-18

Conventional cytogenetic, molecular cytogenic and genetic methods disclosed a broad spectrum of genetic abnormalities leading to gain and loss of chromosomal segments in advanced stage neuroblastoma (NBL). Specific correlation between the genetic findings could delineate distinct genetic pathways, of which the biology and prognostic significance is as yet undetermined. Using spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) on metaphases from 16 patients with advanced stage NBL, it was possible to explore the whole spectrum of rearrangement within complex karyotypes and to detect hidden recurrent translocations. All translocations were unbalanced. The most prevalent recurrent unbalanced translocations resulted in 17q gain in 12 patients (75%), 11q loss in nine patients (56%), and 1p deletion/imbalance in eight patients (50%). The most frequent recurrent translocation was der(11)t(11;17) in six patients. Three cytogenetic pathways could be delineated. The first, with six patients, was characterized by the unbalanced translocation der(11)t(11;17), detected only by SKY, resulting in the concomitant 17q gain and 11q loss. No MYCN amplification or 1p deletion (except one patient with 1p imbalance) were found, while 3p deletion, and complex karyotypes were common. The second subgroup, with four patients, had 17q gain and 1p deletion, and in two patients 11q loss, that was apparent only by FISH. 1p deletion occurred through der(1)t(1;17) or del(1p). The third subgroup of four patients was characterized by MYCN amplification with 17q gain and 1p deletion, very rarely with 11q loss (one patient) through a translocation with a non-17q partner. The SKY subclassifications were in accordance with the findings reported by molecular genetic techniques, and may indicate that distinct oncogenes and suppressor genes are involved in the der(11)t(11;17) pathway of advanced stage NBL.

Heparanase induced by advanced glycation end products (AGEs) promotes macrophage migration involving RAGE and PI3K/AKT pathway

PubMed Central

2013-01-01

Background Advanced glycation end products (AGEs), inflammatory-associated macrophage migration and accumulation are crucial for initiation and progression of diabetic vascular complication. Enzymatic activity of heparanase (HPA) is implicated strongly in dissemination of metastatic tumor cells and cells of the immune system. In addition, HPA enhances the phosphorylation of selected signaling molecules including AKT pathway independent of enzymatic activity. However, virtually nothing is presently known the role of HPA during macrophage migration exposed to AGEs involving signal pathway. Methods These studies were carried out in Ana-1 macrophages. Macrophage viability was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. HPA and AKT protein expression in macrophages are analysed by Western blotting and HPA mRNA expression by real time quantitative RT-PCR. Release of HPA was determined by ELISA. Macrophage migration was assessed by Transwell assays. Results HPA protein and mRNA were found to be increased significantly in AGEs-treated macrophages. Pretreatment with anti-HPA antibody which recognizes the nonenzymatic terminal of HPA prevented AGEs-induced AKT phosphorylation and macrophage migration. LY294002 (PI3k/AKT inhibitor) inhibited AGEs-induced macrophage migration. Furthermore, pretreatment with anti-receptor for advanced glycation end products (RAGE) antibody attenuated AGEs-induced HPA expression, AKT phosphorylation and macrophage migration. Conclusions These data indicate that AGEs-induced macrophage migration is dependent on HPA involving RAGE-HPA-PI3K/AKT pathway. The nonenzymatic activity of HPA may play a key role in AGEs-induced macrophage migration associated with inflammation in diabetic vascular complication. PMID:23442498

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

PubMed Central

Dickinson, Rachel E; Duncan, W Colin

2010-01-01

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. PMID:20100881

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.

Computer based guidance in the modern operating room: a historical perspective.

PubMed

Bova, Frank

2010-01-01

The past few decades have seen the introduction of many different and innovative approaches aimed at enhancing surgical technique. As microprocessors have decreased in size and increased in processing power, more sophisticated systems have been developed. Some systems have attempted to provide enhanced instrument control while others have attempted to provide tools for surgical guidance. These systems include robotics, image enhancements, and frame-based and frameless guidance procedures. In almost every case the system's design goals were achieved and surgical outcomes were enhanced, yet a vast majority of today's surgical procedures are conducted without the aid of these advances. As new tools are developed and existing tools refined, special attention to the systems interface and integration into the operating room environment will be required before increased utilization of these technologies can be realized.

Connecting with guidance counselors to enhance recruitment into nursing of minority teens.

PubMed

Campbell-Heider, Nancy; Sackett, Kay; Whistler, M Patricia

2008-01-01

The purpose of this article was to describe the design, implementation, and outcomes of one strategy used to promote careers in nursing among minority high-school-aged teens-namely, a workshop for guidance counselors in a large urban school system. All guidance counselors in an urban inner city school system were invited to attend a workshop on careers in nursing as part of their monthly continuing education requirements. Thirty-nine (39%) participated in the half-day workshop held at a school of nursing. Most informative were the guidance counselor comments about perceptions of nursing careers that create barriers to recruitment. Guidance counselors reported that (a) many students and parents view nursing as a "dangerous field," (b) negative stereotypes about nursing persist, (c) many students do not plan for the prerequisites for baccalaureate entrance, (d) nursing is perceived as a "narrow" field with few opportunities for advancement, and (e) there is a preference of 2-year programs to get "quick income" over baccalaureate programs and long-term career planning. Faculty and students addressed these issues. Faculty collaboration with guidance counselors is an excellent mechanism to uncover barriers to minority recruitment at the local level. Nursing recruitment activities should be tailored to address these community concerns. In the last 4 years, 24 students from the targeted high school system were offered admission to the University at Buffalo and of this group 17 enrolled in nursing.

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 ...

Brain evolution by brain pathway duplication

PubMed Central

Chakraborty, Mukta; Jarvis, Erich D.

2015-01-01

Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel brain pathways and functions of the nervous system. Here, we review and further develop some insights to a new hypothesis on one mechanism that may contribute to nervous system evolution, in particular by brain pathway duplication. Like gene duplication, we propose that whole brain pathways can duplicate and the duplicated pathway diverge to take on new functions. We suggest that one mechanism of brain pathway duplication could be through gene duplication, although other mechanisms are possible. We focus on brain pathways for vocal learning and spoken language in song-learning birds and humans as example systems. This view presents a new framework for future research in our understanding of brain evolution and novel behavioural traits. PMID:26554045

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…

Contextual cueing improves attentional guidance, even when guidance is supposedly optimal.

PubMed

Harris, Anthony M; Remington, Roger W

2017-05-01

Visual search through previously encountered contexts typically produces reduced reaction times compared with search through novel contexts. This contextual cueing benefit is well established, but there is debate regarding its underlying mechanisms. Eye-tracking studies have consistently shown reduced number of fixations with repetition, supporting improvements in attentional guidance as the source of contextual cueing. However, contextual cueing benefits have been shown in conditions in which attentional guidance should already be optimal-namely, when attention is captured to the target location by an abrupt onset, or under pop-out conditions. These results have been used to argue for a response-related account of contextual cueing. Here, we combine eye tracking with response time to examine the mechanisms behind contextual cueing in spatially cued and pop-out conditions. Three experiments find consistent response time benefits with repetition, which appear to be driven almost entirely by a reduction in number of fixations, supporting improved attentional guidance as the mechanism behind contextual cueing. No differences were observed in the time between fixating the target and responding-our proxy for response related processes. Furthermore, the correlation between contextual cueing magnitude and the reduction in number of fixations on repeated contexts approaches 1. These results argue strongly that attentional guidance is facilitated by familiar search contexts, even when guidance is near-optimal. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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...

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.

An overview of NICE guidance: acute kidney injury.

PubMed

Ellis, Peter; Jenkins, Karen

Acute Kidney Injury (AKI) as a financial, resource and human burden on both the NHS and people with AKI. Clearly if AKI is the cause of much morbidity and mortality and significant amounts of it can be prevented and/or detected earlier, this could only be a good thing. In part, the problem with AKI is that it has historically been regarded as little more than a sequal to other more pressing physical illnesses and therefore not taken as seriously as it might. The 2013 guidance from NICE-clinical guideline 169-and the accompanying pathway, seek to address this with an emphasis on assessment and prevention, identification of disease, management and subsequent chronic disease management ( NICE, 2013a ).

Adverse outcome pathways: a concise introduction for toxicologists

PubMed Central

Vergauwen, Lucia; Hengstler, Jan G.; Angrish, Michelle; Whelan, Maurice

2018-01-01

Adverse outcome pathways are designed to provide a clear-cut mechanistic representation of critical toxicological effects that propagate over different layers of biological organization from the initial interaction of a chemical with a molecular target to an adverse outcome at the individual or population level. Adverse outcome pathways are currently gaining momentum, especially in view of their many potential applications as pragmatic tools in the fields of human toxicology, ecotoxicology and risk assessment. A number of guidance documents, issued by the Organization for Economic Cooperation and Development, as well as landmark papers, outlining best practices to develop, assess and use adverse outcome pathways, have been published in the last few years. The present paper provides a synopsis of the main principles related to the adverse outcome pathway framework for the toxicologist less familiar with this area, followed by two case studies relevant for human toxicology and ecotoxicology. PMID:28660287

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.

The MADD-3 LAMMER Kinase Interacts with a p38 MAP Kinase Pathway to Regulate the Display of the EVA-1 Guidance Receptor in Caenorhabditis elegans

PubMed Central

D’Souza, Serena A.; Rajendran, Luckshika; Bagg, Rachel; van Pel, Derek M.; Moshiri, Houtan; Roy, Peter J.

2016-01-01

The proper display of transmembrane receptors on the leading edge of migrating cells and cell extensions is essential for their response to guidance cues. We previously discovered that MADD-4, which is an ADAMTSL secreted by motor neurons in Caenorhabditis elegans, interacts with an UNC-40/EVA-1 co-receptor complex on muscles to attract plasma membrane extensions called muscle arms. In nematodes, the muscle arm termini harbor the post-synaptic elements of the neuromuscular junction. Through a forward genetic screen for mutants with disrupted muscle arm extension, we discovered that a LAMMER kinase, which we call MADD-3, is required for the proper display of the EVA-1 receptor on the muscle’s plasma membrane. Without MADD-3, EVA-1 levels decrease concomitantly with a reduction of the late-endosomal marker RAB-7. Through a genetic suppressor screen, we found that the levels of EVA-1 and RAB-7 can be restored in madd-3 mutants by eliminating the function of a p38 MAP kinase pathway. We also found that EVA-1 and RAB-7 will accumulate in madd-3 mutants upon disrupting CUP-5, which is a mucolipin ortholog required for proper lysosome function. Together, our data suggests that the MADD-3 LAMMER kinase antagonizes the p38-mediated endosomal trafficking of EVA-1 to the lysosome. In this way, MADD-3 ensures that sufficient levels of EVA-1 are present to guide muscle arm extension towards the source of the MADD-4 guidance cue. PMID:27123983

Concentration dependent requirement for local protein synthesis in motor neuron subtype specific response to axon guidance cues

PubMed Central

Nedelec, Stephane; Peljto, Mirza; Shi, Peng; Amoroso, Mackenzie W.; Kam, Lance C.; Wichterle, Hynek

2012-01-01

Formation of functional motor circuits relies on the ability of distinct spinal motor neuron subtypes to project their axons with high precision to appropriate muscle targets. While guidance cues contributing to motor axon pathfinding have been identified, the intracellular pathways underlying subtype specific responses to these cues remain poorly understood. In particular, it remains controversial whether responses to axon guidance cues depend on axonal protein synthesis. Using a growth cone collapse assay, we demonstrate that mouse embryonic stem cell (ESC) derived spinal motor neurons (ES-MNs) respond to ephrin-A5, Sema3f and Sema3a in a concentration dependent manner. At low doses, ES-MNs exhibit segmental or subtype specific responses, while this selectivity is lost at higher concentrations. Response to high doses of semaphorins and to all doses of ephrin-A5 is protein synthesis independent. In contrast, using microfluidic devices and stripe assays, we show that growth cone collapse and guidance at low concentrations of semaphorins relies on local protein synthesis in the axonal compartment. Similar bimodal response to low and high concentrations of guidance cues is observed in human ES-MNs, pointing to a general mechanism by which neurons increase their repertoire of responses to the limited set of guidance cues involved in neural circuit formation. PMID:22279234

Advances in the understanding of the clinically relevant genetic pathways and molecular aspects of canine mammary tumours. Part 2: invasion, angiogenesis, metastasis and therapy.

PubMed

Santos, A A; Matos, A J F

2015-08-01

Significant advances have been made recently in the understanding of the molecular events and critical pathways associated with and driving cancer of the mammary gland in humans and dogs. The study of canine mammary tumour biology, particularly the interactions of neoplastic cells with stromal and immune cells, is crucial for the development of novel effective therapeutic agents and strategies. This second part of a two-part review discusses some of the latest advances in the understanding of the clinically relevant genetic and molecular pathways involved in metastasis and in the interactions between tumour and stromal cells, including inflammatory and immune cells, cancer-associated fibroblasts, and endothelial cells. Recent experimental data on the role of matrix-degrading proteases and angiogenic factors are also discussed. Finally, the clinical utility of different non-surgical therapeutic modalities is reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Advanced Control and Autonomy Research

NASA Technical Reports Server (NTRS)

Nguyen, Nhan; Ippolito, Corey; Lombaerts, Thomas; Swei, Sean

2017-01-01

This presentation is given at a NASA DLR (German Aerospace Center) meeting at NASA ARC on March 14, 2017. The presentation provides an overview of the Advanced Control and Evolvable Systems (ACES) group at NASA ARC and the research areas in UAS autonomy, stall recovery guidance, and flexible aircraft flight control.

Guidance on Data Quality Assessment for Life Cycle Inventory ...

EPA Pesticide Factsheets

Data quality within Life Cycle Assessment (LCA) is a significant issue for the future support and development of LCA as a decision support tool and its wider adoption within industry. In response to current data quality standards such as the ISO 14000 series, various entities within the LCA community have developed different methodologies to address and communicate the data quality of Life Cycle Inventory (LCI) data. Despite advances in this field, the LCA community is still plagued by the lack of reproducible data quality results and documentation. To address these issues, US EPA has created this guidance in order to further support reproducible life cycle inventory data quality results and to inform users of the proper application of the US EPA supported data quality system. The work for this report was begun in December 2014 and completed as of April 2016.The updated data quality system includes a novel approach to the pedigree matrix by addressing data quality at the flow and the process level. Flow level indicators address source reliability, temporal correlation, geographic correlation, technological correlation and data sampling methods. The process level indicators address the level of review the unit process has undergone and its completeness. This guidance is designed to be updatable as part of the LCA Research Center’s continuing commitment to data quality advancements. Life cycle assessment is increasingly being used as a tool to identify areas of

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.

Micro guidance and control technology overview

NASA Technical Reports Server (NTRS)

Kissel, Glen J.; Hadaegh, Fred Y.

1993-01-01

This paper gives an overview of micro-guidance and control technologies and in the process previews of the technology/user and systems issues presented in the guidance and control session at the workshop. We first present a discussion of the advantages of using micro-guidance and control components and then detail six micro-guidance and control thrusts that could have a revolutionary impact on space missions and systems. Specific technologies emerging in the micro-guidance and control field will be examined. These technologies fall into two broad categories: micro-attitude determination (inertial and celestial) and micro-actuation, control and sensing. Finally, the scope of the workshop's guidance and control panel are presented.

A review of the FDA draft guidance document for software validation: guidance for industry.

PubMed

Keatley, K L

1999-01-01

A Draft Guidance Document (Version 1.1) was issued by the United States Food and Drug Administration (FDA) to address the software validation requirement of the Quality System Regulation, 21 CFR Part 820, effective June 1, 1997. The guidance document outlines validation considerations that the FDA regards as applicable to both medical device software and software used to "design, develop or manufacture" medical devices. The Draft Guidance is available at the FDA web site http:@www.fda.gov/cdrh/comps/swareval++ +.html. Presented here is a review of the main features of the FDA document for Quality System Regulation (QSR), and some guidance for its implementation in industry.

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

Real-time Magnetic Resonance Imaging Guidance for Cardiovascular Procedures

PubMed Central

Horvath, Keith A.; Li, Ming; Mazilu, Dumitru; Guttman, Michael A.; McVeigh, Elliot R.

2008-01-01

Magnetic resonance imaging (MRI) of the cardiovascular system has proven to be an invaluable diagnostic tool. Given the ability to allow for real-time imaging, MRI guidance of intraoperative procedures can provide superb visualization which can facilitate a variety of interventions and minimize the trauma of the operations as well. In addition to the anatomic detail, MRI can provide intraoperative assessment of organ and device function. Instruments and devices can be marked to enhance visualization and tracking. All of which is an advance over standard x-ray or ultrasonic imaging. PMID:18395633

Roundabout geometric design guidance.

DOT National Transportation Integrated Search

2007-06-01

This research report is intended to examine the geometric standards, guidelines, and practices used nationally and by other states to develop recommendations on roundabout design guidance for California. This research serves as a guidance tool in sup...

Advanced aviation environmental modeling tools to inform policymakers

DOT National Transportation Integrated Search

2012-08-19

Aviation environmental models which conform to international guidance have advanced : over the past several decades. Enhancements to algorithms and databases have increasingly : shown these models to compare well with gold standard measured data. The...

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...

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...

An integrated approach for prioritizing pharmaceuticals found in the environment for risk assessment, monitoring and advanced research.

PubMed

Caldwell, Daniel J; Mastrocco, Frank; Margiotta-Casaluci, Luigi; Brooks, Bryan W

2014-11-01

Numerous active pharmaceutical ingredients (APIs), approved prior to enactment of detailed environmental risk assessment (ERA) guidance in the EU in 2006, have been detected in surface waters as a result of advancements in analytical technologies. Without adequate knowledge of the potential hazards these APIs may pose, assessing their environmental risk is challenging. As it would be impractical to commence hazard characterization and ERA en masse, several approaches to prioritizing substances for further attention have been published. Here, through the combination of three presentations given at a recent conference, "Pharmaceuticals in the Environment, Is there a problem?" (Nîmes, France, June 2013) we review several of these approaches, identify salient components, and present available techniques and tools that could facilitate a pragmatic, scientifically sound approach to prioritizing APIs for advanced study or ERA and, where warranted, fill critical data gaps through targeted, intelligent testing. We further present a modest proposal to facilitate future prioritization efforts and advanced research studies that incorporates mammalian pharmacology data (e.g., adverse outcomes pathways and the fish plasma model) and modeled exposure data based on pharmaceutical use. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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

Pollock, S; Keall, P; Keall, R

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 tomore » 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

Recent advances in therapeutic recruitment of mammalian RNAi and bacterial CRISPR-Cas DNA interference pathways as emerging antiviral strategies.

PubMed

Chin, Wei-Xin; Ang, Swee Kim; Chu, Justin Jang Hann

2017-01-01

In invertebrate eukaryotes and prokaryotes, respectively, the RNAi and clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR-Cas) pathways are highly specific and efficient RNA and DNA interference systems, and are well characterised as potent antiviral systems. It has become possible to recruit or reconstitute these pathways in mammalian cells, where they can be directed against desired host or viral targets. The RNAi and CRISPR-Cas systems can therefore yield ideal antiviral therapeutics, capable of specific and efficient viral inhibition with minimal off-target effects, but development of such therapeutics can be slow. This review covers recent advances made towards developing RNAi or CRISPR-Cas strategies for clinical use. These studies address the delivery, toxicity or target design issues that typically plague the in vivo or clinical use of these technologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pathway Analysis in Attention Deficit Hyperactivity Disorder: An Ensemble Approach

PubMed Central

Mooney, Michael A.; McWeeney, Shannon K.; Faraone, Stephen V.; Hinney, Anke; Hebebrand, Johannes; Nigg, Joel T.; Wilmot, Beth

2016-01-01

Despite a wealth of evidence for the role of genetics in attention deficit hyperactivity disorder (ADHD), specific and definitive genetic mechanisms have not been identified. Pathway analyses, a subset of gene-set analyses, extend the knowledge gained from genome-wide association studies (GWAS) by providing functional context for genetic associations. However, there are numerous methods for association testing of gene sets and no real consensus regarding the best approach. The present study applied six pathway analysis methods to identify pathways associated with ADHD in two GWAS datasets from the Psychiatric Genomics Consortium. Methods that utilize genotypes to model pathway-level effects identified more replicable pathway associations than methods using summary statistics. In addition, pathways implicated by more than one method were significantly more likely to replicate. A number of brain-relevant pathways, such as RhoA signaling, glycosaminoglycan biosynthesis, fibroblast growth factor receptor activity, and pathways containing potassium channel genes, were nominally significant by multiple methods in both datasets. These results support previous hypotheses about the role of regulation of neurotransmitter release, neurite outgrowth and axon guidance in contributing to the ADHD phenotype and suggest the value of cross-method convergence in evaluating pathway analysis results. PMID:27004716

Advanced glycation end product-induced astrocytic differentiation of cultured neurospheres through inhibition of Notch-Hes1 pathway-mediated neurogenesis.

PubMed

Guo, Yijing; Wang, Pin; Sun, Haixia; Cai, Rongrong; Xia, Wenqing; Wang, Shaohua

2013-12-23

This study aims to investigate the roles of the Notch-Hes1 pathway in the advanced glycation end product (AGE)-mediated differentiation of neural stem cells (NSCs). We prepared pLentiLox3.7 lentiviral vectors that express short hairpin RNA (shRNA) against Notch1 and transfected it into NSCs. Cell differentiation was analyzed under confocal laser-scanning microscopy. The percentage of neurons and astrocytes was quantified by normalizing the total number of TUJ1+ (Neuron-specific class III β-tubulin) and GFAP+ (Glial fibrillary acidic protein) cells to the total number of Hoechst 33342-labeled cell nuclei. The protein and gene expression of Notch-Hes1 pathway components was examined via western blot analysis and real-time PCR. After 1 week of incubation, we found that AGE-bovine serum albumin (BSA) (400 μg/mL) induced the astrocytic differentiation of cultured neurospheres and inhibited neuronal formation. The expression of Notch-Hes1 pathway components was upregulated in the cells in the AGE-BSA culture medium. Immunoblot analysis indicated that shRNA silencing of Notch1 expression in NSCs significantly increases neurogenesis and suppresses astrocytic differentiation in NSCs incubated with AGE-BSA. AGEs promote the astrocytic differentiation of cultured neurospheres by inhibiting neurogenesis through the Notch-Hes1 pathway, providing a potential therapeutic target for hyperglycemia-related cognitive deficits.

Hybrid surgical guidance based on the integration of radionuclear and optical technologies

PubMed Central

Valdés-Olmos, Renato; Buckle, Tessa; Vidal-Sicart, Sergi

2016-01-01

With the evolution of imaging technologies and tracers, the applications for nuclear molecular imaging are growing rapidly. For example, nuclear medicine is increasingly being used to guide surgical resections in complex anatomical locations. Here, a future workflow is envisioned that uses a combination of pre-operative diagnostics, navigation and intraoperative guidance. Radioguidance can provide means for pre-operative and intraoperative identification of “hot” lesions, forming the basis of a virtual data set that can be used for navigation. Luminescence guidance has shown great potential in the intraoperative setting by providing optical feedback, in some cases even in real time. Both of these techniques have distinct drawbacks, which include inaccuracy in areas that contain a background signal (radioactivity) or a limited degree of signal penetration (luminescence). We, and others, have reasoned that hybrid/multimodal approaches that integrate the use of these complementary modalities may help overcome their individual weaknesses. Ultimately, this will lead to advancement of the field of interventional molecular imaging/image-guided surgery. In this review, an overview of clinically applied hybrid surgical guidance technologies is given, whereby the focus is placed on tracers and hardware. PMID:26943463

78 FR 68459 - Medical Device Development Tools; Draft Guidance for Industry, Tool Developers, and Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-14

... Radiological Health (CDRH) for qualification of medical device development tools (MDDT) for use in device.... Background The draft guidance describes the framework and process for the voluntary CDRH qualification of... science; and (4) more quickly and more clearly communicate with CDRH stakeholders about important advances...

76 FR 43332 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

...: Focused Ultrasound Stimulator System for Aesthetic Use; Availability AGENCY: Food and Drug Administration... the guidance entitled, ``Class II Special Controls Guidance Document: Focused Ultrasound Stimulator System for Aesthetic Use.'' This guidance document describes a means by which focused ultrasound...

Recent trends in metabolic engineering of microorganisms for the production of advanced biofuels.

PubMed

Cheon, Seungwoo; Kim, Hye Mi; Gustavsson, Martin; Lee, Sang Yup

2016-12-01

As climate change has become one of the major global risks, our heavy dependence on petroleum-derived fuels has received much public attention. To solve such problems, production of sustainable fuels has been intensively studied over the past years. Thanks to recent advances in synthetic biology and metabolic engineering technologies, bio-based platforms for advanced biofuels production have been developed using various microorganisms. The strategies for production of advanced biofuels have converged upon four major metabolic routes: the 2-ketoacid pathway, the fatty acid synthesis (FAS) pathway, the isoprenoid pathway, and the reverse β-oxidation pathway. Additionally, the polyketide synthesis pathway has recently been attracting interest as a promising alternative biofuel production route. In this article, recent trends in advanced biofuels production are reviewed by categorizing them into three types of advanced biofuels: alcohols, biodiesel and jet fuel, and gasoline. Focus is given on the strategies of employing synthetic biology and metabolic engineering for the development of microbial strains producing advanced fuels. Finally, the prospects for future advances needed to achieve much more efficient bio-based production of advanced biofuels are discussed, focusing on designing advanced biofuel production pathways coupled with screening, modifying, and creating novel enzymes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Guidance, Navigation, and Control Technology Assessment for Future Planetary Science Missions

NASA Technical Reports Server (NTRS)

Beauchamp, Pat; Cutts, James; Quadrelli, Marco B.; Wood, Lincoln J.; Riedel, Joseph E.; McHenry, Mike; Aung, MiMi; Cangahuala, Laureano A.; Volpe, Rich

2013-01-01

Future planetary explorations envisioned by the National Research Council's (NRC's) report titled Vision and Voyages for Planetary Science in the Decade 2013-2022, developed for NASA Science Mission Directorate (SMD) Planetary Science Division (PSD), seek to reach targets of broad scientific interest across the solar system. This goal requires new capabilities such as innovative interplanetary trajectories, precision landing, operation in close proximity to targets, precision pointing, multiple collaborating spacecraft, multiple target tours, and advanced robotic surface exploration. Advancements in Guidance, Navigation, and Control (GN&C) and Mission Design in the areas of software, algorithm development and sensors will be necessary to accomplish these future missions. This paper summarizes the key GN&C and mission design capabilities and technologies needed for future missions pursuing SMD PSD's scientific goals.

Revealing pathways from payments for ecosystem services to socioeconomic outcomes

PubMed Central

Zhang, Jindong

2018-01-01

Payments for ecosystem services (PES) programs have been widely implemented as a promising tool to conserve ecosystems while facilitating socioeconomic development. However, the underlying pathways (or processes) through which PES programs affect socioeconomic outcomes remain elusive, and existing literature provides little guidance to quantify them. By integrating linkages among PES programs, livelihood activities, and socioeconomic outcomes, we develop a framework to reveal pathways from PES programs to socioeconomic outcomes. We empirically demonstrate the framework’s operationalization and uncover the pathways that lead to unexpected negative effects of two important PES programs on participating households’ income. With improved understanding of the pathways (for example, the programs decreased income through reducing crop production), we provide recommendations to enhance the PES programs’ outcomes in our demonstration site and beyond. Our study highlights the finding that elucidating the pathways from PES programs to their outcomes can help identify specific strategies to achieve ecosystem conservation and socioeconomic development simultaneously. PMID:29750187

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…

Interpreting REACH guidance in the determination of the derived no effect level (DNEL).

PubMed

Kreider, Marisa L; Spencer Williams, E

2010-11-01

Under the new European chemicals regulation, REACH, a new safety value, the Derived No Effect Level (DNEL) must be established for all chemicals manufactured, imported or used in the EU in quantities greater than 10 metric tonnes per year. The DNEL is to be calculated for all relevant exposure pathways, exposure populations, and endpoints of toxicity. The EU has published guidance on how to derive the DNEL, but this guidance has yet to be put into practice and is in some places not prescriptive. Using the Agency for Toxic Substances and Disease Registry (ATSDR) dataset, we have determined inhalation DNELs for styrene. In doing so, we considered what effect key decisions would have on the calculated DNEL. The resulting DNELs were then compared to existing risk criteria values or occupational exposure limits. General population DNELs were generally more conservative than analogous risk criteria (ranging from approximately 0.05 to 2.5 ppm). Worker DNELs are lower than existing occupational standards (ranging from approximately 0.4 to 20 ppm). To our knowledge, this work represents the first rigorous application and interpretation of the EU guidance for determination of a DNEL and will prove useful as a model for determination of other DNELs under REACH. Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Investigation of pathways of advanced glycation end-products accumulation in macrophages.

PubMed

Nagai, Ryoji; Fujiwara, Yukio; Mera, Katsumi; Otagiri, Masaki

2007-04-01

Advanced glycation end-products (AGE) play a role in the pathogenesis of several diseases, including diabetic complications and atherosclerosis. In atherosclerotic lesions of human aortas, AGE are localized in the extracellular matrix and intracellularly in foam cells. Two interpretations are possible for AGE accumulation inside macrophages, one is endocytic uptake of extracellular AGE-proteins by scavenger receptors; the other is intracellular AGE formation inside the macrophages. In the present study, we determined the pathways involved in AGE accumulation inside macrophages. RAW 264.7 cells, a murine macrophage cell line, incubated with BSA and 1600 mM glucose for 40 weeks, recognized heavily modified AGE- BSA. In contrast, the cells showed no ligand activity for mildly modified AGE-BSA, prepared by incubating BSA with 50 mM glucose for 24 weeks. Nepsilon-(carboxymethyl)lysine (CML)-modified proteins of about 65 kDa were detected in human monocyte-derived macrophages incubated for 7 days with 30 mM glucose and phorbol myristate acetate. Furthermore, CML was generated when glycated protein was incubated with hypochloric acid. Taken together, our results indicate that AGE detected inside foam cells in atherosclerotic lesions are generated intracellularly rather than representing endocytic uptake of extracellular AGE-proteins by scavenger receptors.

Regulatory Forum Opinion Piece: Review of FDA Draft Guidance Testicular Toxicity-Evaluation during Drug Development Guidance for Industry.

PubMed

Hukkanen, Renee R; Halpern, Wendy G; Vidal, Justin D

2016-10-01

In July 2015, the U.S. Food and Drug Administration (FDA) posted a new draft guidance entitled "Testicular Toxicity: Evaluation during Drug Development Guidance for Industry," with a 90-day public comment period. As the nonclinical assessment of testicular toxicity often relies on the expert interpretation of pathology affecting the male reproductive tract, this draft guidance is considered directly relevant to the toxicologic pathology community. Therefore, a working group was formed through the Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathologists (STPs) to provide a detailed review of the draft guidance. Specific comments on the guidance were submitted to the FDA by the STP. The draft guidance and all comments received are currently under review with the FDA. This commentary provides a summary of the components of the draft guidance and the comments submitted by the STP with acknowledgment of different perspectives reflected in comments from other respondents. © The Author(s) 2016.

28 CFR 77.4 - Guidance.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., gives advice or guidance to another Department attorney about the other attorney's ethical obligations... good faith provides legal advice or guidance upon request to an investigative agent should not be...

28 CFR 77.4 - Guidance.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., gives advice or guidance to another Department attorney about the other attorney's ethical obligations... good faith provides legal advice or guidance upon request to an investigative agent should not be...

Stressor Identification Guidance Document

EPA Science Inventory

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 doc...

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.

Guidance and New Education for Schools.

ERIC Educational Resources Information Center

Sprinthall, Norman A.

1980-01-01

Details rationale for broad-based school reform including examination of old guidance. General curriculum of schools must include psychological growth as direct object of classroom instruction. Effective guidance role can alter classroom teaching strategies and curriculum content. Guidance theory and practice should lead in seeking school reforms.…

Lifelong guidance: How guidance and counselling support lifelong learning in the contrasting contexts of China and Denmark

NASA Astrophysics Data System (ADS)

Zhang, Zhixin

2016-10-01

Due to the effects of globalisation and rapid technological development, traditional linear life course patterns of the past are gradually disappearing, and this affects education and learning systems as well as labour markets. Individuals are forced to develop lifestyles and survival strategies to manage job insecurity and make their skills and interests meet labour market needs. In modern attempts to develop and implement institutional provision for lifelong learning, guidance and counselling play an important role. The current Danish guidance system is well-organised, highly structured and professionalised. By contrast, Chinese guidance is still fragmented and "sectorisational". This paper explores whether elements of the highly structured and professionalised Danish guidance system and practice might be applicable to the Chinese context. The author begins by outlining international and national factors which are affecting citizens' life and career planning. She then presents and discusses the evolution of guidance and the different elements of provision in each of the two countries. Next, She compares the concepts and goals of "lifelong guidance" in Denmark and China, pointing out their similarities and differences and their respective strengths and weaknesses. The paper concludes with some suggestions for the further development of guidance in China.

77 FR 62270 - Proposed Revision Treatment of Non-Safety Systems for Passive Advanced Light Water Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-12

... for Passive Advanced Light Water Reactors AGENCY: Nuclear Regulatory Commission. ACTION: Standard... Passive Advanced Light Water Reactors.'' The current SRP does not contain guidance on the proposed RTNSS for Passive Advance Light Water Reactors. DATES: Submit comments by November 13, 2012. Comments...

The value and impact of information provided through library services for patient care: developing guidance for best practice.

PubMed

Weightman, Alison; Urquhart, Christine; Spink, Siân; Thomas, Rhian

2009-03-01

Previous impact tool-kits for UK health libraries required updating to reflect recent evidence and changes in library services. The National Knowledge Service funded development of updated guidance. Survey tools were developed based on previous impact studies and a systematic review. The resulting draft questionnaire survey was tested at four sites, and the interview schedule was investigated in a fifth area. A literature search in ASSIA, Google Scholar, INTUTE, LISA, LISTA, SCIRUS, Social Sciences Citation Index (Web of Knowledge), and the major UK University and National Libraries Catalogue (COPAC), identified ways to improve response rates. Other expert advice contributed to the guidance. The resulting guidance contains evidence-based advice and a planning pathway for conducting an impact survey as a service audit. The survey tools (critical incident questionnaire and interview schedule) are available online. The evidence-based advice recommends personalizing the request, assuring confidentiality, and using follow-up reminders. Questionnaires should be brief, and small incentives, such as a lottery draw should be considered. Bias is minimized if the survey is conducted and analysed by independent researchers. The guidance is a starting point for a pragmatic survey to assess the impact of health library services.

76 FR 20992 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-14

...: Low Level Laser System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS... guidance entitled ``Class II Special Controls Guidance Document: Low Level Laser System for Aesthetic Use.'' This guidance document describes a means by which low level laser systems for aesthetic use may comply...

Guidance Program Assessment Procedures for Elementary and Secondary Schools. Georgia Comprehensive Guidance Series.

ERIC Educational Resources Information Center

Gunderson, Margaret S.; Moore, Earl J.

This manual provides a series of assessment instruments that guidance program planners may adopt or adapt to provide a basis for defining the guidance program, educating others about the program, or planning needed program changes. The assessment procedures are designed to gather information about students' needs and progress from the students,…

University role in astronaut life support systems: Extravehicular guidance and stabilization in space

NASA Technical Reports Server (NTRS)

Vonrenner, L. C.

1972-01-01

Two problem areas are reviewed: (1) the nature of and approach to the EVA mission and (2) the guidance and stabilization required of such a mission. The report indicates several broad areas in which additional research is needed to provide an advance to the state-of-the-art. Moreover, the research problems cited were chosen from among many as those most amenable to research and study in the university environment.

Treating aerophagia with contingent physical guidance.

PubMed

Garcia, D; Starin, S; Churchill, R M

2001-01-01

Contingent physical guidance was used to treat chronic aerophagia. This consisted of guiding the participant's hand over her mouth following each attempt to engage in aerophagia. A wristwatch was then correlated with the contingent physical guidance procedure. Responding remained low in the presence of the wristwatch, even after contingent physical guidance was withdrawn.

Policy & Guidance

EPA Pesticide Factsheets

Policy documents represent EPA's official interpretation or view of specific issues. Guidance documents are published to further clarify regulations and to assist in implementation of environmental regulations.

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

"Better pathways of care": suggested improvements to the emergency department management of people with advanced cancer.

PubMed

Jelinek, George A; Boughey, Mark; Marck, Claudia H; Phillip, Jennifer; Weil, Jennifer; Lane, Heather; Weiland, Tracey J

2014-01-01

It is difficult to provide optimal care to people with advanced cancer presenting to emergency departments (EDs). Recent data suggest that the ED environment, the skills and priorities of treating staff, and the lack of clear communication related to goals of care contribute to the difficulty. By exploring the views of emergency, palliative care (PC), and oncology clinicians on the care of these patients, this study aimed to describe potential solutions. This qualitative study involved focus groups with clinicians at two major hospitals and two community PC services in Melbourne, Australia, and semistructured telephone interviews with emergency clinicians from all other Australian states and territories. Discussions were recorded and transcribed verbatim. Thematic analysis identified ways to improve or enhance care. Throughout discussions with 94 clinicians, a number of possible improvements to care were raised; these were broadly grouped into service areas: clinical care, pathways, information access, and education. The provision of care to patients with advanced cancer in the ED occurs across sites, across disciplines, and across teams. To make improvements to care, we must address these complexities. The improvements suggested in this study place the patient (and the patient's family) at the centre of care.

76 FR 44594 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0465] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... guidance document will serve as the special control for rTMS systems. Section 513(f)(2) of the Federal Food...

Nurse Leaders’ Experiences of Implementing Career Advancement Programs for Nurses in Iran

PubMed Central

Sheikhi, Mohammad Reza; Khoshknab, Masoud Fallahi; Mohammadi, Farahnaz; Oskouie, Fatemeh

2015-01-01

Background and purpose: Career advancement programs are currently implemented in many countries. In Iran, the first career advancement program was Nurses’ Career Advancement Pathway. The purpose of this study was to explore nurse leaders’ experiences about implementing the Nurses’ Career Advancement Pathway program in Iran. Methods: This exploratory qualitative study was conducted in 2013. Sixteen nurse managers were recruited from the teaching hospitals affiliated to Shahid Behesthi, Qazvin, and Iran Universities of Medical Sciences in Iran. Participants were recruited using purposive sampling method. Study data were collected through in-depth semi-structured interviews. The conventional content analysis approach was used for data analysis. Results: participants’ experiences about implementing the Nurses’ Career Advancement Pathway fell into three main categories including: a) the shortcomings of performance evaluation, b) greater emphasis on point accumulation, c) the advancement-latitude mismatch. Conclusion: The Nurses’ Career Advancement pathway has several shortcomings regarding both its content and its implementation. Therefore, it is recommended to revise the program. PMID:26156907

Nurse Leaders' Experiences of Implementing Career Advancement Programs for Nurses in Iran.

PubMed

Sheikhi, Mohammad Reza; Fallahi Khoshknab, Masoud; Mohammadi, Farahnaz; Oskouie, Fatemeh

2015-02-24

Career advancement programs are currently implemented in many countries. In Iran, the first career advancement program was Nurses' Career Advancement Pathway. The purpose of this study was to explore nurse leaders' experiences about implementing the Nurses' Career Advancement Pathway program in Iran. This exploratory qualitative study was conducted in 2013. Sixteen nurse managers were recruited from the teaching hospitals affiliated to Shahid Behesthi, Qazvin, and Iran Universities of Medical Sciences in Iran. Participants were recruited using purposive sampling method. Study data were collected through in-depth semi-structured interviews. The conventional content analysis approach was used for data analysis. participants' experiences about implementing the Nurses' Career Advancement Pathway fell into three main categories including: a) the shortcomings of performance evaluation, b) greater emphasis on point accumulation, c) the advancement-latitude mismatch. The Nurses' Career Advancement pathway has several shortcomings regarding both its content and its implementation. Therefore, it is recommended to revise the program.

The Elementary School Guidance Counselor: A Developmental Model.

ERIC Educational Resources Information Center

Gum, Moy F.

The position taken is that elementary schools need a guidance program and an elementary school guidance counselor who is a regular member of a given school staff. However, it is advocated that elementary guidance should not be merely an extension of the secondary guidance program. The viewpoint taken here is that elementary guidance should be…

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,…

Treating aerophagia with contingent physical guidance.

PubMed Central

Garcia, D; Starin, S; Churchill, R M

2001-01-01

Contingent physical guidance was used to treat chronic aerophagia. This consisted of guiding the participant's hand over her mouth following each attempt to engage in aerophagia. A wristwatch was then correlated with the contingent physical guidance procedure. Responding remained low in the presence of the wristwatch, even after contingent physical guidance was withdrawn. PMID:11317995

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.

Is Career Guidance for the Individual or for the Market? Implications of EU Policy for Career Guidance

ERIC Educational Resources Information Center

Bergmo-Prvulovic, Ingela

2014-01-01

This paper explores the essential understanding and underlying perspectives of career implicit in EU career guidance policy in the twenty-first century, as well as the possible implications of these for the future mission of guidance. Career theories, models and concepts that serve career guidance are shaped on the twentieth-century industrial…

BENCHMARK DOSE TECHNICAL GUIDANCE DOCUMENT ...

EPA Pesticide Factsheets

The purpose of this document is to provide guidance for the Agency on the application of the benchmark dose approach in determining the point of departure (POD) for health effects data, whether a linear or nonlinear low dose extrapolation is used. The guidance includes discussion on computation of benchmark doses and benchmark concentrations (BMDs and BMCs) and their lower confidence limits, data requirements, dose-response analysis, and reporting requirements. This guidance is based on today's knowledge and understanding, and on experience gained in using this approach.

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…

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.

Evaluating effectiveness of real-time advanced traveler information systems using a small test vehicle fleet

DOT National Transportation Integrated Search

1997-01-01

ADVANCE was an in-vehicle advanced traveler information system (ATIS) providing route guidance in real time that operated in the northwestern portion and northwest suburbs of Chicago, Illinois. It used probe vehicles to generate dynamically travel ti...

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.

Techniques for Interventional MRI Guidance in Closed-Bore Systems.

PubMed

Busse, Harald; Kahn, Thomas; Moche, Michael

2018-02-01

Efficient image guidance is the basis for minimally invasive interventions. In comparison with X-ray, computed tomography (CT), or ultrasound imaging, magnetic resonance imaging (MRI) provides the best soft tissue contrast without ionizing radiation and is therefore predestined for procedural control. But MRI is also characterized by spatial constraints, electromagnetic interactions, long imaging times, and resulting workflow issues. Although many technical requirements have been met over the years-most notably magnetic resonance (MR) compatibility of tools, interventional pulse sequences, and powerful processing hardware and software-there is still a large variety of stand-alone devices and systems for specific procedures only.Stereotactic guidance with the table outside the magnet is common and relies on proper registration of the guiding grids or manipulators to the MR images. Instrument tracking, often by optical sensing, can be added to provide the physicians with proper eye-hand coordination during their navigated approach. Only in very short wide-bore systems, needles can be advanced at the extended arm under near real-time imaging. In standard magnets, control and workflow may be improved by remote operation using robotic or manual driving elements.This work highlights a number of devices and techniques for different interventional settings with a focus on percutaneous, interstitial procedures in different organ regions. The goal is to identify technical and procedural elements that might be relevant for interventional guidance in a broader context, independent of the clinical application given here. Key challenges remain the seamless integration into the interventional workflow, safe clinical translation, and proper cost effectiveness.

Methods and approaches in the topology-based analysis of biological pathways

PubMed Central

Mitrea, Cristina; Taghavi, Zeinab; Bokanizad, Behzad; Hanoudi, Samer; Tagett, Rebecca; Donato, Michele; Voichiţa, Călin; Drăghici, Sorin

2013-01-01

The goal of pathway analysis is to identify the pathways significantly impacted in a given phenotype. Many current methods are based on algorithms that consider pathways as simple gene lists, dramatically under-utilizing the knowledge that such pathways are meant to capture. During the past few years, a plethora of methods claiming to incorporate various aspects of the pathway topology have been proposed. These topology-based methods, sometimes referred to as “third generation,” have the potential to better model the phenomena described by pathways. Although there is now a large variety of approaches used for this purpose, no review is currently available to offer guidance for potential users and developers. This review covers 22 such topology-based pathway analysis methods published in the last decade. We compare these methods based on: type of pathways analyzed (e.g., signaling or metabolic), input (subset of genes, all genes, fold changes, gene p-values, etc.), mathematical models, pathway scoring approaches, output (one or more pathway scores, p-values, etc.) and implementation (web-based, standalone, etc.). We identify and discuss challenges, arising both in methodology and in pathway representation, including inconsistent terminology, different data formats, lack of meaningful benchmarks, and the lack of tissue and condition specificity. PMID:24133454

A nerve guidance conduit with topographical and biochemical cues: potential application using human neural stem cells

NASA Astrophysics Data System (ADS)

Jenkins, Phillip M.; Laughter, Melissa R.; Lee, David J.; Lee, Young M.; Freed, Curt R.; Park, Daewon

2015-06-01

Despite major advances in the pathophysiological understanding of peripheral nerve damage, the treatment of nerve injuries still remains an unmet medical need. Nerve guidance conduits present a promising treatment option by providing a growth-permissive environment that 1) promotes neuronal cell survival and axon growth and 2) directs axonal extension. To this end, we designed an electrospun nerve guidance conduit using a blend of polyurea and poly-caprolactone with both biochemical and topographical cues. Biochemical cues were integrated into the conduit by functionalizing the polyurea with RGD to improve cell attachment. Topographical cues that resemble natural nerve tissue were incorporated by introducing intraluminal microchannels aligned with nanofibers. We determined that electrospinning the polymer solution across a two electrode system with dissolvable sucrose fibers produced a polymer conduit with the appropriate biomimetic properties. Human neural stem cells were cultured on the conduit to evaluate its ability to promote neuronal growth and axonal extension. The nerve guidance conduit was shown to enhance cell survival, migration, and guide neurite extension.

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. ©2013 Special Care Dentistry Association and Wiley Periodicals, Inc.

Guidance and control 1992; Proceedings of the 15th Annual AAS Rocky Mountain Conference, Keystone, CO, Feb. 8-12, 1992

NASA Astrophysics Data System (ADS)

Culp, Robert D.; Zietz, Richard P.

The present volume on guidance and control discusses advances in guidance, navigation, and control, guidance and control storyboard displays, space robotic control, spacecraft control and flexible body interaction, and the Mission to Planet Earth. Attention is given to applications of Newton's method to attitude determination, a new family of low-cost momentum/reaction wheels, stellar attitude data handling, and satellite life prediction using propellant quantity measurements. Topics addressed include robust manipulator controller specification and design, implementations and applications of a manipulator control testbed, optimizing transparency in teleoperator architectures, and MIMO system identification using frequency response data. Also discussed are instrument configurations for the restructured Earth Observing System, the HIRIS instrument, clouds and the earth's radiant energy system, and large space-based systems for dealing with global change.

Green Positive Guidance and Green Positive Life Counseling for Decent Work and Decent Lives: Some Empirical Results

PubMed Central

Di Fabio, Annamaria; Bucci, Ornella

2016-01-01

This article discusses green positive guidance and green positive life counseling for decent work and decent lives. From a green guidance perspective, the connectedness to nature construct is important both in terms of the meaning of work and life construction. The study discussed in this article analyzed the relationship between empathy and connectedness to nature, controlling for the effects of fluid intelligence and personality traits. In this connection, the Advanced Progressive Matrices, the Big Five Questionnaire, and the Interpersonal Reactivity Index were administered to 144 Italian high school students. The study revealed that connecteness to nature was not associated with fluid intelligence and was only moderately associated with personality traits. It was empathy that showed the highest association with connectedness to nature. The results open new opportunities for future research and interventions in green positive guidance/life counseling and green positive decent work. PMID:26973563

Recent technological advances in computed tomography and the clinical impact therein.

PubMed

Runge, Val M; Marquez, Herman; Andreisek, Gustav; Valavanis, Anton; Alkadhi, Hatem

2015-02-01

Current technological advances in CT, specifically those with a major impact on clinical imaging, are discussed. The intent was to provide for both medical physicists and practicing radiologists a summary of the clinical impact of each advance, offering guidance in terms of utility and day-to-day clinical implementation, with specific attention to radiation dose reduction.

C. elegans dystroglycan coordinates responsiveness of follower axons to dorsal/ventral and anterior/posterior guidance cues

PubMed Central

Johnson, Robert P.; Kramer, James M.

2012-01-01

Neural development in metazoans is characterized by the establishment of initial process tracts by pioneer axons and the subsequent extension of follower axons along these pioneer processes. Mechanisms governing the fidelity of follower extension along pioneered routes are largely unknown. In C. elegans, formation of the right angle-shaped lumbar commissure connecting the lumbar and preanal ganglia is an example of pioneer/follower dynamics. We find that the dystroglycan ortholog DGN-1 mediates the fidelity of follower lumbar commissure axon extension along the pioneer axon route. In dgn-1 mutants, the axon of the pioneer PVQ neuron faithfully establishes the lumbar commissure, but axons of follower lumbar neurons, such as PVC, frequently bypass the lumbar commissure and extend along an oblique trajectory directly toward the preanal ganglion. In contrast, disruption of the UNC-6/netrin guidance pathway principally perturbs PVQ ventral guidance to pioneer the lumbar commissure. Loss of DGN-1 in unc-6 mutants has a quantitatively similar effect on follower axon guidance regardless of PVQ axon route, indicating that DGN-1 does not mediate follower/pioneer adhesion. Instead, DGN-1 appears to block premature responsiveness of follower axons to a preanal ganglion-directed guidance cue which mediates ventral-to-anterior reorientation of lumbar commissure axons. Deletion analysis shows that only the most N-terminal DGN-1 domain is required for these activities. These studies suggest that dystroglycan modulation of growth cone responsiveness to conflicting guidance cues is important for restricting follower axon extension to the tracts laid down by pioneers. PMID:22275151

Integrated navigation, flight guidance, and synthetic vision system for low-level flight

NASA Astrophysics Data System (ADS)

Mehler, Felix E.

2000-06-01

Future military transport aircraft will require a new approach with respect to the avionics suite to fulfill an ever-changing variety of missions. The most demanding phases of these mission are typically the low level flight segments, including tactical terrain following/avoidance,payload drop and/or board autonomous landing at forward operating strips without ground-based infrastructure. As a consequence, individual components and systems must become more integrated to offer a higher degree of reliability, integrity, flexibility and autonomy over existing systems while reducing crew workload. The integration of digital terrain data not only introduces synthetic vision into the cockpit, but also enhances navigation and guidance capabilities. At DaimlerChrysler Aerospace AG Military Aircraft Division (Dasa-M), an integrated navigation, flight guidance and synthetic vision system, based on digital terrain data, has been developed to fulfill the requirements of the Future Transport Aircraft (FTA). The fusion of three independent navigation sensors provides a more reliable and precise solution to both the 4D-flight guidance and the display components, which is comprised of a Head-up and a Head-down Display with synthetic vision. This paper will present the system, its integration into the DLR's VFW 614 Advanced Technology Testing Aircraft System (ATTAS) and the results of the flight-test campaign.

Guidance, Navigation, and Control Techniques and Technologies for Active Satellite Removal

NASA Astrophysics Data System (ADS)

Ortega Hernando, Guillermo; Erb, Sven; Cropp, Alexander; Voirin, Thomas; Dubois-Matra, Olivier; Rinalducci, Antonio; Visentin, Gianfranco; Innocenti, Luisa; Raposo, Ana

2013-09-01

This paper shows an internal feasibility analysis to de- orbit a non-functional satellite of big dimensions by the Technical Directorate of the European Space Agency ESA. The paper focuses specifically on the design of the techniques and technologies for the Guidance, Navigation, and Control (GNC) system of the spacecraft mission that will capture the satellite and ultimately will de-orbit it on a controlled re-entry.The paper explains the guidance strategies to launch, rendezvous, close-approach, and capture the target satellite. The guidance strategy uses chaser manoeuvres, hold points, and collision avoidance trajectories to ensure a safe capture. It also details the guidance profile to de-orbit it in a controlled re-entry.The paper continues with an analysis of the required sensing suite and the navigation algorithms to allow the homing, fly-around, and capture of the target satellite. The emphasis is placed around the design of a system to allow the rendezvous with an un-cooperative target, including the autonomous acquisition of both the orbital elements and the attitude of the target satellite.Analysing the capture phase, the paper provides a trade- off between two selected capture systems: the net and the tentacles. Both are studied from the point of view of the GNC system.The paper analyses as well the advanced algorithms proposed to control the final compound after the capture that will allow the controlled de-orbiting of the assembly in a safe place in the Earth.The paper ends proposing the continuation of this work with the extension to the analysis of the destruction process of the compound in consecutive segments starting from the entry gate to the rupture and break up.

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

32 CFR 2001.16 - Fundamental classification guidance review.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Fundamental classification guidance review. 2001... INFORMATION Classification § 2001.16 Fundamental classification guidance review. (a) Performance of fundamental classification guidance reviews. An initial fundamental classification guidance review shall be...

Encouraging Evidence on a Sector-Focused Advancement Strategy: Two-Year Impacts from the WorkAdvance Demonstration

ERIC Educational Resources Information Center

Hendra, Richard; Greenberg, David H.; Hamilton, Gayle; Oppenheim, Ari; Pennington, Alexandra; Schaberg, Kelsey; Tessler, Betsy L.

2016-01-01

This report summarizes the two-year findings of a rigorous random assignment evaluation of the WorkAdvance model, a sectoral training, and advancement initiative. Launched in 2011, WorkAdvance goes beyond the previous generation of employment programs by introducing demand-driven skills training and a focus on jobs that have career pathways. The…

Planning guidance for emergency response to a hypothetical nuclear attack on Riyadh, Saudi Arabia

NASA Astrophysics Data System (ADS)

Shubayr, Nasser Ali M.

The threat of nuclear attack will remain imminent in an ever-advancing society. Saudi Arabia is not immune to this threat. This dissertation establishes planning guidance for response to a nuclear attack on Riyadh, the capital of Saudi Arabia, based on a hypothetical scenario of a nuclear detonation. A case scenario of a one-megaton thermonuclear bomb detonated at ground level over Riyadh is used to support the thesis. Previous nuclear tests and the Hiroshima and Nagasaki bombings have been used to present possible effects on Riyadh. US planning guidance and lessons learned from the Chernobyl and Fukushima nuclear plants accidents have been used to develop the emergency response guidance. The planning guidance outlines a rapid response to the nuclear detonation. Four damage zones have been identified; severe damage zone, moderate damage zone, light damage zone and dangerous fallout zone. Actions that are recommended, and those that should be avoided, have been determined for each zone. Shelter/ evacuation evaluation for blast-affected and fallout-affected areas is the basis for the recommendation that shelter in place is the best decision for the first hours to days after the attack. Guidelines for medical care response and population monitoring and decontamination are included to reduce the early and long-term effects of the attack. Recommendations to the Saudi Arabian authorities have been made to facilitate suitable preparedness and response for such an event.

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.

Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment.

PubMed

VanGuilder, Heather D; Bixler, Georgina V; Brucklacher, Robert M; Farley, Julie A; Yan, Han; Warrington, Junie P; Sonntag, William E; Freeman, Willard M

2011-10-11

Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline. Three independent cohorts of adult (12-13 months) and aged (26-28 months) F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG). Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6) and Iba1. We report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors) throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance. These data demonstrate a novel, coordinated age-related induction of the MHC II immune

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.

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...

FACILITATING LEARNING AND INDIVIDUAL DEVELOPMENT, TOWARD A THEORY FOR ELEMENTARY GUIDANCE. MINNESOTA GUIDANCE SERIES.

ERIC Educational Resources Information Center

GRAMS, ARMIN

A THEORY UPON WHICH ELEMENTARY GUIDANCE PROGRAMS CAN BE SOUNDLY DESIGNED IS PRESENTED. A MAJOR THEME IS THAT PSYCHOLOGICAL WELL-BEING OR GOOD ADJUSTMENT IS RELATED TO LEARNED, INDIVIDUAL COMPETENCIES SUCH AS COMMUNICATION AND INTERACTION IN DEPTH WITH OTHERS. THE APPROPRIATE CONCERN OF GUIDANCE THEN BECOMES TO FOSTER THESE COMPETENCIES, THUS…

Examining the implementation of NICE guidance: cross-sectional survey of the use of NICE interventional procedures guidance by NHS Trusts.

PubMed

Lowson, Karin; Jenks, Michelle; Filby, Alexandra; Carr, Louise; Campbell, Bruce; Powell, John

2015-06-30

In the UK, NHS hospitals receive large amounts of evidence-based recommendations for care delivery from the National Institute for Health and Care Excellence (NICE) and other organisations. Little is known about how NHS organisations implement such guidance and best practice for doing so. This study was therefore designed to examine the dissemination, decision-making, and monitoring processes for NICE interventional procedures (IP) guidance and to investigate the barriers and enablers to the implementation of such guidance. A cross-sectional survey questionnaire was developed and distributed to individuals responsible for managing the processes around NICE guidance in all 181 acute NHS hospitals in England, Scotland, Wales and Northern Ireland. A review of acute NHS hospital policies for implementing NICE guidance was also undertaken using information available in the public domain and from organisations' websites. The response rate to the survey was 75 % with 135 completed surveys received. Additionally, policies from 25 % of acute NHS hospitals were identified and analysed. NHS acute hospitals typically had detailed processes in place to implement NICE guidance, although organisations recognised barriers to implementation including organisational process barriers, clinical engagement and poor targeting with a large number of guidance issued. Examples of enablers to, and good practice for, implementation of guidance were found, most notably the value of shared learning experiences between NHS hospitals. Implications for NICE were also identified. These included making improvements to the layout of guidance, signposting on the website and making better use of their shared learning platform. Most organisations have robust processes in place to deal with implementing guidance. However, resource limitations and the scope of guidance received by organisations create barriers relating to organisational processes, clinician engagement and financing of new procedures

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...

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.

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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pathway Tools version 19.0 update: software for pathway/genome informatics and systems biology

PubMed Central

Latendresse, Mario; Paley, Suzanne M.; Krummenacker, Markus; Ong, Quang D.; Billington, Richard; Kothari, Anamika; Weaver, Daniel; Lee, Thomas; Subhraveti, Pallavi; Spaulding, Aaron; Fulcher, Carol; Keseler, Ingrid M.; Caspi, Ron

2016-01-01

Pathway Tools is a bioinformatics software environment with a broad set of capabilities. The software provides genome-informatics tools such as a genome browser, sequence alignments, a genome-variant analyzer and comparative-genomics operations. It offers metabolic-informatics tools, such as metabolic reconstruction, quantitative metabolic modeling, prediction of reaction atom mappings and metabolic route search. Pathway Tools also provides regulatory-informatics tools, such as the ability to represent and visualize a wide range of regulatory interactions. This article outlines the advances in Pathway Tools in the past 5 years. Major additions include components for metabolic modeling, metabolic route search, computation of atom mappings and estimation of compound Gibbs free energies of formation; addition of editors for signaling pathways, for genome sequences and for cellular architecture; storage of gene essentiality data and phenotype data; display of multiple alignments, and of signaling and electron-transport pathways; and development of Python and web-services application programming interfaces. Scientists around the world have created more than 9800 Pathway/Genome Databases by using Pathway Tools, many of which are curated databases for important model organisms. PMID:26454094

Dragon (repulsive guidance molecule b) inhibits IL-6 expression in macrophages.

PubMed

Xia, Yin; Cortez-Retamozo, Virna; Niederkofler, Vera; Salie, Rishard; Chen, Shanzhuo; Samad, Tarek A; Hong, Charles C; Arber, Silvia; Vyas, Jatin M; Weissleder, Ralph; Pittet, Mikael J; Lin, Herbert Y

2011-02-01

Repulsive guidance molecule (RGM) family members RGMa, RGMb/Dragon, and RGMc/hemojuvelin were found recently to act as bone morphogenetic protein (BMP) coreceptors that enhance BMP signaling activity. Although our previous studies have shown that hemojuvelin regulates hepcidin expression and iron metabolism through the BMP pathway, the role of the BMP signaling mediated by Dragon remains largely unknown. We have shown previously that Dragon is expressed in neural cells, germ cells, and renal epithelial cells. In this study, we demonstrate that Dragon is highly expressed in macrophages. Studies with RAW264.7 and J774 macrophage cell lines reveal that Dragon negatively regulates IL-6 expression in a BMP ligand-dependent manner via the p38 MAPK and Erk1/2 pathways but not the Smad1/5/8 pathway. We also generated Dragon knockout mice and found that IL-6 is upregulated in macrophages and dendritic cells derived from whole lung tissue of these mice compared with that in respective cells derived from wild-type littermates. These results indicate that Dragon is an important negative regulator of IL-6 expression in immune cells and that Dragon-deficient mice may be a useful model for studying immune and inflammatory disorders.

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.

Breathing guidance in radiation oncology and radiology: A systematic review of patient and healthy volunteer studies.

PubMed

Pollock, Sean; Keall, Robyn; Keall, Paul

2015-09-01

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. 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. 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. 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 clinical impact of breathing guidance

Autonomous Control Modes and Optimized Path Guidance for Shipboard Landing in High Sea States

DTIC Science & Technology

2016-04-28

Contract # N00014-14-C-0004 Autonomous Control Modes and Optimized Path Guidance for Shipboard Landing in High Sea States Progress Report...Aviation (ONR BAA12-SN-0028). This project addresses the Sea Based Aviation (SBA) initiative in Advanced Handling Qualities for Rotorcraft. Landing a...and a degraded visual environment, workload during the landing task begins to approach the limits of a human pilot’s capability. It is a similarly

RESEARCH VISIBILITY. VOCATIONAL EDUCATION IS SERVICE--VOCATIONAL GUIDANCE.

ERIC Educational Resources Information Center

LAW, GORDON F.

NINETEEN REVIEWS IN THIS ISSUE PERTAIN TO VOCATIONAL GUIDANCE AND ARE ORGANIZED BY TOPICS--(1) "SYSTEMS TECHNOLOGY IN GUIDANCE" REVIEWS AN EXPLORATORY STUDY OF INFORMATION PROCESSING PROCEDURES AND COMPUTER APPLICATIONS IN GUIDANCE, AND A CONFERENCE ON SYSTEMS DEVELOPMENT FOR VOCATIONAL GUIDANCE, (2) "CAREER DEVELOPMENT THEORY AND PRACTICE" TREATS…

A needle guidance system for biopsy and therapy using two-dimensional ultrasound

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

Bluvol, Nathan; Sheikh, Allison; Kornecki, Anat

2008-02-15

Image-guided needle biopsies are currently used to provide a definitive diagnosis of breast cancer; however, difficulties in tumor targeting exist as the ultrasound (United States) scan plane and biopsy needle must remain coplanar throughout the procedure to display the actual needle tip position. The additional time associated with aligning and maintaining this coplanar relationship results in increased patient discomfort. Biopsy procedural efficiency is further hindered since needle pathway interpretation is often difficult, especially for needle insertions at large depths that usually require multiple reinsertions. The authors developed a system that would increase the speed and accuracy of current breast biopsymore » procedures using readily available two-dimensional (2D) US technology. This system is composed of a passive articulated mechanical arm that attaches to a 2D US transducer. The arm is connected to a computer through custom electronics and software, which were developed as an interface for tracking the positioning of the mechanical components in real time. The arm couples to the biopsy needle and provides visual guidance for the physician performing the procedure in the form of a real-time projected needle pathway overlay on an US image of the breast. An agar test phantom, with stainless steel targets interspersed randomly throughout, was used to validate needle trajectory positioning accuracy. The biopsy needle was guided by both the software and hardware components to the targets. The phantom, with the needle inserted and device decoupled, was placed in an x-ray stereotactic mammography (SM) machine. The needle trajectory and bead target locations were determined in three dimensions from the SM images. Results indicated a mean needle trajectory accuracy error of 0.75{+-}0.42 mm. This is adequate to sample lesions that are <2 mm in diameter. Chicken tissue test phantoms were used to compare core needle biopsy procedure times between experienced

Non-Participation in Guidance: An Opportunity for Development?

ERIC Educational Resources Information Center

Thomsen, Rie

2014-01-01

This article discusses how new opportunities for guidance can emerge from an analysis of the interplay between the participation (or lack of participation) of the individuals in career guidance, and the career guidance practitioner's response. The article suggests critical psychology as a framework for career guidance research and presents…

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,…

Advanced transport operating system software upgrade: Flight management/flight controls software description

NASA Technical Reports Server (NTRS)

Clinedinst, Winston C.; Debure, Kelly R.; Dickson, Richard W.; Heaphy, William J.; Parks, Mark A.; Slominski, Christopher J.; Wolverton, David A.

1988-01-01

The Flight Management/Flight Controls (FM/FC) software for the Norden 2 (PDP-11/70M) computer installed on the NASA 737 aircraft is described. The software computes the navigation position estimates, guidance commands, those commands to be issued to the control surfaces to direct the aircraft in flight based on the modes selected on the Advanced Guidance Control System (AGSC) mode panel, and the flight path selected via the Navigation Control/Display Unit (NCDU).

Semaphorin3a Promotes Advanced Diabetic Nephropathy

PubMed Central

Aggarwal, Pardeep K.; Veron, Delma; Thomas, David B.; Siegel, Dionicio; Moeckel, Gilbert; Kashgarian, Michael

2015-01-01

The onset of diabetic nephropathy (DN) is highlighted by glomerular filtration barrier abnormalities. Identifying pathogenic factors and targetable pathways driving DN is crucial to developing novel therapies and improving the disease outcome. Semaphorin3a (sema3a) is a guidance protein secreted by podocytes. Excess sema3a disrupts the glomerular filtration barrier. Here, using immunohistochemistry, we show increased podocyte SEMA3A in renal biopsies from patients with advanced DN. Using inducible, podocyte-specific Sema3a gain-of-function (Sema3a+) mice made diabetic with streptozotocin, we demonstrate that sema3a is pathogenic in DN. Diabetic Sema3a+ mice develop massive proteinuria, renal insufficiency, and extensive nodular glomerulosclerosis, mimicking advanced DN in humans. In diabetic mice, Sema3a+ exacerbates laminin and collagen IV accumulation in Kimmelstiel-Wilson-like glomerular nodules and causes diffuse podocyte foot process effacement and F-actin collapse via nephrin, αvβ3 integrin, and MICAL1 interactions with plexinA1. MICAL1 knockdown and sema3a inhibition render podocytes not susceptible to sema3a-induced shape changes, indicating that MICAL1 mediates sema3a-induced podocyte F-actin collapse. Moreover, sema3a binding inhibition or podocyte-specific plexinA1 deletion markedly ameliorates albuminuria and abrogates renal insufficiency and the diabetic nodular glomerulosclerosis phenotype of diabetic Sema3a+ mice. Collectively, these findings indicate that excess sema3a promotes severe diabetic nephropathy and identifies novel potential therapeutic targets for DN. PMID:25475434

Connectome imaging for mapping human brain pathways

PubMed Central

Shi, Y; Toga, A W

2017-01-01

With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. We first introduce the background of diffusion MRI with an emphasis on the technical advances and challenges in state-of-the-art multi-shell acquisition schemes used in the Human Connectome Project. Characterization of the microstructural environment in the human brain is discussed from the tensor model to the general fiber orientation distribution (FOD) models that can resolve crossing fibers in each voxel of the image. Using FOD-based tractography, we describe novel methods for fiber bundle reconstruction and graph-based connectivity analysis. Building upon these novel developments, there have already been successful applications of connectome imaging techniques in reconstructing challenging brain pathways. Examples including retinofugal and brainstem pathways will be reviewed. Finally, we discuss future directions in connectome imaging and its interaction with other aspects of brain imaging research. PMID:28461700

Guidance law simulation studies for complex approaches using the Microwave Landing System (MLS)

NASA Technical Reports Server (NTRS)

Feather, J. B.

1986-01-01

This report documents results for MLS guidance algorithm development conducted by DAC for NASA under the Advance Transport Operating Systems (ATOPS) Technology Studies program (NAS1-18028). The study consisted of evaluating guidance laws for vertical and lateral path control, as well as speed control, by simulating an MLS approach for the Washington National Airport. This work is an extension and generalization of a previous ATOPS contract (NAS1-16202) completed by DAC in 1985. The Washington river approach was simulated by six waypoints and one glideslope change and consisted of an eleven nautical mile approach path. Tracking performance was generated for 10 cases representing several different conditions, which included MLS noise, steady wind, turbulence, and windshear. Results of this simulation phase are suitable for use in future fixed-base simulator evaluations employing actual hardware (autopilot and a performance management system), as well as crew procedures and information requirements for MLS.

Cell-Cell Interactions during pollen tube guidance

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

Daphne Preuss

The long-term goal of this research is to identify the signaling molecules that mediate plant cell-cell interactions during pollination. The immediate goals of this project are to perform genetic and molecular analysis of pollen tube guidance. Specifically, we proposed to: 1. Characterize the pistil components that direct pollen tube navigation using the Arabidopsis thaliana in vitro pollen tube guidance system 2. Identify pistil signals that direct pollen tube guidance by a) using microarrays to profile gene expression in developing pistils, and b) employing proteomics and metabolomics to isolate pollen tube guidance signals. 3. Explore the genetic basis of natural variationmore » in guidance signals, comparing the in vitro interactions between pollen and pistils from A. thaliana and its close relatives.« less

Formation of neuronal pathways in the imaginal discs of Drosophila melanogaster.

PubMed

Jan, Y N; Ghysen, A; Christoph, I; Barbel, S; Jan, L Y

1985-09-01

We have followed the formation of neuronal pathways in different imaginal discs of Drosophila. The pattern is highly reproducible for a given disc type but distinct for each type of discs: in leg discs, several neurons are present before metamorphosis and provide two major pathways that are joined by later neurons; in the wing and haltere discs, a few pairs of neurons appear after the onset of metamorphosis and pioneer the major pathways; in antenna discs, no pioneers are detected before massive neuronal differentiation begins. The mechanisms used for axonal guidance seem common to all discs, and the differences between discs can be accounted for simply by differences in the arrangement and birth time of pioneer neurons. Different subsets of pioneer neurons are deleted by mutations such as scute and engrailed.

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.

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…

Guidance in the Middle Schools.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Bureau of Curriculum Development.

This publication is designed to assist the guidance counselor, the administrator, the supervisors, and other members of the school staff to integrate a developmental guidance program into the total educational process of the preadolescent in an urban society. Special attention is devoted to appropriate topics and techniques for use in individual…

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... POLICY Recalls (Including Product Corrections)-Guidance on Policy, Procedures, and Industry Responsibilities § 7.59 General industry guidance. A recall can be disruptive of a firm's operation and business...

21 CFR 7.59 - General industry guidance.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false General industry guidance. 7.59 Section 7.59 Food... POLICY Recalls (Including Product Corrections)-Guidance on Policy, Procedures, and Industry Responsibilities § 7.59 General industry guidance. A recall can be disruptive of a firm's operation and business...

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... POLICY Recalls (Including Product Corrections)-Guidance on Policy, Procedures, and Industry Responsibilities § 7.59 General industry guidance. A recall can be disruptive of a firm's operation and business...

21 CFR 7.59 - General industry guidance.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false General industry guidance. 7.59 Section 7.59 Food... POLICY Recalls (Including Product Corrections)-Guidance on Policy, Procedures, and Industry Responsibilities § 7.59 General industry guidance. A recall can be disruptive of a firm's operation and business...

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

Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons

PubMed Central

Poliak, Sebastian; Morales, Daniel; Croteau, Louis-Philippe; Krawchuk, Dayana; Palmesino, Elena; Morton, Susan; Cloutier, Jean-François; Charron, Frederic; Dalva, Matthew B; Ackerman, Susan L; Kao, Tzu-Jen; Kania, Artur

2015-01-01

During neural circuit assembly, axonal growth cones are exposed to multiple guidance signals at trajectory choice points. While axonal responses to individual guidance cues have been extensively studied, less is known about responses to combination of signals and underlying molecular mechanisms. Here, we studied the convergence of signals directing trajectory selection of spinal motor axons entering the limb. We first demonstrate that Netrin-1 attracts and repels distinct motor axon populations, according to their expression of Netrin receptors. Quantitative in vitro assays demonstrate that motor axons synergistically integrate both attractive or repulsive Netrin-1 signals together with repulsive ephrin signals. Our investigations of the mechanism of ephrin-B2 and Netrin-1 integration demonstrate that the Netrin receptor Unc5c and the ephrin receptor EphB2 can form a complex in a ligand-dependent manner and that Netrin–ephrin synergistic growth cones responses involve the potentiation of Src family kinase signaling, a common effector of both pathways. DOI: http://dx.doi.org/10.7554/eLife.10841.001 PMID:26633881

New FDA draft guidance on immunogenicity.

PubMed

Parenky, Ashwin; Myler, Heather; Amaravadi, Lakshmi; Bechtold-Peters, Karoline; Rosenberg, Amy; Kirshner, Susan; Quarmby, Valerie

2014-05-01

A "Late Breaking" session was held on May 20 at the 2013 American Association of Pharmaceutical Scientists-National Biotech Conference (AAPS-NBC) to discuss the US Food and Drug Administration's (FDA) 2013 draft guidance on Immunogenicity Assessment for Therapeutic Protein Products. The session was initiated by a presentation from the FDA which highlighted several key aspects of the 2013 draft guidance pertaining to immunogenicity risk, the potential impact on patient safety and product efficacy, and risk mitigation. This was followed by an open discussion on the draft guidance which enabled delegates from biopharmaceutical companies to engage the FDA on topics that had emerged from their review of the draft guidance. The multidisciplinary audience fostered an environment that was conducive to scientific discussion on a broad range of topics such as clinical impact, immune mitigation strategies, immune prediction and the role of formulation, excipients, aggregates, and degradation products in immunogenicity. This meeting report highlights several key aspects of the 2013 draft guidance together with related dialog from the session.

A neural net approach to space vehicle guidance

NASA Technical Reports Server (NTRS)

Caglayan, Alper K.; Allen, Scott M.

1990-01-01

The space vehicle guidance problem is formulated using a neural network approach, and the appropriate neural net architecture for modeling optimum guidance trajectories is investigated. In particular, an investigation is made of the incorporation of prior knowledge about the characteristics of the optimal guidance solution into the neural network architecture. The online classification performance of the developed network is demonstrated using a synthesized network trained with a database of optimum guidance trajectories. Such a neural-network-based guidance approach can readily adapt to environment uncertainties such as those encountered by an AOTV during atmospheric maneuvers.

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.

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…

Career Guidance in Five English Independent Schools

ERIC Educational Resources Information Center

Hutchinson, Jo

2018-01-01

English independent schools are not required to follow government statutory guidance in a number of aspects including career education and guidance, and yet many are actively engaged in careers work and this has caught the attention of policymakers. State schools are subject to statutory guidance but, according to Ofsted and other authorities, the…

Meet Guidance Needs of Older Adults. Module CG C-16 of Category C--Implementing. Competency-Based Career Guidance Modules.

ERIC Educational Resources Information Center

Cook, Patricia; Stewart, Ellen

This learning module, one in a series of competency-based guidance program training packages focusing upon professional and paraprofessional competencies of guidance personnel, deals with meeting the guidance needs of older adults. Addressed in the module are the following topics: describing a negative and a positive bias, stereotype, or attitude…

Pathway analysis of genome-wide association datasets of personality traits.

PubMed

Kim, H-N; Kim, B-H; Cho, J; Ryu, S; Shin, H; Sung, J; Shin, C; Cho, N H; Sung, Y A; Choi, B-O; Kim, H-L

2015-04-01

Although several genome-wide association (GWA) studies of human personality have been recently published, genetic variants that are highly associated with certain personality traits remain unknown, due to difficulty reproducing results. To further investigate these genetic variants, we assessed biological pathways using GWA datasets. Pathway analysis using GWA data was performed on 1089 Korean women whose personality traits were measured with the Revised NEO Personality Inventory for the 5-factor model of personality. A total of 1042 pathways containing 8297 genes were included in our study. Of these, 14 pathways were highly enriched with association signals that were validated in 1490 independent samples. These pathways include association of: Neuroticism with axon guidance [L1 cell adhesion molecule (L1CAM) interactions]; Extraversion with neuronal system and voltage-gated potassium channels; Agreeableness with L1CAM interaction, neurotransmitter receptor binding and downstream transmission in postsynaptic cells; and Conscientiousness with the interferon-gamma and platelet-derived growth factor receptor beta polypeptide pathways. Several genes that contribute to top-ranked pathways in this study were previously identified in GWA studies or by pathway analysis in schizophrenia or other neuropsychiatric disorders. Here we report the first pathway analysis of all five personality traits. Importantly, our analysis identified novel pathways that contribute to understanding the etiology of personality traits. © 2015 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

PubMed Central

Kang, Tae Wook; Rhim, Hyunchul

2015-01-01

Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

Pathway Tools version 19.0 update: software for pathway/genome informatics and systems biology.

PubMed

Karp, Peter D; Latendresse, Mario; Paley, Suzanne M; Krummenacker, Markus; Ong, Quang D; Billington, Richard; Kothari, Anamika; Weaver, Daniel; Lee, Thomas; Subhraveti, Pallavi; Spaulding, Aaron; Fulcher, Carol; Keseler, Ingrid M; Caspi, Ron

2016-09-01

Pathway Tools is a bioinformatics software environment with a broad set of capabilities. The software provides genome-informatics tools such as a genome browser, sequence alignments, a genome-variant analyzer and comparative-genomics operations. It offers metabolic-informatics tools, such as metabolic reconstruction, quantitative metabolic modeling, prediction of reaction atom mappings and metabolic route search. Pathway Tools also provides regulatory-informatics tools, such as the ability to represent and visualize a wide range of regulatory interactions. This article outlines the advances in Pathway Tools in the past 5 years. Major additions include components for metabolic modeling, metabolic route search, computation of atom mappings and estimation of compound Gibbs free energies of formation; addition of editors for signaling pathways, for genome sequences and for cellular architecture; storage of gene essentiality data and phenotype data; display of multiple alignments, and of signaling and electron-transport pathways; and development of Python and web-services application programming interfaces. Scientists around the world have created more than 9800 Pathway/Genome Databases by using Pathway Tools, many of which are curated databases for important model organisms. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

DOE Waste Treatability Group Guidance

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

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 solemore » 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.« less

The low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer.

PubMed

Bizama, Carolina; Benavente, Felipe; Salvatierra, Edgardo; Gutiérrez-Moraga, Ana; Espinoza, Jaime A; Fernández, Elmer A; Roa, Iván; Mazzolini, Guillermo; Sagredo, Eduardo A; Gidekel, Manuel; Podhajcer, Osvaldo L

2014-02-15

Studies on the low-abundance transcriptome are of paramount importance for identifying the intimate mechanisms of tumor progression that can lead to novel therapies. The aim of the present study was to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analyses of the low-abundance transcriptome. The procedure involved an initial subtractive hybridization step, followed by global gene expression analysis using microarrays. We observed profound differences, both at the single gene and gene ontology levels, between the low-abundance transcriptome and the whole transcriptome. Analysis of the low-abundance transcriptome led to the identification and validation by tissue microarrays of novel biomarkers, such as LAMA3 and TTN; moreover, we identified cancer type-specific intracellular pathways and targetable genes, such as IRS2, IL17, IFNγ, VEGF-C, WISP1, FZD5 and CTBP1 that were not detectable by whole transcriptome analyses. We also demonstrated that knocking down the expression of CTBP1 sensitized gastric cancer cells to mainstay chemotherapeutic drugs. We conclude that the analysis of the low-abundance transcriptome provides useful insights into the molecular basis and treatment of cancer. © 2013 UICC.

Encouraging Evidence on a Sector-Focused Advancement Strategy: Two-Year Impacts from the WorkAdvance Demonstration. Preview Summary

ERIC Educational Resources Information Center

Hendra, Richard; Greenberg, David H.; Hamilton, Gayle; Oppenheim, Ari; Pennington, Alexandra; Schaberg, Kelsey; Tessler, Betsy L.

2016-01-01

This report summarizes the two-year findings of a rigorous random assignment evaluation of the WorkAdvance model, a sectoral training and advancement initiative. Launched in 2011, WorkAdvance goes beyond the previous generation of employment programs by introducing demand-driven skills training and a focus on jobs that have career pathways. The…

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.

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…

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.

Ultrasound Guidance for Botulinum Neurotoxin Chemodenervation Procedures.

PubMed

Alter, Katharine E; Karp, Barbara I

2017-12-28

Injections of botulinum neurotoxins (BoNTs) are prescribed by clinicians for a variety of disorders that cause over-activity of muscles; glands; pain and other structures. Accurately targeting the structure for injection is one of the principle goals when performing BoNTs procedures. Traditionally; injections have been guided by anatomic landmarks; palpation; range of motion; electromyography or electrical stimulation. Ultrasound (US) based imaging based guidance overcomes some of the limitations of traditional techniques. US and/or US combined with traditional guidance techniques is utilized and or recommended by many expert clinicians; authors and in practice guidelines by professional academies. This article reviews the advantages and disadvantages of available guidance techniques including US as well as technical aspects of US guidance and a focused literature review related to US guidance for chemodenervation procedures including BoNTs injection.

Progress on micromechanical inertial guidance system

NASA Astrophysics Data System (ADS)

Poth, Tim; Elwell, John

1992-02-01

The development of a lightweight inertial measurement units (IMUs) is described which uses micromechanical gyroscopes and accelerometers. The IMU concept is described in terms of the silicon components of the instrument and the projected size, cost, and accuracies. The gyroscopes and accelerometers are chemically etched from wafers of single-crystal silicon that can yield up to 4000 single instruments from one 4-inch wafer. Particular emphasis is placed on the control-loop analysis, designing the electronics, and increasing the instrument signal. Attention is given to the development of a buffer amplifier that is fabricated on the same substrate as the instrument to minimize readout noise. These advances are important for improving the signal-to-noise ratio, and 12 hrs of testing data show that the control and readout electronics are responsible for most of the residual walk. The IMUs have potential applications in automobile skid detectors and airbags, GPS navigation systems, and in aerospace guidance systems where weight is a primary concern.

Surface Movement Guidance and Control System

DOT National Transportation Integrated Search

1996-12-12

This Advisory Circular (AC) describes the standards and provides guidance in the : development of a Surface Movement Guidance and Control System (SMGCS) plan for : U.S. airports where scheduled Air Carriers are authorized to conduct operations : when...

National Institutes of Health Pathways to Prevention Workshop: Advancing Research to Prevent Youth Suicide.

PubMed

Little, Todd D; Roche, Kathleen M; Chow, Sy-Miin; Schenck, Anna P; Byam, Leslie-Ann

2016-12-06

The National Institutes of Health (NIH) Pathways to Prevention Workshop "Advancing Research to Prevent Youth Suicide" was cosponsored by the NIH Office of Disease Prevention, National Institute of Mental Health, National Institute on Drug Abuse, and National Center for Complementary and Integrative Health. A multidisciplinary working group developed the agenda, and an evidence-based practice center prepared an evidence report that addressed data systems relevant to suicide prevention efforts through a contract with the Agency for Healthcare Research and Quality. During the workshop, experts discussed the evidence and participants commented during open forums. After considering the data from the evidence report, expert presentations, and public comments, an independent panel prepared a draft report that was posted on the NIH Office of Disease Prevention Web site for 5 weeks for public comment. This abridged version of the final report provides a road map for optimizing youth suicide prevention efforts by highlighting strategies for guiding the next decade of research in this area. These strategies include recommendations for improving data systems, enhancing data collection and analysis methods, and strengthening the research and practice community.

Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment

PubMed Central

2011-01-01

Background Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline. Methods Three independent cohorts of adult (12-13 months) and aged (26-28 months) F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG). Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6) and Iba1. Results We report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors) throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance. Conclusions These data demonstrate a novel, coordinated age

Automated low-thrust guidance for the orbital maneuvering vehicle

NASA Technical Reports Server (NTRS)

Rose, Richard E.; Schmeichel, Harry; Shortwell, Charles P.; Werner, Ronald A.

1988-01-01

This paper describes the highly autonomous OMV Guidance Navigation and Control system. Emphasis is placed on a key feature of the design, the low thrust guidance algorithm. The two guidance modes, orbit change guidance and rendezvous guidance, are discussed in detail. It is shown how OMV will automatically transfer from its initial orbit to an arbitrary target orbit and reach a specified rendezvous position relative to the target vehicle.

European Lifelong Guidance Policy Network Representatives' Conceptions of the Role of Information and Communication Technologies Related to National Guidance Policies

ERIC Educational Resources Information Center

Kettunen, Jaana; Vuorinen, Raimo; Ruusuvirta, Outi

2016-01-01

This article reports findings from a phenomenographic investigation into European Lifelong Guidance Policy Network representatives' conceptions of the role of information and communication technologies (ICT) related to national lifelong guidance policies. The role of ICT in relation to national lifelong guidance policies was conceived as (1)…

Repulsive Guidance Molecule is a structural bridge between Neogenin and Bone Morphogenetic Protein

PubMed Central

Healey, Eleanor G.; Bishop, Benjamin; Elegheert, Jonathan; Bell, Christian H.; Padilla-Parra, Sergi; Siebold, Christian

2015-01-01

Repulsive guidance molecules (RGMs) control crucial processes spanning cell motility, adhesion, immune cell regulation and systemic iron metabolism. RGMs signal via two fundamental signaling cascades: the Neogenin (NEO1) and the Bone Morphogenetic Protein (BMP) pathways. Here, we report crystal structures of the N-terminal domains of all human RGM family members in complex with the BMP ligand BMP2, revealing a novel protein fold and a conserved BMP-binding mode. Our structural and functional data suggest a pH-linked mechanism for RGM-activated BMP signaling and offer a rationale for RGM mutations causing juvenile hemochromatosis. We also determined the ternary BMP2–RGM–NEO1 complex crystal structure, which combined with solution scattering and live-cell super-resolution fluorescence microscopy, indicates BMP-induced clustering of the RGM–NEO1 complex. Our results show how RGM acts as the central hub linking BMP and NEO1 and physically connecting these fundamental signaling pathways. PMID:25938661

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.

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0938] Guidance for Industry; Guidance on Abbreviated New Drug Applications: Stability Testing of Drug Substances....'' Because of increases in the number and complexity of ANDAs and FDA's desire to standardize generic drug...

Advanced oxidation chemistry of paracetamol. UV/H(2)O(2)-induced hydroxylation/degradation pathways and (15)N-aided inventory of nitrogenous breakdown products.

PubMed

Vogna, Davide; Marotta, Raffaele; Napolitano, Alessandra; D'Ischia, Marco

2002-08-23

The advanced oxidation chemistry of the antipyretic drug paracetamol (1) with the UV/H(2)O(2) system was investigated by an integrated methodology based on (15)N-labeling and GC-MS, HPLC, and 2D (1)H, (13)C, and (15)N NMR analysis. Main degradation pathways derived from three hydroxylation steps, leading to 1,4-hydroquinone/1,4-benzoquinone, 4-acetylaminocatechol and, to a much lesser extent, 4-acetylaminoresorcine. Oxidation of the primary aromatic intermediates, viz. 4-acetylaminocatechol, 1,4-hydroquinone, 1,4-benzoquinone, and 1,2,4-benzenetriol, resulted in a series of nitrogenous and non-nitrogenous degradation products. The former included N-acetylglyoxylamide, acetylaminomalonic acid, acetylaminohydroxymalonic acid, acetylaminomaleic acid, diastereoisomeric 2-acetylamino-3-hydroxybutanedioic acids, 2-acetylaminobutenedioic acid, 3-acetylamino-4-hydroxy-2-pentenedioic acid, and 2,4-dihydroxy-3-acetylamino-2-pentenedioic acid, as well as two muconic and hydroxymuconic acid derivatives. (15)N NMR spectra revealed the accumulation since the early stages of substantial amounts of acetamide and oxalic acid monoamide. These results provide the first insight into the advanced oxidation chemistry of a 4-aminophenol derivative by the UV/H(2)O(2) system, and highlight the investigative potential of integrated GC-MS/NMR methodologies based on (15)N-labeling to track degradation pathways of nitrogenous species.

Online thesis guidance management information system

NASA Astrophysics Data System (ADS)

Nasution, T. H.; Pratama, F.; Tanjung, K.; Siregar, I.; Amalia, A.

2018-03-01

The development of internet technology in education is still not maximized, especially in the process of thesis guidance between students and lecturers. Difficulties met the lecturers to help students during thesis guidance is the limited communication time and the compatibility of schedule between students and lecturer. To solve this problem, we designed an online thesis guidance management information system that helps students and lecturers to do thesis tutoring process anytime, anywhere. The system consists of a web-based admin app for usage management and an android-based app for students and lecturers.

Navigating through 'a labyrinth' of guidance.

PubMed

Pearson, Susan

2014-09-01

Devising a strategy to deliver safe water to thousands of outlets spread across numerous buildings is always going to be a challenge, so how do you navigate your way through a bewildering labyrinth of sometimes contradictory guidance documents? Is there, in fact, simply too much guidance? Posing this question at a recent one-day conference on waterborne infections in healthcare facilities, Paul Nolan, authorised water engineer (AE), and operations manager for PFI provider, Lend Lease, took delegates through a review of the latest guidance and regulations, as Susan Pearson reports.

Provide Career Guidance to Girls and Women. Module CG C-13 of Category C--Implementing. Competency-Based Career Guidance Modules.

ERIC Educational Resources Information Center

Birk, Janice M.; Colby, Pamela G.

This learning module, one in a series of competency-based guidance program training packages focusing upon professional and paraprofessional competencies of guidance personnel, deals with providing career guidance to girls and women. Addressed in the module are the following topics: society's influence on shaping differential roles and behaviors…

33 CFR 385.5 - Guidance memoranda.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Water Management District shall, in consultation with the Department of the Interior, the Environmental... DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions § 385.5 Guidance memoranda. (a) General. (1) Technical guidance for internal management of Corps of...

33 CFR 385.5 - Guidance memoranda.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Water Management District shall, in consultation with the Department of the Interior, the Environmental... DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions § 385.5 Guidance memoranda. (a) General. (1) Technical guidance for internal management of Corps of...

33 CFR 385.5 - Guidance memoranda.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Water Management District shall, in consultation with the Department of the Interior, the Environmental... DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions § 385.5 Guidance memoranda. (a) General. (1) Technical guidance for internal management of Corps of...

HANDBOOK: HAZARDOUS WASTE INCINERATION MEASUREMENT GUIDANCE

EPA Science Inventory

This publication, Volume III of the Hazardous Waste Incineration Guidance Series, contains general guidance to permit writers in reviewing hazardous waste incineration permit applications and trial burn plans. he handbook is a how-to document dealing with how incineration measure...

On the design of fuzzified trajectory shaping guidance law.

PubMed

Lin, Chun-Liang; Lin, Yu-Ping; Chen, Kai-Ming

2009-04-01

Midcourse guidance is commonly designed to save as much energy as possible so that the missile's final speed can be maximized while entering the homing stage. For this purpose, a competitive guidance design should be able to generate an admissible flight trajectory as to bring the interceptor to a superior altitude for a favorable target engagement. In this paper, a new adaptive trajectory shaping guidance scheme based on the adaptive fuzzy inference system, which is capable of generating a variety of trajectories for efficient target interception, is presented. The guidance law is developed with the aim of saving the interceptor's energy conservation while improving performance robustness. Applications of the presented approach have included a variety of mission oriented guidance, such as cruise missile guidance, anti-ballistic missile guidance, etc.

Advances in the Immunobiological Therapies for Advanced Melanoma.

PubMed

Pérez Gago, M C; Saavedra Santa Gadea, O; de la Cruz-Merino, L

2017-10-01

Metastatic or locally advanced unresectable melanoma carries a high morbidity and mortality. However, notable advances have been made in recent years in the systemic treatment of this disease, with the appearance of targeted therapy using tyrosine kinase inhibitors that block the mitogen activated protein kinase pathway, and of modern immunotherapy with immune-modulating monoclonal antibodies. In this paper, we provide an update of available data on new immune therapies and we review the clinical development that led to their approval for use in routine clinical practice. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

Organizing a Community Advanced Pharmacy Practice Experience

PubMed Central

Koenigsfeld, Carrie Foust; Tice, Angela L

2006-01-01

Setting up a community advanced pharmacy practice experience can be an overwhelming task for many pharmacy preceptors. This article provides guidance to pharmacist preceptors in developing a complete and effective community advanced pharmacy practice experience (APPE). When preparing for the APPE, initial discussions with the college or school of pharmacy are key. Benefits, training, and requirements should be addressed. Site preparation, including staff education, will assist in the development process. The preceptor should plan orientation day activities and determine appropriate evaluation and feedback methods. With thorough preparation, the APPE will be rewarding for both the student and the pharmacy site. PMID:17136163

Organizing a community advanced pharmacy practice experience.

PubMed

Koenigsfeld, Carrie Foust; Tice, Angela L

2006-02-15

Setting up a community advanced pharmacy practice experience can be an overwhelming task for many pharmacy preceptors. This article provides guidance to pharmacist preceptors in developing a complete and effective community advanced pharmacy practice experience (APPE). When preparing for the APPE, initial discussions with the college or school of pharmacy are key. Benefits, training, and requirements should be addressed. Site preparation, including staff education, will assist in the development process. The preceptor should plan orientation day activities and determine appropriate evaluation and feedback methods. With thorough preparation, the APPE will be rewarding for both the student and the pharmacy site.

Differential Game Theory Application to Intelligent Missile Guidance

DTIC Science & Technology

2013-06-01

guidance (OG) and game theoretic guidance ( GTG ). One reason for this development is the fact that the implementation hardware for the guidance system has...state estimation techniques such as the Kalman Filter and others, it is now feasible to implement the OG, GTG and GTG +AI ‘intelligent’ guidance on...both PN and APN as special cases of OG and GTG ; this connection is further explored in this report. The desire to reduce weapon life-cycle cost

Breathing guidance in radiation oncology and radiology: A systematic review of patient and healthy volunteer studies

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

Pollock, Sean, E-mail: sean.pollock@sydney.edu.au; Keall, Paul; Keall, Robyn

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 withinmore » 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

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.

50% Advanced Energy Design Guides: Preprint

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

Bonnema, E.; Leach, M.; Pless, S.

2012-07-01

This paper presents the process, methodology, and assumptions for the development of the 50% Energy Savings Advanced Energy Design Guides (AEDGs), a design guidance document that provides specific recommendations for achieving 50% energy savings above the requirements of ANSI/ASHRAE/IESNA Standard 90.1-2004 in four building types: (1) Small to medium office buildings, (2) K-12 school buildings, (3) Medium to big box retail buildings, (4) Large hospital buildings.

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. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Advanced Metering Installations – A Perspective from Federal Sites

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

Earni, Shankar

2016-05-02

This report is intended to provide guidance to the United States Department of Energy (DOE) and other federal agencies to highlight some of the existing practices related to advanced building metering systems. This study identified some of the existing actions related to advanced meter data and proposes how advanced metered data can be employed to develop robust cost effective measurement and verification (M&V) strategies. This report proposes an integrated framework on how advanced meter data can be used to identify energy conservation opportunities and to develop proactive M&V strategies to ensure that the savings for energy projects are being realized.more » This information will help improve metering, feedback, and dashboard implementations for reducing energy use at DOE facilities, based on lessons learned from various advanced metering implementations.« less

75 FR 68364 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-05

... European Protocol for the Quality Control of the Physical and Technical Aspects of Mammography Screening... entitled ``Physical Laboratory Testing, Breast Compression System'' to follow the Mammography Quality...] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...

77 FR 14403 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0167] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Norovirus Serological Reagents; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0149] (Formerly 2007D-0309) Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph Electrodes; Availability AGENCY: Food and Drug...

76 FR 22906 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-25

...: Topical Oxygen Chamber for Extremities; Availability AGENCY: Food and Drug Administration, HHS. ACTION... entitled, ``Class II Special Controls Guidance Document: Topical Oxygen Chamber for Extremities.'' This guidance document was developed as a special control to support the reclassification of the topical oxygen...

The Status of Career Guidance in Michigan Schools. An Opinion Research Study of Career Guidance Professionals.

ERIC Educational Resources Information Center

Michigan State Dept. of Education, Lansing.

Project Outreach, the opinion research division of the Michigan State Board of Education, conducted a study on the current status of career guidance in Michigan public schools, using in-depth telephone interviews with career guidance professionals (N=445) in November and December of 1989. The interview questionnaire, developed with the advice of…

Comprehensive Career Guidance. Methods Guide. K-6 Career.

ERIC Educational Resources Information Center

Moore, Earl J.; And Others

This methods guide is intended to assist elementary school guidance workers in implementing a comprehensive career guidance program. Three major areas are considered. First, the life career development perspective is examined as a framework for organizing guidance objectives and practices so that there is a developmental, integrative…

Neurotactin functions in concert with other identified CAMs in growth cone guidance in Drosophila.

PubMed

Speicher, S; García-Alonso, L; Carmena, A; Martín-Bermudo, M D; de la Escalera, S; Jiménez, F

1998-02-01

We have isolated and characterized mutations in Drosophila neurotactin, a gene that encodes a cell adhesion protein widely expressed during neural development. Analysis of both loss and gain of gene function conditions during embryonic and postembryonic development revealed specific requirements for neurotactin during axon outgrowth, fasciculation, and guidance. Furthermore, embryos of some double mutant combinations of neurotactin and other genes encoding adhesion/signaling molecules, including neuroglian, derailed, and kekkon1, displayed phenotypic synergy. This result provides evidence for functional cooperativity in vivo between the adhesion and signaling pathways controlled by neurotactin and the other three genes.

JPL basic research review. [research and advanced development

NASA Technical Reports Server (NTRS)

1977-01-01

Current status, projected goals, and results of 49 research and advanced development programs at the Jet Propulsion Laboratory are reported in abstract form. Areas of investigation include: aerodynamics and fluid mechanics, applied mathematics and computer sciences, environment protection, materials science, propulsion, electric and solar power, guidance and navigation, communication and information sciences, general physics, and chemistry.

76 FR 61098 - Guidance for 1-Hour SO2

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-03

...Notice is hereby given that the EPA has posted its draft non- binding guidance titled, ``Guidance for 1-Hour SO2 NAAQS SIP Submissions'' on its Web site. The EPA invites public comments on this guidance document during the comment period specified below, and plans to issue an updated version of the guidance after reviewing timely submitted comments.

Child Guidance for Child Caregivers: Student Laboratory Manual.

ERIC Educational Resources Information Center

Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

Designed to enhance student knowledge of and skills in child guidance in group care settings, this manual provides 50 laboratory experiences for five units. Units cover foundations and assumptions (2 laboratory experiences), developmental factors (8), indirect guidance (14), direct guidance (14), and strategies (12). Each unit includes performance…

Mapping the Future: Young People and Career Guidance.

ERIC Educational Resources Information Center

St. John-Brooks, Caroline

This report examines the strengths and weaknesses of educational and career guidance in seven Organisation for Economic Development (OECD) countries. Chapter 1 defines educational and career guidance as embracing three key elements: educational, career, and personal/social guidance. Described in chapter 2 is the role of educational and career…

European Universities' Guidance on Research Integrity and Misconduct.

PubMed

Aubert Bonn, Noémie; Godecharle, Simon; Dierickx, Kris

2017-02-01

Research integrity is imperative to good science. Nonetheless, many countries and institutions develop their own integrity guidance, thereby risking incompatibilities with guidance of collaborating institutions. We retrieved guidance for academic integrity and misconduct of 18 universities from 10 European countries and investigated accessibility, general content, principles endorsed, and definitions of misconduct. Accessibility and content differ substantially between institutions. There are general trends of common principles of integrity and definitions of misconduct, yet differences remain. Parallel with previous research, we distinguish different approaches in integrity guidance; one emphasizes broad values of integrity, and the other details negative behaviors of misconduct. We propose that a balance between both approaches is necessary to preserve trust, meaning, and realism of guidance on research integrity.

76 FR 6622 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-07

...: Contact Cooling System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION... entitled ``Class II Special Controls Guidance Document: Contact Cooling System for Aesthetic Use.'' This guidance document describes a means by which contact cooling systems for aesthetic use may comply with the...

76 FR 48870 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-09

... selection inclusion and exclusion criteria section. The revisions define and differentiate the required... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...

Coral Reef Guidance

EPA Pesticide Factsheets

Guidance prepared by EPA and Army Corps of Engineers concerning coral reef protection under the Clean Water Act, Marine Protection, Research, and Sanctuaries Act, Rivers and Harbors Act, and Federal Project Authorities.

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.

28 CFR 36.608 - Guidance concerning model codes.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Guidance concerning model codes. 36.608... Codes § 36.608 Guidance concerning model codes. Upon application by an authorized representative of a... relevant model code and issue guidance concerning whether and in what respects the model code is consistent...

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.

Guidance Counsellor Strategies for Handling Bullying

ERIC Educational Resources Information Center

Power-Elliott, Michleen; Harris, Gregory E.

2012-01-01

The purpose of this exploratory-descriptive study was to examine how guidance counsellors in the province of Newfoundland and Labrador would handle a specific verbal-relational bullying incident. Also of interest was guidance counsellor involvement and training in bullying programmes and Positive Behaviour Supports. Data for this study was…

Career Guidance for Special Needs Learners.

ERIC Educational Resources Information Center

White, Francis A., Jr.

1982-01-01

A career guidance institute for educators working with handicapped and disadvantaged learners included 10 hours of seminar/classroom guidance experiences devoted to theory. Each participant then undertook a 40-hour work internship designed to provide experiences and information about entry-level jobs that special needs learners could perform. (SK)

Educational Guidance for Adults. Identifying Competences.

ERIC Educational Resources Information Center

Oakeshott, Martin

A brief study conducted for the Further Education Unit, Great Britain, defined the competencies associated with educational guidance for adults. The objective was to develop a qualification for educational guidance workers with adults. The project provided an example of applying a competence model to a "higher level" interpersonal field…

Robot-assisted endoscope guidance versus manual endoscope guidance in functional endonasal sinus surgery (FESS).

PubMed

Eichhorn, Klaus Wolfgang; Westphal, Ralf; Rilk, Markus; Last, Carsten; Bootz, Friedrich; Wahl, Friedrich; Jakob, Mark; Send, Thorsten

2017-10-01

Having one hand occupied with the endoscope is the major disadvantage for the surgeon when it comes to functional endoscopic sinus surgery (FESS). Only the other hand is free to use the surgical instruments. Tiredness or frequent instrument changes can thus lead to shaky endoscopic images. We collected the pose data (position and orientation) of the rigid 0° endoscope and all the instruments used in 16 FESS procedures with manual endoscope guidance as well as robot-assisted endoscope guidance. In combination with the DICOM CT data, we tracked the endoscope poses and workspaces using self-developed tracking markers. All surgeries were performed once with the robot and once with the surgeon holding the endoscope. Looking at the durations required, we observed a decrease in the operating time because one surgeon doing all the procedures and so a learning curve occurred what we expected. The visual inspection of the specimens showed no damages to any of the structures outside the paranasal sinuses. Robot-assisted endoscope guidance in sinus surgery is possible. Further CT data, however, are desirable for the surgical analysis of a tracker-based navigation within the anatomic borders. Our marker-based tracking of the endoscope as well as the instruments makes an automated endoscope guidance feasible. On the subjective side, we see that RASS brings a relief for the surgeon.

75 FR 6209 - Guidance for Industry and Food and Drug Administration; Guidance for the Use of Bayesian...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0410] (formerly Docket No. 2006D-0191) Guidance for Industry and Food and Drug Administration; Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials; Availability AGENCY: Food and Drug...

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.

Guidance and Counseling Personnel and Programs in Nevada.

ERIC Educational Resources Information Center

Nevada Univ., Reno. Research and Educational Planning Center.

Data were collected on guidance and counseling programs and guidance personnel in Nevada schools. Questionnaires were mailed to all 309 practicing school counselors in Nevada; the response rate was 72%. Guidance counselors in Nevada were primarily female, Caucasian, and middle-aged. Mean number of years as a counselor was 9 years, and most…

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…

Quality Guidance: A Sectoral Analysis. NICEC Project Report.

ERIC Educational Resources Information Center

Watts, A. G.; Sadler, Jackie

This report reviews the structure of the guidance field and provides a sector-by-sector analysis of current quality assurance arrangements in the United Kingdom. Part 1 presents an outline of the guidance sector, including some key concepts, structures, and roles. It defines guidance and other terms; discusses the three main categories…

VLSI chips for vision-based vehicle guidance

NASA Astrophysics Data System (ADS)

Masaki, Ichiro

1994-02-01

Sensor-based vehicle guidance systems are gathering rapidly increasing interest because of their potential for increasing safety, convenience, environmental friendliness, and traffic efficiency. Examples of applications include intelligent cruise control, lane following, collision warning, and collision avoidance. This paper reviews the research trends in vision-based vehicle guidance with an emphasis on VLSI chip implementations of the vision systems. As an example of VLSI chips for vision-based vehicle guidance, a stereo vision system is described in detail.

PredGuid+A: Orion Entry Guidance Modified for Aerocapture

NASA Technical Reports Server (NTRS)

Lafleur, Jarret

2013-01-01

PredGuid+A software was developed to enable a unique numerical predictor-corrector aerocapture guidance capability that builds on heritage Orion entry guidance algorithms. The software can be used for both planetary entry and aerocapture applications. Furthermore, PredGuid+A implements a new Delta-V minimization guidance option that can take the place of traditional targeting guidance and can result in substantial propellant savings. PredGuid+A allows the user to set a mode flag and input a target orbit's apoapsis and periapsis. Using bank angle control, the guidance will then guide the vehicle to the appropriate post-aerocapture orbit using one of two algorithms: Apoapsis Targeting or Delta-V Minimization (as chosen by the user). Recently, the PredGuid guidance algorithm was adapted for use in skip-entry scenarios for NASA's Orion multi-purpose crew vehicle (MPCV). To leverage flight heritage, most of Orion's entry guidance routines are adapted from the Apollo program.

3-D ultrasound guidance of surgical robotics: a feasibility study.

PubMed

Pua, Eric C; Fronheiser, Matthew P; Noble, Joanna R; Light, Edward D; Wolf, Patrick D; von Allmen, Daniel; Smith, Stephen W

2006-11-01

Laparoscopic ultrasound has seen increased use as a surgical aide in general, gynecological, and urological procedures. The application of real-time, three-dimensional (RT3D) ultrasound to these laparoscopic procedures may increase information available to the surgeon and serve as an additional intraoperative guidance tool. The integration of RT3D with recent advances in robotic surgery also can increase automation and ease of use. In this study, a 1-cm diameter probe for RT3D has been used laparoscopically for in vivo imaging of a canine. The probe, which operates at 5 MHz, was used to image the spleen, liver, and gall bladder as well as to guide surgical instruments. Furthermore, the three-dimensional (3-D) measurement system of the volumetric scanner used with this probe was tested as a guidance mechanism for a robotic linear motion system in order to simulate the feasibility of RT3D/robotic surgery integration. Using images acquired with the 3-D laparoscopic ultrasound device, coordinates were acquired by the scanner and used to direct a robotically controlled needle toward desired in vitro targets as well as targets in a post-mortem canine. The rms error for these measurements was 1.34 mm using optical alignment and 0.76 mm using ultrasound alignment.

Image Guidance in Stem Cell Therapeutics: Unfolding the Blindfold.

PubMed

Bukhari, Amirali B; Dutta, Shruti; De, Abhijit

2015-01-01

Stem cell therapeutics is the future of regenerative medicine in the modern world. Many studies have been instigated with the hope of translating the outcome for the treatment of several disease conditions ranging from heart and neuronal disease to malignancies as grave as cancers. Stem cell therapeutics undoubtedly holds great promise on the front of regenerative medicine, however, the correct distribution and homing of these stem cells to the host site remained blinded until the recent advances in the discipline of molecular imaging. Herein, we discuss the various imaging guidance applied for determination of the proper delivery of various types of stem cell used as therapeutics for various maladies. Additionally, we scrutinize the use of several indirect labeling mechanisms for efficient tagging of the reporter entity for image guidance. Further, the promise of improving patient healthcare has led to the initiation of several clinical trials worldwide. However, in number of the cases, the benefits arrive with a price heavy enough to pose a serious health risk, one such being formation of teratomas. Thus numerous challenges and methodological obstacles must be overcome before their eloquent clinical impact can be realized. Therefore, we also discuss several clinical trials that have taken into consideration the various imaging guided protocols to monitor correct delivery and understand the distribution of therapeutic stem cells in real time.

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

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…

The vision guidance and image processing of AGV

NASA Astrophysics Data System (ADS)

Feng, Tongqing; Jiao, Bin

2017-08-01

Firstly, the principle of AGV vision guidance is introduced and the deviation and deflection angle are measured by image coordinate system. The visual guidance image processing platform is introduced. In view of the fact that the AGV guidance image contains more noise, the image has already been smoothed by a statistical sorting. By using AGV sampling way to obtain image guidance, because the image has the best and different threshold segmentation points. In view of this situation, the method of two-dimensional maximum entropy image segmentation is used to solve the problem. We extract the foreground image in the target band by calculating the contour area method and obtain the centre line with the least square fitting algorithm. With the help of image and physical coordinates, we can obtain the guidance information.

Mobile C-arm cone-beam CT for guidance of spine surgery: Image quality, radiation dose, and integration with interventional guidance

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

Schafer, S.; Nithiananthan, S.; Mirota, D. J.

isocenter, and {approx}3-4 lower at the exit side). The in-room dose (microsievert) per unit scan dose (milligray) ranged from {approx}21 {mu}Sv/mGy on average at tableside to {approx}0.1 {mu}Sv/mGy at 2.0 m distance to isocenter. All protocols involve surgical staff stepping behind a shield wall for each CBCT scan, therefore imparting {approx}zero dose to staff. Protocol implementation in preclinical cadaveric studies demonstrate integration of the C-arm with a navigation system for spine surgery guidance-specifically, minimally invasive vertebroplasty in which the system provided accurate guidance and visualization of needle placement and bone cement distribution. Cumulative dose including multiple intraoperative scans was {approx}11.5 mGy for CBCT-guided thoracic vertebroplasty and {approx}23.2 mGy for lumbar vertebroplasty, with dose to staff at tableside reduced to {approx}1 min of fluoroscopy time ({approx}40-60 {mu}Sv), compared to 5-11 min for the conventional approach. Conclusions: Intraoperative CBCT using a high-performance mobile C-arm prototype demonstrates image quality suitable to guidance of spine surgery, with task-specific protocols providing an important basis for minimizing radiation dose, while maintaining image quality sufficient for surgical guidance. Images demonstrate a significant advance in spatial resolution and soft-tissue visibility, and CBCT guidance offers the potential to reduce fluoroscopy reliance, reducing cumulative dose to patient and staff. Integration with a surgical guidance system demonstrates precise tracking and visualization in up-to-date images (alleviating reliance on preoperative images only), including detection of errors or suboptimal surgical outcomes in the operating room.« less

Integrating mechanisms of visual guidance in naturalistic language production.

PubMed

Coco, Moreno I; Keller, Frank

2015-05-01

Situated language production requires the integration of visual attention and linguistic processing. Previous work has not conclusively disentangled the role of perceptual scene information and structural sentence information in guiding visual attention. In this paper, we present an eye-tracking study that demonstrates that three types of guidance, perceptual, conceptual, and structural, interact to control visual attention. In a cued language production experiment, we manipulate perceptual (scene clutter) and conceptual guidance (cue animacy) and measure structural guidance (syntactic complexity of the utterance). Analysis of the time course of language production, before and during speech, reveals that all three forms of guidance affect the complexity of visual responses, quantified in terms of the entropy of attentional landscapes and the turbulence of scan patterns, especially during speech. We find that perceptual and conceptual guidance mediate the distribution of attention in the scene, whereas structural guidance closely relates to scan pattern complexity. Furthermore, the eye-voice span of the cued object and its perceptual competitor are similar; its latency mediated by both perceptual and structural guidance. These results rule out a strict interpretation of structural guidance as the single dominant form of visual guidance in situated language production. Rather, the phase of the task and the associated demands of cross-modal cognitive processing determine the mechanisms that guide attention.

Application of multislice spiral CT for guidance of insertion of thoracic spine pedicle screws: an in vitro study.

PubMed

Wang, Juan; Zhou, Yicheng; Hu, Ning; Wang, Renfa

2006-01-01

To investigate the value of the guidance of three dimensional (3-D) reconstruction of multi-slice spiral CT (MSCT) for the placement of pedicle screws, the 3-D anatomical data of the thoracic pedicles were measured by MSCT in two embalmed human cadaveric thoracic pedicles spines (T1-T10) to guide the insertion of pedicle screws. After pulling the screws out, the pathways were filled with contrast media. The PW, PH, TSA and SSA of developed pathways were measured on the CT images and they were also measured on the real objects by caliper and goniometer. Analysis of variance demonstrated that the difference between the CT scans and real objects had no statistical significance (P > 0.05). Moreover, the difference between pedicle axis and developed pathway also had no statistical significance (P > 0.05). The data obtained from 3-D reconstruction of MSCT demonstrated that individualized standards, are not only accurate but also helpful for the successful placement of pedicle screws.

75 FR 48973 - Draft Guidance for Industry: Prevention of Salmonella

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-12

...] Draft Guidance for Industry: Prevention of Salmonella Enteritidis in Shell Eggs During Production... entitled ``Prevention of Salmonella Enteritidis in Shell Eggs During Production, Storage, and Transportation'' (the draft guidance). The draft guidance, when finalized, will provide guidance to egg producers...

48 CFR 427.104 - General guidance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false General guidance. 427.104... REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS General 427.104 General guidance. As used in FAR part 27, the agency head or agency head designee is the Senior Procurement Executive, except under FAR 27.306(a) and (b...

33 CFR 385.5 - Guidance memoranda.

Code of Federal Regulations, 2010 CFR

2010-07-01

... sources of water will occur as a result of implementation of the Plan (§ 385.36(b)). (b) Special processes..., implementation, and management of one specific individual feature of the Plan, this section does not require... § 385.5 Guidance memoranda. (a) General. (1) Technical guidance for internal management of Corps of...

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.

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

Enabling technologies for Chinese Mars lander guidance system

NASA Astrophysics Data System (ADS)

Jiang, Xiuqiang; Li, Shuang

2017-04-01

Chinese first Mars exploration activity, orbiting landing and roaming collaborative mission, has been programmed and started. As a key technology, Mars lander guidance system is intended to serve atmospheric entry, descent and landing (EDL) phases. This paper is to report the formation process of enabling technology road map for Chinese Mars lander guidance system. First, two scenarios of the first-stage of the Chinese Mars exploration project are disclosed in detail. Second, mission challenges and engineering needs of EDL guidance, navigation, and control (GNC) are presented systematically for Chinese Mars exploration program. Third, some useful related technologies developed in China's current aerospace projects are pertinently summarized, especially on entry guidance, parachute descent, autonomous hazard avoidance and safe landing. Finally, an enabling technology road map of Chinese Mars lander guidance is given through technological inheriting and improving.

Molecular Pathways: Extracting Medical Knowledge from High Throughput Genomic Data

PubMed Central

Goldstein, Theodore; Paull, Evan O.; Ellis, Matthew J.; Stuart, Joshua M.

2013-01-01

High-throughput genomic data that measures RNA expression, DNA copy number, mutation status and protein levels provide us with insights into the molecular pathway structure of cancer. Genomic lesions (amplifications, deletions, mutations) and epigenetic modifications disrupt biochemical cellular pathways. While the number of possible lesions is vast, different genomic alterations may result in concordant expression and pathway activities, producing common tumor subtypes that share similar phenotypic outcomes. How can these data be translated into medical knowledge that provides prognostic and predictive information? First generation mRNA expression signatures such as Genomic Health's Oncotype DX already provide prognostic information, but do not provide therapeutic guidance beyond the current standard of care – which is often inadequate in high-risk patients. Rather than building molecular signatures based on gene expression levels, evidence is growing that signatures based on higher-level quantities such as from genetic pathways may provide important prognostic and diagnostic cues. We provide examples of how activities for molecular entities can be predicted from pathway analysis and how the composite of all such activities, referred to here as the “activitome,” help connect genomic events to clinical factors in order to predict the drivers of poor outcome. PMID:23430023

Contact guidance is cell cycle-dependent.

PubMed

Pourfarhangi, Kamyar Esmaeili; De La Hoz, Edgar Cardenas; Cohen, Andrew R; Gligorijevic, Bojana

2018-09-01

Cancer cell migration is essential for metastasis, during which cancer cells move through the tumor and reach the blood vessels. In vivo , cancer cells are exposed to contact guidance and chemotactic cues. Depending on the strength of such cues, cells will migrate in a random or directed manner. While similar cues may also stimulate cell proliferation, it is not clear whether cell cycle progression affects migration of cancer cells and whether this effect is different in random versus directed migration. In this study, we tested the effect of cell cycle progression on contact guided migration in 2D and 3D environments, in the breast carcinoma cell line, FUCCI-MDA-MB-231. The results were quantified from live cell microscopy images using the open source lineage editing and validation image analysis tools (LEVER). In 2D, cells were placed inside 10 μ m-wide microchannels to stimulate contact guidance, with or without an additional chemotactic gradient of the soluble epidermal growth factor. In 3D, contact guidance was modeled by aligned collagen fibers. In both 2D and 3D, contact guidance was cell cycle-dependent, while the addition of the chemo-attractant gradient in 2D increased cell velocity and persistence in directionally migrating cells, regardless of their cell cycle phases. In both 2D and 3D contact guidance, cells in the G1 phase of the cell cycle outperformed cells in the S/G2 phase in terms of migration persistence and instantaneous velocity. These data suggest that in the presence of contact guidance cues in vivo , breast carcinoma cells in the G1 phase of the cell cycle may be more efficient in reaching the neighboring vasculature.

Guidance, Gender Equity and Technology Education.

ERIC Educational Resources Information Center

Silverman, Suzanne; Pritchard, Alice M.

A study examined the role of guidance in girls' decisions about whether or not to take technology education as an elective in high school and to consider future careers in technological fields. The researchers reviewed the literature on guidance and looked at the results of interventions designed to attract girls to nontraditional fields. Eighteen…

Autonomous Guidance Strategy for Spacecraft Formations and Reconfiguration Maneuvers

NASA Astrophysics Data System (ADS)

Wahl, Theodore P.

A guidance strategy for autonomous spacecraft formation reconfiguration maneuvers is presented. The guidance strategy is presented as an algorithm that solves the linked assignment and delivery problems. The assignment problem is the task of assigning the member spacecraft of the formation to their new positions in the desired formation geometry. The guidance algorithm uses an auction process (also called an "auction algorithm''), presented in the dissertation, to solve the assignment problem. The auction uses the estimated maneuver and time of flight costs between the spacecraft and targets to create assignments which minimize a specific "expense'' function for the formation. The delivery problem is the task of delivering the spacecraft to their assigned positions, and it is addressed through one of two guidance schemes described in this work. The first is a delivery scheme based on artificial potential function (APF) guidance. APF guidance uses the relative distances between the spacecraft, targets, and any obstacles to design maneuvers based on gradients of potential fields. The second delivery scheme is based on model predictive control (MPC); this method uses a model of the system dynamics to plan a series of maneuvers designed to minimize a unique cost function. The guidance algorithm uses an analytic linearized approximation of the relative orbital dynamics, the Yamanaka-Ankersen state transition matrix, in the auction process and in both delivery methods. The proposed guidance strategy is successful, in simulations, in autonomously assigning the members of the formation to new positions and in delivering the spacecraft to these new positions safely using both delivery methods. This guidance algorithm can serve as the basis for future autonomous guidance strategies for spacecraft formation missions.

What We Know about Guided Pathways: Helping Students to Complete Programs Faster. Research Overview

ERIC Educational Resources Information Center

Bailey, Thomas; Jaggars, Shanna Smith; Jenkins, Davis

2015-01-01

The idea behind guided pathways is straightforward. College students are more likely to complete a degree in a timely fashion if they choose a program and develop an academic plan early on, have a clear road map of the courses they need to take to complete a credential, and receive guidance and support to help them stay on plan. However, most…

MEK inhibition in the treatment of advanced melanoma.

PubMed

Salama, April K S; Kim, Kevin B

2013-10-01

The RAS-RAF-MEK-ERK pathway is considered to be the most important signal transduction pathway in melanoma, and alterations in this pathway via various genetic mutations, such as BRAF and NRAS mutations, are known to be important drivers of melanomagenesis. As MEK is an essential intermediary kinase protein within this pathway, inhibition of MEK has been of a great interest as a molecular target therapy in melanoma. In fact, trametinib, a selective MEK inhibitor, has been shown to have a survival benefit over cytotoxic chemotherapy in patients with V600 BRAF-mutant metastatic melanoma, leading to the FDA approval for this patient population. MEK inhibitors may also be useful in treatment of advanced melanoma harboring other genetic mutations, such as NRAS and GNAQ/GNA11 mutations. Here, we review and discuss the preclinical and clinical data regarding MEK inhibitors and their role in the treatment of advanced melanoma.

State Indoor Radon Grants Guidance and Tools

EPA Pesticide Factsheets

This guidance explains the standardized state template for SIRG measures,as required by the OMB and answers questions about the template. The Program guidance is intended to reconcile all legal, policy and programmatic changes that affected SIRG.

The revised HSE fatigue guidance

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

Stacey, A.; Sharp, J.V.

1995-12-31

Fatigue cracking has been a principal cause of damage to North Sea structures and consequently considerable attention has been given to the development of guidance for the prediction of fatigue performance. The fatigue guidance of the Offshore Safety Division of the Health and Safety Executive (HSE) was recently revised and published, following a significant offshore industry review in the period 1987 to 1990, and is based on the results of a considerable amount of research and development work on the fatigue behavior of welded tubular and plated joints. As a result of this review, the revised fatigue guidance incorporates severalmore » new clauses and recommendations. The revised recommendations apply to joint classification, basic design S-N curves for welded joints and cast or forged steel components, the thickness effect, the effects of environment and the treatment of low and high stress ranges. Additionally, a new appendix on the derivation of stress concentration factors is included. The new clauses cover high strength steels, bolts and threaded connectors, moorings, repaired joints and the use of fracture mechanics analysis. This paper presents an overview of the revisions to the fatigue guidance, the associated background technical information and aspects of the fatigue behavior of offshore structures which are considered to require further investigation. 67 refs., 7 figs., 8 tabs.« less

Case Studies in Practical Career Guidance, Number 7: Developmental Career Guidance Project Detroit Public Schools, Detroit, Michigan.

ERIC Educational Resources Information Center

Scott, Thelma J.

The Developmental Career Guidance (DCG) project is a K-12 career guidance demonstration project operating at three high schools and 18 feeder schools in the Detroit Public School District. Directed from Wayne State University, DCG has centers at the high schools and each of the feeder schools. From the centers, students voluntarily can draw…

The adverse outcome pathway knowledge base

EPA Science Inventory

The rapid advancement of the Adverse Outcome Pathway (AOP) framework has been paralleled by the development of tools to store, analyse, and explore AOPs. The AOP Knowledge Base (AOP-KB) project has brought three independently developed platforms (Effectopedia, AOP-Wiki, and AOP-X...

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.

National ethics guidance in Sub-Saharan Africa on the collection and use of human biological specimens: a systematic review.

PubMed

Barchi, Francis; Little, Madison T

2016-10-22

Ethical and regulatory guidance on the collection and use of human biospecimens (HBS) for research forms an essential component of national health systems in Sub-Saharan Africa (SSA), where rapid advances in genetic- and genomic-based technologies are fueling clinical trials involving HBS and the establishment of large-scale biobanks. An extensive multi-level search for publicly available ethics regulatory guidance was conducted for each SSA country. A second review documented active trials listed in the WHO International Clinical Trials Registry Platform as of January 2015 in which HBS collection was specified in the protocol. Findings were combined to determine the extent to which countries that are study sites for HBS-related research are supported by regulatory guidance language on the collection, use, ownership and storage of biospecimens. Of the 49 SSA countries, 29 had some form of national ethics guidance, yet only 17 provided language relating to HBS-related research, with specific guidance on consent (14), ownership (6), reuse (10), storage (9), and export/import/transfer (13). Ten countries accounted for 84 % of the active clinical trials involving the collection of HBS in SSA. All except one of these countries were found to have some national guidance in the form of regulations, codes of ethics, and/or standard operating procedures; however, only seven of the ten offered any language specific to HBS. Despite the fact that the bulk of registered clinical trials in SSA involving HBS, as well as existing and proposed sites for biorepositories under the H3Africa Initiative, are currently situated in countries with the most complete ethics and regulatory guidance, variability in the regulations themselves may create challenges for planned and future pan-African collaborations and may require legislative action at the national level to revise. Countries in SSA that still lack regulatory guidance on HBS will require extensive health system strengthening in

Regulation of Ubiquitin Enzymes in the TGF-β Pathway.

PubMed

Iyengar, Prasanna Vasudevan

2017-04-20

The transforming growth factor-β (TGF-β) pathway has a tumor suppressor role in normal and premalignant cells but promotes oncogenesis in advanced cancer cells. Components of the pathway are tightly controlled by ubiquitin modifying enzymes and aberrations in these enzymes are frequently observed to dysregulate the pathway causing diseases such as bone disorders, cancer and metastasis. These enzymes and their counterparts are increasingly being tested as druggable targets, and thus a deeper understanding of the enzymes is required. This review summarizes the roles of specific ubiquitin modifying enzymes in the TGF-β pathway and how they are regulated.

75 FR 76079 - Sound Incentive Compensation Guidance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... DEPARTMENT OF THE TREASURY Office of Thrift Supervision Sound Incentive Compensation Guidance... on the following information collection. Title of Proposal: Sound Incentive Compensation Guidance... Sound Compensation Practices adopted by the Financial Stability Board (FSB) in April 2009, as well as...

Neuronal clues to vascular guidance.

PubMed

Suchting, Steven; Bicknell, Roy; Eichmann, Anne

2006-03-10

The development of the vertebrate vascular system into a highly ordered and stereotyped network requires precise control over the branching and growth of new vessels. Recent research has highlighted the important role of genetic programs in regulating vascular patterning and in particular has established a crucial role for families of molecules previously described in controlling neuronal guidance. Like neurons, new vessels are guided along the correct path by integrating attractive and repulsive cues from the external environment. This is achieved by specialised endothelial cells at the leading tip of vessel sprouts which express receptor proteins that couple extracellular guidance signals with the cytoskeletal changes necessary to alter cell direction. Here, we review the genetic and in vitro evidence implicating four families of ligand-receptor signalling systems common to both neuronal and vessel guidance: the Ephrins and Eph receptors; Semaphorins, Neuropilins and Plexin receptors; Netrin and Unc5 receptors; and Slits and Robo receptors.

Recent advances in radiation cancer therapy

NASA Astrophysics Data System (ADS)

Ma, C.-M. Charlie

2007-03-01

This paper presents the recent advances in radiation therapy techniques for the treatment of cancer. Significant improvement has been made in imaging techniques such as CT, MRI, MRS, PET, ultrasound, etc. that have brought marked advances in tumor target and critical structure delineation for treatment planning and patient setup and target localization for accurate dose delivery in radiation therapy of cancer. Recent developments of novel treatment modalities including intensity-modulated x-ray therapy (IMXT), energy- and intensity modulated electron therapy (MERT) and intensity modulated proton therapy (IMPT) together with the use of advanced image guidance have enabled precise dose delivery for dose escalation and hypofractionation studies that may result in better local control and quality of life. Particle acceleration using laser-induced plasmas has great potential for new cost-effective radiation sources that may have a great impact on the management of cancer using radiation therapy.

Structure of the Repulsive Guidance Molecule (RGM)—Neogenin Signaling Hub

PubMed Central

Bell, Christian H.; Bishop, Benjamin; Tang, Chenxiang; Gilbert, Robert J.C.; Aricescu, A. Radu; Pasterkamp, R. Jeroen; Siebold, Christian

2016-01-01

Repulsive guidance molecule family members (RGMs) control fundamental and diverse cellular processes, including motility and adhesion, immune cell regulation, and systemic iron metabolism. However, it is not known how RGMs initiate signaling through their common cell-surface receptor, neogenin (NEO1). Here, we present crystal structures of the NEO1 RGM-binding region and its complex with human RGMB (also called dragon). The RGMB structure reveals a previously unknown protein fold and a functionally important autocatalytic cleavage mechanism and provides a framework to explain numerous disease-linked mutations in RGMs. In the complex, two RGMB ectodomains conformationally stabilize the juxtamembrane regions of two NEO1 receptors in a pH-dependent manner. We demonstrate that all RGM-NEO1 complexes share this architecture, which therefore represents the core of multiple signaling pathways. PMID:23744777

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.

Visual search guidance is best after a short delay

PubMed Central

Schmidt, Joseph; Zelinsky, Gregory J.

2011-01-01

Search displays are typically presented immediately after a target cue, but in the real-world, delays often exist between target designation and search. Experiments 1 and 2 asked how search guidance changes with delay. Targets were cued using a picture or text label, each for 3000ms, followed by a delay up to 9000ms before the search display. Search stimuli were realistic objects, and guidance was quantified using multiple eye movement measures. Text-based cues showed a non-significant trend towards greater guidance following any delay relative to a no-delay condition. However, guidance from a pictorial cue increased sharply 300–600 msec after preview offset. Experiment 3 replicated this guidance enhancement using shorter preview durations while equating the time from cue onset to search onset, demonstrating that the guidance benefit is linked to preview offset rather than a more complete encoding of the target. Experiment 4 showed that enhanced guidance persists even with a mask flashed at preview offset, suggesting an explanation other than visual priming. We interpret our findings as evidence for the rapid consolidation of target information into a guiding representation, which attains its maximum effectiveness shortly after preview offset. PMID:21295053

78 FR 53792 - Draft Guidance for Reciprocity

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-30

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0186] Draft Guidance for Reciprocity AGENCY: Nuclear... Commission (NRC) is revising its licensing guidance for reciprocity. The NRC is requesting public comment on... Work in Agreement State Jurisdiction (Reciprocity).'' The document has been updated from the previous...

40 CFR 56.6 - Dissemination of policy and guidance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) REGIONAL CONSISTENCY § 56.6 Dissemination of policy and guidance. The Assistant Administrators of... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Dissemination of policy and guidance... to disseminate policy and guidance. They shall distribute material under foregoing systems to the...

40 CFR 56.6 - Dissemination of policy and guidance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) REGIONAL CONSISTENCY § 56.6 Dissemination of policy and guidance. The Assistant Administrators of... 40 Protection of Environment 5 2011-07-01 2011-07-01 false Dissemination of policy and guidance... to disseminate policy and guidance. They shall distribute material under foregoing systems to the...

OECD Review of Career Guidance Policies. Norway: Country Note.

ERIC Educational Resources Information Center

Organisation for Economic Cooperation and Development, Paris (France).

Norway's career guidance system and policies were evaluated. The review team met with policymakers and guidance practitioners in the public and private sectors, analyzed data from a national questionnaire, and reviewed pertinent documentation. The evaluation focused on the following areas: splitting educational/vocational guidance from personal…

Guidance strategies and analysis for low thrust navigation

NASA Technical Reports Server (NTRS)

Jacobson, R. A.

1973-01-01

A low-thrust guidance algorithm suitable for operational use was formulated. A constrained linear feedback control law was obtained using a minimum terminal miss criterion and restricting control corrections to constant changes for specified time periods. Both fixed- and variable-time-of-arrival guidance were considered. The performance of the guidance law was evaluated by applying it to the approach phase of the 1980 rendezvous mission with the comet Encke.

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.

Pathway Profiling and Rational Trial Design for Studies in Advanced Stage Cervical Carcinoma: A Review and a Perspective

PubMed Central

Scholl, Susy M. E.; Kenter, Gemma; Kurzeder, Christian; Beuzeboc, Philippe

2011-01-01

Multiple genetic abnormalities will have occurred in advanced cervical cancer and multiple targeting is likely to be needed to control tumor growth. To date, dominant therapeutic targets under scrutiny for cervical cancer treatment have been EGFR pathway and angiogenesis inhibition as well as anti-HPV vaccines. The potentially most effective targets to be blocked may be downstream from the membrane receptor or at the level of the nucleus. Alterations of the pathways involved in DNA repair and in checkpoint activations, as well as the specific site of HPV genome integration, appear worth assessing. For genetic mutational analysis, complete exon sequencing may become the norm in the future but at this stage frequent mutations (that matter) can be verified by PCR analysis. A precise documentation of relevant alterations of a large spectrum of protein biomarkers can be carried out by reverse phase protein array (RPPA) or by multiplex analysis. Clinical decision-making on the drug(s) of choice as a function of the biological alteration will need input from bio-informatics platforms as well as novel statistical designs. Endpoints are yet to be defined such as the loss (or reappearance) of a predictive biomarker. Single or dual targeting needs to be explored first in relevant preclinical animal and in xenograft models prior to clinical deployment. PMID:22091418

Dragon (repulsive guidance molecule b, RGMb) is a novel gene that promotes colorectal cancer growth.

PubMed

Shi, Ying; Chen, Guo-Bin; Huang, Xiao-Xiao; Xiao, Chuan-Xing; Wang, Huan-Huan; Li, Ye-Sen; Zhang, Jin-Fang; Li, Shao; Xia, Yin; Ren, Jian-Lin; Guleng, Bayasi

2015-08-21

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer death. However, the molecular mechanisms underlying CRC initiation, growth and metastasis are poorly understood. Dragon (RGMb), a member of the repulsive guidance molecule (RGM) family, has been recently identified as a co-receptor for bone morphogenetic protein (BMP) signaling, but the role of Dragon in CRC development is undefined. Here, we show that Dragon expression was increased in colon cancer tissues compared to control tissues in CAC mouse model and in human patients. Dragon promoted proliferation of CT26.WT and CMT93 colon cancer cells and accelerated tumor growth in the xenograft mouse model. Dragon's action on colon cancer development was mediated via the BMP4-Smad1/5/8 and Erk1/2 pathways. Therefore, our results have revealed that Dragon is a novel gene that promotes CRC growth through the BMP pathway. Dragon may be exploited as a potential therapeutic target for CRC treatment.

Dragon (repulsive guidance molecule b, RGMb) is a novel gene that promotes colorectal cancer growth

PubMed Central

Shi, Ying; Chen, Guo-Bin; Huang, Xiao-Xiao; Xiao, Chuan-Xing; Wang, Huan-Huan; Li, Ye-Sen; Zhang, Jin-Fang; Li, Shao; Xia, Yin; Ren, Jian-Lin; Guleng, Bayasi

2015-01-01

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer death. However, the molecular mechanisms underlying CRC initiation, growth and metastasis are poorly understood. Dragon (RGMb), a member of the repulsive guidance molecule (RGM) family, has been recently identified as a co-receptor for bone morphogenetic protein (BMP) signaling, but the role of Dragon in CRC development is undefined. Here, we show that Dragon expression was increased in colon cancer tissues compared to control tissues in CAC mouse model and in human patients. Dragon promoted proliferation of CT26.WT and CMT93 colon cancer cells and accelerated tumor growth in the xenograft mouse model. Dragon's action on colon cancer development was mediated via the BMP4-Smad1/5/8 and Erk1/2 pathways. Therefore, our results have revealed that Dragon is a novel gene that promotes CRC growth through the BMP pathway. Dragon may be exploited as a potential therapeutic target for CRC treatment. PMID:26029998

NICE-Accredited Commissioning Guidance for Weight Assessment and Management Clinics: a Model for a Specialist Multidisciplinary Team Approach for People with Severe Obesity.

PubMed

Welbourn, Richard; Dixon, John; Barth, Julian H; Finer, Nicholas; Hughes, Carly A; le Roux, Carel W; Wass, John

2016-03-01

Despite increasing prevalence of obesity, no country has successfully implemented comprehensive pathways to provide advice to all the severely obese patients that seek treatment. We aimed to formulate pathways for referral into and out of weight assessment and management clinics (WAMCs) that include internal medicine/primary care physicians as part of a multidisciplinary team that could provide specialist advice and interventions, including referral for bariatric surgery. Using a National Institute of Health and Care Excellence (NICE)-accredited process, a Guidance Development Group conducted a literature search identifying existing WAMCs. As very few examples of effective structures and clinical pathways existed, the current evidence base for optimal assessment and management of bariatric surgery patients was used to reach a consensus. The model we describe could be adopted internationally by health services to manage severely obese patients.

[Process of institutional child guidance counseling reflected by the Central Continuing Education of the Federal Conference for Child Guidance Counseling].

PubMed

Pfeifer, W K

2000-12-01

The Bundeskonferenz für Erziehungsberatung (bke) is the federation for child guidance and family-counseling in Germany. Members are the working groups for child guidance and family-counseling of the Länder, where the employees of the child guidance are organized. The federation was founded in 1962. It is sponsored by the Federal Ministry for Family, Seniors, Women and Youth. Further education for professional youth workers is central mission of bke. The constitution of the federation lais down these contents. Every autumn the bke publishes the program for further education for the following year in a brochure called Zentrale Weiterbildung--the program for child guidance, family counseling and youth counseling. A special Kommission Zentrale Weiterbildung acquires the contents of the program for further education und selects the referents. Since 1968 the Zentrale Weiterbildung of Bundeskonferenz für Erziehungsberatung offers events for professional youth workers in child guidance, family counseling. The program for further education contributes the quality of the institution of child guidance. After a time with above average use of the program for further education with therapeutical focal point, the orientation of the program changes to child and youth services. A constant number of counselors use the program. Beside the change of contents there was a change to effectiveness of contents and a reduction of participants.

Concept development of automatic guidance for rotorcraft obstacle avoidance

NASA Technical Reports Server (NTRS)

Cheng, Victor H. L.

1990-01-01

The automatic guidance of rotorcraft for obstacle avoidance in nap-of-the-earth flight is studied. A hierarchical breakdown of the guidance components is used to identify the functional requirements. These requirements and anticipated sensor capabilities lead to a preliminary guidance concept, which has been evaluated via computer simulations.

10 CFR 420.32 - Program guidance/solicitation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 3 2012-01-01 2012-01-01 false Program guidance/solicitation. 420.32 Section 420.32 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION STATE ENERGY PROGRAM Implementation of Special Projects... more project(s) under the special projects financial assistance with a detailed program guidance...

10 CFR 420.32 - Program guidance/solicitation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Program guidance/solicitation. 420.32 Section 420.32 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION STATE ENERGY PROGRAM Implementation of Special Projects... more project(s) under the special projects financial assistance with a detailed program guidance...

10 CFR 420.32 - Program guidance/solicitation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 3 2014-01-01 2014-01-01 false Program guidance/solicitation. 420.32 Section 420.32 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION STATE ENERGY PROGRAM Implementation of Special Projects... more project(s) under the special projects financial assistance with a detailed program guidance...

10 CFR 420.32 - Program guidance/solicitation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 3 2011-01-01 2011-01-01 false Program guidance/solicitation. 420.32 Section 420.32 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION STATE ENERGY PROGRAM Implementation of Special Projects... more project(s) under the special projects financial assistance with a detailed program guidance...

10 CFR 420.32 - Program guidance/solicitation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 3 2013-01-01 2013-01-01 false Program guidance/solicitation. 420.32 Section 420.32 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION STATE ENERGY PROGRAM Implementation of Special Projects... more project(s) under the special projects financial assistance with a detailed program guidance...

77 FR 48591 - State Rail Plan Guidance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... Plan Guidance AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Request for Public Comment on Proposed State Rail Plan Guidance. SUMMARY: FRA is publishing this notice to... plans. State rail plans are documents that are required under Section 303 of the Passenger Rail...

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

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. Copyright © 2011 Elsevier Ltd. All rights reserved.

Guidance of visual attention by semantic information in real-world scenes

PubMed Central

Wu, Chia-Chien; Wick, Farahnaz Ahmed; Pomplun, Marc

2014-01-01

Recent research on attentional guidance in real-world scenes has focused on object recognition within the context of a scene. This approach has been valuable for determining some factors that drive the allocation of visual attention and determine visual selection. This article provides a review of experimental work on how different components of context, especially semantic information, affect attentional deployment. We review work from the areas of object recognition, scene perception, and visual search, highlighting recent studies examining semantic structure in real-world scenes. A better understanding on how humans parse scene representations will not only improve current models of visual attention but also advance next-generation computer vision systems and human-computer interfaces. PMID:24567724

UV DISINFECTION GUIDANCE MANUAL FOR THE ...

EPA Pesticide Factsheets

Provides technical information on selection, design and operation of UV systems; provides regulatory agencies with guidance and the necessary tools to assess UV systems at the design, start-up, and routine operation phase; provides manufacturers with the testing and performance standards for UV components and systems for treating drinking water. Provide guidance to water systems, regulators and manufacturers on UV disinfection of drinking water.

Genetic and Environmental Pathways in Type 1 Diabetes Complications

DTIC Science & Technology

2009-09-01

increased risk of T1D-Nephropathy (T1DN) and is usually accompanied by other diabetic -related complications such as retinopathy , neuropathy, blood...Genetic and Environmental Pathways in Type 1 Diabetes Complications PRINCIPAL INVESTIGATOR: Massimo Trucco, M.D...To) 27 August 2008 – 26 August 2009 4. TITLE AND SUBTITLE Genetic and Environmental Pathways in Type 1 Diabetes Complications New Advanced

An Investigation of the Guidance Counselling Needs of Adults with Dyslexia in the Adult Educational Guidance Initiative (AEGI)

ERIC Educational Resources Information Center

Elftorp, Petra; Hearne, Lucy

2014-01-01

The experiences of adult learners with dyslexia is an under-researched area in Ireland at present. This article will discuss the findings from phase one of a mixed methods research study, which is investigating the guidance counselling needs of clients with dyslexia within the Adult Education Guidance Initiative (AEGI). The research is underpinned…

River City High School Guidance Services: A Conceptual Model.

ERIC Educational Resources Information Center

American Coll. Testing Program, Iowa City, IA.

This model describes how the guidance staff at a hypothetical high school communicated the effectiveness of the guidance program to students, parents, teachers, and administrators. A description of the high school is presented, and guidance services and personnel are described. A conceptual model responding to student needs is outlined along with…

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.

SIAH and EGFR, Two RAS Pathway Biomarkers, are Highly Prognostic in Locally Advanced and Metastatic Breast Cancer.

PubMed

van Reesema, Lauren L Siewertsz; Zheleva, Vasilena; Winston, Janet S; Jansen, Rick J; O'Connor, Carolyn F; Isbell, Andrew J; Bian, Minglei; Qin, Rui; Bassett, Patricia T; Hinson, Virginia J; Dorsch, Kimberly A; Kirby, Brad W; Van Sciver, Robert E; Tang-Tan, Angela M; Harden, Elizabeth A; Chang, David Z; Allen, Cynthia A; Perry, Roger R; Hoefer, Richard A; Tang, Amy H

2016-09-01

Metastatic breast cancer exhibits diverse and rapidly evolving intra- and inter-tumor heterogeneity. Patients with similar clinical presentations often display distinct tumor responses to standard of care (SOC) therapies. Genome landscape studies indicate that EGFR/HER2/RAS "pathway" activation is highly prevalent in malignant breast cancers. The identification of therapy-responsive and prognostic biomarkers is paramount important to stratify patients and guide therapies in clinical oncology and personalized medicine. In this study, we analyzed matched pairs of tumor specimens collected from 182 patients who received neoadjuvant systemic therapies (NST). Statistical analyses were conducted to determine whether EGFR/HER2/RAS pathway biomarkers and clinicopathological predictors, alone and in combination, are prognostic in breast cancer. SIAH and EGFR outperform ER, PR, HER2 and Ki67 as two logical, sensitive and prognostic biomarkers in metastatic breast cancer. We found that increased SIAH and EGFR expression correlated with advanced pathological stage and aggressive molecular subtypes. Both SIAH expression post-NST and NST-induced changes in EGFR expression in invasive mammary tumors are associated with tumor regression and increased survival, whereas ER, PR, and HER2 were not. These results suggest that SIAH and EGFR are two prognostic biomarkers in breast cancer with lymph node metastases. The discovery of incorporating tumor heterogeneity-independent and growth-sensitive RAS pathway biomarkers, SIAH and EGFR, whose altered expression can be used to estimate therapeutic efficacy, detect emergence of resistant clones, forecast tumor regression, differentiate among partial responders, and predict patient survival in the neoadjuvant setting, has a clear clinical implication in personalizing breast cancer therapy. This work was supported by the Dorothy G. Hoefer Foundation for Breast Cancer Research (A.H. Tang); Center for Innovative Technology (CIT

Guidance on Annual Compliance Certifications

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.

Halon 1301 management planning guidance

NASA Astrophysics Data System (ADS)

1995-05-01

This ETL provides guidance to help the Base Civil Engineer (BCE) and other users manage inventories of Halon 1301, an ozone depleting substance used in many facility fire protection systems. This guidance will allow Halon 1301 users to develop the transition plans necessary to implement the DOD and Air Force policies on ozone depleting substances. Attachment 3 to this ETL contains detailed instructions on how to develop a Base Halon 1 301 Management Plan and comply with Air Force policies and regulations designed to minimize dependency on Halon 1301.

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

21 CFR 7.59 - General industry guidance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false General industry guidance. 7.59 Section 7.59 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENFORCEMENT POLICY Recalls (Including Product Corrections)-Guidance on Policy, Procedures, and Industry...

Visual search guidance is best after a short delay.

PubMed

Schmidt, Joseph; Zelinsky, Gregory J

2011-03-25

Search displays are typically presented immediately after a target cue, but in the real-world, delays often exist between target designation and search. Experiments 1 and 2 asked how search guidance changes with delay. Targets were cued using a picture or text label, each for 3000ms, followed by a delay up to 9000ms before the search display. Search stimuli were realistic objects, and guidance was quantified using multiple eye movement measures. Text-based cues showed a non-significant trend towards greater guidance following any delay relative to a no-delay condition. However, guidance from a pictorial cue increased sharply 300-600ms after preview offset. Experiment 3 replicated this guidance enhancement using shorter preview durations while equating the time from cue onset to search onset, demonstrating that the guidance benefit is linked to preview offset rather than a more complete encoding of the target. Experiment 4 showed that enhanced guidance persists even with a mask flashed at preview offset, suggesting an explanation other than visual priming. We interpret our findings as evidence for the rapid consolidation of target information into a guiding representation, which attains its maximum effectiveness shortly after preview offset. Copyright © 2011 Elsevier Ltd. All rights reserved.

Key Performance Indicators for the Assessment of Pediatric Pharmacotherapeutic Guidance

PubMed Central

Barrett, Jeffrey S.; Patel, Dimple; Jayaraman, Bhuvana; Narayan, Mahesh; Zuppa, Athena

2008-01-01

Given the paucity of actual guidance provided for managing pediatric drug therapy, prescribing caregivers must be able to draw on the limited published information in pediatrics and/or guidance provided in adults with some account for expected pediatric response. Guidance for managing drug therapy in children is clearly desirable. Our objectives were to construct key performance indicators (KPIs) for pediatric pharmacotherapy guidance to identify drugs where pharmacotherapy guidance would be most beneficial. A pilot survey to assess variation in caregiver appreciation for pediatric dosing guidance has also been constructed to provide a complementary subjective assessment. Three KPI categories, drug utilization (based on hospital admission and billing data collected from 2001 through 2006), medical need, and guidance outcome value along with a KPI composite score have been proposed. Low scores are favored with respect to prioritization for pharmacotherapy guidance. The pilot survey consisted of 15 questions to assess 1) physician knowledge regarding dosing guidance, 2) attitudes toward dose modification and patient individualization, 3) the accessibility, ease of use and appropriateness of existing data stores, and 4) frequency of dosing modification, consultation of dosing compendiums and estimate of success rate in dosing guidance. Pilot results suggest that dosing guidance is generally viewed as important and that the existing resources are insufficient to guide recommendations for all drugs. While the majority of respondents check more than one resource less than 25% of the time, at least 25% of the respondents check more than one resource 25–50% of the time. The majority viewed the relevance of dosing guidance very important to the management of drug therapy. The questionnaire is being extended to the primary care centers, the Kids First Network and specialty care centers. Results will guide the development of decision support systems (DSS) that provide

Key performance indicators for the assessment of pediatric pharmacotherapeutic guidance.

PubMed

Barrett, Jeffrey S; Patel, Dimple; Jayaraman, Bhuvana; Narayan, Mahesh; Zuppa, Athena

2008-07-01

Given the paucity of actual guidance provided for managing pediatric drug therapy, prescribing caregivers must be able to draw on the limited published information in pediatrics and/or guidance provided in adults with some account for expected pediatric response. Guidance for managing drug therapy in children is clearly desirable. Our objectives were to construct key performance indicators (KPIs) for pediatric pharmacotherapy guidance to identify drugs where pharmacotherapy guidance would be most beneficial. A pilot survey to assess variation in caregiver appreciation for pediatric dosing guidance has also been constructed to provide a complementary subjective assessment. Three KPI categories, drug utilization (based on hospital admission and billing data collected from 2001 through 2006), medical need, and guidance outcome value along with a KPI composite score have been proposed. Low scores are favored with respect to prioritization for pharmacotherapy guidance. The pilot survey consisted of 15 questions to assess 1) physician knowledge regarding dosing guidance, 2) attitudes toward dose modification and patient individualization, 3) the accessibility, ease of use and appropriateness of existing data stores, and 4) frequency of dosing modification, consultation of dosing compendiums and estimate of success rate in dosing guidance. Pilot results suggest that dosing guidance is generally viewed as important and that the existing resources are insufficient to guide recommendations for all drugs. While the majority of respondents check more than one resource less than 25% of the time, at least 25% of the respondents check more than one resource 25-50% of the time. The majority viewed the relevance of dosing guidance very important to the management of drug therapy. The questionnaire is being extended to the primary care centers, the Kids First Network and specialty care centers. Results will guide the development of decision support systems (DSS) that provide patient

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…

Middle School Developmental Guidance. "Steps to Success."

ERIC Educational Resources Information Center

Orange County Public Schools, Orlando, FL.

This document articulates the goals and objectives of the middle school guidance program in Orange County, Florida Public Schools system. Professional roles and responsibilities are discussed, as well as program implementation. These goals to assist students are listed for the middle school guidance program: (1) understanding the school…

Highly Effective Photonic Cue for Repulsive Axonal Guidance

PubMed Central

Black, Bryan J.; Gu, Ling; Mohanty, Samarendra K.

2014-01-01

In vivo nerve repair requires not only the ability to regenerate damaged axons, but most importantly, the ability to guide developing or regenerating axons along paths that will result in functional connections. Furthermore, basic studies in neuroscience and neuro-electronic interface design require the ability to construct in vitro neural circuitry. Both these applications require the development of a noninvasive, highly effective tool for axonal growth-cone guidance. To date, a myriad of technologies have been introduced based on chemical, electrical, mechanical, and hybrid approaches (such as electro-chemical, optofluidic flow and photo-chemical methods). These methods are either lacking in desired spatial and temporal selectivity or require the introduction of invasive external factors. Within the last fifteen years however, several attractive guidance cues have been developed using purely light based cues to achieve axonal guidance. Here, we report a novel, purely optical repulsive guidance technique that uses low power, near infrared light, and demonstrates the guidance of primary goldfish retinal ganglion cell axons through turns of up to 120 degrees and over distances of ∼90 µm. PMID:24717339

Highly effective photonic cue for repulsive axonal guidance.

PubMed

Black, Bryan J; Gu, Ling; Mohanty, Samarendra K

2014-01-01

In vivo nerve repair requires not only the ability to regenerate damaged axons, but most importantly, the ability to guide developing or regenerating axons along paths that will result in functional connections. Furthermore, basic studies in neuroscience and neuro-electronic interface design require the ability to construct in vitro neural circuitry. Both these applications require the development of a noninvasive, highly effective tool for axonal growth-cone guidance. To date, a myriad of technologies have been introduced based on chemical, electrical, mechanical, and hybrid approaches (such as electro-chemical, optofluidic flow and photo-chemical methods). These methods are either lacking in desired spatial and temporal selectivity or require the introduction of invasive external factors. Within the last fifteen years however, several attractive guidance cues have been developed using purely light based cues to achieve axonal guidance. Here, we report a novel, purely optical repulsive guidance technique that uses low power, near infrared light, and demonstrates the guidance of primary goldfish retinal ganglion cell axons through turns of up to 120 degrees and over distances of ∼90 µm.

Guidance of Nonlinear Nonminimum-Phase Dynamic Systems

NASA Technical Reports Server (NTRS)

Devasia, Santosh

1996-01-01

The research work has advanced the inversion-based guidance theory for: systems with non-hyperbolic internal dynamics; systems with parameter jumps; and systems where a redesign of the output trajectory is desired. A technique to achieve output tracking for nonminimum phase linear systems with non-hyperbolic and near non-hyperbolic internal dynamics was developed. This approach integrated stable inversion techniques, that achieve exact-tracking, with approximation techniques, that modify the internal dynamics to achieve desirable performance. Such modification of the internal dynamics was used (a) to remove non-hyperbolicity which is an obstruction to applying stable inversion techniques and (b) to reduce large preactuation times needed to apply stable inversion for near non-hyperbolic cases. The method was applied to an example helicopter hover control problem with near non-hyperbolic internal dynamics for illustrating the trade-off between exact tracking and reduction of preactuation time. Future work will extend these results to guidance of nonlinear non-hyperbolic systems. The exact output tracking problem for systems with parameter jumps was considered. Necessary and sufficient conditions were derived for the elimination of switching-introduced output transient. While previous works had studied this problem by developing a regulator that maintains exact tracking through parameter jumps (switches), such techniques are, however, only applicable to minimum-phase systems. In contrast, our approach is also applicable to nonminimum-phase systems and leads to bounded but possibly non-causal solutions. In addition, for the case when the reference trajectories are generated by an exosystem, we developed an exact-tracking controller which could be written in a feedback form. As in standard regulator theory, we also obtained a linear map from the states of the exosystem to the desired system state, which was defined via a matrix differential equation.

American Society of Clinical Oncology guidance statement: the cost of cancer care.

PubMed

Meropol, Neal J; Schrag, Deborah; Smith, Thomas J; Mulvey, Therese M; Langdon, Robert M; Blum, Diane; Ubel, Peter A; Schnipper, Lowell E

2009-08-10

Advances in early detection, prevention, and treatment have resulted in consistently falling cancer death rates in the United States. In parallel with these advances have come significant increases in the cost of cancer care. It is well established that the cost of health care (including cancer care) in the United States is growing more rapidly than the overall economy. In part, this is a result of the prices and rapid uptake of new agents and other technologies, including advances in imaging and therapeutic radiology. Conventional understanding suggests that high prices may reflect the costs and risks associated with the development, production, and marketing of new drugs and technologies, many of which are valued highly by physicians, patients, and payers. The increasing cost of cancer care impacts many stakeholders who play a role in a complex health care system. Our patients are the most vulnerable because they often experience uneven insurance coverage, leading to financial strain or even ruin. Other key groups include pharmaceutical manufacturers that pass along research, development, and marketing costs to the consumer; providers of cancer care who dispense increasingly expensive drugs and technologies; and the insurance industry, which ultimately passes costs to consumers. Increasingly, the economic burden of health care in general, and high-quality cancer care in particular, will be less and less affordable for an increasing number of Americans unless steps are taken to curb current trends. The American Society of Clinical Oncology (ASCO) is committed to improving cancer prevention, diagnosis, and treatment and eliminating disparities in cancer care through support of evidence-based and cost-effective practices. To address this goal, ASCO established a Cost of Care Task Force, which has developed this Guidance Statement on the Cost of Cancer Care. This Guidance Statement provides a concise overview of the economic issues facing stakeholders in the cancer

Parental attitudes regarding behavior guidance of dental patients with autism.

PubMed

Marshall, Jennifer; Sheller, Barbara; Mancl, Lloyd; Williams, Bryan J

2008-01-01

The purposes of this study were to evaluate: (1) parents' ability to predict dental treatment cooperation by their autistic child; (2) behavior guidance techniques (BGTs) used during treatment; and (3) parental attitudes regarding basic and advanced BGTs. Data were collected from 85 parent/autistic child pairs and their dentists using surveys and treatment records. Parents most accurately predicted if their child would permit an examination in the dental chair (> or = 88%) and would cooperate for radiographs (> or = 84%). BGTs utilized most often (> 50%) were positive verbal reinforcement (PVR), tell-show-do (TSD), mouthprops, and rewards. In general, basic BGTs were more acceptable (> 81%) than advanced BGTs (>54%). The most acceptable techniques (>90%) in order were: PVR, TSD, distraction, rewards, general anesthesia, hand-holding by parent, and mouth-props. When parents evaluated only BGTs used for their child, all BGTs, including a stabilization device, were highly acceptable (> 91%), except for staff restraint (74%). Parents were accurate in predicting cooperation for some procedures. The most acceptable and efficacious BGTs in order were: PVR, TSD, distraction, rewards, and hand-holding by parent. Parental perceptions of BGTs were influenced by whether or not they had been used for their child.

Automatic guidance and control laws for helicopter obstacle avoidance

NASA Technical Reports Server (NTRS)

Cheng, Victor H. L.; Lam, T.

1992-01-01

The authors describe the implementation of a full-function guidance and control system for automatic obstacle avoidance in helicopter nap-of-the-earth (NOE) flight. The guidance function assumes that the helicopter is sufficiently responsive so that the flight path can be readily adjusted at NOE speeds. The controller, basically an autopilot for following the derived flight path, was implemented with parameter values to control a generic helicopter model used in the simulation. Evaluation of the guidance and control system with a 3-dimensional graphical helicopter simulation suggests that the guidance has the potential for providing good and meaningful flight trajectories.

Waypoints Following Guidance for Surface-to-Surface Missiles

NASA Astrophysics Data System (ADS)

Zhou, Hao; Khalil, Elsayed M.; Rahman, Tawfiqur; Chen, Wanchun

2018-04-01

The paper proposes waypoints following guidance law. In this method an optimal trajectory is first generated which is then represented through a set of waypoints that are distributed from the starting point up to the final target point using a polynomial. The guidance system then works by issuing guidance command needed to move from one waypoint to the next one. Here the method is applied for a surface-to-surface missile. The results show that the method is feasible for on-board application.

Design and Testing of a Low Noise Flight Guidance Concept

NASA Technical Reports Server (NTRS)

Williams, David H.; Oseguera-Lohr, Rosa M.; Lewis, Elliot T.

2004-01-01

A flight guidance concept was developed to assist in flying continuous descent approach (CDA) procedures designed to lower the noise under the flight path of jet transport aircraft during arrival operations at an airport. The guidance consists of a trajectory prediction algorithm that was tuned to produce a high-efficiency, low noise flight profile with accompanying autopilot and flight display elements needed by the flight control system and pilot to fly the approach. A key component of the flight guidance was a real-time display of energy error relative to the predicted flight path. The guidance was integrated with the conventional Flight Management System (FMS) guidance of a modern jet transport airplane and tested in a high fidelity flight simulation. A charted arrival procedure, which allowed flying conventional arrivals, CDA arrivals with standard guidance, and CDA arrivals with the new low noise guidance, was developed to assist in the testing and evaluation of the low noise guidance concept. Results of the simulation testing showed the low noise guidance was easy to use by airline pilot test subjects and effective in achieving the desired noise reduction. Noise under the flight path was reduced by at least 2 decibels in Sound Exposure Level (SEL) at distances from about 3 nautical miles out to about 17.5 nautical miles from the runway, with a peak reduction of 8.5 decibels at about 10.5 nautical miles. Fuel consumption was also reduced by about 17% for the LNG conditions compared to baseline runs for the same flight distance. Pilot acceptance and understanding of the guidance was quite high with favorable comments and ratings received from all test subjects.

Dynamic mobility applications policy analysis : policy and institutional issues for freight advanced traveler information systems (FRATIS).

DOT National Transportation Integrated Search

2014-10-30

This report documents policy considerations for the Freight Advanced Traveler Information System, or FRATIS. FRATIS applications provide freight-specific route guidance and optimize drayage operations so that load movements are coordinated between fr...

Flu Vaccine Guidance for Patients with Immune Deficiency

MedlinePlus

... Vaccine Guidance for Patients with Immune Deficiency Share | Flu Vaccine Guidance for Patients with Immune Deficiency This ... is the best tool for prevention of the flu, should patients with immune deficiency be given the ...

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.

Novel agents for advanced pancreatic cancer

PubMed Central

Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

2015-01-01

Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

76 FR 411 - Regulatory Guidance Concerning Electronic Signatures and Documents

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-04

... Concerning Electronic Signatures and Documents AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of regulatory guidance. SUMMARY: FMCSA issues regulatory guidance concerning the... regulatory guidance concerning the use of electronic signatures and documents to comply with FMCSA...

Mission-based guidance system design for autonomous UAVs

NASA Astrophysics Data System (ADS)

Moon, Jongki

The advantages of UAVs in the aviation arena have led to extensive research activities on autonomous technology of UAVs to achieve specific mission objectives. This thesis mainly focuses on the development of a mission-based guidance system. Among various missions expected for future needs, autonomous formation flight (AFF) and obstacle avoidance within safe operation limits are investigated. In the design of an adaptive guidance system for AFF, the leader information except position is assumed to be unknown to a follower. Thus, the only measured information related to the leader is the line-of-sight (LOS) range and angle. Adding an adaptive element with neural networks into the guidance system provides a capability to effectively handle leader's velocity changes. Therefore, this method can be applied to the AFF control systems that use a passive sensing method. In this thesis, an adaptive velocity command guidance system and an adaptive acceleration command guidance system are developed and presented. Since relative degrees of the LOS range and angle are different depending on the outputs from the guidance system, the architecture of the guidance system changes accordingly. Simulations and flight tests are performed using the Georgia Tech UAV helicopter, the GTMax, to evaluate the proposed guidance systems. The simulation results show that the neural network (NN) based adaptive element can improve the tracking performance by effectively compensating for the effect of unknown dynamics. It has also been shown that the combination of an adaptive velocity command guidance system and the existing GTMax autopilot controller performs better than the combination of an adaptive acceleration command guidance system and the GTMax autopilot controller. The successful flight evaluation using an adaptive velocity command guidance system clearly shows that the adaptive guidance control system is a promising solution for autonomous formation flight of UAVs. In addition, an

The Well-Being Outcomes of Career Guidance

ERIC Educational Resources Information Center

Robertson, Peter J.

2013-01-01

The potential for career guidance to impact on well-being has received insufficient attention in the UK. There are both conceptual and empirical reasons to expect that the impacts may be positive, but a lack of evidence directly testing this proposition. Career guidance has commonalities with therapeutic counselling suggesting analogous effects,…

Bioinformatic Integration of Molecular Networks and Major Pathways Involved in Mice Cochlear and Vestibular Supporting Cells.

PubMed

Requena, Teresa; Gallego-Martinez, Alvaro; Lopez-Escamez, Jose A

2018-01-01

Background : Cochlear and vestibular epithelial non-hair cells (ENHCs) are the supporting elements of the cellular architecture in the organ of Corti and the vestibular neuroepithelium in the inner ear. Intercellular and cell-extracellular matrix interactions are essential to prevent an abnormal ion redistribution leading to hearing and vestibular loss. The aim of this study is to define the main pathways and molecular networks in the mouse ENHCs. Methods : We retrieved microarray and RNA-seq datasets from mouse epithelial sensory and non-sensory cells from gEAR portal (http://umgear.org/index.html) and obtained gene expression fold-change between ENHCs and non-epithelial cells (NECs) against HCs for each gene. Differentially expressed genes (DEG) with a log2 fold change between 1 and -1 were discarded. The remaining genes were selected to search for interactions using Ingenuity Pathway Analysis and STRING platform. Specific molecular networks for ENHCs in the cochlea and the vestibular organs were generated and significant pathways were identified. Results : Between 1723 and 1559 DEG were found in the mouse cochlear and vestibular tissues, respectively. Six main pathways showed enrichment in the supporting cells in both tissues: (1) "Inhibition of Matrix Metalloproteases"; (2) "Calcium Transport I"; (3) "Calcium Signaling"; (4) "Leukocyte Extravasation Signaling"; (5) "Signaling by Rho Family GTPases"; and (6) "Axonal Guidance Si". In the mouse cochlea, ENHCs showed a significant enrichment in 18 pathways highlighting "axonal guidance signaling (AGS)" ( p = 4.37 × 10 -8 ) and "RhoGDI Signaling" ( p = 3.31 × 10 -8 ). In the vestibular dataset, there were 20 enriched pathways in ENHCs, the most significant being "Leukocyte Extravasation Signaling" ( p = 8.71 × 10 -6 ), "Signaling by Rho Family GTPases" ( p = 1.20 × 10 -5 ) and "Calcium Signaling" ( p = 1.20 × 10 -5 ). Among the top ranked networks, the most biologically significant network contained the

Pre-Publication to the Planning for Natural Disaster Debris Guidance

EPA Pesticide Factsheets

EPA is requesting comment on the draft update of the Planning for Natural Disaster Debris Guidance, along with two other documents. This Guidance is an update of the Planning for Natural Disaster Debris guidance that EPA published in March 2008.

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.

Wallerian Degeneration Beyond the Corticospinal Tracts: Conventional and Advanced MRI Findings.

PubMed

Chen, Yin Jie; Nabavizadeh, Seyed Ali; Vossough, Arastoo; Kumar, Sunil; Loevner, Laurie A; Mohan, Suyash

2017-05-01

Wallerian degeneration (WD) is defined as progressive anterograde disintegration of axons and accompanying demyelination after an injury to the proximal axon or cell body. Since the 1980s and 1990s, conventional magnetic resonance imaging (MRI) sequences have been shown to be sensitive to changes of WD in the subacute to chronic phases. More recently, advanced MRI techniques, such as diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI), have demonstrated some of earliest changes attributed to acute WD, typically on the order of days. In addition, there is increasing evidence on the value of advanced MRI techniques in providing important prognostic information related to WD. This article reviews the utility of conventional and advanced MRI techniques for assessing WD, by focusing not only on the corticospinal tract but also other neural tracts less commonly thought of, including corticopontocerebellar tract, dentate-rubro-olivary pathway, posterior column of the spinal cord, corpus callosum, limbic circuit, and optic pathway. The basic anatomy of these neural pathways will be discussed, followed by a comprehensive review of existing literature supported by instructive clinical examples. The goal of this review is for readers to become more familiar with both conventional and advanced MRI findings of WD involving important neural pathways, as well as to illustrate increasing utility of advanced MRI techniques in providing important prognostic information for various pathologies. Copyright © 2016 by the American Society of Neuroimaging.

Profile of vismodegib and its potential in the treatment of advanced basal cell carcinoma.

PubMed

Macha, Muzafar A; Batra, Surinder K; Ganti, Apar Kishor

2013-01-01

Basal cell carcinoma (BCC) is the most common human malignancy. Recent advances in our understanding of the critical biologic pathways implicated in the development and progression of BCC have led to the development of the first molecular targeted therapy for this disease. The hedgehog pathway is mutated in virtually all patients with BCC and recent trials with vismodegib, an inhibitor of this pathway, have shown significant responses. This review will discuss the importance of the hedgehog pathway in the pathogenesis of BCC and describe in detail the pharmacology of vismodegib in relation to its activity in advanced BCC.

Profile of vismodegib and its potential in the treatment of advanced basal cell carcinoma

PubMed Central

Macha, Muzafar A; Batra, Surinder K; Ganti, Apar Kishor

2013-01-01

Basal cell carcinoma (BCC) is the most common human malignancy. Recent advances in our understanding of the critical biologic pathways implicated in the development and progression of BCC have led to the development of the first molecular targeted therapy for this disease. The hedgehog pathway is mutated in virtually all patients with BCC and recent trials with vismodegib, an inhibitor of this pathway, have shown significant responses. This review will discuss the importance of the hedgehog pathway in the pathogenesis of BCC and describe in detail the pharmacology of vismodegib in relation to its activity in advanced BCC. PMID:23940421

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…

WIPP waste characterization program sampling and analysis guidance manual

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

Not Available

1991-01-01

The Waste Isolation Pilot Plant (WIPP) Waste Characterization Program Sampling and Analysis Guidance Manual (Guidance Manual) provides a unified source of information on the sampling and analytical techniques that enable Department of Energy (DOE) facilities to comply with the requirements established in the current revision of the Quality Assurance Program Plan (QAPP) for the WIPP Experimental-Waste Characterization Program (the Program). This Guidance Manual includes all of the sampling and testing methodologies accepted by the WIPP Project Office (DOE/WPO) for use in implementing the Program requirements specified in the QAPP. This includes methods for characterizing representative samples of transuranic (TRU) wastesmore » at DOE generator sites with respect to the gas generation controlling variables defined in the WIPP bin-scale and alcove test plans, as well as waste container headspace gas sampling and analytical procedures to support waste characterization requirements under the WIPP test program and the Resource Conservation and Recovery Act (RCRA). The procedures in this Guidance Manual are comprehensive and detailed and are designed to provide the necessary guidance for the preparation of site specific procedures. The use of these procedures is intended to provide the necessary sensitivity, specificity, precision, and comparability of analyses and test results. The solutions to achieving specific program objectives will depend upon facility constraints, compliance with DOE Orders and DOE facilities' operating contractor requirements, and the knowledge and experience of the TRU waste handlers and analysts. With some analytical methods, such as gas chromatography/mass spectrometry, the Guidance Manual procedures may be used directly. With other methods, such as nondestructive/destructive characterization, the Guidance Manual provides guidance rather than a step-by-step procedure.« less

A Decade in the MIST: Learnings from Investigations of Drug Metabolites in Drug Development under the "Metabolites in Safety Testing" Regulatory Guidance.

PubMed

Schadt, Simone; Bister, Bojan; Chowdhury, Swapan K; Funk, Christoph; Hop, Cornelis E C A; Humphreys, W Griffith; Igarashi, Fumihiko; James, Alexander D; Kagan, Mark; Khojasteh, S Cyrus; Nedderman, Angus N R; Prakash, Chandra; Runge, Frank; Scheible, Holger; Spracklin, Douglas K; Swart, Piet; Tse, Susanna; Yuan, Josh; Obach, R Scott

2018-06-01

Since the introduction of metabolites in safety testing (MIST) guidance by the Food and Drug Administration in 2008, major changes have occurred in the experimental methods for the identification and quantification of metabolites, ways to evaluate coverage of metabolites, and the timing of critical clinical and nonclinical studies to generate this information. In this cross-industry review, we discuss how the increased focus on human drug metabolites and their potential contribution to safety and drug-drug interactions has influenced the approaches taken by industry for the identification and quantitation of human drug metabolites. Before the MIST guidance was issued, the method of choice for generating comprehensive metabolite profile was radio chromatography. The MIST guidance increased the focus on human drug metabolites and their potential contribution to safety and drug-drug interactions and led to changes in the practices of drug metabolism scientists. In addition, the guidance suggested that human metabolism studies should also be accelerated, which has led to more frequent determination of human metabolite profiles from multiple ascending-dose clinical studies. Generating a comprehensive and quantitative profile of human metabolites has become a more urgent task. Together with technological advances, these events have led to a general shift of focus toward earlier human metabolism studies using high-resolution mass spectrometry and to a reduction in animal radiolabel absorption/distribution/metabolism/excretion studies. The changes induced by the MIST guidance are highlighted by six case studies included herein, reflecting different stages of implementation of the MIST guidance within the pharmaceutical industry. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

G-Guidance Interface Design for Small Body Mission Simulation

NASA Technical Reports Server (NTRS)

Acikmese, Behcet; Carson, John; Phan, Linh

2008-01-01

The G-Guidance software implements a guidance and control (G and C) algorithm for small-body, autonomous proximity operations, developed under the Small Body GN and C task at JPL. The software is written in Matlab and interfaces with G-OPT, a JPL-developed optimization package written in C that provides G-Guidance with guaranteed convergence to a solution in a finite computation time with a prescribed accuracy. The resulting program is computationally efficient and is a prototype of an onboard, real-time algorithm for autonomous guidance and control. Two thruster firing schemes are available in G-Guidance, allowing tailoring of the software for specific mission maneuvers. For example, descent, landing, or rendezvous benefit from a thruster firing at the maneuver termination to mitigate velocity errors. Conversely, ascent or separation maneuvers benefit from an immediate firing to avoid potential drift toward a second body. The guidance portion of this software explicitly enforces user-defined control constraints and thruster silence times while minimizing total fuel usage. This program is currently specialized to small-body proximity operations, but the underlying method can be generalized to other applications.

Initial contact guidance during cell spreading is contractility-independent.

PubMed

Sales, Adrià; Holle, Andrew W; Kemkemer, Ralf

2017-08-02

A wide variety of cell types exhibit substrate topography-based behavior, also known as contact guidance. However, the precise cellular mechanisms underlying this process are still unknown. In this study, we investigated contact guidance by studying the reaction of human endothelial cells (ECs) to well-defined microgroove topographies, both during and after initial cell spreading. As the cytoskeleton plays a major role in cellular adaptation to topographical features, two methods were used to perturb cytoskeletal structures. Inhibition of actomyosin contractility with the chemical inhibitor blebbistatatin demonstrated that initial contact guidance events are independent of traction force generation. However, cell alignment to the grooved substrate was altered at later time points, suggesting an initial 'passive' phase of contact guidance, followed by a contractility-dependent 'active' phase that relies on mechanosensitive feedback. The actin cytoskeleton was also perturbed in an indirect manner by culturing cells upside down, resulting in decreased levels of contact guidance and suggesting that a possible loss of contact between the actin cytoskeleton and the substrate could lead to cytoskeleton impairment. The process of contact guidance at the microscale was found to be primarily lamellipodia driven, as no bias in filopodia extension was observed on micron-scale grooves.

Methods of Farm Guidance

ERIC Educational Resources Information Center

Vir, Dharm

1971-01-01

A survey of teaching methods for farm guidance workers in India, outlining some approaches developed by and used in other nations. Discusses mass educational methods, group educational methods, and the local leadership method. (JB)

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.

Career Guidance Continuum.

ERIC Educational Resources Information Center

Varmecky, John A.

1989-01-01

Describes the art career guidance programs at Johnstown High School (Pennsylvania). Programs include high school art students' visits to elementary and junior high schools, an "Artist at Work" exhibit at a shopping mall, and an art career guide for high school students. The programs have increased interest in art careers from grade…

Development and installation of an advanced beam guidance system on Viking`s 2.4 megawatt EB furnace

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

Motchenbacher, C.A.; Grosse, I.A.

1994-12-31

Viking Metallurgical is a manufacturer of titanium alloy and superalloy seamless ring forgings for the aerospace industry. For more than 20 years Viking has used electron beam cold hearth melting to recover titanium alloy scrap and to produce commercially pure titanium ingot for direct forging. In the 1970`s Viking pioneered electron beam cold hearth melting and in 1983 added a two-gun, 2.4 MW furnace. As part of Vikings efforts to improve process control we have commissioned and installed a new electron beam guidance system. The system is capable of generating virtually unlimited EB patterns resulting in improved melt control.

Quieter pavements guidance document

DOT National Transportation Integrated Search

2013-02-01

This report provides guidance and better practice recommendations to the National Park : Service for selecting pavement surfaces to minimize tire-pavement noise. The report : contains an overview of common technologies and methods for quieter pavemen...

Minimal metabolic pathway structure is consistent with associated biomolecular interactions

PubMed Central

Bordbar, Aarash; Nagarajan, Harish; Lewis, Nathan E; Latif, Haythem; Ebrahim, Ali; Federowicz, Stephen; Schellenberger, Jan; Palsson, Bernhard O

2014-01-01

Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we introduce an unbiased, pathway structure for genome-scale metabolic networks defined based on principles of parsimony that do not mimic canonical human-defined textbook pathways. Instead, these minimal pathways better describe multiple independent pathway-associated biomolecular interaction datasets suggesting a functional organization for metabolism based on parsimonious use of cellular components. We use the inherent predictive capability of these pathways to experimentally discover novel transcriptional regulatory interactions in Escherichia coli metabolism for three transcription factors, effectively doubling the known regulatory roles for Nac and MntR. This study suggests an underlying and fundamental principle in the evolutionary selection of pathway structures; namely, that pathways may be minimal, independent, and segregated. PMID:24987116

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.

Emerging role of Hippo signalling pathway in bladder cancer.

PubMed

Xia, Jianling; Zeng, Ming; Zhu, Hua; Chen, Xiangjian; Weng, Zhiliang; Li, Shi

2018-01-01

Bladder cancer (BC) is one of the most common cancers worldwide with a high progression rate and poor prognosis. The Hippo signalling pathway is a conserved pathway that plays a crucial role in cellular proliferation, differentiation and apoptosis. Furthermore, dysregulation and/or malfunction of the Hippo pathway is common in various human tumours, including BC. In this review, an overview of the Hippo pathway in BC and other cancers is presented. We focus on recent data regarding the Hippo pathway, its network and the regulation of the downstream co-effectors YAP1/TAZ. The core components of the Hippo pathway, which induce BC stemness acquisition, metastasis and chemoresistance, will be emphasized. Additional research on the Hippo pathway will advance our understanding of the mechanism of BC as well as the development and progression of other cancers and may be exploited therapeutically. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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